Influence of genetic and cardiometabolic risk factors in Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Cardiometabolic and genetic risk factors play an important role in the trajectory of AD. Cardiometabolic risk factors including diabetes, mid-life obesity, mid-life hypertension and elevated cholesterol have been linked with cognitive decline in AD subjects. These potential risk factors associated with cerebral metabolic changes which fuel AD pathogenesis have been suggested to be the reason for the disappointing clinical trial results. In appreciation of the risks involved, using search engines such as PubMed, Scopus, MEDLINE and Google Scholar, a relevant literature search on cardiometabolic and genetic risk factors in AD was conducted. We discuss the role of genetic as well as established cardiovascular risk factors in the neuropathology of AD. Moreover, we show new evidence of genetic interaction between several genes potentially involved in different pathways related to both neurodegenerative process and cardiovascular damage.

Comprehensive geriatric assessment in older adults with cancer: Recommendations by the Italian Society of Geriatrics and Gerontology (SIGG).

INTRODUCTION: Optimizing the approach to older adults with cancer is now a priority given the increasing frequency of new cancer diagnoses that are made in the older population. The comprehensive geriatric assessment (CGA) represents the gold-standard for (1) defining prognosis and ability to withstand cancer treatments, (2) exploring the multiple aspects that define the complexity of frail older persons, and (3) designing person-tailored interventions. MATERIALS AND METHODS: In this document, based on a comprehensive revision of the literature, the Italian Society for Geriatrics and Gerontology proposes a CGA model (ONCOGER CGA) to be adopted by oncology centers for their routine approach to older patients with cancer. RESULTS AND DISCUSSION: A widespread use of this standardized CGA format will facilitate comparisons across institutions, promote studies based on a multidimensional patient assessment, and foster the inclusion of geriatric endpoints in oncological clinical trials. Furthermore, we predict that the use of a standardized CGA approach will increase the integration of geriatricians into oncology care teams with the final result of improving therapeutic choices and clinical outcomes.

Thyroid hormones ratio is a major prognostic marker in advanced metastatic colorectal cancer: Results from the phase III randomised CORRECT trial.

BACKGROUND: Free triiodothyronine (FT3)/free thyroxine (FT4) ratio is an index estimating the peripheral activity of thyroid hormones. In a previous experience, we identified a prognostic role for FT3/FT4 ratio in chemorefractory patients treated with regorafenib. Therefore, we planned this post hoc analysis of the phase III CORRECT trial of regorafenib versus placebo. METHODS: Seven hundred fifty-eight out of 760 randomised patients (503 in the regorafenib and 255 in the placebo arm) were evaluable for the present analyses, based on availability of FT3 and FT4 baseline values. Co-primary objectives were to explore the predictive role of FT3/FT4 ratio in patients treated with regorafenib compared with placebo and to validate the prognostic value of FT3/FT4 ratio in the CORRECT trial. RESULTS: For patients randomised to regorafenib, median overall survival (OS) was 4.0, 7.5 and 9.8 months in low, intermediate and high FT3/FT4 ratio subgroups, respectively. Hazard ratio (HR) for OS was 0.40 (p < 0.0001) when comparing intermediate versus low and 0.32 (p < 0.0001) when comparing high versus low FT3/FT4 ratio. In the placebo arm, median OS was 3.3, 5.6 and 7.7 months, in the three subgroups. HR for OS was 0.47 (p < 0.0001) when comparing intermediate versus low and 0.33 (p < 0.0001) when comparing high versus low. FT3/FT4 ratio retained its association with OS in the multivariate model in both arms. CONCLUSIONS: While rejecting the predictive effect of baseline FT3/FT4 ratio, present data strengthen the prognostic role of the ratio, pave the way for direct clinical application, underline the need for a better biological understanding and suggest possible therapeutic implications for thyroid hormones.

Immunotherapy in Underrepresented Populations of Patients with Cancer: Do We Have Enough Evidence at Present? A Focus on Patients with Major Viral Infections and Autoimmune Disorders.

