Cerebrospinal fluid and blood neurofilament light chain levels in amyotrophic lateral sclerosis and frontotemporal degeneration: A meta-analysis.

BACKGROUND AND PURPOSE: Neurofilament light chain (NFL) has been shown to be increased in amyotrophic lateral sclerosis (ALS) and, to a lesser extent, in frontotemporal dementia (FTD). A meta-analysis of NFL in ALS and FTD was performed. METHODS: Available studies comparing cerebrospinal fluid and blood NFL levels in ALS versus neurologically healthy controls (NHCs), other neurological diseases (ONDs) and ALS mimics, as well as in FTD and related entities (behavioural variant of FTD and frontotemporal lobar degeneration syndromes) versus NHCs, ONDs and other dementias were evaluated. RESULTS: In ALS, both cerebrospinal fluid and blood levels of NFL were higher compared to other categories. In FTD, behavioural variant of FTD and frontotemporal lobar degeneration syndromes, NFL levels were consistently higher compared to NHCs; however, several comparisons with ONDs and other dementias did not demonstrate significant differences. DISCUSSION: Amyotrophic lateral sclerosis is characterized by higher NFL levels compared to most other conditions. In contrast, NFL is not as good at discriminating FTD from other dementias.

Interventions aimed to increase average 24-h systolic blood pressure reduce blood pressure drops in patients with reflex syncope and orthostatic intolerance.

AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.

Delirium in nursing home residents: is there a role of antidepressants? A cross sectional study.

BACKGROUND: Delirium is strongly associated with poor health outcomes, yet it is frequently underdiagnosed. Limited research on delirium has been conducted in Nursing Homes (NHs). Our aim is to assess delirium prevalence and its associated factors, in particular pharmacological prescription, in this care setting. METHODS: Data from the Italian "Delirium Day" 2016 Edition, a national multicenter point-prevalence study on patients aged 65 and older were analyzed to examine the associations between the prevalence of delirium and its subtypes with demographics and information about medical history and pharmacological treatment. Delirium was assessed using the Assessment test for delirium and cognitive impairment (4AT). Motor subtype was evaluated using the Delirium Motor Subtype Scale (DMSS). RESULTS: 955 residents, from 32 Italian NHs with a mean age of 84.72 ± 7.78 years were included. According to the 4AT, delirium was present in 260 (27.2%) NHs residents, mainly hyperactive (35.4%) or mixed subtypes (20.7%). Antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) was associated with lower delirium prevalence in univariate and multivariate analyses. CONCLUSIONS: The high prevalence of delirium in NHs highlights the need to systematically assess its occurrence in this care settings. The inverse association between SSRIs and delirium might imply a possible preventive role of this class of therapeutic agents against delirium in NHs, yet further studies are warranted to ascertain any causal relationship between SSRIs intake and reduced delirium incidence.

Phase angle (PhA) in overweight and obesity: evidence of applicability from diagnosis to weight changes in obesity treatment.

Phase angle (PhA) is a recently proposed marker of nutritional status in many clinical conditions. Its use in patients with obesity presents different critical concerns due to the higher variability of the two measured parameters (resistance, R, and reactance, Xc) that contribute to the determination of PhA. Controversial is the relation between PhA and BMI that might vary with graded levels of obesity due to the variation in fat and free fat mass. Obesity is frequently associated with metabolic, hepatic, cardiovascular and kidney diseases that introduce variations in PhA values, in relation to multimorbidity and severity degree of these diseases. It is reported that the improvement of clinical condition is associated with a positive change in PhA. Also, the treatment of obesity with weight loss might confirm this effect, but with different responses in relation to the type and duration of the intervention applied. In fact, the effect appears not only related to the percentage of weight loss but also the possible loss of free fat mass and the nutritional, metabolic and structural modifications that might follow each therapeutic approach to decrease body weight. We can conclude that the PhA could be used as marker of health status in patients with obesity supporting an appropriate weight loss intervention to monitor efficacy and fat free mass preservation.

Frailty and post-operative delirium influence on functional status in patients with hip fracture: the GIOG 2.0 study.

