Publications by authors named "Massimo De Martinis"

49 Publications

Invasive Ductal Breast Cancer with Osteoclast-Like Giant Cells: A Case Report Based on the Gene Expression Profile for Changes in Management.

J Pers Med 2021 Feb 23;11(2). Epub 2021 Feb 23.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

We report the case of a 49-year-old woman diagnosed with a rare histotype of early breast cancer (BC), invasive ductal carcinoma with osteoclast-like giant cells (OGCs), from the perspective of gene profile analysis tests. The patient underwent a quadrantectomy of the right breast with removal of 2 cm neoplastic nodule and three ipsilateral sentinel lymph nodes. The Oncotype Dx gave a recurrence score (RS) of 23, and taking into account the patient's age, an RS of 23 corresponds to a chemotherapy benefit of 6.5%. After a multidisciplinary collegial discussion, and in consideration of the patient's age, the absence of comorbidity, the premenopausal state, the rare histotype and the Oncotype Dx report, the patient was offered adjuvant chemotherapy treatment followed by hormone therapy. This case may be an example of the utility of integrating gene expression profiling tests into clinical practice in the adjuvant treatment decision of a rare histotype BC. The Oncotype Dx test required to supplement the histological examination made us opt for the proposal of a combined treatment of adjuvant chemotherapy followed by adjuvant hormone therapy. It demonstrates the importance of considering molecular tests and, in particular, the Oncotype Dx, in estimating the risk of disease recovery at 10 years in order to identify patients who benefit from hormone therapy alone versus those who benefit from the addition of chemotherapy, all with a view toward patient-centered oncology. Here, we discuss the possible validity and limitations of the Oncotype Dx in a rare luminal A-like histotype with high infiltrate of stromal/inflammatory cells.
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http://dx.doi.org/10.3390/jpm11020156DOI Listing
February 2021

Bone Health Risks Associated with Finasteride and Dutasteride Long-Term Use.

World J Mens Health 2020 Nov 26. Epub 2020 Nov 26.

Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

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http://dx.doi.org/10.5534/wjmh.200138DOI Listing
November 2020

Predicting cardiovascular involvement in systemic sclerosis for a timely and better treatment approach.

Eur J Prev Cardiol 2020 Jun 16. Epub 2020 Jun 16.

Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy.

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http://dx.doi.org/10.1177/2047487320932256DOI Listing
June 2020

IL-33/Vitamin D Crosstalk in Psoriasis-Associated Osteoporosis.

Front Immunol 2020 8;11:604055. Epub 2021 Jan 8.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Patients with psoriasis (Pso) and, in particular, psoriatic arthritis (PsoA) have an increased risk of developing osteoporosis (OP). It has been shown that OP is among the more common pathologies associated with Pso, mainly due to the well-known osteopenizing conditions coexisting in these patients. Pso and OP share common risk factors, such as vitamin D deficiency and chronic inflammation. Interestingly, the interleukin (IL)-33/ST2 axis, together with vitamin D, is closely related to both Pso and OP. Vitamin D and the IL-33/ST2 signaling pathways are closely involved in bone remodeling, as well as in skin barrier pathophysiology. The production of anti-osteoclastogenic cytokines, e.g., IL-4 and IL-10, is promoted by IL-33 and vitamin D, which are stimulators of both regulatory and Th2 cells. IL-33, together with other Th2 cytokines, shifts osteoclast precursor differentiation towards macrophage and dendritic cells and inhibits receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis by regulating the expression of anti-osteoclastic genes. However, while the vitamin D protective functions in OP and Pso have been definitively ascertained, the overall effect of IL-33 on bone and skin homeostasis, because of its pleiotropic action, is still controversial. Emerging evidence suggests a functional link between vitamin D and the IL-33/ST2 axis, which acts through hormonal influences and immune-mediated effects, as well as cellular and metabolic functions. Based on the actions of vitamin D and IL-33 in Pso and OP, here, we hypothesize the role of their crosstalk in the pathogenesis of both these pathologies.
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http://dx.doi.org/10.3389/fimmu.2020.604055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819870PMC
January 2021

Gender Differences in Osteoporosis: A Single-Center Observational Study.

World J Mens Health 2020 Nov 26. Epub 2020 Nov 26.

Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

Purpose: Osteoporosis affects more than 200 million people worldwide: its prevalence increases with age and is actually growing due to the constant population aging. Women are at greater risk than men, but in recent years it has become increasingly evident that osteoporosis represents a significantly important problem also for men. However, osteoporosis in men is still poorly studied, underdiagnosed and inadequately treated.

