The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes.

Background: A delay in reaching HbA1c targets in patients with newly-diagnosed type 2 diabetes (T2D) is associated with an increased long-term risk of developing cardiovascular diseases (CVD), a phenomenon referred to as legacy effect. Whether an early introduction of glucose-lowering drugs with proven benefit on CVD can attenuate this phenomenon is unknown. Methods: Using data derived from a large Italian clinical registry, i.e. the AMD Annals, we identified 251,339 subjects with newly-diagnosed T2D and without CVD at baseline. Through Cox regressions adjusted for multiple risk factors, we examined the association between having a mean HbA1c between 7.1 and 8% or >8%, compared with ≤7%, for various periods of early exposure (0-1, 0-2, 0-3 years) and the development of later (mean subsequent follow-up 4.6 ± 2.9 years) CVD, evaluated as a composite of myocardial infarction, stroke, coronary or peripheral revascularization, and coronary or peripheral bypass. We performed this analysis in the overall cohort and then splitting the population in two groups of patients: those that introduced sodium-glucose transport protein 2 inhibitors (SGLT-2i) during the exposure phase and those not treated with these drugs. Findings: Considering the whole cohort, subjects with both a mean HbA1c between 7.1 and 8% and >8%, compared with patients attaining a mean HbA1c ≤ 7%, showed an increased risk of developing the outcome in all the three early exposure periods assessed, with the highest risk observed in patients with mean HbA1c > 8% in the 3 years exposure period (hazard ratio [HR]1.33; 95% confidence interval [CI] 1.063-1.365). The introduction of SGLT-2i during the exposure periods of 0-1 and 0-2 years eliminated the association between poor glycemic control and the outcome (p for interaction 0.006 and 0.003, respectively, vs. patients with the same degree of glycemic control but not treated with these drugs). Interpretation: Among patients with newly diagnosed T2D and free of CVD at baseline, a poor glycemic control in the first three years after diagnosis is associated with an increased subsequent risk of CVD. This association is no longer evident when SGLT-2i are introduced in the first two years, suggesting that these drugs attenuate the phenomenon of legacy effect. An early treatment with these drugs might thus promote a long-lasting benefit in patients not attaining proper glycemic control after T2D diagnosis. Funding: This work was supported, in part, by the Italian Ministry of Health (Ricerca Corrente) to IRCCS MultiMedica.

Thoracic ultrasound combined with low-dose computed tomography may represent useful screening strategy in highly exposed population in the industrial city of Taranto (Italy).

Objectives: We validated a screening protocol in which thoracic ultrasound (TUS) acts as a first-line complementary imaging technique in selecting patients which may deserve a second-line low-dose high resolution computed tomography (HRCT) scan among a population of asymptomatic high-risk subjects for interstitial lung abnormalities (ILA) and lung cancer. Due to heavy environmental pollution burden, the district Tamburi of Taranto has been chosen as "case study" for this purpose. Methods: From July 2018 to October 2020, 677 patients aged between 45 and 65 year and who had been living in the Tamburi district of Taranto for at least 10 years were included in the study. After demographic, clinical and risk factor exposition data were collected, each participant underwent a complete TUS examination. These subjects were then asked to know if they agreed to perform a second-level examination by low-dose HRCT scan. Results: On a total of 167 subjects (24.7%) who agreed to undergo a second-level HRCT, 85 patients (50.9%) actually showed pleuro-pulmonary abnormalities. Interstitial abnormalities were detected in a total of 36 patients on HRCT scan. In particular, 34 participants presented subpleural ILAs, that were classified in the fibrotic subtype in 7 cases. The remaining 2 patients showed non-subpleural interstitial abnormalities. Subpleural nodules were observed in 46 patients. TUS showed an overall diagnostic accuracy of 88.6% in detecting pleuro-pulmonary abnormalities in comparison with HRCT scan, with a sensitivity of 95.3%, a specificity of 81.7%, a positive predictive value of 84.4% and a negative predictive value of 94.4%. The matched evaluation of specific pulmonary abnormalities on HRTC scan (i.e., interstitial abnormalities or pulmonary nodules) with determinate sonographic findings revealed a reduction in both TUS sensibility and specificity. Focusing TUS evaluation on the assessment of interstitial abnormalities, a thickened pleural line showed a sensitivity of 63.9% and a specificity of 69.5%, hypoechoic striae showed a sensitivity of 38.9% and a specificity of 90.1% and subpleural nodules showed a sensitivity of 58.3% and a specificity of 77.1%. Regarding to the assessment of subpleural nodules, TUS showed a sensitivity of 60.9% and a specificity of 81.0%. However, the combined employment of TUS examination and HRCT scans allowed to identify 34 patients with early subpleural ILA and to detect three suspicious pulmonary nodules (of which two were intraparenchymal and one was a large subpleural mass), which revealed to be lung cancers on further investigations. Conclusion: A first-line TUS examination might aid the identification of subjects highly exposed to environmental pollution, who could benefit of a second-line low-dose HRCT scan to find early interstitial lung diseases as well as lung cancer. Protocol registration code: PLEURO-SCREENING-V1.0_15 Feb, 17.