The safety and activity of immune checkpoint inhibitors have been characterized in interventional and observational studies. However, only small studies have specifically investigated these agents in patients who are excluded or underrepresented in clinical trials, frequently referred to as "special populations" or "underrepresented populations." These include older adults, those with dysregulated immune activation, patients with a compromised immune function, and those carrying major viral infections, lymphoproliferative diseases, and major organ dysfunctions. Therefore, there remains substantial uncertainty regarding the use of immune checkpoint inhibitors in these specific settings. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project, with the contribution of oncologists and other specialists, to retrieve the existing evidence on the use of immunotherapy in patients with solid and hematological cancers with the final aim to provide an expert guidance. The results of this effort are presented in this article, which is focused on patients with major viral infections or those with immune dysregulation/autoimmune diseases, and could be useful to guide decisions in clinical practice and to design prospective clinical trials focusing on the use of immunotherapy in these populations. IMPLICATIONS FOR PRACTICE: Substantial uncertainty remains regarding the use of immune checkpoint inhibitors in "underrepresented" patients, such as older adults, those with dysregulated immune activation, and patients with a compromised immune function, major viral infections, lymphoproliferative diseases or major organ dysfunctions. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project to retrieve the existing evidence on the use of immunotherapy in underrepresented patients with cancer in order provide an expert guidance. The results of this effort, with a focus on patients with major viral infections or those with immune dysregulation/autoimmune diseases, are presented in this article and could be useful to guide decisions both in clinical practice and to design clinical trials.

Effectiveness of Multi-Prognostic Index in older patients with advanced malignancies treated with immunotherapy.

BACKGROUND: Older adults with cancer are less likely to be offered treatment for cost-benefit concern. The Multi-Prognostic Index (MPI) has been validated in various clinical settings for survival estimation. We aimed to evaluate MPI as a screening tool for older adults with cancer eligible to receive immunotherapy. PATIENTS AND METHODS: Older adults with advanced or metastatic cancer, admitted to the Oncology Day Hospital of the University Hospital of Pisa from January 2017 to May 2018, eligible to receive immunotherapy were prospectively enrolled. In addition to routine oncological evaluation, each patient received a comprehensive geriatric assessment with MPI calculation. Overall survival (Cox-adjusted curve) was stratified by tertiles of MPI score. Drug toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03: June 14, 2010). RESULTS: Seventy-nine patients [26.6% women, mean age (±SD) 74.0 ±â€¯6.1 years] were enrolled with the following diagnosis: melanoma (51.9%), non-small cell lung cancer (25.3%), renal cell cancer (12.7%), urothelial cancer (8.9%) and Merkel cell carcinoma (1.2%). Median follow-up was 7 months (range 1-35). The patients' survival rate resulted progressively longer proceeding from the first to the third MPI tertile [HR 1.76 (0.49-6.31) Vs 2nd tertile, p < 0.05; HR 5.33 (1.68-16.89) Vs 3rd tertile, p < 0.01]. CONCLUSIONS: MPI score is an effective tool for the stratification of older patients with cancer eligible for immunotherapy with checkpoint inhibitors. Further studies are required to achieve conclusive remarks on MPI usefulness in different underlying tumor types.

30-Day Potentially Preventable Hospital Readmissions In Older Patients: Clinical Phenotype And Health Care Related Risk Factors.