Materials And Methods: We conducted an observational study to identify any gender disparities in osteoporosis screening. For this purpose we observed people consecutively admitted at our Outpatient Service for the Diagnosis of Osteoporosis during the last 3 years. Patients underwent clinical and laboratory assessment and bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry. Bone turnover serum markers have been evaluated and stratified according to gender.

Results: Out of 3,752 patients, 2,376 subjects who met the inclusion criteria were identified. As expected, the great majority (94.5%) of the screened subjects were women and only 5.4% were men. Women exhibited lower BMD compared to men (T-score values: -2.33±1.14 vs. -1.31±1.55; p<0.001), whereas the prevalence of fractures in osteoporotic men was significantly higher (50% vs. 31%; p<0.001). Women had lower vitamin D and higher bone remodeling markers compared to men. Secondary osteoporosis was more frequent in men (66.67%) than in women (20.83%) and the calculated risk for hip fractures was higher in osteoporotic men compared to women (11.47±10.62 vs. 6.87±7.73; p<0.001).

Conclusions: Here we highlighted that men are under-screened for osteoporosis and exhibit secondary osteoporosis more frequently than women.
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http://dx.doi.org/10.5534/wjmh.200099DOI Listing
November 2020

Denosumab in breast cancer patients receiving aromatase inhibitors: A single-center observational study of effectiveness in adjuvant setting.

Indian J Cancer 2020 10 17. Epub 2020 Oct 17.

Allergy and Clinical Immunology Unit, Center for the Diagnosis and Treatment of Osteoporosis, AUSL 04 Teramo; Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy.

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http://dx.doi.org/10.4103/ijc.IJC_16_20DOI Listing
October 2020

MicroRNAs, bone and microbiota.

Bone 2021 Mar 23;144:115824. Epub 2020 Dec 23.

Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy; Allergy and Clinical Immunology Unit, Center for the diagnosis and treatment of Osteoporosis, AUSL 04 Teramo, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.bone.2020.115824DOI Listing
March 2021

The Osteoporosis/Microbiota Linkage: The Role of miRNA.

Int J Mol Sci 2020 Nov 24;21(23). Epub 2020 Nov 24.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.
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http://dx.doi.org/10.3390/ijms21238887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727697PMC
November 2020

Real-life use of denosumab 120 mg every 12 weeks in prolonged treatment over 2 years of patients with breast cancer bone metastases.

J BUON 2020 Jul-Aug;25(4):1799-1804

Medical Oncology Unit, Department of Oncology, AUSL 04 Teramo, Italy.

Purpose: To analyze the activity and safety of denosumab (DNS) 120 mg every 3 months over 2 years of standard treatment (120 mg SC every 4 weeks) of patients with breast cancer bone metastases in real life.

Methods: We prospectively analyzed the activity and safety of denosumab 120 mg every 3 months and 120 mg every 4 weeks in the treatment of 22 patients with breast cancer bone metastases over 2 years of standard treatment. All patients received specific concomitant antineoplastic treatment, chemotherapy or endocrine therapy and/or target therapy. Oral daily calcium (≥500 mg) and vitamin D (≥1000 U) supplement was recommended.

Results: Of the 22 patients treated with denosumab, 4 (18.1%) had at least 1 skeletal related event (SRE); 3 (13.6%) had 1 SRE and 1 patient (4.5%) had 2 SRE, all 10% treated with radiotherapy. Overall, no denosumab-related G3 adverse events occurred; in particular, no cases of osteonecrosis of the jaw have been recorded. The decrease in serum calcium levels was mild (G1, 2 patients, 9%), and recovered in a short time (within 2 weeks) with an increase in the oral support of calcium and vitamin D.

Conclusions: Denosumab confirms a good activity profile in terms of delaying and preventing SREs in breast cancer patients and a good safety profile. It represents an optimal treatment resource which doesn't necessitate renal function monitoring and has the convenience of a subcutaneous administration.
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October 2020

Association between Corrected QT Interval and C-Reactive Protein in Patients with Inflammatory Bowel Diseases.

Medicina (Kaunas) 2020 Jul 30;56(8). Epub 2020 Jul 30.

