Serum triiodothyronine-to-thyroxine (T3/T4) ratio predicts therapeutic outcome to biological therapies in elderly IBD patients.

INTRODUCTION: Rates of elderly patients with inflammatory bowel diseases (IBDs) are increasing, and biomarkers are needed to optimise their therapies. Serum triiodothyronine-to-thyroxine (T3/T4) ratio has been correlated with geriatric patient frailty. AIM: To assess the suitability of T3/T4 ratio as a response marker to biologics in elderly patients with IBD. METHODS: Patients with IBD over 60 years old were enrolled, when starting biological therapy. Therapeutic outcome was assessed after 54 weeks of treatment as mucosal healing (Mayo endoscopic score < 2 for ulcerative colitis; ulcer disappearance for Crohn's disease) and clinical remission (Partial Mayo Score < 2 for ulcerative colitis; Harvey-Bradshaw Index < 5 for Crohn's disease). T3/T4 ratio was evaluated at baseline, and its association with therapeutic outcomes was tested by multivariable logistic regression and receiver operating characteristic (ROC). RESULTS: We enrolled 80 patients; 44 achieved clinical remission and 36 mucosal healing. Baseline T3/T4 ratio was higher in patients with mucosal healing, as compared with those without mucosal healing (P < 0.0001), regardless of the disease type or biological drug (OR 6.4 [2.9-14.3] for each T3/T4 unit increase, P < 0.0001). A cut point of 3.3 was identified as the optimal threshold of baseline T3/T4 ratio for predicting mucosal healing, providing 78% sensitivity and 89% specificity (area under the ROC curve 0.88 [0.79-0.94]; positive and negative likelihood ratios 6.8 [2.9-15.9] and 0.3 [0.1-0.5] respectively). CONCLUSIONS: T3/T4 ratio seems a reliable tool for predicting therapeutic outcome of biological therapy in elderly patients with IBD. If validated, the assessment of this parameter before starting biological treatment might be suggested.

Pneumonia Lung Ultrasound Score (PLUS): A New Tool for Detecting Pneumonia in the Oldest Patients.

OBJECTIVES: To compare the diagnostic accuracy of lung ultrasound (LUS) and standard chest X-ray (CXR) in older patients admitted to an acute-care geriatric ward for suspected acute pneumonia, and to develop an easy-to-use diagnostic tool, now called Pneumonia Lung Ultrasound Score (PLUS), for early risk stratification. DESIGN: Prospective, single-center, cohort study. SETTING: Acute-care geriatric ward of tertiary care center. PARTICIPANTS: Individuals, aged 65 years and older, with suspected acute pneumonia. MEASUREMENTS: Participants were stratified according to the Multidimensional Prognostic Index. All the patients underwent CXR and LUS, whereas chest computed tomography was performed in case of mismatch between LUS and CXR. Using logistic multivariate regression, we assessed the influence of age, sex, multimorbidity, cognitive impairment, and clinical biomarkers in the misdiagnosis of acute pneumonia. Finally, an easy-to-perform diagnostic tool based on the combination of biomarkers (brain natriuretic peptide, high-sensitivity C-reactive protein, and partial pressure arterial oxygen/fraction of inspired oxygen ratio) and LUS was realized. A receiver operating characteristic curve was used to verify the predictive accuracy of PLUS, CXR, and LUS in pneumonia diagnosis. RESULTS: A total of 132 subjects (69% women; mean age = 85.3 ± 6.9 years) were enrolled in the study. Acute pneumonia was diagnosed in 94 of 132 cases. LUS showed higher diagnostic accuracy compared with CXR (0.91 (95% confidence interval (CI) = 0.85-0.93) vs 0.67 (95% CI = 0.58-0.75)) in detecting pneumonic consolidations. A higher degree of cognitive impairment was associated with both LUS and CXR pneumonia misdiagnosis (odds ratio = 1.30 (95% CI = 1.04-1.65)). PLUS showed higher predictive accuracy in the diagnosis of acute pneumonia compared with LUS (AUC = 0.92 (95% CI = 0.87-0.98) vs 0.86 (95% CI = 0.80-0.96); P = .029). CONCLUSIONS: This study confirms the higher diagnostic accuracy of LUS compared with CXR for acute pneumonia in older adults. Nonetheless, the accuracy of PLUS, an easy-to-use, biomarker-derived diagnostic tool, was superior to LUS regardless of patients' degree of frailty.

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.

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.

Caudate dopaminergic denervation and visual hallucinations: evidence from a ¹²³I-FP-CIT SPECT study.

OBJECTIVE: The pathogenesis of visual hallucinations (VHs) in Parkinson's disease (PD) has been considered multifactorial. In the pathophysiology of VHs a combination of impaired visual processing and attention has been reported. Imaging studies evidenced a role of the primary visual system and visual association areas as well as a dysfunctional activation of frontal areas in the occurrence of VHs. Due to the functional connections between basal ganglia and frontal areas, a role of basal ganglia and of the fronto-striatal circuits in the pathogenesis of VHs may be postulated. Aim of this study is to unveil whether a presynaptic dopamine deficiency at baseline may predict the development of VHs. METHODS: A group of 18 non demented PD patients with VHs was matched with 18 non demented PD patients without VHs as regards age of onset of disease, disease duration and severity and levodopa equivalent dose. We retrospectively analyzed the (123)I-FP CIT SPECT performed on the two groups at the onset of their disease. The striatal uptake values in the two groups were examined, in order to evaluate nigrostriatal differences between the groups with different behavioral phenotype. RESULTS: The group of patients with VHs had a significant reduction (p < 0.05) in right caudate uptake values at baseline when compared with patients without VHs. No significant differences were found between the groups regarding left caudate and putaminal uptake values. CONCLUSIONS: The frontal impairment reported in PD patients with VHs may be due to a right caudate dysfunction, as it is connected to the frontal brain areas via neuronal loops.