Allostatic Load as an Insight into the Psychological Burden after Primary Treatment in Women with Breast Cancer: Influence of Physical Side Effects and Pain Perception.

Breast cancer (BC) diagnosis and treatment have become a cumulative long-standing chronic disease impairment, causing stress and turning into an allostatic load (AL) framework. This study aimed to investigate the relationship between physical issues and mental health in patients with BC after medical treatment. We conducted an observational study of 61 female patients with BC, and clinical and psychological markers have been detected. We conducted descriptive statistics, ANOVA analyses, correlations, and mediation analyses to verify the effect of the comorbidity index on psychological dimensions. The findings showed high levels of distress and moderate pain, and 32.8% of the patients showed moderate physical impairment. Significant effects of "age" and "physical issues" were found. The adult group reported a higher incidence of physical issues, and the group of patients reporting moderate physical impairment seemed more depressed than patients with mild physical issues. Finally, the comorbidity condition mediated the presence of signs of depression. Patients with BC seemed to experience negative emotions related to comorbidities associated with compromised activities of daily living. Our findings highlighted allostatic overload as a predictive framework to better understand the mental health of women with BC diagnoses to tailor effective psychological treatments for enhanced recovery.

Sex, Allergic Diseases and Omalizumab.

Gender differences are increasingly emerging in every area of medicine including drug therapy; however, specific gender-targeted studies are infrequent. Sex is a fundamental variable, which cannot be neglected. When optimizing therapies, gender pharmacology must always be considered in order to improve the effectiveness and safety of the use of drugs. Knowledge of gender differences promotes appropriate use of therapies and greater health protection for both genders. Further development of gender research would make it possible to report on differences in the assimilation and response of the female organism as compared to the male, in order to identify potential risks and benefits that can be found between genders. Furthermore, a better understanding of sex/gender-related influences, with regard to pharmacological activity, would allow the development of personalized "tailor-made" medicines. Here, we summarize the state of knowledge on the role of sex in several allergic diseases and their treatment with omalizumab, the first biologic drug authorized for use in the field of allergology.

Cholinergic Urticaria, an Effective and Safe "Off Label" Use of Dupilumab: A Case Report with Literature Review.

Cholinergic Urticaria (CholU) is a form of generalized urticaria induced by an increase in core body temperature that activates the sweat reflex. Clinically it is characterized by localized and highly itchy wheals with surrounding erythema and can occur in response to exercise, hot baths and/or emotional stress. Dupilumab is a fully human monoclonal antibody specifically designed to simultaneously inhibit the activity of interleukin-4 (IL-4) and interleukin-13 (IL-13), which play a key role in the inflammation cascade of type 2. We report the case of a 26-year-old man suffering from CholU for 3 years, unresponsive to standard treatment in which off-label therapy was undertaken with Dupilumab, 600 mg subcutaneous as a loading dose and then 300 mg every 15 days. The daily Visual Analogue Scale (VAS) score was used to assess the efficacy of the therapy. Already after the first two administrations, the patient no longer had CholU episodes and resumed regular sporting activity, with a marked improvement in the quality of life. A possible mechanism of Dupilumab in reducing the manifestations of CholU is the blocking of the IL-4 pathway and the expression of the high-affinity IgE receptor (FcεR1) on B cells, mast cells (MCs) and basophils. By decreasing the production of FcεR1, the adhesion of IgE to the surface of MCs decreases with consequent reduction of MCs activation and histamine release. Further experience and large-scale studies may be needed to establish whether Dupilumab can be a therapeutic alternative in CholU, especially in patients who do not respond to standard treatment.

Raynaud's phenomenon in a drummer player: Microvascular disorder and nailfold video capillaroscopic findings.

