Resolution of inflammation is altered in chronic heart failure and entails a dysfunctional responsiveness of T lymphocytes.

Chronic heart failure (CHF) is characterized by an ongoing nonresolving inflammatory status, where T lymphocytes seem critical. It has been recently recognized that transition from acute to chronic inflammation could be caused by defects in resolving inflammation, the resolution of which is mediated by a novel family of ω-3-derived specialized proresolving lipid mediators such as resolvins. We analyzed 27 elderly patients with CHF and 23 healthy age-matched control subjects, and we reported significantly lower levels of D-series resolvin (RvD)1 in plasma of patients with CHF that were associated with a reduced ability of their leukocytes to produce this lipid via its biosynthetic enzyme 15-lipoxygenase and that correlated with gas exchange dysfunction. Furthermore, when pretreating ex vivo peripheral blood mononuclear cells of patients with CHF with RvD1 or RvD2, we found that neither of them was able to modulate the immune response of CD8+ and CD4+ T cells in terms of proinflammatory cytokine production, namely TNF-α, IFN-γ, IL-17, and IL-2. Such impaired T-cell responsiveness in patients with CHF was associated with a significant reduction in mRNA and protein expression of RvD1 receptor GPR32, suggesting a defective signaling in the proresolving pathway. We conclude that patients with CHF show alterations in producing proresolving mediator RvD1 and a failure of adaptive immune cells in responding to the anti-inflammatory actions of RvDs that may contribute to the progression of chronic inflammation. Thus, the proresolution pathway might be a potential candidate to design better treatments for CHF aimed at reducing T cell-mediated chronic inflammation.-Chiurchiù, V., Leuti, A., Saracini, S., Fontana, D., Finamore, P., Giua, R., Padovini, L., Incalzi, R. A., Maccarrone, M. Resolution of inflammation is altered in chronic heart failure and entails a dysfunctional responsiveness of T lymphocytes.

Electrophoretic α1-globulin for screening of α1-antitrypsin deficient variants.

Background Available screening procedures for the detection of α1-antitrypsin-deficient (AATD) mutations have suboptimal cost-effectiveness ratios. The aim in this study was to evaluate and compare the viability of a composite approach, primarily based on the α1-globulin fraction, in identifying AAT genetic analysis eligible patients against standard screening procedures, based on clinically compatible profiling and circulating AAT < 1 g/L. Methods A total of 21,094 subjects were screened for AATD and deemed eligible when meeting one of these criteria: α1-globulin ≤2.6%; α1-globulin 2.6%-2.9% and AST: >37 U/L and ALT: > 78 U/L; α1-globulin %: 2.9-4.6% and AST: >37 U/L and ALT: >78 U/L and erythrocyte sedimentation rate (ESR) >34 mm/h and C-reactive protein (CRP) >3 mg/L. Subjects were genotyped for the AAT gene mutation. Detection rates, including those of the rarest variants, were compared with results from standard clinical screenings. Siblings of mutated subjects were included in the study, and their results compared. Results Eighty-two subjects were identified. Among these, 51.2% were found to carry some Pi*M variant versus 15.9% who were clinically screened. The detection rates of the screening, including relatives, were: 50.5% for the proposed algorithm and 18.9% for the clinically-based screening. Pi*M variant prevalence in the screened population was in line with previous studies. Interestingly, 46% of subjects with Pi*M variants had an AAT plasma level above the 1 g/L threshold. Conclusions A composite algorithm primarily based on the α1-globulin fraction could effectively identify carriers of Pi*M gene mutation. This approach, not requiring clinical evaluation or AAT serum determination, seems suitable for clinical and epidemiological purposes.

Bone Mineral Density and Cognitive Decline in Elderly Women: Results from the InCHIANTI Study.

Osteoporosis and cognitive impairment, which are highly prevalent conditions in elderly populations, share several risk factors. This study aims at evaluating the association of bone mineral density (BMD) with prevalent and incident cognitive impairment after a 3-year follow-up. We studied 655 community-dwelling women aged 65+ participating in the InCHIANTI study, who had been followed for 3 years. Total, trabecular, and cortical BMD were estimated by peripheral quantitative computed tomography using standard transverse scans at 4 and 38 % of the tibial length. Cognitive performance was evaluated using the Mini-Mental State Examination and the Trail Making Tests (TMT) A and B; a MMSE score <24 was adopted to define cognitive impairment. The TMT A-B score was calculated as the difference between TMT-A and TMT-B times (ΔTMT). The association of cognitive performance after 3 years with baseline indices of BMD was assessed by logistic and linear regression analyses. Cortical, but not trabecular, BMD was independently associated with incident cognitive impairment (OR 0.93, 95 % CI 0.88-0.98; P = 0.012), worsening cognitive performance (OR 0.96, 95 % CI 0.92-0.98; P = 0.039), and worsening performance in ΔTMT (OR 0.96, 95 % CI 0.92-0.99; P = 0.047). Increasing cortical BMD tertiles was associated with decreasing probability of incident cognitive impairment (P for linear trend =0.001), worsening cognitive performance (P = 0.013), and a worsening performance below the median value (P for linear trend <0.0001). In older women, low BMD might represent an independent and early marker of subsequent cognitive impairment. Physicians should assess and monitor cognitive performance in the routine management of elderly women with osteoporosis.