Albuminuria improves R2CHA2DS2-VASc score in predicting mortality in high cardiovascular risk population.

BACKGROUND AND AIMS: The CHA2DS2-VASc score estimates the risk of cardioembolism in patients with atrial fibrillation (AF). It also predicts vascular events and death in different clinical settings, even in the absence of AF. The R2CHA2DS2-VASc score, obtained by adding the glomerular filtration rate to CHA2DS2-VASc, shows a higher prediction ability for new events and all-cause mortality. The present study aims to assess whether the addition of albuminuria to R2CHA2DS2-VASc score further improves its discrimination ability in predicting all-cause mortality in a sample of high cardiovascular risk population. METHODS AND RESULTS: Prospective, monocentric, observational study, evaluating a subset of 737 subjects consecutively undergoing to coronary angiography at Coronary Unit of Scientific Institute "Casa Sollievo della Sofferenza" from June 2016 to December 2018. The presence of albuminuria was significantly associated with all-cause mortality (p < 0.0001). Any one-point increase of Alb-R2CHA2DS2-VASc score increased mortality of about 1.5-fold (adjusted HR 1.49; 95%CI: 1.37-1.63; p < 0.0001). Considering tertiles of Alb-R2CHA2DS2-VASc, the third tertile showed a 9.5-fold increased risk of mortality (HR 9.52; 95% CI: 5.15-17.60, p < 0.001). Comparing the two scores, the Alb-R2CHA2DS2-VASc score (C-statistic = 0.751; 95%CI: 0.69-0.81) outperformed the R2-CHA2DS2-VASc score (C-statistic = 0.736; 95%CI: 0.68-0.961) in predicting mortality (delta C-statistic = 0.015; 95%CI: 0.001-0.029). The better prediction ability of the Alb-R2CHA2DS2-VASc score was also proven by an IDI of 0.024 (p < 0.0001) and a relative IDI of 24.11% (p < 0.0001), with an NRI = 0.608 (p < 0.00001). CONCLUSIONS: The addition of albuminuria to R2CHA2DS2-VASc significantly and independently predicts the risk of all-cause mortality in a sample of high CV risk patients. Moreover, Alb-R2CHA2DS2-VASc outperforms R2CHA2DS2-VASc.

Identifying Predictors Associated with Risk of Death or Admission to Intensive Care Unit in Internal Medicine Patients with Sepsis: A Comparison of Statistical Models and Machine Learning Algorithms.