Cardiology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Electrocardiograph abnormalities (i.e., QT interval prolongation) have been described in inflammatory bowel diseases (IBD). We aimed to measure the QT interval in a cohort of patients with IBD and to analyze its relationship with clinical and inflammatory activity. We performed a cross-sectional study that included 38 IBD outpatients and 38 "age- and sex-matched" healthy controls. Nine patients had active IBD, and 29 were in clinical remission. Among the latter, 10 patients had sustained (lasting >1 year) and 19 had short-term remission (≤1 year). Corrected QT (QTc) interval was measured on standard 12-lead electrocardiograph. A systematic review of the literature on studies investigating the QT interval in patients with IBD was also performed. QTc interval values were similar between IBD patients and healthy controls (417.58 ± 22.05 ms vs. 409.13 ± 19.61 ms, respectively; : 0.479). Patients with active IBD had significantly higher QTc values (435.11 ± 27.31 ms) than both controls (409.13 ± 19.61 ms) and patients in remission (412.14 ± 17.33 ms) (: 0.031). Post hoc analysis showed that the difference in QTc values between active IBD and remission was attributable to the group of patients with sustained remission ( < 0.05). Lastly, a significant correlation between QTc interval and C-reactive protein (CRP) values was observed (Spearman test: r = 0.563; : 0.0005). Our study demonstrates an association between QTc duration and both clinical and inflammatory activity in patients with IBD. The higher the CRP value, the longer is the QTc duration. For practical purposes, all patients with active IBD should undergo a standard ECG. Prescription of drugs able to modify the QT interval should be avoided in patients with active IBD. The systematic review of the literature indicated that this is the first published study demonstrating an association between the QTc duration and CRP values in patients with IBD.
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http://dx.doi.org/10.3390/medicina56080382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466199PMC
July 2020

Sex and Gender Influences on Cancer Immunotherapy Response.

Biomedicines 2020 Jul 21;8(7). Epub 2020 Jul 21.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

The global burden of cancer is growing and a wide disparity in the incidence, malignancy and mortality of different types of cancer between each sex has been demonstrated. The sex specificity of cancer appears to be a relevant issue in the management of the disease, and studies investigating the role of sex and gender are becoming extremely urgent. Sex hormones are presumably the leading actors of sex differences in cancer, especially estrogens. They modulate gene expression, alter molecules and generate disparities in effectiveness and side effects of anticancer therapies. Recently immunotherapy aims to improve anticancer treatment strategies reducing off-target effects of chemotherapy and direct cancer cells killing. It is recognized as a fruitful strategy to treat and possible to cure cancer. Immunotherapeutic agents are used to activate or boost the activation of the immune system to fight cancer cells through physiological mechanisms often evaded in the offensive march of the disease. These therapeutic strategies have allowed new successes, but also have serious adverse effects including non-specific inflammation and autoimmunity. Sex and gender issues are of primary importance in this field, due to their recognized role in inflammation, immunity and cancer, and the clarification and understanding of these aspects is a necessary step to increase the responses and to diminish the adverse effects of immunotherapy. This review describes the available knowledge on the role of sex and gender in cancer immunotherapy, and will offer insights to stimulate the attention and practice of clinicians and researchers in a gender perspective of new cancer treatment strategies.
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http://dx.doi.org/10.3390/biomedicines8070232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400663PMC
July 2020

Osteoporosis in Skin Diseases.

Int J Mol Sci 2020 Jul 3;21(13). Epub 2020 Jul 3.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Osteoporosis (OP) is defined as a generalized skeletal disease characterized by low bone mass and an alteration of the microarchitecture that lead to an increase in bone fragility and, therefore, an increased risk of fractures. It must be considered today as a true public health problem and the most widespread metabolic bone disease that affects more than 200 million people worldwide. Under physiological conditions, there is a balance between bone formation and bone resorption necessary for skeletal homeostasis. In pathological situations, this balance is altered in favor of osteoclast (OC)-mediated bone resorption. During chronic inflammation, the balance between bone formation and bone resorption may be considerably affected, contributing to a net prevalence of osteoclastogenesis. Skin diseases are the fourth cause of human disease in the world, affecting approximately one third of the world's population with a prevalence in elderly men. Inflammation and the various associated cytokine patterns are the basis of both osteoporosis and most skin pathologies. Moreover, dermatological patients also undergo local or systemic treatments with glucocorticoids and immunosuppressants that could increase the risk of osteoporosis. Therefore, particular attention should be paid to bone health in these patients. The purpose of the present review is to take stock of the knowledge in this still quite unexplored field, despite the frequency of such conditions in clinical practice.
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http://dx.doi.org/10.3390/ijms21134749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370296PMC
July 2020

Hyperhomocysteinemia is Associated with Inflammation, Bone Resorption, Vitamin B12 and Folate Deficiency and MTHFR C677T Polymorphism in Postmenopausal Women with Decreased Bone Mineral Density.

