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Summary: Background: Despite the overall improvement in care, people with type 2 diabetes (T2D) experience an excess risk of end-stage kidney disease. We evaluated the long-term effectiveness of dapagliflozin on kidney function and albuminuria in patients with T2D. Methods: We included patients with T2D who initiated dapagliflozin or comparators from 2015 to 2020. Propensity score matching (PSM) was performed to balance the two groups. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from baseline to the end of observation. Secondary endpoints included changes in albuminuria and loss of kidney function. Findings: We analysed two matched groups of 6197 patients each. The comparator group included DPP-4 inhibitors (40%), GLP-1RA (22.3%), sulphonylureas (16.1%), pioglitazone (8%), metformin (5.8%), or acarbose (4%). Only 6.4% had baseline eGFR 30 mg/g. During a mean follow-up of 2.5 year, eGFR declined significantly less in the dapagliflozin vs comparator group by 1.81 ml/min/1.73 m2 (95% C.I. from 1.13 to 2.48; p

Introduction Low glomerular filtration rate (GFR) is a leading cause of reduced lifespan in type 2 diabetes. Unravelling biomarkers capable to identify high-risk patients can help tackle this burden. We investigated the association between 188 serum metabolites and kidney function in type 2 diabetes and then whether the associated metabolites improve two established clinical models for predicting GFR decline in these patients.Research design and methods Two cohorts comprising 849 individuals with type 2 diabetes (discovery and validation samples) and a follow-up study of 575 patients with estimated GFR (eGFR) decline were analyzed.Results Ten metabolites were independently associated with low eGFR in the discovery sample, with nine of them being confirmed also in the validation sample (ORs range 1.3–2.4 per 1SD, p values range 1.9×10−2–2.5×10−9). Of these, five metabolites were also associated with eGFR decline (ie, tiglylcarnitine, decadienylcarnitine, total dimethylarginine, decenoylcarnitine and kynurenine) (β range −0.11 to −0.19, p values range 4.8×10−2 to 3.0×10−3). Indeed, tiglylcarnitine and kynurenine, which captured all the information of the other three markers, improved discrimination and reclassification (all p

Summary: 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.

ObjectivesWe 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.MethodsFrom 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.ResultsOn 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.ConclusionA 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 codePLEURO-SCREENING-V1.0_15 Feb, 17.

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.

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 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.

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.

Pulmonary artery stump thrombosis (PAST) represents a possible complication after lung surgery. We report the case of a 59-year-old man who presented with dyspnoea about 4 years after right pneumonectomy due to squamous cell lung cancer. A CT-scan showed the presence of pulmonary artery stump thrombosis. Although there was no evidence of pulmonary embolism, given the clinical features and radiological shape of the thrombus, anticoagulation treatment with low-molecular-weight heparin was started with improvement of symptoms. The patient was discharged on anticoagulant treatment and a pulmonary CT-scan performed 4 months later showed an almost complete resolution of the PAST. Pathophysiological mechanisms of PAST are still unknown, although several hypotheses have been proposed. However, the decision to treat PAST with anticoagulants is still controversial. A review of literature will be provided in order to discuss risk factors, possible etiologies and to highlight clinical and radiological characteristics that could suggest to treat this condition, in particular when there is an increased risk of complications.