Background: Sepsis is a time-dependent disease: the early recognition of patients at risk for poor outcome is mandatory. Aim: To identify prognostic predictors of the risk of death or admission to intensive care units in a consecutive sample of septic patients, comparing different statistical models and machine learning algorithms. Methods: Retrospective study including 148 patients discharged from an Italian internal medicine unit with a diagnosis of sepsis/septic shock and microbiological identification. Results: Of the total, 37 (25.0%) patients reached the composite outcome. The sequential organ failure assessment (SOFA) score at admission (odds ratio (OR): 1.83; 95% confidence interval (CI): 1.41-2.39; p < 0.001), delta SOFA (OR: 1.64; 95% CI: 1.28-2.10; p < 0.001), and the alert, verbal, pain, unresponsive (AVPU) status (OR: 5.96; 95% CI: 2.13-16.67; p < 0.001) were identified through the multivariable logistic model as independent predictors of the composite outcome. The area under the receiver operating characteristic curve (AUC) was 0.894; 95% CI: 0.840-0.948. In addition, different statistical models and machine learning algorithms identified further predictive variables: delta quick-SOFA, delta-procalcitonin, mortality in emergency department sepsis, mean arterial pressure, and the Glasgow Coma Scale. The cross-validated multivariable logistic model with the least absolute shrinkage and selection operator (LASSO) penalty identified 5 predictors; and recursive partitioning and regression tree (RPART) identified 4 predictors with higher AUC (0.915 and 0.917, respectively); the random forest (RF) approach, including all evaluated variables, obtained the highest AUC (0.978). All models' results were well calibrated. Conclusions: Although structurally different, each model identified similar predictive covariates. The classical multivariable logistic regression model was the most parsimonious and calibrated one, while RPART was the easiest to interpret clinically. Finally, LASSO and RF were the costliest in terms of number of variables identified.

Abdominal Lymphadenopathies: Lymphoma, Brucellosis or Tuberculosis? Multidisciplinary Approach-Case Report and Review of the Literature.

Abdominal pain represents a frequent symptom for referral to emergency departments and/or internal medicine outpatient setting. Similarly, fever, fatigue and weight loss are non-specific manifestations of disease. The present case describes the diagnostic process in a patient with abdominal pain and a palpable abdominal mass. Abdominal ultrasonography confirmed the presence of a mass in the mesogastrium. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans oriented toward calcific lymphadenopathies with increased metabolism in the positron emission tomography-computed tomography (PET-CT) scan. Laboratory examinations were inconclusive, although serology for Brucella and the Quantiferon test were positive. After multidisciplinary discussion, the patient underwent surgical excision of the abdominal mass. Histological examination excluded malignancies and oriented toward brucellosis in a patient with latent tuberculosis. The patient was treated with rifampin 600 mg qd and doxycycline 100 mg bid for 6 weeks with resolution of the symptoms. In addition, rifampin was continued for a total of 6 months in order to treat latent tuberculosis. This case underlines the need for a multidisciplinary approach in the diagnostic approach to abdominal lymphadenopathies.

Circadian Genes Expression Patterns in Disorders Due to Enzyme Deficiencies in the Heme Biosynthetic Pathway.

Heme is a member of the porphyrins family of cyclic tetrapyrroles and influences various cell processes and signalling pathways. Enzyme deficiencies in the heme biosynthetic pathway provoke rare human inherited metabolic diseases called porphyrias. Protein levels and activity of enzymes involved in the heme biosynthetic pathway and especially 5'-Aminolevulinate Synthase 1 are featured by 24-h rhythmic oscillations driven by the biological clock. Heme biosynthesis and circadian pathways intermingle with mutual modulatory roles. Notably, heme is a ligand of important cogs of the molecular clockwork, which upon heme binding recruit co-repressors and inhibit the transcription of numerous genes enriching metabolic pathways and encoding functional proteins bringing on crucial cell processes. Herein, we assessed mRNA levels of circadian genes in patients suffering from porphyrias and found several modifications of core clock genes and clock-controlled genes expression, associated with metabolic and electrolytic changes. Overall, our results show an altered expression of circadian genes accompanying heme biosynthesis disorders and confirm the need to deepen the knowledge of the mechanisms through which the alteration of the circadian clock circuitry could take part in determining signs and symptoms of porphyria patients and then again could represent a target for innovative therapeutic strategies.

CHA2DS2-VASc and R2CHA2DS2-VASc scores predict mortality in high cardiovascular risk population.

