Recognizing menopause in women with amenorrhea induced by cytotoxic chemotherapy for endocrine-responsive early breast cancer.

Abstract Cytotoxic anticancer treatment may induce amenorrhea or menopause to a variable extent. These side effects may not only impair or impede fertility but also cause sexual dysfunction, bone loss, and menopausal symptoms, with a strikingly negative effect on quality of life in many women. Aromatase inhibitors (AIs) are a recommended adjuvant endocrine treatment option in postmenopausal patients affected by early breast cancer (EBC) but are contraindicated in premenopausal women and in those with residual ovarian function. Women over 40 years of age with chemotherapy-induced amenorrhea (CIA) and routine hormonal levels consistent with menopause may receive an AI as adjuvant endocrine treatment. For these women, the tools available to identify menopause do not appear to be completely reliable. This review focused on the pathophysiology of ovarian toxicity induced by cytotoxic agents and on potentially useful methods to diagnose chemotherapy-induced menopause in patients treated with adjuvant chemotherapy for endocrine-responsive EBC. Moreover, practical approaches are proposed to distinguish true menopausal women, who would benefit from AIs, from those with transient or persistent CIA

Wake interaction in offshore wind farms with mesoscale derived inflow condition and sea waves

Numerical simulation is an indispensable tool for the design and optimization of wind farms layout and control strategies for energy loss reduction. Achieving consistent simulation results is strongly related to the definition of reliable weather and sea conditions, as well as the use of accurate computational fluid dynamics (CFD) models for the simulation of the wind turbines and wakes. Thus, we present a case study aiming to evaluate the wake-rotor interaction between offshore multi-MW wind turbines modelled using the Actuator Line Model (ALM) and realistic wind inflow conditions. In particular, the interaction between two DTU10 wind turbines is studied for two orientations of the upstream turbine rotor, simulating the use of a yaw-based wake control strategy. Realistic wind inflow conditions are obtained using a multi-scale approach, where the wind field is firstly computed using mesoscale numerical weather prediction (NWP). Then, the mesoscale vertical wind profile is used to define the wind velocity and turbulence boundary conditions for the high-fidelity CFD simulations. Sea waves motion is also imposed using a dynamic mesh approach to investigate the interaction between sea waves, surface boundary layer, and wind turbine wakes and loads

Epidemiology of simultaneous medullary and papillary thyroid carcinomas (MTC/PTC): An Italian multicenter study

Background: The concomitant presence of papillary thyroid cancer (PTC) and medullary TC (MTC) is rare. In this multicentric study, we documented the epidemiological characteristics, disease conditions and clinical outcome of patients with simultaneous MTC/PTC. Methods: We collected data of patients with concomitant MTC/PTC at 14 Italian referral centers. Results: In total, 183 patients were enrolled. Diagnosis was mostly based on cytological examination (n = 58, 32%). At diagnosis, in the majority of cases, both PTC (n = 142, 78%) and MTC (n = 100, 54%) were at stage I. However, more cases of stage II\u2013IV were reported with MTC (stage IV: n = 27, 15%) compared with PTC (n = 9, 5%). Information on survival was available for 165 patients: 109 patients (66%) were disease-free for both PTC and MTC at the last follow-up. Six patients died from MTC. Median time to progression was 123 months (95% confidence interval (CI): 89.3\u2013156.7 months). Overall, 45% of patients were disease-free after >10 years from diagnosis (125 months); this figure was 72.5% for PTC and 51.1% for MTC. Conclusions: When MTC and PTC are concurrent, the priority should be given to the management of MTC since this entity appears associated with the most severe impact on prognosis

A rare case of pituitary melanoma metastasis: a dramatic and prolonged response to dabrafenib-trametinib therapy