PURPOSE: Early readmission rate has been regarded as an indicator of in-hospital and post-discharge quality of care. Evaluating the contributing factors is crucial to optimize the healthcare and target the intervention. In this study we evaluated the potential for preventing 30-day hospital readmission in a cohort of older patients and identified possible risk factors for readmission. PATIENTS AND METHODS: Diagnosis-Related Group (DRG) codes of patients consecutively hospitalized for acute disease in the Geriatrics Unit of the University Hospital of Pisa within a 1-year window were recorded. All the patients had received a comprehensive geriatric assessment. Crossing and elaboration of the DRG codes was performed by the Potentially Preventable Readmission Grouping software (3M™ Corporation). DRG codes were classified as stand-alone admissions (SA), index admissions (IA) and potentially preventable readmissions (PPR) within a time window of 30 days after discharge. RESULTS: In total, 1263 SA and 171 IA were identified, with an overall PPR rate of 11.9%. Hospitalizations were significantly longer in IA and PPR than SA (p<0.05). The more frequent readmission causes were acute heart failure, pulmonary edema, sepsis, pneumonia and stroke. In acute heart failure a nonlinear U-shaped readmission trend (with nadir at 5 days of hospitalization) was observed while, in all the other DRG codes, the PPR rate increased with increasing length of hospitalization. Comprehensive geriatric assessment showed a significantly lower degree of disability and comorbidity in SA than IA patients. At stepwise regression analysis, a high degree of disability and comorbidity as well as the diagnosis of sepsis emerged as independent risk factors for PPR. CONCLUSION: Addressing PPR is crucial, especially in older patients. The adequacy of treatment during hospitalization (especially in cases of sepsis) as well as the setting of a comprehensive discharge plan, accounting for comorbidity and disability of the patients, are essential to reduce PPR.

Overt and Subclinical Hypothyroidism in the Elderly: When to Treat?

Hypothyroidism is characterized by increased thyrotropin (TSH) levels and reduced free thyroid hormone fractions while, subclinical hypothyroidism (sHT) by elevated serum TSH in the face of normal thyroid hormones. The high frequency of hypothyroidism among the general population in Western Countries made levothyroxine (LT4) one of the 10 most prescribed drugs. However, circulating TSH has been demonstrated to increase with aging, regardless the existence of an actual thyroid disease. Thus, when confronting an increase in circulating TSH levels in the elderly, especially in the oldest old, it is important to carry an appropriate diagnostic path, comprehensive of clinical picture as well as laboratory and imaging techniques. In the current review, we summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly-therapy. The treatment of choice for hypothyroid patients is hormone replacement with LT4 but, it is important to consider multiple factors before commencing the therapy, from the age dependent TSH increase to the presence of an actual thyroid disease and comorbidities. When treatment is necessary, a tailored therapy should be chosen, considering poly-pharmacy and frailty. A careful follow-up and treatment re-assessment should be always considered to avoid the risk of over-treatment. It is important to stress the need of educating the patient for a correct administration of LT4, particularly when poly-therapy is in place, and the importance of a tailored therapeutic approach and follow-up, to avoid overtreatment.

Hypothyroidism in the Elderly: Who Should Be Treated and How?

Hypothyroidism is among the most frequent chronic diseases in the elderly, and levothyroxine (l-T4) is worldwide within the 10 drugs more prescribed in the general population. Hypothyroidism is defined by increased serum thyroid-stimulating hormone (TSH) values and reduced circulating free thyroid hormones, whereas subclinical hypothyroidism (sHT) is characterized by free hormone fractions within the normal ranges and has been divided into two classes, depending on circulating TSH levels (above or below 10 mIU/L). Given that during aging, a natural trend toward higher values of circulating TSH has been reported, it is necessary to verify carefully the diagnosis of sHT to tailor an appropriate follow-up and ad hoc therapy, avoiding unnecessary or excessive treatment. In the current review, we evaluate the state of the art on hypothyroidism in the elderly with special focus on the effect of sHT on cognition and the cardiovascular system function. We also summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with an elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly therapy. In conclusion, personalized therapy is crucial in good clinical practice, and in the management of older patients with sHT, multiple factors must be considered, including age-dependent TSH cutoffs, thyroid autoimmunity, the burden of comorbidities, and the possible presence of frailty. l-T4 is the drug of choice for the treatment of hypothyroid older people, but the risk of overtreatment, potential adverse drug reactions, and patient compliance should always be considered and thyroid status periodically reassessed.