BACKGROUND: The CHA2 DS2 -VASc score, widely used to estimate cardioembolic risk in patients with atrial fibrillation (AF), appears to be useful also in predicting vascular adverse events and death in different sets of patients without AF. The R2 CHA2 DS2 -VASc score, which includes renal impairment, allows a better prediction of death and thromboembolism in patients without AF. The aims of our study were to assess, in a large sample of patients at high cardiovascular (CV) risk, (i) the correlation between CHA2 DS2 -VASc and R2 CHA2 DS2 -VASc with all-cause mortality, and (ii) to compare the performances of CHA2 DS2 -VASc and R2 CHA2 DS2 -VASc in predicting all-cause mortality. METHODS: In this single-centre prospective observational study, conducted at the Research Hospital 'Casa Sollievo della Sofferenza' between June 2016 and December 2018, 1017 CV patients at high risk of undergoing coronary angiography were enrolled. RESULTS: CHA2DS2-VASc and R2 CHA2 DS2 -VASc scores significantly associated with all-cause mortality. For each one-point increase in CHA2 DS2 -VASc or R2 CHA2 DS2 -VASc scores, mortality increased by almost 1.5-fold. The R2 CHA2 DS2 -VASc score (C-statistic = 0.71; 95% CI = 0.65-76) outperformed the CHA2 DS2 -VASc score (C-statistic = 0.66; 95% CI = 0.61-0.71) in predicting 4-year mortality (delta C-statistic = 0.05; 95% CI = 0.02-0.07). The better predictive ability of the R-CHA2 DS2 -VASc score was also demonstrated by an IDI = 0.027 (95% CI = 0.021-0.034, p < .00001) and a relative IDI = 62.8% (95% CI = 47.9%-81.3%, p < .00001). The R2 CHA2 DS2 -VASc score correctly reclassified the patients with a NRI = 0.715 (95% = 0.544-0.940, p < .00001). CONCLUSIONS: The CHA2DS2-VASc and R2 CHA2 DS2 -VASc scores are useful predictors of all-cause mortality in subjects at high CV risk, with the R2 CHA2 DS2 -VASc score being the best performer.

Echocardiographic markers of early alcoholic cardiomyopathy: Six-month longitudinal study in heavy drinking patients.

BACKGROUND: The development of alcoholic cardiomyopathy (ACM) is related to chronic excessive alcohol use. However, features of early-stage ACM are still unclear. We assessed echocardiographic characteristics of patients with alcohol dependence (DSM-IV criteria) during a six-month treatment period. METHODS: Active drinking patients, heavy alcohol users, without heart disease, referred to our Alcohol Addiction Unit were enrolled in the study. After signing informed consent, patients started outpatient treatment program. Echocardiography was performed at enrollment, then three and six months afterwards, by cardiologists blinded to drinking status. RESULTS: Forty-three patients (36 males, 7 females) were enrolled. At six months, 20 patients (46.5%) reduced alcohol consumption below heavy drinking levels. Although within normal range, baseline mean IVS thickness and mean LVDD were significantly higher (p < 0.001) and mean EF significantly reduced (p = 0.009), as compared to age-matched mean references. Mean E/A ratio, DcT and LA diameter were significantly different (p < 0.001) from mean references, but within normal range. Baseline mean E/e' ratio was significantly higher than the mean reference (p < 0.001) and out of the normal range. A significant correlation between the number of drinks per drinking days in the 7 days before baseline assessment and E/e' ratio was observed (p = 0.028). After six months, a trend-level reduction of mean E/e' ratio (p = 0.051) was found in the whole sample; this reduction was statistically significant (p = 0.041) among patients reducing drinking, compared to baseline. CONCLUSIONS: Altered E/e' ratio may characterize early-ACM before the occurrence of relevant echocardiographic alterations. The reduction of alcohol consumption could restore this alteration after six months.

Contribution of rare variants in monogenic diabetes-genes to early-onset type 2 diabetes.