Background: In the current coronavirus disease-2019 (COVID-19) pandemic, lung ultrasound (LUS) has been extensively employed to evaluate lung involvement and proposed as a useful screening tool for early diagnosis in the emergency department (ED), prehospitalization triage, and treatment monitoring of COVID-19 pneumonia. However, the actual effectiveness of LUS in characterizing lung involvement in COVID-19 is still unclear. Our aim was to evaluate LUS diagnostic performance in assessing or ruling out COVID-19 pneumonia when compared with chest CT (gold standard) in a population of SARS-CoV-2-infected patients.Methods: A total of 260 consecutive RT-PCR confirmed SARS-CoV-2-infected patients were included in the study. All the patients underwent both chest CT scan and concurrent LUS at admission, within the first 6–12 h of hospital stay.Results: Chest CT scan was considered positive when showing a “typical” or “indeterminate” pattern for COVID-19, according to the RSNA classification system. Disease prevalence for COVID-19 pneumonia was 90.77%. LUS demonstrated a sensitivity of 56.78% in detecting lung alteration. The concordance rate for the assessment of abnormalities by both methods increased in the case of peripheral distribution and middle-lower lung location of lesions and in cases of more severe lung involvement. A total of nine patients had a “false-positive” LUS examination. Alternative diagnosis included chronic heart disease (six cases), bronchiectasis (two cases), and subpleural emphysema (one case). LUS specificity was 62.50%. Collateral findings indicative of overlapping conditions at chest CT were recorded also in patients with COVID-19 pneumonia and appeared distributed with increasing frequency passing from the group with mild disease (17 cases) to that with severe disease (40 cases).Conclusions: LUS does not seem to be an adequate tool for screening purposes in the ED, due to the risk of missing some lesions and/or to underestimate the actual extent of the disease. Furthermore, the not specificity of LUS implies the possibility to erroneously classify pre-existing or overlapping conditions as COVID-19 pneumonia. It seems more safe to integrate a positive LUS examination with clinical, epidemiological, laboratory, and radiologic findings to suggest a “virosis.” Viral testing confirmation is always required.

In patients presenting with classical features of CAP (i.e., new peripheral pulmonary consolidations and symptoms including fever, cough, and dyspnea), a clinical response to the appropriate therapy occurs in few days. When clinical improvement has not occurred and chest imaging findings are unchanged or worse, a more aggressive approach is needed in order to exclude other non-infective lesions (including neoplasms). International guidelines do not currently recommend the use of transthoracic ultrasound (TUS) as an alternative to chest X-ray (CXR) or chest computed tomography (CT) scan for the diagnosis of CAP. However, a fundamental role for TUS has been established as a guide for percutaneous needle biopsy (US-PNB) in pleural and subpleural lesions. In this retrospective study, we included 36 consecutive patients whose final diagnosis, made by a US-guided percutaneous needle biopsy (US-PTNB), was infectious organizing pneumonia (OP). Infective etiology was confirmed by additional information from microbiological and cultural studies or with a clinical follow-up of 6–12 months after a second-line antibiotic therapy plus corticosteroids. All patients have been subjected to a chest CT and a systematic TUS examination before biopsy. This gave us the opportunity to explore TUS performance in assessing CT findings of infective OP. TUS sensitivity and specificity in detecting air bronchogram and necrotic areas were far lower than those of CT scan. Conversely, TUS showed superiority in the detection of pleural effusion. Although ultrasound findings did not allow the characterization of chronic subpleural lesions, TUS confirmed to be a valid diagnostic aid for guiding percutaneous needle biopsy of subpleural consolidations.

BackgroundAngiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy.Methods and findingsVARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion.ConclusionsRisk/benefit profile of study treatments was similar. Dual renin-angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients.Trial registrationEudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.

Abstract Background Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage ≥3 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage ≥3 CKD in a large cohort of patients affected by T1DM. Methods A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage ≥3 CKD (eGFR 30% from baseline was evaluated. Results The mean estimated GFR was 98 ± 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions Albuminuria and eGFR reduction represent independent risk factors for incident stage ≥3 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening.

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.

Abstract Background We described, in a large sample of patients with type 1 diabetes mellitus (T1DM) and GFR ≤ 60 mL/min/1.73 m2 (with or without albuminuria), the differences in the clinical features associated with the two different chronic kidney disease phenotypes and we investigated, in a subset of patients, the modulating role of albuminuria on kidney disease progression. Methods Clinical data of 1395 patients with T1DM were extracted from electronic medical records. Results Albuminuria was detected in 676 (48.5%) patients, with the remaining 719 (51.5%) patients having normoalbuminuric renal impairment. Those with albuminuria showed an evident worse cardiovascular risk profile as compared to patients with normoalbuminuria. A subgroup of 582 patients was followed up over a 4-year period. One hundred and twenty five patients (21.5%) showed a loss of eGFR > 30%. The proportion of patients reaching the renal outcome was significantly higher among those with baseline albuminuria as compared to patients with normoalbuminuria (P