Introduction: Pituitary metastases (PM) are rare events and to date only very few cases of melanoma PM have been described in literature up to now. Case Presentation: We describe the clinical history of a 33-year-old male patient who underwent surgical excision of an inter-scapular melanoma in 2008. The subsequent follow-up was negative for ~10 years. In September 2018, due to the onset of a severe headache, the patient underwent a brain magnetic resonance imaging, which showed an expansive mass in the saddle and suprasellar region with a maximum diameter of 17 mm. Pituitary function tests and visual field were normal. Worsening of the headache and the appearance of a left eye ptosis led the patient to surgical removal of the lesion in October 2018. The histological examination unexpectedly showed metastasis of the melanoma. Post-operative hormonal assessment showed secondary hypothyroidism and hypoadrenalism, which were both promptly treated, and a mild hypogonadism. Three months after surgery, a sellar MRI showed a persistent, increased pituitary mass (3 cm of diameter); fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) detected an increased radiopharmaceutical uptake in the sellar region. Due to the persistence of the disease and the evidence of a BRAF V600E mutation, in February 2019, the patient underwent a combined treatment with dabrafenib (a BRAF inhibitor) and trametinib (mitogen-activated extracellular signal-regulate kinase inhibitor). Sellar MRI performed 6 months later showed no evidence of mass in the sellar region. The patient was in a good clinical condition and did not complain of headaches or other symptoms; there were no significant side-effects from the anticancer therapy. After 13 months of treatment, the patient showed no recurrence of the disease on morphological imaging. Anticancer therapy was confirmed, replacement therapies with hydrocortisone and levothyroxine continued and the pituitary-gonadal axis was restored. Conclusion: This is a very interesting case, both for the rarity of the pituitary melanoma metastasis and for the singular therapeutic course carried out by the patient. This is the first case of a pituitary melanoma metastasis with BRAF mutation, successfully treated with the combination of dabrafenib and trametinib after incomplete surgical removal

Indirect basal metabolism estimation in tailoring recombinant human TSH administration in patients affected by differentiated thyroid cancer: A hypothesis-generating study

Purpose: Recombinant human TSH (rhTSH) is currently used in follow-up of patients affected by differentiated thyroid cancer (DTC). Age, sex, weight, body mass index, body surface area (BSA) and renal function are known factors affecting serum TSH peak levels, but the proper rhTSH dose to deliver to single patient remains elusive. In this study, the correlations of basal metabolic rates with serum TSH peak following rhTSH administration were investigated.Methods: We evaluated 221 patients affected by thyroid cancer that received a standard dose rhTSH. Blood samples were collected at pre-established time points. Data on body weight, height, and BSA were collected. The Mifflin-St Jeor and Fleisch equations were used to assess basal metabolism.Results: The median value (range) of serum TSH peaks was 142 +/- 53 mu U/ml. Serum TSH peaks were significantly lower in males than in females (p = 0.04). TSH values also increased with age. Data showed a significant decrease of TSH peak levels at day 3 from the administration of rhTSH when basal metabolic rates increased (p = 0.002 and p = 0.009, respectively). Similar findings were observed at day 5 (p = 0.004 and p = 0.04, respectively). A multivariate analysis of several factors revealed that patients' basal metabolism (obtained using the Mifflin-St Jeor but not Fleisch equation) predicts serum TSH level peak at day 3 (p < 0.001). These results were used to generate a new formula based on Mifflin-StJeor equation which reveals as a promising tool in tailoring rhTSH dose.Conclusion: Basal metabolism appears an improving factor in tailoring diagnostic rhTSH dose in patients affected by DTC

Renormalization of total sets of states into generalized bases with a resolution of the identity

YesA total set of states for which we have no resolution of the identity (a `pre-basis'), is considered in a finite dimensional Hilbert space. A dressing formalism renormalizes them into density matrices which resolve the identity, and makes them a `generalized basis', which is practically useful. The dresssing mechanism is inspired by Shapley's methodology in cooperative game theory, and it uses Mobius transforms. There is non-independence and redundancy in these generalized bases, which is quantifi ed with a Shannon type of entropy. Due to this redundancy, calculations based on generalized bases, are sensitive to physical changes and robust in the presence of noise. For example, the representation of an arbitrary vector in such generalized bases, is robust when noise is inserted in the coeffcients. Also in a physical system with ground state which changes abruptly at some value of the coupling constant, the proposed methodology detects such changes, even when noise is added to the parameters in the Hamiltonian of the system