Prognostic Value of Thyroid Hormone Ratios in Patients With Advanced Metastatic Colorectal Cancer Treated With Regorafenib: The TOREADOR Study.

BACKGROUND: The impact of free triiodothyronine (FT3)/free thyroxine (FT4) ratio on survival in hospitalized geriatric patients was recently described. Up today, there are no data regarding the prognostic role of FT3/FT4 ratio in patients with advanced cancer. We evaluated the impact of FT3/FT4 ratio on survival in patients with refractory colorectal cancer (CRC) treated with regorafenib. METHODS: Patients with metastatic CRC treated with regorafenib with available clinical data and baseline measurement of FT3, FT4, and thyroid-stimulating hormone (TSH) were considered eligible. Exploratory analyses included subjects treated at Istituto Oncologico Veneto. A confirmatory analysis was planned based on FT3/FT4 ratio tertile results, and a validation cohort was built on data retrieved from University of Cagliari. RESULTS: In an exploratory cohort, the median overall survival in patients with low, intermediate, and high FT3/FT4 ratios, according to tertiles' value, was 4.8, 5.0, and 7.6 months, respectively (P = .003). The differences were significant in the multivariate model (hazard ratio, 0.43; 95% confidence interval, 0.28-0.68; P = .0003). Confirmatory results were obtained in a validation cohort, both in univariate (P = .0002) and in multivariate (hazard ratio, 0.56; 95% confidence interval, 0.36-0.88; P = .0118) models. CONCLUSIONS: High baseline FT3/FT4 ratio is strongly associated to better outcome in patients with progressive metastatic CRC treated with regorafenib. Further investigations are ongoing to draw definitive conclusions regarding a potential predictive effect.

Degree of Peripheral Thyroxin Deiodination, Frailty, and Long-Term Survival in Hospitalized Older Patients.

Context: Although the association between low free triiodothyronine (FT3) and poor outcome has been extensively reported in literature, the degree of peripheral thyroxin deiodination and its relationship with frailty and survival in hospitalized older patients has not yet been fully established. The aim of the current study was to evaluate the possible correlation between FT3/free thyroxine (FT4) ratio reduction, an indirect marker of thyroxin deiodination impairment, and frailty status and survival in hospitalized older patients. Methods: We consecutively enrolled older patients, hospitalized in the geriatrics ward of the University of Pisa. At admission, Multidimensional Geriatric Assessment (MGA) and Multi Prognostic Index (MPI), an indirect measure of frailty, were obtained from all the patients. Causes of hospitalization and prevalence of delirium were recorded. Blood samples for FT3, FT4, and thyrotropin value evaluation were drawn after an overnight fast. Results: A total of 643 patients (83.8 ± 7.4 years, 53% women) were studied. FT3 was inversely and strongly correlated, whereas FT4 was moderately positively correlated with MGA parameters, MPI score (P < 0.001 and P < 0.05, respectively), and survival (P < 0.001 and P = 0.09, respectively). FT3/FT4 ratio reduction was highly associated with worse MGA (P < 0.001) and MPI scores (P < 0.0001), even in patients without low FT3. The inclusion of FT3 in the final model of multivariate Cox regression confirmed the independent role of FT3/FT4 ratio in predicting survival (P = 0.005). Conclusion: Overall, our study documented a strong association between FT3/FT4 ratio reduction, a surrogate marker of peripheral thyroxin deiodination, and frailty. Moreover, FT3/FT4 ratio value emerged as independent marker of survival, even in patients with normal FT3 values.

Thyroid Disrupting Chemicals.