Abstract Background Diabetic kidney disease (DKD) is a major burden in elderly patients with type 2 diabetes (T2DM). Low estimated glomerular filtration rate (eGFR+, 75 years) as compared to the younger groups (

Background: The primary aim of this study was to confirm the validity of intraoperative lung ultrasound (ILU) as a safe and effective method of localization for difficult to visualize pulmonary nodules during Video-Assisted Thoracoscopic Surgery (VATS) and open thoracotomy. The secondary aim was to enhance knowledge on the morphological patterns of presentation of pulmonary nodules on direct ultrasound examination. Materials and methods: 131 patients with lung nodule and indication for surgery were enrolled. All patients underwent pre-operative imaging of the chest, including Chest Computed Tomography (CT) and Transthoracic Ultrasound (TUS), and surgical procedures for histological assessment of pulmonary nodules (VATS or open thoracotomy). Results: The identification of 100.00% of lung nodules was allowed by ILU, while the detection rate of digital palpation was 94.66%. It was not possible to associate any specific ILU echostructural pattern to both benign or malignant lesions. However, the actual histological margins of the lesions in the operating samples were corresponding to those visualized at ILU in 125/131 (95.42%) cases. No complications have been reported with ILU employment. Conclusions: In our experience, ILU performed during both open surgery and VATS demonstrated to be a reliable and safe method for visualization and localization of pulmonary nodules non previously assessed on digital palpation. In addition, ILU showed to allow a clear nodule’s margins’ definition matching, in most cases, with the actual histological margins.

(1) Background: The aim of this study was to conduct a prospective analysis on the diagnostic accuracy of transthoracic ultrasound-guided percutaneous needle biopsy (TUS-PNB) for the histological assessment of peripheral lung lesions and to assess the performance of transthoracic ultrasound (TUS) examination vs. chest CT (gold standard) in the differentiation between malignant and benign peripheral lung lesions. (2) Methods: A total of 961 consecutive patients with subpleural pulmonary lesions were enrolled. All the patients received a CT scan with contrast; 762 patients underwent TUS-PTNB for suspicion of malignancy, and the remaining 199 enrolled patients underwent only TUS examination as a part of routine follow-up for known non-malignant subpleural consolidations. (3) Results: Among the 762 TUS-guided biopsies, there were 627 (82.28%) malignant lesions, 82 (10.76%) benign lesions, and 53 (6.96%) indeterminate lesions. The overall diagnostic accuracy was 93.04%. The rates of pneumothorax not requiring chest-tube insertion and self-limited hemoptysis were 0.79 and 0.26%, respectively. Patients were divided into two groups based on the benign or malignant nature of the subpleural consolidations. On TUS, both malignant and benign lesions showed mostly irregular margins and a hypoechoic pattern, but no differences were assessed in terms of sonographic margins and pattern between the two groups. There was poor agreement between TUS and chest CT in assessing air bronchograms and necrotic areas. The only finding in the detection of which TUS showed superiority compared to chest-CT was pleural effusion. (4) Conclusions: TUS-PNB was confirmed to be an effective and safe diagnostic method for peripheral pulmonary consolidation, but their sonographic pattern did not allow to rule out a malignant nature. A pre-operative evaluation on CT images, combined with the possibility of performing additional immunohistochemical and cytological investigations and the experience of the medical staff, may improve the diagnostic yield of TUS-guided biopsies.