Int J Environ Res Public Health 2020 06 15;17(12). Epub 2020 Jun 15.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Osteoporosis is an age-related bone disease, affecting mainly postmenopausal women, characterized by decreased bone mineral density (BMD) and consequent risk of fractures. Homocysteine (Hcy), a sulfur-aminoacid whose serum level is regulated by methylenetrahydrofolate reductase (MTHFR) activity and vitamin B12 and folate as cofactors, is a risk factor for inflammatory diseases. Literature data concerning the link between Hcy and osteoporosis are still debated. The aim of our study was to assess the relationship among Hcy and BMD, inflammation, vitamin status and bone turnover in postmenopausal osteoporosis. In 252 postmenopausal women, BMD was measured by dual-energy X-ray absorptiometry (DXA). In addition to serum Hcy, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and bone turnover markers (bone alkaline phosphatase-BAP, osteocalcin-OC, C-terminal telopeptide of type I collagen (CTX), vitamin deficiencies and MTHFR-C677T polymorphism were evaluated. Hcy, inflammation, bone resorption markers and prevalence of C677T polymorphism were higher, whereas vitamin D, B12, folate, and bone formation markers were lower in women with decreased BMD compared to those with normal BMD. Our results suggest a significant association between Hcy, BMD and inflammation in postmenopausal osteoporosis. The regulation of Hcy overproduction and the modulation of the inflammatory substrate could represent additional therapeutic approaches for osteoporosis prevention.
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http://dx.doi.org/10.3390/ijerph17124260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345373PMC
June 2020

Microvascular Damage in a Young Female Archer Assessed by Nailfold Videocapillaroscopy: A Case Report.

Int J Environ Res Public Health 2020 06 12;17(12). Epub 2020 Jun 12.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Archers are known to be exposed to the risk of developing various injuries, including less described microvascular damages, which can however heavily affect the performance of athletes. Nailfold videocapillaroscopy is a safe, proven and non-invasive method that allows us to examine the nail capillaries and diagnose vascular anomalies in athletes suffering from the consequences of microtrauma caused by repeated use of fingertips. The detection of defined capillaroscopic pictures is the basis for the follow-up and suggests carrying out further clinical investigations to exclude underlying pathologies. In women this aspect is even more important since they are more frequently affected by autoimmune diseases such as scleroderma which can cause microcirculation alterations. We report the case of a 16-year-old woman who has been practicing archery for five years. She had been complaining for two years about painful fingertips, worsening in the last year. Through videocapillaroscopy, carried out by using a ×200 optical probe-equipped videocapillaroscope connected to image analyzer software (VideoCap software 3.0; DS Medica, Milan, Italy), we detected changes in the microvasculature compatible with a non-specific pattern. The findings of these anomalies suggest a diagnostic analysis aimed at excluding the presence of systemic diseases such as scleroderma. Once these conditions are excluded, and assuming that the documented alterations are due to the particular muscular effort and vibrations to which the fingers are subjected in shooting, we suggest follow-up to keep under control possible further developments and clinical changes. As far as we know, this is the first report that documents and describes the condition of microvascular changes in an archer. Archers, similar to other athletes who mainly use fingertips such as volleyball players, are more exposed to the development of digital traumas that can induce alterations in the microcirculation. We suggest that a periodic capillaroscopy should be included in the health surveillance program of these athletes, in fact this simple, reliable, non-invasive and inexpensive diagnostic tool is able to recognize early signs of microvascular damage and then suggest indications for further investigations and or follow-up.
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http://dx.doi.org/10.3390/ijerph17124218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344696PMC
June 2020

Predicting cardiovascular involvement in systemic sclerosis for a timely and better treatment approach.

Eur J Prev Cardiol 2020 Jun 15:2047487320932256. Epub 2020 Jun 15.

Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy.

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http://dx.doi.org/10.1177/2047487320932256DOI Listing
June 2020

Breast cancer patients receiving denosumab during adjuvant aromatase inhibitors treatment: who are the "inadequate responders" patients to denosumab?

J BUON 2020 Mar-Apr;25(2):648-654

Medical Oncology Unit, Department of Oncology, AUSL 04 Teramo, Italy.

Purpose: Adjuvant hormone therapy with aromatase inhibitors (AIs) through the induction of tissue hypo-estrogenism induces an increase in osteoclast activity and inhibition of osteoblast activity through the production of RANKL. This is a relevant cause of comorbility in women affected by breast cancer with negative impact on quality of life. We conducted an observational study on patients treated with AIs and denosumab to compare responders and inadequate responders.

Methods: The study design was a historical cohort survey that represented a 42-month follow-up period for patients on hormone treatment with AI for breast cancer and concomitant denosumab (Prolia®) at 60 mg subcutaneously every 6 months. Sixty-eight patients treated consecutively at our Medical Oncology Unit were studied. The comparison was carried out by stratifying on the basis of age, body mass index (BMI), weight, carboxy-terminal collagen crosslink (CTX), lumbar spine and femoral T-scores, FRAX 10-year probability of a fracture, FRAX 10-year probability of a major osteoporotic fracture at baseline and at the end of follow-up.