The burden of comorbidity is associated with symptomatic polymicrobial urinary tract infection among institutionalized elderly.

BACKGROUND: Urinary tract infections (UTIs), often sustained by polymicrobial flora (p-UTIs), are a common finding among nursing home patients, and associated with adverse outcomes and increased healthcare costs. P-UTIs have been extensively studied with regard to microbiological aspects. However, little is known about the characteristics of the host. AIMS: The aim of this study is to verify to which extent comorbidity characterizes elderly nursing home patients with p-UTIs. METHODS: We enrolled 299 patients with culture-positive UTI consecutively admitted to the nursing home of the "Fondazione San Raffaele Cittadella della Carità", Taranto, Italy. P-UTI was diagnosed when two uropathogens were simultaneously isolated. The burden of comorbidity was quantified using the Charlson comorbidity score index. Logistic regression analysis was used to assess the adjusted association of the variables of interest with the presence of p-UTI. RESULTS: P-UTIs were detected in 118/299 (39%) patients. According to logistic regression, the presence of p-UTIs was independently associated with the Charlson index (OR 1.70; 95% CI 1.06-2.72; P = .026). This association remained also after excluding participants without urinary catheter (OR 1.88; 95% CI 1.13-3.11; P = .015). DISCUSSION: The presence of P-UTIs is associated with the burden of comorbidity, but not with individual diseases. CONCLUSIONS: Older nursing home patients with comorbidity should be screened for the presence of p-UTIs; further studies are needed to evaluate the impact of early detection and treatment of p-UTIs on the development of comorbidity.

Predictors of undernutrition in COPD patients.

BACKGROUND & AIMS: Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by persistent respiratory symptoms and airflow limitation. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report recommends smoking cessation, pharmacological therapy and pulmonary rehabilitation, but this clinical course can be negatively influenced by undernutrition, a condition documented in about 20% of COPD patients. An altered energy balance characterized by an insufficient intake of energy and nutrients is the primary cause of undernutrition, therefore the aim of this study is to investigate whether clinical and instrumental variables collected during a routine respiratory assessment associate with an altered energy balance in order to identify COPD patients at higher risk of undernutrition worth of further assessment. METHODS: A total of forty-nine participants with a diagnosis of stable COPD were included in this mono-center and longitudinal study. Subjects underwent a multidimensional assessment including evaluation of medical history, evaluation of pulmonary function, evaluation of nutritional status, evaluation of energy intake and resting energy expenditure (REE) using EPIC questionnaire and indirect-calorimetry (IC), respectively, evaluation of physical impairment and mood status. RESULTS: The 24% of participants was at risk of undernutrition with a mean energy intake, total protein intake and lipid intake significantly lower than not at risk subjects, while REE was significantly higher. Age, sex, multimorbidity, disability and depression, and pulmonary function tests were not associated with a negative energy balance, with the exception of the Cumulative Illness Rating Scale (CIRS) severity index, which showed a significant association. CONCLUSION: Clinical evaluation and pulmonary function tests are unable to reliably predict undernutrition in COPD patients, so a nutritional screening should always be forecast in this population based on an accurate evaluation of energy intake and expenditure and body composition.

Energy expenditure and intake in COPD: The extent of unnoticed unbalance by predicting REE.

Undernourishment is promoted by an unbalance between energy expenditure and intake. Resting energy expenditure (REE) in chronic obstructive pulmonary disease (COPD) is commonly predicted using the Harris-Benedict (HB) and the Angelillo-Moore (AM) formulas, however no study has investigated to which extent COPD patients with an energy unbalance go unnoticed when REE is predicted rather than measured with indirect calorimetry. This study demonstrates that 66% and 25% of negatively unbalanced patients go unnoticed when using HB and AM, respectively, urging to discourage the use of REE predicting formulas in clinical practice, at least in cases at risk of undernourishment.

The Association of Olfactory Dysfunction, Frailty, and Mortality Is Mediated by Inflammation: Results from the InCHIANTI Study.