Endocrine disruptor compounds are exogenous agents able to interfere with a gland function, exerting their action across different functional passages, from the synthesis to the metabolism and binding to receptors of the hormone produced. Several issues, such as different levels and time of exposure and different action across different ages as well as gender, make the study of endocrine disruptors still a challenge. The thyroid is very sensitive to the action of disruptors, and considering the importance of a correct thyroid function for physical and cognitive functioning, addressing this topic should be considered a priority. In this review, we examined the most recent studies, many of them concentrating on maternal and child exposure, conducted to assess the impact of industrial chemicals which showed an influence on thyroid function. So far, the number of studies conducted on that topic is not sufficient to provide solid conclusions and lead to homogeneous guidelines. The lack of uniformity is certainly due to differences in areas and populations examined, the different conditions of exposures and the remarkable inter-subject variability. Nonetheless, the European Commission for Health and Food Safety is implementing recommendations to ensure that substances identified as endocrine disruptors will be withdrawn from the market.

P2X7 Receptor and APOE Polymorphisms and Survival from Heart Failure: A Prospective Study in Frail Patients in a Geriatric Unit.

Heart failure (HF) is one of the most frequent cause of hospitalization in elderly and often coexists with concurrent geriatric syndromes, like cognitive disturbances; various pathophysiological mechanisms are shared by HF and cognitive decline, notably a substrate of low-grade inflammation. We investigated whether SNPs in the purinergic receptor (P2X7R) and apolipoprotein (APO) E genes, both involved in a series of inflammatory responses, are associated to HF or cognitive impairment and are able to predict post-discharge mortality in the elderly. We prospectively analyzed 198 patients (age 85 ± 8 years, predominantly females) admitted to a Geriatric unit for acute HF, whose diagnosis was based on clinical signs, brain natriuretic peptide (BNP) values and ecocardiography in uncertain diagnosis (BNP values between 100 and 400 pg/mL); cognitive performance was assesed by Short Portable Mental Status Questionnaire (SPMSQ). In all the participants, SNPs rs208294 and rs3751143 for P2X7R gene and rs429558 and rs7412 for APOE gene were assessed. Information on all-cause mortality was adjudicated by medical records review 36 months after discharge. We found no relationship between P2X7R and APOE polymorphisms and 36-month post-discharge mortality; a better outcome for overall survival was observed in patients with BNP values below the median (281 pg/mL) (p=0.002) persisting after adjustment for renal function and age, and in those with cognitive impairment (p<0.001). Patients harboring APOE-ε4 genotype showed higher BNP concentrations than noncarriers (1289.9 ± 226.9 vs 580.5 ± 90.2 pg/mL respectively,p=0.004), whereas none of the studied SNPs were associated to impairment in cognitive performance. In conclusion, neither P2X7R or APOE genotype seem to predict long-term mortality in elderly patients. Interestingly, APOE-ε4 genotype was associated to higher BNP values, suggesting a putative interaction between genetic and biochemical markers in identifying people at risk for HF.

HASHIMOTO THYROIDITIS AND VESTIBULAR DYSFUNCTION.

OBJECTIVE: The aim of this review was to analyze the existing literature concerning the relationship between Hashimoto thyroiditis (HT) and vestibular dysfunction. METHODS: We used electronic databases (PubMed, EMBASE, Cochrane Library) to search and collect all published articles about the association between HT and vestibular disorders. RESULTS: Several observational and retrospective studies have postulated a relationship between thyroid autoimmunity and vestibular disorders. In most cases, an appropriate control group was lacking, and the impact of thyroid functional status could not precisely be established. In recent years, two well-designed prospective studies have provided convincing evidence that the association is not random. One article reported that patients with Ménière disease (MD) had a significantly higher prevalence of positive anti-thyroid autoantibody as compared to healthy controls. Moreover, more than half of MD patients had either positive anti-thyroid or non-organ-specific autoantibody titers, compared to less than 30% of both patients with unilateral vestibular paresis without cochlear involvement and healthy controls. Another study found that patients with benign paroxysmal positional vertigo (BPPV) had significantly higher serum thyroid-stimulating hormone and antithyroid autoantibody levels than healthy controls. Additionally, almost one-fifth of euthyroid patients with HT had signs of BPPV. CONCLUSION: The published results indicate that patients with MD or BPPV are potential candidates to also develop HT. Thus, in HT patients, the presence of even slight symptoms or signs potentially related to vestibular lesions should be carefully investigated. ABBREVIATIONS: AITD = autoimmune thyroid disease; BPPV = benign paroxysmal positional vertigo; EH = endolymphatic hydrops; HT = Hashimoto thyroiditis; L-T4 = L-thyroxine; MD = Ménière disease; PS = Pendred syndrome; Tg = thyroglobulin; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone.