BACKGROUND: This study analyzes the effect of frailty and Post-Operative Delirium (POD) on the functional status at hospital discharge and at 4-month follow-up in patients with hip fracture (HF). METHODS: Multicenter prospective observational study of older patients with HF admitted to 12 Italian Orthogeriatric centers (July 2019-August 2022). POD was assessed using the 4AT. A 26-item Frailty Index (FI) was created using data collected on admission. The outcome measures were Cumulated Ambulation Score (CAS) ≤ 2 at discharge and a telephone-administered CAS ≤ 2 after 4 months. Poisson regression models were used to assess the effect of frailty and POD on outcomes. RESULTS: 984 patients (median age 84 years, IQR = 79-89) were recruited: 480 (48.7%) were frail at admission, 311 (31.6%) developed POD, and 158 (15.6%) had both frailty and POD. In a robust Poisson regression, frailty alone (Relative Risk, RR = 1.56, 95% Confidence Intervals, CI 1.19-2.04, p = 0.001) and its combination with POD (RR = 2.57, 95% CI 2.02-3.26, p < 0.001) were associated with poor functional status at discharge. At 4-month follow-up, the combination of frailty with POD (RR 3.65, 95% CI 1.85-7.2, p < 0.001) increased the risk of poor outcome more than frailty alone (RR 2.38, 95% CI 1.21-4.66, p < 0.001). CONCLUSIONS: POD development exacerbates the negative effect that frailty exerts on functional outcomes in HF patients.

Association between hypotension during 24†h ambulatory blood pressure monitoring and reflex syncope: the SynABPM 1 study.

AIMS: Diagnostic criteria for ambulatory blood pressure monitoring (ABPM) in patients with suspected reflex syncope are lacking. The study hypothesis was that patients with reflex syncope have a higher prevalence of systolic blood pressure (SBP) drops on ABPM. METHODS AND RESULTS: ABPM data from reflex syncope patients and controls, matched by average 24 h SBP, age, sex, and hypertension were compared. Patients with constitutional hypotension, orthostatic hypotension, and predominant cardioinhibition during carotid sinus massage or prolonged electrocardiogram monitoring or competing causes of syncope were excluded. Daytime and nighttime SBP drops (<110, 100, 90, 80 mmHg) were assessed. Findings were validated in an independent sample. In the derivation sample, daytime SBP drops were significantly more common in 158 syncope patients than 329 controls. One or more daytime drops <90 mmHg achieved 91% specificity and 32% sensitivity [odds ratio (OR) 4.6, P < 0.001]. Two or more daytime drops <100 mmHg achieved 84% specificity and 40% sensitivity (OR 3.5, P = 0.001). Results were confirmed in the validation sample of 164 syncope patients and 164 controls: one or more daytime SBP drops <90 mmHg achieved 94% specificity and 29% sensitivity (OR 6.2, P < 0.001), while two or more daytime SBP drops <100 mmHg achieved 83% specificity and 35% sensitivity (OR 2.6, P < 0.001). CONCLUSION: SBP drops during ABPM are more common in reflex syncope patients than in controls. Cut-off values that may be applied in clinical practice are defined. This study expands the current indications for ABPM to patients with reflex syncope.

Metformin use is associated with a decrease in the risk of hospitalization and mortality in COVID-19 patients with diabetes: A population-based study in Lombardy.

AIM: To compare the association of metformin use and coronavirus disease 2019 (COVID-19) outcomes in a cohort of 31 966 patients with diabetes in Lombardy. METHODS: We used a COVID-19 linkable administrative regional database to select patients with diabetes who were aged 40 years or older. They had at least two prescriptions of antidiabetic drugs in 2019 and a positive test for severe acute respiratory syndrome coronavirus-2 from 15 February 2020 to 15 March 2021. The association of metformin use and clinical outcomes was assessed by multivariable logistic regression analyses and after propensity score matching (PSM). Clinical outcomes were all-cause mortality, in-hospital mortality, hospitalization for COVID-19, and admission to an intensive care unit (ICU). RESULTS: In multivariable models, metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66-0.75), in-hospital mortality (OR 0.68; 95% CI 0.63-0.73), hospitalization for COVID-19 (OR 0.86; 95% CI 0.81-0.91), and ICU admission (OR 0.81; 95% CI 0.69-0.94) compared with metformin non-users. Results were similar after PSM; metformin was associated with a significantly lower risk of total mortality (OR 0.79; 95% CI 0.73-0.86), in-hospital mortality (OR 0.74; 95% CI 0.67-0.81), and ICU admission (OR 0.77; 95% CI 0.63-0.95). CONCLUSIONS: In this large cohort, metformin use was associated with a protective effect in COVID-19 clinical outcomes, suggesting that it might be a potentially useful drug to prevent severe COVID-19 disease, although randomized controlled trials (RCTs) are needed to confirm this. While awaiting the results of RCTs, we suggest continuing prescribing metformin to COVID-19 patients with diabetes.