Background and Aims: The WHO has solicited all countries to eliminate HCV by 2030. The Italian government started routine screening for HCV infection in January 2021, initially targeting subjects born between 1969 and 1989. With the aim of achieving micro-elimination, we designed a hospital-wide project focusing on inpatients born from 1935 to 1985 and conducted it in our institution. Method: All inpatients aged 35 to 85, admitted from 10 February 2020 to 9 February 2021 for many different diseases and conditions underwent HCV antibody (HCVAb) testing by third-generation ELISA. When positive, reflex HCV RNA testing and genotyping were performed. Clinical history, fibrosis diagnosis, laboratory data and concomitant medications were available for all. Results: The HCV screening rate of inpatients was 100%. In total, 11,748 participants were enrolled, of whom 53.50% were male. The HCVAb positivity rate was 3.03%. The HCVAb rate increased with age and was higher for patients born between 1935 and 1944 (4.81%). The rate of HCV RNA positivity was 0.97%. The vast majority (80.70%) of HCV RNA-positive participants were 55 or older; in about 40% of cases, HCV RNA-positive patients were unaware of their infection. Although 16 patients died after HCV chronic infection diagnosis (two due COVID-19) or HCV treatment prescription (one due to COVID-19), 74.56% of patient HCV diagnoses were linked to HCV treatment, despite their co-morbidities. All patients older than 65 who died had an active HCV infection. Conclusion: The present study revealed a rate of active HCV infections among inpatients lower than what has been reported in the past in the general population; this appears to be a result of the widespread use of pangenotypic direct-acting antiviral agents (DAAs). The overall rate of active infection was lower than the rate observed in the 1935–1954 cohort. The high rate of inpatients unaware of HCV infections and the high number of deaths among subjects with an active HCV infection born from 1935 to 1954, suggest that, at least in southern Italy, targeted screening of this birth cohort may be required to reduce the number of undiagnosed cases and hidden infections.

Clinical manifestations accompanying respiratory failure with insidious and rapidly progressive onset are often non-specific. Symptoms such as a cough, dyspnea, and fever are common to a large number of inflammatory, infectious, or neoplastic diseases. During the COVID-19 pandemic it is essential to limit the use of hospital services and inappropriate diagnostic techniques. A particular radiological pattern can orient the clinical and laboratory scenario and guide the diagnostic workup. A 58-year-old woman was admitted to our COVID-19 unit for suspected coronavirus infection. She was complaining of worsening dyspnea, tachycardia, and low grade fever. A chest X-ray showed diffuse, alveolar, and interstitial lung involvement with micronodules tending to coalescence. This radiographic pattern known as “galaxy sign”, consistent with diffuse, coalescing nodular miliary pulmonary involvement, simulating a non-specific alveolar opacification of the lungs is typical of a few pneumological differential diagnoses, represented by sarcoidosis, tuberculosis, pneumoconiosis, and metastatic lesions, and virtually excludes an interstitial viral pneumonitis. The use of endoscopic techniques can, in such cases, confirm the clinical suspicion for initiating appropriate targeted therapies.

Abstract We evaluated 2,656 patients with type 1 diabetes mellitus and preserved renal function from the database of the Italian Association of Clinical Diabetologists network to identify clinical predictors for the development of chronic kidney disease. We measured estimated glomerular filtration rate (eGFR), urinary albumin excretion, HbA1c, lipids, blood pressure. Over a 5-year period 4.3% (n = 115) developed reduced eGFR (

Abstract Resistin has been firmly associated with all-cause mortality. We investigated, whether, in patients with type 2 diabetes (T2D), this association is sustained by a cause-effect relationship. A genotype risk score (GRS), created by summing the number of resistin increasing alleles of two genome-wide association studies (GWAS)-derived single nucleotide polymorphisms (SNPs), serum resistin measurements and all-cause death records were obtained in 1,479 (403 events/12,454 person-years), patients with T2D from three cohorts, Gargano Heart Study-prospective design (n = 350), Gargano Mortality Study (n = 698) and Foggia Mortality Study (n = 431), from Italy. GRS was strongly associated with serum resistin in a non-linear fashion (overall p = 3.5 * 10−7) with effect size modest for GRS = 1 and 2 and much higher for GRS >3, with respect to GRS = 0. A significant non-linear association was observed also between GRS and all-cause mortality (overall p = 3.3 * 10−2), with a low effect size for GRS = 1 and 2, and nearly doubled for GRS ≥ 3, with respect to GRS = 0. Based on the above-reported associations, each genetic equivalent SD increase in log-resistin levels showed a causal hazard ratio of all-cause mortality equal to 2.17 (95%CI: 1.22–3.87), thus providing evidence for a causal role of resistin in shaping the risk of mortality in diabetic patients.