Clinical differences among the elderly admitted to the emergency department for accidental or unexplained falls and syncope.

It is difficult to distinguish unexplained falls (UFs) from accidental falls (AFs) or syncope in older people. This study was designed to compare patients referred to the emergency department (ED) for AFs, UFs or syncope. Data from a longitudinal study on adverse drug events diagnosed at the ED (ANCESTRAL-ED) in older people were analyzed in order to select cases of AF, syncope, or UF. A total of 724 patients (median age: 81.0 [65-105] years, 66.3% female) were consecutively admitted to the ED (403 AF, 210 syncope, and 111 UF). The number of psychotropic drugs was the only significant difference in patients with AF versus those with UF (odds ratio [OR] 1.44; 95% confidence interval 1.17-1.77). When comparing AF with syncope, female gender, musculoskeletal diseases, dementia, and systolic blood pressure >110 mmHg emerged as significantly associated with AF (OR 0.40 [0.27-0.58], 0.40 [0.24-0.68], 0.35 [0.14-0.82], and 0.31 [0.20-0.49], respectively), while valvulopathy and the number of antihypertensive drugs were significantly related to syncope (OR 2.51 [1.07-5.90] and 1.24 [1.07-1.44], respectively). Upon comparison of UF and syncope, the number of central nervous system drugs, female gender, musculoskeletal diseases, and SBP >110 mmHg were associated with UF (OR 0.65 [0.50-0.84], 0.52 [0.30-0.89], 0.40 [0.20-0.77], and 0.26 [0.13-0.55]), respectively. These results indicate specific differences, in terms of demographics, medical/pharmacological history, and vital signs, among older patients admitted to the ED for AF and syncope. UF was associated with higher use of psychotropic drugs than AF. Our findings could be helpful in supporting a proper diagnostic process when evaluating older patients after a fall.

Stereotactic Body Radiotherapy in Patients with Lung Oligometastases from Colorectal Cancer.

AIM: To assess the role of stereotactic body radiotherapy (SBRT) in pulmonary metastases from colorectal cancer (CRC). PATIENTS AND METHODS: Thirty-three consecutive patients with pulmonary metastases from CRC who received SBRT were included in the analysis. The primary endpoints were local and systemic progression-free survival, a secondary endpoint was the safety profile of SBRT. RESULTS: A total of 56 lesions were treated with SBRT. A single nodule was treated in 15 patients, two in 13 and three in five. The radiotherapy dose and the adopted fractionations were 24-27 Gy as a single fraction for 40 lesions and 27-42 Gy in three fractions (2-3 times a week) for the other 16 lesions. After a median follow-up of 22.8 months (range=1.3-45.7 months), the median progression-free survival of the irradiated sites was 13.4 months. CONCLUSION: SBRT can be considered as local therapy in patients with lung metastases from CRC.

The difference in activity of daily living (ADL) and mortality in patients aged over 80 years with femoral neck fracture treated with hemiarthroplasty or osteosynthesis at 2 years of follow-up.