AIM: This study investigated whether rare, deleterious variants in monogenic diabetes-genes are associated with early-onset type 2 diabetes (T2D). METHODS: A nested case-control study was designed from 9712 Italian patients with T2D. Individuals with age at diabetes onset ≤35 yrs (n = 300; cases) or ≥65 yrs (n = 300; controls) were selected and screened for variants in 27 monogenic diabetes-genes by targeted resequencing. Rare (minor allele frequency-MAF <1%) and possibly deleterious variants were collectively tested for association with early-onset T2D. The association of a genetic risk score (GRS) based on 17 GWAS-SNPs for T2D was also tested. RESULTS: When all rare variants were considered together, each increased the risk of early-onset T2D by 65% (allelic OR =1.64, 95% CI: 1.08-2.48, p = 0.02). Effects were similar when the 600 study participants were stratified according to their place of recruitment (Central-Southern Italy, 182 cases vs. 142 controls, or Rome urban area, 118 vs. 158, p for heterogeneity=0.53). Progressively less frequent variants showed increasingly stronger effects in the risk of early-onset T2D for those with MAF <0.001% (OR=6.34, 95% CI: 1.87-22.43, p = 0.003). One unit of T2D-GRS significantly increased the risk of early-onset T2D (OR 1.09, 95% CI: 1.01-1.18; p = 0.02). This association was stronger among rare variants carriers as compared to non-carriers (p = 0.02). CONCLUSION: Rare variants in monogenic-diabetes genes are associated with an increased risk of early-onset T2D, and interact with common T2D susceptibility variants in shaping it. These findings might help develop prediction tools to identify individuals at high risk of developing T2D in early adulthood.

Circulating Metabolites Associate With and Improve the Prediction of All-Cause Mortality in Type 2 Diabetes.

Death rate is increased in type 2 diabetes. Unraveling biomarkers of novel pathogenic pathways capable to identify high-risk patients is instrumental to tackle this burden. We investigated the association between serum metabolites and all-cause mortality in type 2 diabetes and then whether the associated metabolites mediate the effect of inflammation on mortality risk and improve ENFORCE (EstimatioN oF mORtality risk in type2 diabetic patiEnts) and RECODe (Risk Equation for Complications Of type 2 Diabetes), two well-established all-cause mortality prediction models in diabetes. Two cohorts comprising 856 individuals (279 all-cause deaths) were analyzed. Serum metabolites (n = 188) and pro- and anti-inflammatory cytokines (n = 7) were measured. In the pooled analysis, hexanoylcarnitine, kynurenine, and tryptophan were significantly and independently associated with mortality (hazard ratio [HR] 1.60 [95% CI 1.43-1.80]; 1.53 [1.37-1.71]; and 0.71 [0.62-0.80] per 1 SD). The kynurenine-to-tryptophan ratio (KTR), a proxy of indoleamine-2,3-dioxygenase, which degrades tryptophan to kynurenine and contributes to a proinflammatory status, mediated 42% of the significant association between the antiatherogenic interleukin (IL) 13 and mortality. Adding the three metabolites improved discrimination and reclassification (all P < 0.01) of both mortality prediction models. In type 2 diabetes, hexanoylcarnitine, tryptophan, and kynurenine are associated to and improve the prediction of all-cause mortality. Further studies are needed to investigate whether interventions aimed at reducing KTR also reduce the risk of death, especially in patients with low IL-13.

Factors Associated with Delirium in COVID-19 Patients and Their Outcome: A Single-Center Cohort Study.