In the last years, transthoracic ultrasound (TUS) has regained a growing interest from both clinicians and radiologists as a useful and non-invasive diagnostic tool for the study of many pleuropulmonary conditions, including interstitial lung diseases. Intraoperative lung ultrasound (ILU) is an ultrasound technique, developed for lung surface assessment during video-assisted thoracoscopic surgery procedures. It has been developed considering ultrasound basic physical principles for images generation and interpretation. Most of the TUS findings are due to the high difference in acoustic impedance between the chest-wall structures and the air in the lungs. In this brief communication, we compared ILU and TUS images in interstitial lung diseases. Most of the TUS artifacts-based diagnostic algorithms should be reappraised.

Background: The management of septic patients hospitalized in Internal Medicine wards represents a challenge due to their complexity and heterogeneity, and a high mortality rate. Among the available prognostic tools, procalcitonin (PCT) is considered a marker of bacterial infection. Furthermore, an association between vitamin D deficiency and poor sepsis-related outcomes has been described. Objectives: To evaluate the prognostic accuracy of two consecutive PCT determinations (Delta-PCT) and of vitamin D levels in predicting mortality in a population of patients with microbiological identified sepsis admitted to Internal Medicine wards. Methods: This is a sub-analysis of a previous prospective study. A total of 80 patients had at least two available consecutive PCT determinations, while 63 had also vitamin D. Delta-PCT was defined as a reduction of PCT > 50% after 48 h, >75% after 72 h, and >85% after 96 h. Mortality rate at 28- and 90-days were considered as main outcome. Results: Mortality rate was 18.7% at 28-days and 30.0% at 90-days. Baseline PCT levels did not differ between survived and deceased patients (28-days: p = 0.525; 90-days: p = 0.088). A significantly higher proportion of survived patients showed Delta-PCT (28-days: p = 0.002; 90-days: p < 0.001). Delta-PCT was associated with a lower 28-days (p = 0.007; OR = 0.12, 95%CI 0.02–0.46) and 90-days mortality (p = 0.001; OR = 0.17, 95%CI 0.06–0.48). A significantly higher proportion of deceased patients showed severe vitamin D deficiency (28-days: p = 0.047; 90-days: p = 0.049). Severe vitamin D deficiency was associated with a higher 28-days (p = 0.058; OR = 3.95, 95%CI 1.04–19.43) and 90-days mortality (p = 0.054; OR = 2.94, 95%CI 1.00–9.23). Conclusions: Delta-PCT and vitamin D represent two useful tests for predicting prognosis of septic patients admitted to Internal Medicine wards.

Background and Objectives: The potential role of lung ultrasound (LUS) in characterizing lung involvement in Coronavirus disease 2019 (COVID-19) is still debated. The aim of the study was to estimate sensitivity of admission LUS for the detection of SARS-CoV-2 lung involvement using Chest-CT (Computed Tomography) as reference standard in order to assess LUS usefulness in ruling out COVID-19 pneumonia in the Emergency Department (ED). Methods: Eighty-two patients with confirmed COVID-19 and signs of lung involvement on Chest-CT were consecutively admitted to our hospital and recruited in the study. Chest-CT and LUS examination were concurrently performed within the first 6–12h from admission. Sensitivity of LUS was calculated using CT findings as a reference standard. Results: Global LUS sensitivity in detecting COVID-19 pulmonary lesions was 52%. LUS sensitivity ranged from 8% in case of focal and sporadic ground-glass opacities (mild disease), to 52% for a crazy-paving pattern (moderate disease) and up to 100% in case of extensive subpleural consolidations (severe disease), although LUS was not always able to detect all the consolidations assessed at Chest-CT. LUS sensitivity was higher in detecting a typical Chest-CT pattern (60%) and abnormalities showing a middle-lower zone predominance (79%). Conclusions: As admission LUS may result falsely negative in most cases, it should not be considered as a reliable imaging tool in ruling out COVID-19 pneumonia in patients presenting in ED. It may at least represent an expanded clinical evaluation that needs integration with other diagnostic tests (e.g., nasopharyngeal swab, Chest-CT).

