Usefulness of the SARC-F questionnaire and the measurement of the hand grip strength in predicting short-term mortality in older patients hospitalized for acute heart failure.

PURPOSE: Sarcopenia is a potentially reversible syndrome that increases the risk of cardiogenic cachexia and adverse outcomes in older patients with heart failure (HF). Despite its clinical significance, sarcopenia remains underdiagnosed due to the complexities of comprehensive assessment in patients with acute HF. This study aimed to evaluate whether the SARC-F questionnaire, its inviduals components, and the handgrip strength test (HGS) can predict short-term prognostic risk in very old patients recently discharged after acute HF. METHODS: We consecutively enrolled patients aged 75 years or older hospitalized with acute HF in the Geriatrics Unit of a tertiary care hospital. All patients underwent physical examination, complete blood tests, point-of-care ultrasound, and a comprehensive geriatric assessment, including physical performance through SARC-F and HGS. The thirty-day post-discharge mortality rate was assessed by phone interview. RESULTS: Out of 184 patients hospitalized with acute HF who were enrolled in the study (mean [SD], 86.8 [5.9] years, 60.3% female), 47 died within 30 days after discharge. By multivariate logistic analysis, HGS (ß = - 0.73 ± 0.03, p = 0.008) and SARC-F [adjusted OR = 1.18 (CI 95% 1.03-1.33), p = 0.003] resulted independently associated with mortality. Furthermore, two SARC-F sub-items, namely, limitation in rising from a chair and history of falls [aOR: 3.26 (CI95% 1.27-8.34), p = 0.008; aOR: 3.30 (CI 95% 1.28-8.49), p = 0.01; respectively] emerged as determinants of 30-days mortality. CONCLUSION: SARC-F and HGS test independently predict 30-day post-discharge mortality in oldest-old patients hospitalized for acute HF.

Prognostic Value of Glycated Hemoglobin in Frail Older Diabetic Patients With Hip Fracture.

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 significant difference in mortality was found across HbA1c tertiles; however, frail diabetic patients in the second and third HbA1c tertiles showed higher mortality risk compared to the robust counterparts (26.9% vs 5%, p=0.001 for T2 and 43.5% vs 13.3%, p=<0.05 for T3), while no difference was observed among those in T1. Conclusions: Frail patients with HbA1c ≥ 48 mmol/L showed an increased mortality risk as compared to robust counterparts. CFS represents an important tool to select diabetic subjects with higher likelihood of adverse outcome.

Proteomic analysis of fine-needle aspiration in differential diagnosis of thyroid nodules.

Thyroid nodules are common in the general population and vary widely in their propensity to harbor thyroid malignancies. The category of follicular lesion of undetermined significance, for instance, carries only a 15% risk of malignancy. The overarching aim of this work was the proteomic study of thyroid cancer because more effort needs to be placed on differentiating malignant thyroid nodules to avoid unnecessary thyroidectomy. We used 2-dimensional electrophoresis coupled to nano-liquid chromatography electrospray ionization tandem mass spectrometry, to examine fine-needle aspiration (FNA), which was easily attainable from the wash of the syringe used for classical FNA biopsy. Overall, we found 25 different proteins able to discriminate benign from malignant samples. The different expression of moesin; annexin A1 (ANXA1); cornulin (CRNN); lactate dehydrogenase; enolase; protein DJ-1; and superoxide dismutase was confirmed in FNA by enzyme-linked immunosorbent assay or Western blot. Receiver operating characteristic curves were calculated to investigate the discriminative power of our marker. The best performance in diagnosis was obtained by combining ANXA1, enolase, protein DJ-1, superoxide dismutase, and CRNN. In addition, the most highly ranked proteins, from the perspective of follicular lesion of undetermined significance, were ANXA1 and CRNN. The research of these candidate biomarkers has then been widened to other biological fluids, such as serum and whole saliva. In conclusion, we believe that when a decision by a thyroid nodule biopsy cannot be distinctly made, the combination of our biomarkers may be one of the criteria to be taken into account for the final decision, together with the identification of ANXA1 in serum and saliva.

Presence in the pre-surgical fine-needle aspiration of potential thyroid biomarkers previously identified in the post-surgical one.

Fine-needle aspiration biopsy (FNA) is usually applied to distinguish benign from malignant thyroid nodules. However, cytological analysis cannot always allow a proper diagnosis. We believe that the improvement of the diagnostic capability of pre-surgical FNA could avoid unnecessary thyroidectomy. In a previous study, we performed a proteome analysis to examine FNA collected after thyroidectomy. With the present study, we examined the applicability of these results on pre-surgical FNA. We collected pre-surgical FNA from 411 consecutive patients, and to obtain a correct comparison with our previous results, we processed only benign (n=114), papillary classical variant (cPTC) (n=34) and papillary tall cell variant (TcPTC) (n=14) FNA. We evaluated levels of five proteins previously found up-regulated in thyroid cancer with respect to benign nodules. ELISA and western blot (WB) analysis were used to assay levels of L-lactate dehydrogenase B chain (LDHB), Ferritin heavy chain, Ferritin light chain, Annexin A1 (ANXA1), and Moesin in FNA. ELISA assays and WB analysis confirmed the increase of LDHB, Moesin, and ANXA1 in pre-surgical FNA of thyroid papillary cancer. Sensitivity and specificity of ANXA1 were respectively 87 and 94% for cPTC, 85 and 100% for TcPTC. In conclusion, a proteomic analysis of FNA from patients with thyroid nodules may help to distinguish benign versus malignant thyroid nodules. Moreover, ANXA1 appears to be an ideal candidate given the high sensitivity and specificity obtained from ROC curve analysis.

MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration.

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.