Algorithm of the major and minor diagnostic criteria for active myopic choroidal neovascularization.

PURPOSE: To propose an algorithm of the major and minor diagnostic criteria for macular myopic choroidal neovascularization (mCNV). METHODS: This single-center, retrospective, cross-sectional study was based in Istituto Auxologico Italiano, Milan, Italy. Two authors evaluated the clinical and imaging parameters of eyes with high myopia (spherical equivalent of -6D or less) and suspected to have naïve, recurrent, or inactive mCNV. Recordings of the eyes that met the inclusion criteria were then independently evaluated by two other senior retinal specialists. Fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), and OCT angiography were used for multimodal imaging. RESULTS: One-hundred and twenty-two eyes (n = 107; 39 men, 68 women) were included in the study. The mean patient age was 66 years (range, 22-89 years). There were 83 and 39 eyes in the active mCNV and control groups, respectively. The best diagnostic algorithm had positive- and negative-predictive values of 89% and 85%, respectively, and was based on four criteria: leakage/staining on FA, retinal thickening, fuzzy area on SD-OCT, and recent metamorphopsia. When excluding FA-derived findings, retinal pigment epithelium (RPE) features played a diagnostic role in 33 eyes (27%). Twenty-seven eyes with active mCNV (32%) did not have the fuzzy area. Taken singularly, no clinical or imaging parameter had both sensitivity and specificity greater than 78%. Matching of 2 or 3 biomarkers did not yield a sensitivity or specificity greater than 79%. Sensitivities and specificities ≥ 90% were found in ten criteria combinations that included four to five biomarkers. The most frequent were metamorphopsia, fuzzy area, retinal thickening, and leakage. Less frequently, they included hemorrhage, staining, and RPE features such as elevation, flattening, and focal interruption. For all the parameters, the agreement between the investigators was good (Cohen k ≥ 0.66), being the lowest when detecting the ELM interruption within the lesion. CONCLUSIONS: A combination of at least four clinical and biological markers yielded the highest positive- and negative-predictive values. More ("major") and less ("minor") frequent diagnostic criteria are proposed.

Assessing the mortality risk in older patients hospitalized with a diagnosis of sepsis: the role of frailty and acute organ dysfunction.

BACKGROUND: A prognostic stratification of mortality risk in older patients with sepsis admitted to medical wards is often challenging. AIMS: To evaluate the ability of the Sequential Organ Failure Assessment (SOFA) score, serum biomarkers (lactate and C-Reactive Protein, CRP), and measures of comorbidity and frailty in predicting in-hospital and 6-month mortality in a cohort of older patients admitted to an Acute Geriatric Unit (AGU) with a diagnosis of sepsis. METHODS: All patients aged 70 years and over consecutively admitted to our AGU with sepsis in the study period were included. At admission, a Comprehensive Geriatric Assessment including two measures of frailty (Clinical Frailty Scale [CFS], Frailty Index [FI]) was obtained. To assess the predictivity of candidate prognostic markers, the Area Under the Receiver-Operating Characteristic (AUROC) curves were analyzed. A multivariate logistic regression analysis was also performed. RESULTS: We included 240 patients (median age = 85, IQR = 80-89, 40.8% women), of whom 33.8% died before discharge, and 60.4% at 6 months. The SOFA score (AUROC = 0.678, 95% CI 0.610-0.747) and CRP serum levels (AUROC = 0.606, 95% CI 0.532-0.680) were good predictors of in-hospital mortality. The CFS (AUROC = 0.703, 95% CI 0.637-0.768) and the FI (AUROC = 0.677, 95% CI 0.607-0.746) better predicted 6-month mortality. Results of the regression analysis confirmed the findings of the AUROC study. The combined assessment of SOFA and measures of frailty improved the performance of the model both in the short and the long term. CONCLUSIONS: Both the severity of organ dysfunction and frailty scores should be addressed on AGU admission to establish the short- and long-term outcomes of older patients with sepsis.