Background: The diagnosis of Coronavirus disease 2019 (COVID-19) relies on the positivity of nasopharyngeal swab. However, a significant percentage of symptomatic patients may test negative. We evaluated the reliability of COVID-19 diagnosis made by radiologists and clinicians and its accuracy versus serology in a sample of patients hospitalized for suspected COVID-19 with multiple negative swabs. Methods: Admission chest CT-scans and clinical records of swab-negative patients, treated according to the COVID-19 protocol or deceased during hospitalization, were retrospectively evaluated by two radiologists and two clinicians, respectively. Results: Of 254 patients, 169 swab-confirmed cases and one patient without chest CT-scan were excluded. A total of 84 patients were eligible for the reliability study. Of these, 21 patients died during hospitalization; the remaining 63 underwent serological testing and were eligible for the accuracy evaluation. Of the 63, 26 patients showed anti-Sars-Cov-2 antibodies, while 37 did not. The inter-rater agreement was “substantial” (kappa 0.683) between radiologists, “moderate” (kappa 0.454) between clinicians, and only “fair” (kappa 0.341) between radiologists and clinicians. Both radiologic and clinical evaluations showed good accuracy compared to serology. Conclusions: The radiologic and clinical diagnosis of COVID-19 for swab-negative patients proved to be sufficiently reliable and accurate to allow a diagnosis of COVID-19, which needs to be confirmed by serology and follow-up.

Alcohol Use Disorder (AUD) is a chronic and relapsing condition characterized by harmful alcohol intake and behavioral-cognitive changes. AUD is the most common cause of liver disease in the Western world. Alcohol abstinence is the cornerstone of therapy in alcoholic patients affected with liver disease. Medical recommendations, brief motivational interventions and psychosocial approach are essential pieces of the treatment for these patients; however, their efficacy alone may not be enough to achieve total alcohol abstinence. The addition of pharmacological treatment could improve clinical outcomes in AUD patients. Moreover, pharmacological treatments for AUD are limited in patients with advanced liver disease, since impaired liver function affects drugs metabolism and could increase the risk of drugs-related hepatotoxicity. At present, only baclofen has been tested in RCTs in patients with advanced liver disease. This medication was effective to reduce alcohol intake, to promote alcohol abstinence and to prevent relapse in AUD patients affected by liver cirrhosis. In addition, the drug showed a safe profile in these patients. In this review, clinical studies about efficacy and safety of baclofen administration in patients with AUD and advanced liver disease will be reviewed. Open question about the most appropriate dose of the drug, duration of the treatment and need of additional studies will also be discussed.

Non-alcoholic fatty liver disease (NAFLD) is the most frequent hepatic pathology in the Western world and may evolve into steatohepatitis (NASH), increasing the risk of cirrhosis, portal hypertension and hepatocellular carcinoma. NAFLD derives from the accumulation of hepatic fat due to discrepant free fatty acid metabolism. Other factors contributing to this are deranged nutrients and bile acids fluxes as well as alterations in nuclear receptors, hormones, and intermediary metabolites, which impact on signaling pathways involved in metabolism and inflammation. Autophagy and host gut-microbiota interplay are also relevant to NAFLD pathogenesis. Notably, liver metabolic pathways and bile acid synthesis as well as autophagic and immune/inflammatory processes all show circadian patterns driven by the biological clock. Gut microbiota impacts on the biological clock, at the same time as the appropriate timing of metabolic fluxes, hormone secretion, bile acid turnover, autophagy and inflammation with behavioural cycles of fasting/feeding and sleeping/waking is required to circumvent hepatosteatosis, indicating significant interactions of the gut and circadian processes in NAFLD pathophysiology. Several time-related factors and processes interplay in NAFLD development, with the biological clock proposed to act as a network level hub. Deranged physiological rhythms (chronodisruption) may also play a role in liver steatosis pathogenesis. The current article reviews how the circadian clock circuitry intimately interacts with several mechanisms involved in the onset of hepatosteatosis and its progression to NASH, thereby contributing to the global NAFLD epidemic.