BACKGROUND: A significant proportion of patients with coronavirus disease 2019 (COVID-19) suffer from delirium during hospitalization. This single-center observational study investigates the occurrence of delirium, the associated risk factors and its impact on in-hospital mortality in an Italian cohort of COVID 19 inpatients. METHODS: Data were collected in the COVID units of a general medical hospital in the South of Italy. Socio-demographic, clinical and pharmacological features were collected. Diagnosis of delirium was based on a two-step approach according to 4AT criteria and DSM5 criteria. Outcomes were: dates of hospital discharge, Intensive Care Unit (ICU) admission, or death, whichever came first. Univariable and multivariable proportional hazards Cox regression models were estimated, and risks were reported as hazard ratios (HR) along with their 95% confidence intervals (95% CI). RESULTS: A total of 47/214 patients (22%) were diagnosed with delirium (21 hypoactive, 15 hyperactive, and 11 mixed). In the multivariable model, four independent variables were independently associated with the presence of delirium: dementia, followed by age at admission, C-reactive protein (CRP), and Glasgow Coma Scale. In turn, delirium was the strongest independent predictor of death/admission to ICU (composite outcome), followed by Charlson Index (not including dementia), CRP, and neutrophil-to-lymphocyte ratio. The probability of reaching the composite outcome was higher for patients with the hypoactive subtype than for those with the hyperactive subtype. CONCLUSIONS: Delirium was the strongest predictor of poor outcome in COVID-19 patients, especially in the hypoactive subtype. Several clinical features and inflammatory markers were associated with the increased risk of its occurrence. The early recognition of these factors may help clinicians to select patients who would benefit from both non-pharmacological and pharmacological interventions in order to prevent delirium, and in turn, reduce the risk of admission to ICU or death.

Remdesivir significantly reduces SARS-CoV-2 viral load on nasopharyngeal swabs in hospitalized patients with COVID-19: A retrospective case-control study.

Remdesivir is a broad-spectrum antiviral agent able to inhibit the RNA polymerase of SARS-CoV-2. At present, studies focusing on the effect of remdesivir on viral load (VL) are few and with contrasting results. Aim of the present study was to evaluate the effect of remdesivir on SARS-CoV-2 VL from nasopharyngeal swabs (cycle threshold criterion) in a sample of patients treated with the drug, compared with patients who did not receive the antiviral treatment. This retrospective analysis evaluated patients with (1) real-time polymerase chain reaction (RT-PCR) confirmed COVID-19 diagnosis and (2) availability of at least two positive nasopharyngeal swabs analysed with the same analytic platform (ORF target gene, Ingenius ELITe, ELITechGroup, Puteaux, France). Upper respiratory specimens from nasopharyngeal swabs were collected at admission (T0) and 7-14 days after treatment, upon clinical decision. A total of 27 patients treated with remdesivir (Group A) met the inclusion criteria and were compared with 18 patients (Group B) treated with standard care, matched for baseline clinical characteristics. At baseline, both remdesivir-treated and nontreated patients showed comparable VLs (21.73 ± 6.81 vs. 19.27 ± 5.24, p = 0.348). At the second swab, remdesivir-treated patients showed a steeper VL reduction with respect to controls (34.28 ± 7.73 vs. 27.22 ± 3.92; p < 0.001). Longitudinal linear model estimated a mean decrease in cycle threshold equal to 0.61 (SE: 0.09) per day in remdesivir-treated versus 0.33 (SE: 0.10) per day in remdesivir nontreated patients (p for heterogeneity = 0.045). The present study shows that the administration of remdesivir in hospitalized COVID-19 patients significantly reduces the VL on nasopharyngeal swabs.

Low eGFR and albuminuria independently predict all-cause mortality in high-risk subjects undergoing coronary arteriography.

Individuals with Chronic Kidney Disease (CKD) are at high risk for cardiovascular morbidity and mortality. The aim of this study was to examine the relationship between renal dysfunction and all-cause mortality in a sample of subjects undergoing coronary angiography (CA). We evaluated 1017 subjects who consecutively underwent CA. Glomerular filtration rate (eGFR) was estimated by CKD-EPI and urinary albumin excretion reported as urinary albumin-to-creatinine ratio. Vital status was ascertained by interrogating the Italian Health Card Database. One-thousand-seventeen subjects (759 M/258F) were enrolled into the study from 2016 to 2018. One-hundred-fourteen deaths occurred during a median follow-up of 44 months. The whole population was divided in two subgroups according to the presence/absence of low eGFR (i.e. < 60 ml/min/1.73 m2). Subjects with low baseline eGFR had a worse clinical profile than subjects with preserved kidney function. The risk of death in subjects with eGFR < 60 ml/min/1.73 m2 was almost three times higher than in subjects with preserved kidney function: fully adjusted HR 2.70 (95% CI 1.56-4.67). The presence of albuminuria also predicted a high risk of death: fully adjusted HR 2.09 (95% CI 1.17-3.73) and HR 4.26 (95% CI 2.18-8.33), microalbuminuria or macroalbuminuria, respectively, being normoalbuminuria the reference group. Again, the increased risk remained significant after adjusting for several potential confounders. In conclusion, kidney disease measures (i.e. low eGFR or albuminuria) independently predict increased risk for all-cause death in a large sample of subjects undergoing CA. These results have a relevant clinical impact.