Prevalence and features of delirium in older patients admitted to rehabilitation facilities: a multicenter study.

BACKGROUND: Delirium is thought to be common across various settings of care; however, still little research has been conducted in rehabilitation. AIM: We investigated the prevalence of delirium, its features and motor subtypes in older patients admitted to rehabilitation facilities during the three editions of the "Delirium Day project". METHODS: We conducted a cross-sectional study in which 1237 older patients (age ≥ 65 years old) admitted to 50 Italian rehabilitation wards during the three editions of the "Delirium Day project" (2015 to 2017) were included. Delirium was evaluated through the 4AT and its motor subtype with the Delirium Motor Subtype Scale. RESULTS: Delirium was detected in 226 patients (18%), and the most recurrent motor subtype was mixed (37%), followed by hypoactive (26%), hyperactive (21%) and non-motor one (16%). In a multivariate Poisson regression model with robust variance, factors associated with delirium were: disability in basic (PR 1.48, 95%CI: 1.17-1.9, p value 0.001) and instrumental activities of daily living (PR 1.58, 95%CI: 1.08-2.32, p value 0.018), dementia (PR 2.10, 95%CI: 1.62-2.73, p value < 0.0001), typical antipsychotics (PR 1.47, 95%CI: 1.10-1.95, p value 0.008), antidepressants other than selective serotonin reuptake inhibitors (PR 1.3, 95%CI: 1.02-1.66, p value 0.035), and physical restraints (PR 2.37, 95%CI: 1.68-3.36, p value < 0.0001). CONCLUSION: This multicenter study reports that 2 out 10 patients admitted to rehabilitations had delirium on the index day. Mixed delirium was the most prevalent subtype. Delirium was associated with unmodifiable (dementia, disability) and modifiable (physical restraints, medications) factors. Identification of these factors should prompt specific interventions aimed to prevent or mitigate delirium.

Clinical benefits of sex steroids given as a priming prior to GH provocative test or as a growth-promoting therapy in peripubertal growth delays: Results of a retrospective study among ENDO-ERN centres.

OBJECTIVES: Sex steroids, administered as a priming before GH stimulation tests (GHST) to differentiate between growth hormone deficiency (GHD) and constitutional delay of growth and puberty (CDGP) or as growth-promoting therapy using low-dose sex steroids (LDSS) in CDGP, are much debated. We aimed to compare auxological outcomes of CDGP or GHD children undergoing primed or unprimed GHST and to evaluate LDSS treatment in CDGP. DESIGN: Retrospective study among three paediatric University Hospitals in Italy and UK. METHODS: 184 children (72 females) aged 12.4 ± 2.08 years underwent primed (/P+ ) or unprimed (/P- ) GHST and were followed up until final height (FH). CDGP patients were untreated (CDG P- ) or received LDSS (CDGP+ ). The cohort included 34 CDG P- /P+ , 12 CDGP+ /P+ , 51 GHD/P+ , 29 CDG P- /P- , 2 CDGP+ /P- and 56 GHD/P- . FH standard deviation score (SDS), Δ SDS FH-target height (TH) and degree of success (-1 ≤ Δ SDS FH-SDS TH ≤ +1) were outcomes of interest. RESULTS: GHD/P+ had better FH-SDS (-0.87 vs -1.49; P = .023) and ΔSDS FH-TH (-0.35 vs -0.77; P = .002) than CDGP- /P+ . Overall, GHD/P+ showed the highest degree of success (90%, P = .006). Regardless of priming, both rhGH and LDSS improved degree of success compared to no treatment (89% and 86% vs 63%, P = .0009). GHD/P+ showed a trend towards a higher proportion of permanent GHD compared to GHD/P- (30.43% vs 15.09%; P = .067). CONCLUSION: In peripubertal children, priming before GHST improves diagnostic accuracy of GHST for idiopathic GHD. LDSS treatment improves auxological outcomes in CDGP.

Association between renin-angiotensin-aldosterone system inhibitors and risk of dementia: A meta-analysis.