Results: Calculating and comparing the FRAX 10-year probability of hip fragility fracture at baseline in the subgroup of responders and in the inadequate responders subgroup, we found a statistically significant difference (p=0.039). Similarly, a statistically significant difference was found between the two subgroups of patients in terms of FRAX 10-year probability of hip fragility at the end of follow-up (p=0.014) and FRAX 10-year probability of a mayor osteoporotic fracture at the end of follow-up (p=0.043).

Conclusion: This study suggests the need to control weight in breast cancer survivors and adjuvant AIs treatment in order not only to reduce the incidence of disease relapse but also to safeguard bone health undergoing treatment with denosumab. Indeed, patients tend to respond inadequately to denosumab if they are not careful to control their body weight.
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January 2021

Neuroendocrine Cancer of the Breast: A Rare Entity.

J Clin Med 2020 May 13;9(5). Epub 2020 May 13.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Neuroendocrine breast cancer (NEBC) is a rare histotype of breast carcinoma that presents, in most cases, positive hormone receptors and negative HER2. Indeed, the analysis of gene expression profiles revealed that NEBC belongs mainly to the luminal subtype. Cases of HER2-positive and triple-negative NEBC are rare. The cardinal treatment of early NEBC is surgery, similar to the treatment of invasive non-special histological type carcinoma. The use of radiotherapy follows the criteria applied in infiltrating breast cancer of non-special histotype. In the post-operative phase, therefore after the surgical treatment of mammary quadrantectomy, or mastectomy associated with homolateral sentinel lymph node removal ± axillary dissection, based on the histopathological characteristics of the tumor, the use of chemotherapy (anthracycline + taxane) and/or hormone therapy, whether or not associated with anti-HER2 therapy (trastuzumab) is the rule. Literature data report the use of cisplatin and etoposide, as in small cell lung cancers. Most of the information currently available derive from single case reports or a series of clinical cases; it follows the difficulty of formulating definite recommendations on the correct management of this histological type of breast cancer. This review describes available knowledge on this rare entity to improve the diagnostic and therapeutic strategies and offer insights to stimulate exploration of the many aspects still unknown.
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http://dx.doi.org/10.3390/jcm9051452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291290PMC
May 2020

Food Allergy Insights: A Changing Landscape.

Arch Immunol Ther Exp (Warsz) 2020 Apr 1;68(2). Epub 2020 Apr 1.

Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

The panorama of food allergies (FA) has changed profoundly in recent years. In light of recent advances in knowledge of pathogenetic mechanisms and a greater attention to the multifaceted range of possible clinical manifestations, there is a need for a critical review of past classifications. Changes in nutrition, environment and lifestyles around the world are modifying the global FA epidemiology and new FA phenotypes are also emerging. Furthermore, both biotechnological advances in this field and recent personalized therapies have improved the diagnostic and therapeutic approach to FA. Consequently, both the prevention and clinical management of FA are rapidly changing and new therapeutic strategies are emerging, even revolutionizing the current medical practice. Given the significant increase in the prevalence of FA in recent years, the objective of this review is to provide an updated and complete overview of current knowledge in its etiopathogenesis, diagnostics and therapy, useful not only for a better understanding of this frequent and complex pathology but also for practical guidance in its clinical management.
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http://dx.doi.org/10.1007/s00005-020-00574-6DOI Listing
April 2020

Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review.

Medicina (Kaunas) 2020 Mar 19;56(3). Epub 2020 Mar 19.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy.

Alarmins are endogenous mediators released by cells following insults or cell death to alert the host's innate immune system of a situation of danger or harm. Many of these, such as high-mobility group box-1 and 2 (HMGB1, HMGB2) and S100 (calgranulin proteins), act through RAGE (receptor for advanced glycation end products), whereas the IL-1 and IL-33 cytokines bind the IL-1 receptors type I and II, and the cellular receptor ST2, respectively. The alarmin family and their signal pathways share many similarities of cellular and tissue localization, functions, and involvement in various physiological processes and inflammatory diseases including osteoporosis. The aim of the review was to evaluate the role of alarmins in osteoporosis. A bibliographic search of the published scientific literature regarding the role of alarmins in osteoporosis was organized independently by two researchers in the following scientific databases: Pubmed, Scopus, and Web of Science. The keywords used were combined as follows: "alarmins and osteoporosis", "RAGE and osteoporosis", "HMGB1 and osteoporosis", "IL-1 and osteoporosis", "IL 33 and osteopororsis", "S100s protein and osteoporosis". The information was summarized and organized in the present review. We highlight the emerging roles of alarmins in various bone remodeling processes involved in the onset and development of osteoporosis, as well as their potential role as biomarkers of osteoporosis severity and progression. Findings of the research suggest a potential use of alarmins as pharmacological targets in future therapeutic strategies aimed at preventing bone loss and fragility fractures induced by aging and inflammatory diseases.
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http://dx.doi.org/10.3390/medicina56030138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142770PMC
March 2020

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment.