Drummers are usually exposed to intensive physical stress and occupational diseases that have been only partially investigated. The majority of studies focus on musculoskeletal problems while microvascular abnormalities have been less considered. We report on a case of a 19-year-old drummer affected by Raynaud's phenomenon. The patient underwent nailfold video capillaroscopy that showed a non-specific pattern, with granular flow, dyshomogeneous capillary morphology, increased efferent/afferent loop ratio and many enlarged capillaries. The continuous exposition to vibration in drummers could determinate microvascular abnormalities with related cold induced disorders and Raynaud's phenomenon. Nailfold video capillaroscopy is a tool that allows to detect the alterations of the microcirculation and to carry out the follow-up of the patients with low cost, non-invasiveness, repeatability, high sensibility and specificity.

Capillaroscopic Evidence of Microvascular Damage in Volleyball Players.

Volleyball players experience repetitive stress that involves their hands and, in particular, their fingers. Literature reports that repetitive trauma can lead to local vascular abnormalities, such as reduced capillarization and lower resting blood flow. These anomalies could be related to the presence of dysfunctional endothelium. The aim of this study is to correlate the capillaroscopic findings by nailfold video capillaroscopy (NVC) to volleyball practice in order to early detect possible anomalies and perform an adequate follow-up to avoid damages that could negatively affect sport practice and the players' health status. In this study, 38 subjects were enrolled, 19 volleyball players and 19 healthy non-players as a comparison group. In almost all the players, we found capillaroscopic alterations of the "aspecific pattern" type without substantial gender differences. We may assume that the repeated traumas involving players' fingers can negatively modify their microcirculation. Based on these observations, it could be a desirable clinical practice to screen professional volleyball players with NVC in order to implement preventive strategies aimed at protecting the health of athletes.

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

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.

Sex differences in the efficacy of omalizumab in the treatment of chronic spontaneous urticaria.

BACKGROUND: Omalizumab is shown to be effective in the treatment of chronic spontaneous urticaria (CSU), a disease with high personal and social impact. Sex differences in CSU are recognized with women more frequently affected. Scarce is the knowledge about response to omalizumab between sex groups. We sought to identify any differences based on the sex of patients receiving omalizumab. METHODS: We evaluated data of patients diagnosed with CSU refractory to high-dose second-generation H1 antihistamines and treated with 300 mg omalizumab every 4 weeks for 6 months and then at relapse. RESULTS: Discussion: All patients, regardless of sex, age, or any other factor, achieved the clinical remission of the disease after the first 3 doses with a reduction of the disease activity indices and impact on the quality of life. Recurrences predominate in men, two months after the suspension of the drug. Respect to sex and recurrence we did not find any correlation with age, body mass index, peripheral eosinophil counts, total IgE levels, D-dimer, plasma prothrombine level or C-reactive protein. We found no sex differences in tolerability and safety. CSU in girls may persist longer and have worse prognosis, but no one has so far noted sex differences in response to omalizumab. CONCLUSIONS: Although there are no certainties on the mechanism of action of omalizumab in CSU, the noticeable difference in response between males and females lead us to suppose a role of the hormonal balance both on the pathogenesis of the CSU and on the efficacy of OmAb.

The Microbiota-Bone-Allergy Interplay.

Emerging knowledge suggests an increasing importance of gut microbiota in health and disease. Allergy and bone metabolism are closely interconnected, and the possible negative effects of common therapies are not the only aspects of this relationship. The immune system is influenced by the microbiota-host interactions, and several pieces of evidence suggest the existence of an interplay between microbiota, bone metabolism, and allergies. Understanding these inter-relationships is essential for the development of new potential strategies of treatment and prevention targeting microbiota. A wide range of substances and germs, prebiotics and probiotics, are capable of influencing and modifying the microbiota. Prebiotics and probiotics have been shown in several studies to have different actions based on various factors such as sex, hormonal status, and age. In this review, we summarize the latest knowledge on the topic, and we discuss practical implications and the need for further studies.

Osteoporosis in Skin Diseases.

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.

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

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.

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

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.

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

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.

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

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-ß), 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.