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Background: Machine-learning techniques have been recently utilized to predict the probability of unfavorable outcomes among elderly patients suffering from heart failure (HF); yet none has integrated an assessment for frailty and comorbidity. This research seeks to determine which machine-learning-based phenogroups that incorporate frailty and comorbidity are most strongly correlated with death or readmission at hospital for HF within six months following discharge from hospital. Methods: In this single-center, prospective study of a tertiary care center, we included all patients aged 65 and older discharged for acute decompensated heart failure. Random forest analysis and a Cox multivariable regression were performed to determine the predictors of the composite endpoint. By k-means and hierarchical clustering, those predictors were utilized to phenomapping the cohort in four different clusters. Results: A total of 571 patients were included in the study. Cluster analysis identified four different clusters according to frailty, burden of comorbidities and BNP. As compared with Cluster 4, we found an increased 6-month risk of poor outcomes patients in Cluster 1 (very frail and comorbid; HR 3.53 [95% CI 2.30–5.39]), Cluster 2 (pre-frail with low levels of BNP; HR 2.59 [95% CI 1.66–4.07], and in Cluster 3 (pre-frail and comorbid with high levels of BNP; HR 3.75 [95% CI 2.25–6.27])). Conclusions: In older patients discharged for ADHF, the cluster analysis identified four distinct phenotypes according to frailty degree, comorbidity, and BNP levels. Further studies are warranted to validate these phenogroups and to guide an appropriate selection of personalized, model of care.

The aim of this single-center, open-label, randomized controlled study was to evaluate which formulation of vitamin D—between cholecalciferol and calcifediol—is most effective in the treatment of hypovitaminosis D in older adults. Demographic characteristics, clinical history, and comprehensive geriatric assessment were recorded at admission. Eligible patients were randomly assigned an equivalent vitamin D supplement, either with cholecalciferol or calcifediol, from the time of hospital admission to three months after discharge. Among the 140 older patients included (mean age 83 ± 6.6 years, 57.8% females), 69 received cholecalciferol and 71 received calcifediol. The mean plasma values of 25-hydroxyvitamin D3 (25OH-vitamin D3) found at the time of enrollment were 16.8 ± 9.9 ng/mL in patients receiving cholecalciferol and 18.8 ± 13.3 ng/mL in those treated with calcifediol (p = 0.31). At the three month follow-up, the mean concentration of 25OH-vitamin D3 was significantly higher in patients treated with calcifediol than in those receiving cholecalciferol (30.7 ± 8.4 vs. 45.4 ± 9.8 ng/mL, respectively; p < 0.001). Supplementation with either cholecalciferol or calcifediol effectively results in reaching the optimal circulating values of 25OH-vitamin D3 in older patients suffering from hypovitaminosis D. However, supplementation with calcifediol led to average circulating values of 25OH-vitamin D3 that were significantly higher (over 50%) than those obtained with cholecalciferol.

Background: Previous studies have shown increased risk of fracture in older patients with poor or strict glycemic control (glycated hemoglobin, HbA1c, ≥ 8% or < 6-7% respectively); however, these reports did not investigate the oldest-old population. Comprehensive geriatric assessment (CGA) and a patient-centered approach have been proven to improve the quality of care in the management of Type 2 Diabetes Mellitus (T2DM) in the older patients, but data regarding T2DM in patients with fragility fractures are still lacking. Aim: To investigate the prognostic role of HbA1c and frailty level in older diabetic patients admitted for hip fracture. Methods: Prospective observational cohort study conducted on diabetic geriatric patients consecutively hospitalized for hip fracture in the orthogeriatric unit of a tertiary care hospital. Preoperative comprehensive geriatric assessment (CGA) was performed. Using the Clinical Frailty Scale (CFS), diabetic patients were categorized in robust (CFS < 5) and frail (CFS ≥ 5), and further stratified according to HbA1c values [Tertile 1 (T1) HbA1c < 48 mmol/mol, Tertile 2 (T2) 48-58 mmol/mol and Tertile 3 (T3) > 58 mmol/mol). Comparisons between continuous variables were performed with analysis of non-parametric test for independent samples, while relationships between categorical variables were assessed by chi-square test. Using logistic multivariate regression, we evaluated the determinants of 1-year all-cause mortality in diabetic older patients with hip fracture. Results: Among the 1319 older patients (mean age 82.8 ± 7.5 years, 75.9% females) hospitalized for hip fracture, 204 (15.5%) had a previous diagnosis of T2DM. T2DM patients showed an increased proportion of multiple concurrent fractures occurred during the accidental fall or syncope (12.7% vs 11.2%, p=0.02). One-year mortality after hip fracture surgery was significantly higher in T2DM as compared to not diabetic patients (21.2% vs 12.5%, p<0.001). No si

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 reassessment should be always considered to avoid the risk of overtreatment. 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.