A Grassmann integral equation

The present study introduces and investigates a new type of equation which is called Grassmann integral equation in analogy to integral equations studied in real analysis. A Grassmann integral equation is an equation which involves Grassmann integrations and which is to be obeyed by an unknown function over a (finite-dimensional) Grassmann algebra G_m. A particular type of Grassmann integral equations is explicitly studied for certain low-dimensional Grassmann algebras. The choice of the equation under investigation is motivated by the effective action formalism of (lattice) quantum field theory. In a very general setting, for the Grassmann algebras G_2n, n = 2,3,4, the finite-dimensional analogues of the generating functionals of the Green functions are worked out explicitly by solving a coupled system of nonlinear matrix equations. Finally, by imposing the condition G[{\bar\Psi},{\Psi}] = G_0[{\lambda\bar\Psi}, {\lambda\Psi}] + const., 0<\lambda\in R (\bar\Psi_k, \Psi_k, k=1,...,n, are the generators of the Grassmann algebra G_2n), between the finite-dimensional analogues G_0 and G of the (``classical'') action and effective action functionals, respectively, a special Grassmann integral equation is being established and solved which also is equivalent to a coupled system of nonlinear matrix equations. If \lambda \not= 1, solutions to this Grassmann integral equation exist for n=2 (and consequently, also for any even value of n, specifically, for n=4) but not for n=3. If \lambda=1, the considered Grassmann integral equation has always a solution which corresponds to a Gaussian integral, but remarkably in the case n=4 a further solution is found which corresponds to a non-Gaussian integral. The investigation sheds light on the structures to be met for Grassmann algebras G_2n with arbitrarily chosen n.Comment: 58 pages LaTeX (v2: mainly, minor updates and corrections to the reference section; v3: references [4], [17]-[21], [39], [46], [49]-[54], [61], [64], [139] added

The Day-to-Day Impact of Urogenital Aging: Perspectives from Racially/Ethnically Diverse Women

Urogenital symptoms affect up to half of women after menopause, but their impact on women’s day-to-day functioning and wellbeing is poorly understood. Postmenopausal women aged 45 to 80 years reporting urogenital dryness, soreness, itching, or pain during sex were recruited to participate in in-depth focus groups to discuss the impact of their symptoms. Focus groups were homogenous with respect to race/ethnicity and stratified by age (for White or Black women) or language (for Latina women). Transcripts of sessions were analyzed according to grounded theory. Six focus groups were conducted, involving 44 women (16 White, 14 Black, 14 Latina). Five domains of functioning and wellbeing affected by symptoms were identified: sexual functioning, everyday activities, emotional wellbeing, body image, and interpersonal relations. For some participants, symptoms primarily affected their ability to have and enjoy sex, as well as be responsive to their partners. For others, symptoms interfered with everyday activities, such as exercising, toileting, or sleeping. Participants regarded their symptoms as a sign that they were getting old or their body was deteriorating; women also associated symptoms with a loss of womanhood or sexuality. Additionally, participants reported feeling depressed, embarrassed, and frustrated about their symptoms, and expressed reluctance to discuss them with friends, family, or health care providers. Urogenital symptoms can have a marked impact on sexual functioning, everyday activities, emotional wellbeing, body image, and interpersonal relations after menopause. Clinicians may need to question women actively about these symptoms, as many are reluctant to seek help for this problem

Development of a dso-market on flexibility services

BACKGROUND: Several of the currently used anticancer drugs may variably affect thyroid function, with impairment ranging from modified total but not free concentration of thyroid hormones to overt thyroid disease. SUMMARY: Cytotoxic agents seem to alter thyroid function in a relatively small proportion of adult patients. Anticancer hormone drugs may mainly alter serum levels of thyroid hormone-binding proteins without clinically relevant thyroid dysfunction. Old immunomodulating drugs, such as interferon-α and interleukin-2, are known to induce variably high incidence of autoimmune thyroid dysfunction. Newer immune checkpoint inhibitors, such as anti-CTLA4 monoclonal antibodies, are responsible for a relatively low incidence of thyroiditis and may induce secondary hypothyroidism resulting from hypophysitis. Central hypothyroidism is a well-recognized side effect of bexarotene. Despite their inherent selectivity, tyrosine kinase inhibitors may cause high rates of thyroid dysfunction. Notably, thyroid toxicity seems to be restricted to tyrosine kinase inhibitors targeting key kinase-receptors in angiogenic pathways, but not other kinase-receptors (e.g., epidermal growth factor receptors family or c-KIT). In addition, a number of these agents may also increase the levothyroxine requirement in thyroidectomized patients. CONCLUSIONS: The pathophysiology of thyroid toxicity induced by many anticancer agents is not fully clarified and for others it remains speculative. Thyroid dysfunction induced by anticancer agents is generally manageable and dose reduction or discontinuation of these agents is not required. The prognostic relevance of thyroid autoimmunity, overt and subclinical hypothyroidism induced by anticancer drugs, the value of thyroid hormone replacement in individuals with abnormal thyrotropin following anticancer systemic therapy, and the correct timing of replacement therapy in cancer patients need to be defined more accurately in well-powered prospective clinical trials