OBJECTIVE: To evaluate the association of all RAAS inhibitors, ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on dementia onset (any dementia, Alzheimer's disease and vascular dementia) using a meta-analytic approach. METHODS: A systematic MEDLINE search was carried out to identify all observational studies published up to the 30th September 2020 evaluating the association between RAAS inhibitors and risk of dementia. Studies were included if original investigations considering incident dementia cases, with ACEIs and/or ARBs as exposure and other antihypertensives (AHs) use as reference, and if reporting association estimates and relative variability measures. Random effect pooled relative risks (pRR) and the corresponding 95% confidence intervals (95%CI) were calculated according to DerSimonian and Laird's (DL) or to Hartung Knapp Sidik Jonkman (HKSJ) method depending on the number of studies and between-studies heterogeneity. A linear mixed meta-regression model (MM) was applied to take into account correlation among association estimates from the same study. RESULTS: 15 studies were included in the meta-analysis. ARBs but not ACEIs' use led to a significant reduction of the risk of any dementia (pRR 0.78, 95%CIMM 0.70-0.87) and Alzheimer's disease (pRR 0.73, 95%CIMM 0.60-0.90). Moreover, when compared to ACEIs, ARBs reduced of 14% the risk of any dementia (pRR 0.86, 95%CIDL 0.79-0.94). CONCLUSIONS: ARBs but not ACEIs led to a reduction in the risk of any dementia. The difference between ARBs and ACEIs in terms of preventive effectiveness could be due to distinct profiles of antagonism towards independent receptor pathways or to differential influences on amyloid metabolism.

Association of infrapopliteal medial arterial calcification with lower-limb amputations in high-risk patients: A systematic review and meta-analysis.

Medial arterial calcification (MAC) is a known risk factor for cardiovascular morbidity. The association between vascular calcifications and poor outcome in several vascular districts suggest that infrapopliteal MAC could be a risk factor for lower-limb amputation (LLA). This study's objective is to review the available literature focusing on the association between infrapopliteal MAC and LLA in high-risk patients. The PubMed and Embase databases were systematically searched. We selected original studies reporting the association between infrapopliteal MAC and LLAs in patients with diabetes and/or peripheral artery disease (PAD). Estimates were pooled using either a fixed-effects or a random-effects model meta-analysis. Heterogeneity was evaluated using the Q and I2 statistics. Publication bias was investigated with a funnel plot and Egger test. The trim-and-fill method was designed to estimate the possibly missing studies. Influence analysis was conducted to search studies influencing the final result. Test of moderators was used to compare estimates in good versus non-good-quality studies. Fifteen articles satisfied the selection criteria (n = 6489; median follow-up: 36 months). MAC was significantly associated with LLAs (pooled adjusted risk ratio (RR): 2.27; 95% CI: 1.89-2.74; I2 = 25.3%, Q-test: p = 0.17). This association was kept in the subgroup of patients with diabetes (RR: 2.37; 95% CI: 1.76-3.20) and patients with PAD (RR: 2.48; 95% CI: 1.72-3.58). The association was maintained if considering as outcome only major amputations (RR: 2.11; 95% CI: 1.46-3.06). Our results show that infrapopliteal MAC is associated with LLAs, thus suggesting MAC as a possible new marker of the at-risk limb.

Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy.

BACKGROUND: Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19. METHODS: We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 ± 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization. RESULTS: Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 ± 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 ± 8.5 ng/mL and 25.4 ± 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 14.4 ± 8.6 ng/mL and 43.0 (19.0-56.0) pg/mL, respectively], than in those not requiring ICU admission [22.4 ± 1.4 ng/mL, p = 0.0001 and 16.0 (8.0-32.0) pg/mL, p = 0.0002, respectively]. Similar differences were found when comparing COVID-19 patients who died in hospital [13.2 ± 6.4 ng/mL and 45.0 (28.0-99.0) pg/mL] with survivors [19.3 ± 12.0 ng/mL, p = 0.035 and 21.0 (10.5-45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (ρ - 0.284, p = 0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p = 0.011] regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95-0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count. CONCLUSION: In our COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were independent predictors of COVID-19 severity and mortality.

Frailty, post-operative delirium and functional status at discharge in patients with hip fracture.