BACKGROUND: Olfactory dysfunction might unveil the association between ageing and frailty, as it is associated with declining cognitive function, depression, reduced physical performance, reduced dietary intake, and mortality; all these conditions are characterized by increased levels of inflammatory parameters. The present study is aimed at evaluating the association between olfactory dysfunction, frailty, and mortality and whether such association might be mediated by inflammation. METHODS: We analysed data of 1035 participants aged 65+ enrolled in the "InCHIANTI" study. Olfactory function was tested by the recognition of the smells of coffee, mint, and air. Olfactory dysfunction was defined as lack of recognition of at least two smells. Considering the items "shrinking," "exhaustion," "sedentariness," "slowness," and "weakness" included in the Fried definition, frailty was defined as the presence of at least three criteria, prefrailty of one or two, and robustness of none. Serum interleukin-6 (IL-6) was measured in duplicate by high-sensitivity enzyme-linked immunosorbent assays. Logistic regression was adopted to assess the association of frailty with olfactory function, as well as with the increasing number of olfactory deficits. Cox regression was used to test the association between olfactory dysfunction and 9-year survival. RESULTS: Olfactory dysfunction was associated with frailty, after adjusting (OR 1.94, 95% CI = 1.07-3.51; P = .028); analysis of the interaction term indicated that the association varied according to interleukin-6 levels (P for interaction = .005). Increasing levels of olfactory dysfunction were associated with increasing probability of being frail. Also, olfactory dysfunction was associated with reduced survival (HR 1.52, 95% CI = 1.16-1.98; P = .002); this association varied according to the presence of frailty (P for interaction = .017) and prefrailty status (P for interaction = .046), as well as increased interleukin-6 levels (P for interaction = .011). CONCLUSIONS: Impairment of olfactory function might represent a marker of frailty, prefrailty, and consequently reduced survival in an advanced age. Inflammation might represent the possible link between these conditions.

Self-Reported Masticatory Dysfunction and Mortality in Community Dwelling Elderly Adults: A 9-Year Follow-Up.

OBJECTIVES: To evaluate the association, if any, between masticatory dysfunction (MD) and mortality in older adults. DESIGN: The Invecchiare in Chianti (InCHIANTI) Study, a cohort study with 9-year follow-up. SETTING: Tuscany, Italy. PARTICIPANTS: Individuals aged 65 and older (N = 1,155). MEASUREMENTS: MD was self-reported; Cox regression was used to assess the association between self-reported MD and 9-year all-cause mortality. This association was also evaluated after stratifying according to use of dentures. Analyses were adjusted for potential confounders, including demographic characteristics, lifestyle habits, comorbidities, nutrient intake, medications, and objective parameters. RESULTS: Four hundred five (35%) participants reported MD. Over the 9-year follow-up, 475 (41%) subjects died. According to Cox regression analysis, self-reported MD was associated with higher mortality (relative risk (RR) = 1.23, 95% confidence interval (CI) = 1.02-1.48), after adjusting for potential confounders. In participants with self-reported MD, uncorrected edentulism was the condition associated with the greatest risk of mortality (RR = 2.10, 95% CI = 1.07-4.14); use of dentures seemed to blunt this association (RR = 1.12, 95% CI = 0.87-1.44). CONCLUSION: Self-reported MD, chiefly when due to uncorrected edentulism, is associated with 9-year all-cause mortality in community-dwelling elderly adults. Further studies are needed to evaluate whether the timely correction of MD using adequate dentures can increase the survival of older adults.

Pre-polysomnographic assessment using the Pittsburgh Sleep Quality Index questionnaire is not useful in identifying people at higher risk for obstructive sleep apnea.

BACKGROUND: Polysomnography remains the diagnostic gold standard for obstructive sleep apnea syndrome (OSAS), but it is time consuming and requires dedicated personnel and setting. It may be more useful to plan a polysomnogram based on a preliminary screening. OBJECTIVE: To verify whether a questionnaire of general quality of sleep, the Pittsburgh Sleep Quality Index (PSQI), could outperform a dedicated questionnaire (Epworth Sleep Scale: ESS) in targeting OSAS patients in an at risk population. METHODS: 254 consecutive subjects attending the outpatient clinic for respiratory diseases were clinically evaluated for sleep apnea and referred to a 12 channel night-time polysomnography. All patients were administered the ESS and the PSQI before the procedure. The correlation between the Apnoea/Hypopnoea Index (AHI) and the global score of the PSQI was calculated; Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), Diagnostic accuracy and the area under the receiver operating characteristic curve (AUC) were calculated. ESS performance was used as a control reference. RESULTS: The mean age was 65.8 (standard deviation: 12.1) and the study group was 68.4% male. The mean BMI was 38.5; SD 7.7. Prevalence of OSAS in the study population was 55.5%; OSAS was severe in 60.5% of OSAS patients. ESS was significantly, but weakly, correlated with the AHI (AHI vs ESS: R = 0.308; p < 0.001), whereas PSQI was not (R = 0.037; p = 0.581). Both PSQI and ESS, however, performed unsatisfactorily: sensitivity 37.8% and 69.7%; Specificity 76.1% and 31.0%; Diagnostic Accuracy 57.5% and 49.8%; PPV 60% and 48.7%; NPV 56.3% and 52.2%; AUC 0.589 and 0.509, respectively. CONCLUSIONS: The PSQI score is not helpful in the pre-polysomnographic assessment of people with suspected OSAS. Further studies are required to provide reliable pre-clinical instruments targeting patients amenable to polysomnography.