Int J Mol Sci 2020 Feb 24;21(4). Epub 2020 Feb 24.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Allergies are rapidly worsening in recent decades, representing the most common immunological diseases. The mechanism of disorders such as asthma, rhinocongiuntivitis, urticaria, atopic dermatitis, food and drug allergies, and anaphylaxis still remain unclear and consequently treatments is mostly still symptomatic and aspecific while developments of new therapies are limited. A growing amount of data in the literature shows us how the prevalence of allergic diseases is different in both sexes and its changes over the course of life. Genes, hormones, environmental and immunological factors affect sex disparities associated with the development and control of allergic diseases, while they more rarely are considered and reported regarding their differences related to social, psychological, cultural, economic, and employment aspects. This review describes the available knowledge on the role of sex and gender in allergies in an attempt to improve the indispensable gender perspective whose potential is still underestimated while it represents a significant turning point in research and the clinic. It will offer insights to stimulate exploration of the many aspects still unknown in this relationship that could ameliorate the preventive, diagnostic, and therapeutic strategies in allergic diseases.
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http://dx.doi.org/10.3390/ijms21041535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073150PMC
February 2020

New Perspectives in Food Allergy.

Int J Mol Sci 2020 Feb 21;21(4). Epub 2020 Feb 21.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

The improvement of the knowledge of the pathophysiological mechanisms underlying the tolerance and sensitization to food antigens has recently led to a radical change in the clinical approach to food allergies. Epidemiological studies show a global increase in the prevalence of food allergy all over the world and manifestations of food allergy appear increasingly frequent also in elderly subjects. Environmental and nutritional changes have partly changed the epidemiology of allergic reactions to foods and new food allergic syndromes have emerged in recent years. The deepening of the study of the intestinal microbiota has highlighted important mechanisms of immunological adaptation of the mucosal immune system to food antigens, leading to a revolution in the concept of immunological tolerance. As a consequence, new prevention models and innovative therapeutic strategies aimed at a personalized approach to the patient affected by food allergy are emerging. This review focuses on these new perspectives and their practical implications in the management of food allergy, providing an updated view of this complex pathology.
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http://dx.doi.org/10.3390/ijms21041474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073187PMC
February 2020

IL-33/IL-31 Axis in Osteoporosis.

Int J Mol Sci 2020 Feb 13;21(4). Epub 2020 Feb 13.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

The study of the immunoskeletal interface has led to the discovery of numerous cytokines involved in the regulation of bone remodeling, providing valuable information on the pathogenesis of osteoporosis. The role of inflammatory cytokines of the Th1 and Th17 profile in osteoporosis is well known. Here we focus on two newly discovered Th2 cytokines, IL-31 and IL-33, whose implications in osteoporosis are recently emerging. Clinical and experimental observations suggest an important role of the IL-33/IL-31 axis in osteoporosis. IL-33 induces IL-31 secretion by Th2 cells and inhibits RANKL-dependent osteoclastogenesis, thus counteracting bone loss. IL-31 influences Th1/Th17 osteoclastogenetic inflammation and limits Th2 osteoprotective processes, thus favoring osteoporosis. Better knowledge of the role of IL-31 and IL-33 and their receptor complexes in osteoporosis could provide an interesting perspective for the development of new and more effective therapies, possibly with less side effects.
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http://dx.doi.org/10.3390/ijms21041239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072890PMC
February 2020

Does Allergy Break Bones? Osteoporosis and Its Connection to Allergy.

Int J Mol Sci 2020 Jan 21;21(3). Epub 2020 Jan 21.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Osteoporosis and allergic diseases are important causes of morbidity, and traditionally their coexistence has been attributed to causality, to independent processes, and they were considered unrelated. However, the increasing knowledge in the field of osteoimmunology and an increasing number of epidemiological and biological studies have provided support to a correlation between bone and allergy that share pathways, cells, cytokines and mediators. If the link between allergic pathology and bone alterations appears more subtle, there are conditions such as mastocytosis and hypereosinophilic or hyper-IgE syndromes characterized by the proliferation of cells or hyper-production of molecules that play a key role in allergies, in which this link is at least clinically more evident, and the diseases are accompanied by frank skeletal involvement, offering multiple speculation cues. The pathophysiological connection of allergy and osteoporosis is currently an intriguing area of research. The aim of this review is to summarize and bring together the current knowledge and pursue an opportunity to stimulate further investigation.
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http://dx.doi.org/10.3390/ijms21030712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037724PMC
January 2020

Nailfold Capillaroscopic Findings in an Orthopedic Surgeon: Reversible Abnormalities after the Cessation of Radiation Exposure.