OBJECTIVE: To explore the effect of frailty, alone and in combination with post-operative delirium (POD), on the risk of poor function at discharge in patients with hip fracture (HF). METHODS: This is a prospective cohort study of patients with HF admitted to an Orthogeriatric Unit (OGU) between October 1, 2011 and March 15, 2019. POD was assessed using the 4AT and the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5-edition criteria. A 22-items Frailty Index (FI) was created using the data collected on admission. The outcome measure was the Cumulated Ambulation Score (CAS) score at discharge. A log-binomial regression model was used to assess the effect of frailty and POD on CAS. RESULTS: A total of 988 patients (median age = 84.9 years, Interquartile range = 80.6-89.2) were included: 360 patients (36.4%) were frail and 411 (42%) developed POD. Poor functional status at discharge (CAS score ≤2) was more common in frail than non-frail patients (68.3% vs. 53.8%, p < 0.001) In a regression adjusted for confounders, frailty alone (Relative Risk, RR = 1.33, 95% Confidence Intervals, CI = 1.14-1.55) and POD alone (RR 1.38, 95% CI = 1.2-1.59) were associated with poor functional status at discharge; when combined, frailty and POD had an interaction, yielding a mild increase in the risk of poor outcome (RR 1.47, 95% CI = 1.28-1.69). CONCLUSIONS: In older patients undergoing HF surgery, frailty, POD and their combination, are associated with poor functional status at discharge.

Identification of dietary patterns in a general population of North Italian adults and their association with arterial stiffness. The RoCAV study.

BACKGROUND AND AIMS: The aims of this study were to identify dietary patterns in a general population of North Italian adults and to investigate the cross-sectional association between prevalent dietary patterns and arterial stiffness. METHODS AND RESULTS: Participants to the RoCAV study without chronic diseases at recruitment and with reliable dietary data were included. The food-frequency EPIC questionnaire was used to evaluate dietary habits. Dietary patterns were estimated using principal components analysis and Mediterranean diet adherence score (MedS). Carotid-femoral pulse wave velocity (cfPWV) was used as proxy of arterial stiffness. Basing on data from 2640 subjects (1608 men and 1032 women, mean ± SD 65.5 ± 6.7 years), four principal components (PC) were retained, explaining 24% of the overall variance. Considering 1284 subjects with cfPWV (mean ± SD 10.7 ± 2.5 m/s) data available, adherence to PC1 (Western-like dietary pattern) was associated with higher stiffness values (+0.29 m/s cfPWV for 1 SD increase of PC1, 95% CI:0.08,0.50; p = 0.007) in a multivariate model. Conversely, adherence to PC2 (Mediterranean-like) was not related to cfPWV values (-0.18, 95% CI: -0.36, 0.004; p = 0.06). Likewise, MedS and other PC patterns did not show any significant association with cfPWV. Mediation analysis showed that the association between Western-like dietary pattern and cfPWV is mediated by higher levels of leucocytes (9.2% of the effect, p = 0.047). CONCLUSIONS: Our study in a Southern European population identified a Western-like dietary pattern associated with an increased cfPWV, a proxy of arterial stiffness. The association with cfPWV was in part mediated by inflammatory status.

When to Suspect Hidden Hypercortisolism in Type 2 Diabetes: A Meta-Analysis.

OBJECTIVE: To investigate whether the available literature helps to identify the characteristics of patients with type 2 diabetes (T2D) more frequently associated with hidden hypercortisolism (HidHyCo). METHODS: A meta-analysis was performed using studies that assessed both the prevalence of HidHyCo in patients with T2D and the characteristics of these patients with and without HidHyCo. The DerSimonian and Laird (DSL) and Hartung-Knapp-Sidik-Jonkman (HKSJ) methods were utilized. RESULTS: Among the 18 available studies, 6 provided the necessary data. The association between HidHyCo and advanced T2D (based on the patients' description given in each study in the presence of microvascular/macrovascular complications or insulin treatment plus hypertension or hypertension treated with 2 or more drugs), hypertension, insulin treatment, and dyslipidemia was reported in 5 (2184 patients), 6 (2283 patients), 3 (1440 patients), and 3 (987 patients) studies, respectively. HidHyCo was associated with advanced T2D as assessed by both the DSL (odds ratio [OR], 3.4; 95% confidence interval [95% CI], 2.12-5.67) and HKSJ (OR, 3.60; 95% CI, 2.03-6.41) methods and with the prevalence of hypertension or insulin treatment as assessed by the DSL method (OR, 1.92; 95% CI, 1.05-3.50 and OR, 2.29; 95% CI, 1.07-4.91, respectively) but not as assessed by the HKSJ method. CONCLUSION: Patients with advanced T2D have a higher prevalence of HidHyCo. These data inform about the selection of patients with T2D for HidHyCo screening.