INTRODUCTION: Hip fractures are one of the major causes of morbidity and mortality in the elderly and outcomes following hip fracture have been the focus of several studies over recent decades. Among all types of fall-related injuries, hip fractures cause the greatest number of deaths, lead to severe health problems and reduce quality of life. Improving the outcome of hip fracture surgery has thus become one of the main areas of interest for orthopaedic surgeons. The aim of this study was to compare the difference in activity of daily living (ADL) and mortality between patients aged over 80 years with hip fracture treated with osteosynthesis versus prosthesis at 2 years of follow-up. MATERIALS AND METHODS: The data were collected on admission and during in-hospital stay. Information recorded on admission included: age, sex, type and mechanism of fracture, functional and cognitive status, comorbidity, and severity of illness. Prefracture functional status was measured. The follow-up was clinical and radiographical, or was by telephone for patients who were not able to come to the clinic. Patients aged over 80 years who underwent a single surgical procedure treated with intramedullary nail or hemiarthroplasty were included in the study. RESULTS: A total of 174 patients (45 male and 129 female) were included in the study. The two treatment groups were comparable for all preoperative parameters except for preoperative haemoglobin, which was an average of 1g/dl higher in the patients given hemiarthroplasty compared with those treated with intramedullary nail (t-test: p<0.05). The average observation period was 594.99days; the number of deaths was 62 of 164 contacted patients, and the survival rate at 2 years was 62.2%. There was increased mortality in patients who underwent hemiarthroplasty (Log-rank Mantel-Cox, p: 0,048). The difference in ADL between preoperative and follow-up is not statistically significant between the two groups. DISCUSSION: In the literature, there are few specific studies that consider these parameters in this population. However, these findings are consistent with the findings from other studies. CONCLUSION: Patients who received hemiarthroplasty have a higher mortality risk than those treated with intramedullary nail; there are no differences in ADL at follow-up.

Cognitive Function and the Ageing Process: The Peculiar Role of Mild Thyroid Failure.

BACKGROUND: Over the last decades an increasing body of evidence suggested a possible relationship between thyroid hormone (TH) and the ageing process, and several efforts have been made to determine the actual role of TH dynamic during human life. It is still unclear whether the serum level shift of Thyroid Stimulating Hormone toward higher value, observed during ageing, is a normal adaptive response associated with senescence or an actual mild thyroid dysfunction. A growing body of evidence supports the hypothesis of a reset of the hypothalamus-pituitary-thyroid axis in order to contrast the catabolic status of the ageing process. On the other hand, several meta-analyses showed a direct link between subclinical hypothyroidism (sHT) and cardiovascular events (both ischemic heart disease and stroke), although mainly in individuals younger than 65 years. Similarly, a recent meta-analysis documented consistent data on a positive relationship between sHT and cognitive impairment, but only in individuals younger than 75 years. CONCLUSION: The available data suggest a complex relationship between mild thyroid failure and the ageing process as well as the development and progression of several cardiovascular and neurological diseases. In this paper, we reviewed the scientific English literature on sHT and the ageing process focusing on experimental evidences related to cognitive impairment and dementia. Moreover, we focused on new patents of treatments potentially able to improve the care of sHT patients, especially in the elderly, where treatment drawbacks may have negative impact on the long term outcome.

Long-Term PSA Control with Repeated Stereotactic Body Radiotherapy in a Patient with Oligometastatic Castration-Resistant Prostate Cancer.

Prostate cancer (PCa) is one of the most common malignancies and main causes of cancer death in Western countries. In the presence of metastatic disease, systemic treatment remains the main clinical option. However, since the introduction of highly sensitive imaging techniques, a new clinical 'entity' of metastatic patients with a limited number of lesions has been defined: oligometastatic patients. In this patient group, the use of stereotactic body radiotherapy (SBRT) or other local therapies against all active sites of disease revealed by 18F-choline positron emission tomography/computed tomography (PET/CT) could achieve sufficient prostate-specific antigen (PSA) control. However, a clear benefit of this procedure in terms of significant endpoints is yet to be demonstrated. This case report describes our experience with treating a castration-resistant PCa patient with 18F-choline PET/CT-guided SBRT. Because of the occurrence of 5 metachronous lesions over 4 years, the pattern of recurrence was defined by the local multidisciplinary team as oligometastatic disease, and the patient was treated with 5 courses of SBRT which yielded good PSA control. He started systemic therapy with abiraterone acetate almost 5 years after the diagnosis of recurrent PCa.