Radiat Res 2020 03 26;193(3):236-240. Epub 2019 Dec 26.

Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

Interventional fluoroscopy is a leading source of occupational ionizing radiation exposure for medical personnel. For example, orthopedic surgeons represent one occupation where the risk of exposure is large. This occupational hazard is the result of a cumulative dose of radiation over time. Adverse health effects induced by low-dose radiation exposure can arise from daily procedures performed over an entire career. Many of the radiation-induced effects that may develop are transient erythema, permanent epilation, dry desquamation, dermal necrosis and telangiectasia; these effects have occurred on the skin of fingers of interventionalists. Nailfold videocapillaroscopy (NVC) is a non-invasive technique useful for early detection of radiation-induced effects on microcirculation of fingernails. Here we report on a case of an orthopedic surgeon exposed to radiation for 30 years during his professional career. He performed NVC before and after the end of his professional career, and regression of the microcirculatory abnormalities were documented after cessation of radiation exposure. To our knowledge, this is the first published work in which the regression of chronic low-dose radiation-induced alterations of finger microvessels have been described and documented.
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http://dx.doi.org/10.1667/RR15435.1DOI Listing
March 2020

mTOR Links Tumor Immunity and Bone Metabolism: What are the Clinical Implications?

Int J Mol Sci 2019 Nov 21;20(23). Epub 2019 Nov 21.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) plays a crucial role in the control of cellular growth, proliferation, survival, metabolism, angiogenesis, transcription, and translation. In most human cancers, alterations to this pathway are common and cause activation of other downstream signaling pathways linked with oncogenesis. The mTOR pathway modulates the interactions between the stroma and the tumor, thereby affecting both tumor immunity and angiogenesis. Inflammation is a hallmark of cancer, playing a central role in the tumor dynamics, and immune cells can exert antitumor functions or promote the growth of cancer cells. In this context, mTOR may regulate the activity of macrophages and T cells by regulating the expression of cytokines/chemokines, such as interleukin (IL)-10 and transforming growth factor (TGF-β), and/or membrane receptors, such as cytotoxic T-Lymphocyte protein 4 (CTLA-4) and Programmed Death 1 (PD-1). Furthermore, inhibitors of mammalian target of rapamycin are demonstrated to actively modulate osteoclastogenesis, exert antiapoptotic and pro-differentiative activities in osteoclasts, and reduce the number of lytic bone metastases, increasing bone mass in tumor-bearing mice. With regard to the many actions in which mTOR is involved, the aim of this review is to describe its role in the immune system and bone metabolism in an attempt to identify the best strategy for therapeutic opportunities in the metastatic phase of solid tumors.
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http://dx.doi.org/10.3390/ijms20235841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928935PMC
November 2019

Food Allergies and Ageing.

Int J Mol Sci 2019 Nov 8;20(22). Epub 2019 Nov 8.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

All over the world, there is an increase in the overall survival of the population and the number of elderly people. The incidence of allergic reactions is also rising worldwide. Until recently, allergies, and in particular food allergies (FAs), was regarded as a pediatric problem, since some of them start in early childhood and may spontaneously disappear in adulthood. It is being discovered that, on the contrary, these problems are increasingly affecting even the elderly. Along with other diseases that are considered characteristics of advanced age, such as cardiovascular, dysmetabolic, autoimmune, neurodegenerative, and oncological diseases, even FAs are increasingly frequent in the elderly. An FA is a pleiomorphic and multifactorial disease, characterized by an abnormal immune response and an impaired gut barrier function. The elderly exhibit distinct FA phenotypes, and diagnosis is difficult due to frequent co-morbidities and uncertainty in the interpretation of in vitro and in vivo tests. Several factors render the elderly susceptible to FAs, including the physiological changes of aging, a decline in gut barrier function, the skewing of adaptive immunity to a Th2 response, dysregulation of innate immune cells, and age-related changes of gut microbiota. Aging is accompanied by a progressive remodeling of immune system functions, leading to an increased pro-inflammatory status where type 1 cytokines are quantitatively dominant. However, serum Immunoglobulin E (IgE) levels and T helper type 2 (Th2 cytokine production have also been found to be increased in the elderly, suggesting that the type 2 cytokine pattern is not necessarily defective in older age. Dysfunctional dendritic cells in the gut, defects in secretory IgA, and decreased T regulatory function in the elderly also play important roles in FA development. We address herein the main immunologic aspects of aging according to the presence of FAs.
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http://dx.doi.org/10.3390/ijms20225580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888073PMC
November 2019

Osteoporosis: Current and Emerging Therapies Targeted to Immunological Checkpoints.