Transthoracic ultrasound shear wave elastography for the study of subpleural lung lesions.

PURPOSE: The aim of this study was to assess whether new-generation shear wave elastography (SWE) is suitable for the characterization of lung subpleural lesions. METHODS: In total, 190 consecutive patients with subpleural lung lesions received ultrasonography and SWE. Patients with suspected malignancy underwent ultrasound-guided transthoracic needle biopsy. Final diagnoses were made on the basis of patients' clinical course, microbiological studies, and histological results. SWE was also performed in 25 healthy volunteers. RESULTS: We found no statistically significant differences in stiffness between lung carcinomas, lung metastases, and pneumonia (P=0.296) or between different histological types of lung cancer (P=0.393). Necrosis was associated with reduced stiffness in pneumonia. Excluding necrotic lesions, pneumonia showed higher stiffness than lung carcinomas (2.95±0.68 m/s vs. 2.60±0.54 m/s, P=0.006). Chronic pneumonia showed increased stiffness (3.03±0.63 m/s), probably due to the presence of fibrotic tissue on histology. Pleural effusion was associated with a statistically significant reduction in stiffness, both in lung carcinomas (P=0.004) and lung metastases (P=0.002). The presence of air in healthy lung tissue may lead to incorrect speed estimates due to shear wave reflection (very high values, 14.64±2.19 m/s). CONCLUSION: Transthoracic SWE could not distinguish lung malignancy from pneumonia, or between different histological types of lung carcinomas. In particular, SWE seems unable to resolve the clinical dilemma of chronic subpleural consolidations.

Low GFR amplifies the association between coronary three-vessel disease and all-cause mortality.

BACKGROUND AND AIM: Three vessels disease (3VD) has been associated with worse prognosis and higher mortality. Chronic kidney disease (CKD) is an independent risk factor for premature death, mostly due to coronary artery disease (CAD). We aim to examine the prognostic impact of 3VD on all-cause mortality in a cohort of high cardiovascular risk subjects undergoing coronary angiography (CA) and to explore whether low eGFR (<60 ml/min/1.73 m2) modulates the risk of all-cause mortality associated to 3VD. METHODS AND RESULTS: One-thousand-seventeen subjects (759 M, mean age 68.4 ± 11 years) consecutive subjects undergoing CA from 2016 to 2018 were evaluated. Subjects were classified according to the severity of CAD as follows: group "three vessels disease" (3VD), and "no three vessels disease" (No 3VD). Serum creatinine was measured to estimate glomerular filtration rate (eGFR). The whole population was divided into 4 groups (A, B, C, D), according to the presence/absence of low eGFR and/or 3VD. One-hundred-fourteen deaths occurred (median follow-up:44 months). The risk of death in subjects with 3VD was almost 2-time higher than subject without 3VD (adjusted HR = 1.61; 95% CI 1.094-2.373, p = 0.0157). Among 4 subgroups, subjects with low eGFR and 3VD (Group D) had the highest risk of death (adjusted HR = 3.881; 95% CI 2.256-6.676, p < 0.0001). CONCLUSIONS: Low eGFR significantly amplifies the risk of all-cause mortality associated to 3VD. Our results strengthen the role of kidney disease as a risk multiplier for cardiovascular and all-cause mortality and highlight the need to prevent its onset and progression.