Obstructive sleep apnoea treatment and blood pressure: which phenotypes predict a response? A systematic review and meta-analysis.

The treatment for obstructive sleep apnoea (OSA) with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is associated with blood pressure (BP) reduction; however, the overall effect is modest. The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effect of such treatments on BP was to identify subgroups of patients who respond best to treatment.The article search was performed in three different databases with specific search terms and selection criteria. From 2289 articles, we included 68 RCTs that compared CPAP or MADs with either passive or active treatment. When all the studies were pooled together, CPAP and MADs were associated with a mean BP reduction of -2.09 (95% CI -2.78- -1.40) mmHg for systolic BP and -1.92 (95% CI -2.40- -1.43) mmHg for diastolic BP and -1.27 (95% CI -2.34- -0.20) mmHg for systolic BP and -1.11 (95% CI -1.82- -0.41) mmHg for diastolic BP, respectively. The subgroups of patients who showed a greater response were those aged <60 years (systolic BP -2.93 mmHg), with uncontrolled BP at baseline (systolic BP -4.14 mmHg) and with severe oxygen desaturations (minimum arterial oxygen saturation measured by pulse oximetry <77%) at baseline (24-h systolic BP -7.57 mmHg).Although this meta-analysis shows that the expected reduction of BP by CPAP/MADs is modest, it identifies specific characteristics that may predict a pronounced benefit from CPAP in terms of BP control. These findings should be interpreted with caution; however, they are particularly important in identifying potential phenotypes associated with BP reduction in patients treated for OSA.

Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database.

BACKGROUND AND OBJECTIVE: OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort. METHODS: This cross-sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5 years, mean BMI: 30.5 kg/m2 ) with significant OSA (defined as AHI ≥ 10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI > 25 events/hour of sleep) and patients without significant PLMS (PLMSI < 25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency). RESULTS: The univariate analysis of SBP showed an increment of BP equal to 4.70 mm Hg (P < 0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64 mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP. CONCLUSION: PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.

Prevalence, clinical correlates, and burden of undiagnosed aortic stenosis in older patients: a prospective study in a non-cardiologic acute hospital ward.

BACKGROUND: The epidemiology of aortic stenosis (AS) in older patients admitted to non-cardiologic acute hospital wards and the effect of AS on mid-term survival are incompletely reported. In a cohort of very old patients admitted to an acute geriatric unit (AGU), we aimed to assess: (1) the prevalence of newly and previously diagnosed AS; and (2) the association between AS severity and patients' 6-month mortality. METHODS: The patients consecutively admitted in two AGU rooms from February 2016 to February 2018 were assessed with echocardiography and AS severity was defined according to standard criteria. We assessed frailty using a 34-item Frailty Index (34-FI), which was operationalized using health variable information, and the Clinical Frailty Scale (CFS). Vital status at 6 months was extracted from Regional Register of Birth and Death. RESULTS: Two hundred and three patients (mean age 84.5 ± 6.0 SD, female gender 56.1%) were included. Of these, 57 (28.1%) had AS, mild in 9 (4.5%), moderate in 32 (16.1%) and severe in 16 (8.1%). A new diagnosis of AS was obtained in 42 (73.7%) patients, of whom 33 (78.6%) had moderate or severe AS. At 6 months, 61 (28.9%) patients died. In multiple regression models, after adjusting for covariates, frailty, as assessed with both FI and CFS, was independent predictor of 6-month mortality whereas AS was not. CONCLUSIONS: Among older patients admitted to non-cardiologic acute hospital wards, AS was common and frequently underdiagnosed. The severity of AS was not associated with increased 6-month mortality, whereas frailty was the most important predictor.