Curr Med Chem 2020 ;27(37):6356-6372

Department of Life, Health, & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

Osteoporosis is a skeletal pathology characterized by compromised bone strength leading to increased risk of fracture, mainly the spine and hip fractures. Osteoporosis affects more than 200 million people worldwide and because of the skeletal fractures it causes, represents a major cause of morbidity, disability and mortality in older people. Recently, the new discoveries of osteoimmunology have clarified many of the pathogenetic mechanisms of osteoporosis, helping to identify new immunological targets for its treatment opening the way for new and effective therapies with biological drugs. Currently, there are basically two monoclonal antibodies for osteoporosis therapy: denosumab and romosozumab. Here, we focus on the modern approach to the osteoporosis management and in particular, on current and developing biologic drugs targeted to new immunological checkpoints, in the landscape of osteoimmunology.
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http://dx.doi.org/10.2174/0929867326666190730113123DOI Listing
January 2021

Nailfold capillaroscopic findings in a semi-professional volleyball player.

Clin Hemorheol Microcirc 2020 ;74(3):281-285

Department of Life, Health, and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

Volleyball players are exposed to the possibility of several well recognized injuries, among which microvascular abnormalities are the less described and studied, although they could diminish their ability and performance. Capillaroscopy is a simple, non-invasive method to diagnose vascular abnormalities in athletes suffering for the consequences of repeated application of pressure by local trauma on the fingertips. The detected capillaroscopic picture will be the base for the follow-up and will indicate the possible need for further investigations aimed at excluding other occulted conditions. At our knowledge, this is the first report describing and documenting the related microvascular abnormalities in a volleyball player. This case emphasizes the fact that volleyball players among other athletes, whose hands are exposed to repeated fingertips trauma may suffer from microcirculation damage, for which reason they should be able to access an effective health surveillance program able to detect the first signs and offer the most appropriate clinical support.
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http://dx.doi.org/10.3233/CH-190667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242845PMC
July 2020

Successful Treatment With Omalizumab in a Child With Asthma and Urticaria: A Clinical Case Report.

Front Pediatr 2019 5;7:213. Epub 2019 Jun 5.

Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

Childhood urticaria is not rare, although its persistence is less frequent. In children, chronic spontaneous urticaria (CSU) is associated with comorbidities, including asthma, allergic rhinitis, or atopic dermatitis, and many children with CSU have a family history of atopy. The therapeutic approach to CSU in children is the same one recommended by international guidelines for treatment of chronic urticaria in adults. In the European Union, according to the European Medicine Agency, omalizumab is the add-on drug of choice for the management of CSU in adult and adolescent patients (from 12 years of age) with inadequate response to H1 antihistamine therapy. In addition, in children (6 to <12 years of age), it is the add-on therapy of choice to improve asthma control. The management of children with urticaria under 12 is a therapeutic area with few certainties, where omalizumab can be administered only "off-label."
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http://dx.doi.org/10.3389/fped.2019.00213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593296PMC
June 2019

Solar Urticaria, a Disease with Many Dark Sides: Is Omalizumab the Right Therapeutic Response? Reflections from a Clinical Case Report.

Open Med (Wars) 2019 7;14:403-406. Epub 2019 Jun 7.

Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy Allergy an Clinical Immunology Unit, AUSL 04 Teramo, Italy.

Solar urticaria is a rare type of photodermatosis that significantly reduces the quality of life of the subjects affected, with a risk of anaphylaxis should the entire body be exposed to the sun. Patients are forced to modify and limit their normal activities, and since the symptoms are triggered by exposure to sun, which is difficult if not impossible to avoid in everyday life, a safe and effective therapy appears to be essential. Unfortunately, traditional therapies in a discrete number of patients are unable to provide adequate and safe answers. We describe the case of an 18-year-old woman who began to manifest the first symptoms walking under the spring sunshine. A few minutes after sun exposure, itching and burning sensation began, followed immediately by erythema appearance in the photoexposed skin areas. She was treated with non-sedating H1-blocking antihistamines and leukotriene antagonist with no success, so we decided to treat with omalizumab. The satisfactory response after the failure of previous standard therapeutic strategies, confirms the effectiveness of this molecule in the treatment of solar urticaria, which despite what reported in several studies, has not yet been recognized and authorized by the competent Health Authorities in the treatment of this condition.
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http://dx.doi.org/10.1515/med-2019-0042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572395PMC
June 2019