Background. Drug-induced hyperthyroidism is a rare condition linked to dietary supplements, iodine-con-taining medications and intentional or unintentional over ingestion of levothyroxine; its detection is important since, if left untreated, thyroid storm can develop, carrying a mortality rate of 20-50%. Case presentation. Here we describe the case of an oldest old (84 years) woman, with severe cognitive impairment and immobilization syndrome attending our geriatric ward for aspiration pneumonia. During the fifth day of hospitalization, while pneumonia and respiratory symptoms were improving, tachycardia persisted (heart rate 130 bpm), associated with tremors and lack of sleep. The patient was affected by multinodular goiter and, a diagnosis of thyrotoxicosis was documented by elevated serum free thyroxine and free triiodothy-ronine levels (4.7 ng/dL and 6.6 ng/L, respectively), associated with undetectable thyroid-stimulating hormone (TSH 0.04 mIU/L), elevated urinary iodine excretion (849 µg/L) and normal serum thyroglobulin levels (10 ng/ mL).131I thyroid scan showed diffuse low uptake, suggesting iatrogenic thyrotoxicosis. The patient suffered from immobilization syndrome with bedsores that had been medicated twice a week with iodoform gauzes for one year. Prior to starting the use of iodoform dressings the patient was documented euthyroid. Conclusions. Over the past century, few cases have been described regarding possible severe toxicity caused by the use of iodoform gauzes, all of them presenting with neurovegetative symptoms as vomiting, altered sensor, which disappeared after withdrawn of the medication, but iatrogenic thyrotoxicosis was never demonstrated. Thus, to our knowledge, this is the first report documenting the onset of thyrotoxicosis induced by lasting use of iodoform gauzes.

Background: Fine needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains undetermined for 20% of nodules. Aim: We investigated the diagnostic potential of a set of 6 marker genes to distinguish benign and malignant thyroid nodules. Subjects and methods: The prospective study included 153 thyroid samples obtained by FNA of thyroid nodules from 151 patients (56 benign, 43 malignant, and 54 nodules with undetermined cytology). Gene expression was evaluated by quantitative real-time PCR and statistical analysis of data was performed. All samples were analyzed for V600E BRAF mutation. Results: A decrease in TTF3 and HGD1 expression was observed in malignant nodules with respect to benign ones, while an increase in PLAB expression was demonstrated in these nodules. The decision model was valid for 88 of 99 cases of benign and malignant nodules, with a total of 11 false positive or negative predictions. The obtained malignant/benign phenotype prediction was also valid for 37 of 54 cases of nodules with undetermined cytology with a total of 8 false positive and 9 false negative predictions. V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules, and in 1/54 undetermined nodules. Conclusions: The expression profiles of genes (TFF3, HGD1, and PLAB) allowed a good prediction for the differentiation of benign thyroid lesions and thyroid cancer starting from cells of FNA; however, this assay showed limitations when applied to discriminate thyroid nodules with undetermined cytology. ©2012, Editrice Kurtis

Objective: MicroRNAs (miRNAs) are small endogenous noncoding RNAs that pair with target messengers regulating gene expression. Changes in miRNA levels occur in thyroid cancer. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytological diagnosis remains undetermined for 20% of nodules. Design: In this study, we evaluated the expression of seven miRNAs in benign nodules, papillary thyroid carcinomas (PTCs), and undetermined nodules at FNA. Methods: The prospective study included 141 samples obtained by FNA of thyroid nodules from 138 patients. miRNA expression was evaluated by quantitative RT-PCR and statistical analysis of data was performed. Genetic analysis of codon 600 of BRAF gene was also performed. Results: Using data mining techniques, we obtained a criterion to classify a nodule as benign or malignant on the basis of miRNA expression. The decision model based on the expression of miR-146b, miR-155, and miR-221 was valid for 86/88 nodules with determined cytology (97.73%), and adopting cross-validation techniques we obtained a reliability of 78.41%. The prediction was valid for 31/53 undetermined nodules with 16 false-positive and six false-negative predictions. The mutated form V600E of BRAF gene was demonstrated in 19/43 PTCs and in 1/53 undetermined nodules. Conclusions: The expression profiles of three miRNAs allowed us to distinguish benign from PTC starting from FNA. When the assay was applied to discriminate thyroid nodules with undetermined cytology, a low sensitivity and specificity despite the low number of false-negative predictions was obtained, limiting the practical interest of the method. © 2012 European Society of Endocrinology