We performed a real-life analysis of clinical and laboratory parameters, in orally treated T2DM patients aiming at identifying predictors of insulin treatment initiation. Overall, 366955 patients (55.8% males, age 65 ± 11 years, diabetes duration 7 ± 8 years) were followed up between 2004 and 2011. Each patient was analyzed step-by-step until either eventually starting insulin treatment or getting to the end of the follow-up period. Patients switching to insulin showed a worse global risk profile, longer disease duration (10 ± 9 years vs. 6 ± 7 years, respectively; p

BackgroundApparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes mellitus (T2D) and entails worse cardiovascular prognosis. The impact of aTRH and long‐term achievement of recommended blood pressure (BP) values on renal outcome remains largely unknown. We assessed the role of aTRH and BP on the development of chronic kidney disease in patients with T2D and hypertension in real‐life clinical practice. Methods and ResultsClinical records from a total of 29 923 patients with T2D and hypertension, with normal baseline estimated glomerular filtration rate and regular visits during a 4‐year follow‐up, were retrieved and analyzed. The association between time‐updated BP control (ie, 75% of visits with BP

Metabolic Syndrome (Mets) and increased serum uric acid (SUA), are well known renal risk predictors and often coexist in patients with type 2 diabetes (T2D). Whether they independently contribute to the onset of CKD is at present unclear.Within the AMD Annals database we identified patients with T2D and normal renal function and urine albumin excretion at baseline and regular follow-up visits during a 4-year period. Blood pressure, BMI, HDL, triglycerides, and SUA were available in 14,267 patients. The association between Mets and/or hyperuricemia (HU, top fifth gender specific quintile) and the occurrence of renal outcomes were evaluated.At baseline 59% of patients (n = 8,408) showed Mets and 18% (n = 2,584) HU. Over the 4-year follow-up, 14% (n = 1,990) developed low eGFR (i.e. below 60 mL/min/1.73 m2), and 26% (n = 3,740) albuminuria. After adjustment for confounders, BP≥130/85, low HDL, triglycerides ≥150 and HU were independently related to the development of low eGFR (1.57, P

Diabetic kidney disease affects up to forty percent of patients with diabetes during their lifespan. Prevention and treatment of diabetic kidney disease is currently based on optimal glucose and blood pressure control. Renin−angiotensin aldosterone inhibitors are considered the mainstay treatment for hypertension in diabetic patients, especially in the presence of albuminuria. Whether strict blood pressure reduction entails a favorable renal outcome also in non-albuminuric patients is at present unclear. Results of several clinical trials suggest that an overly aggressive blood pressure reduction, especially in the context of profound pharmacologic inhibition of the renin−angiotensin−aldosterone system may result in a paradoxical worsening of renal function. On the basis of this evidence, it is proposed that blood pressure reduction should be tailored in each individual patient according to renal phenotype.

Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease (CKD). Diabetic nephropathy (DN) is determined by specific pathological structural and functional alterations of the kidneys in patients with diabetes, and its clinical manifestations are albuminuria and decline of glomerular filtration rate (GFR). Apart from renin−angiotensin−aldosterone system (RAAS) inhibitors, no other drugs are currently available as therapy for diabetic kidney disease (DKD). Glucagon-like peptide-1 receptor (GLP-1R) agonists are a new class of anti-hyperglycemic drugs which have been demonstrated to prevent the onset of macroalbuminuria and reduce the decline of GFR in diabetic patients. These drugs may exert their beneficial actions on the kidneys through blood glucose- and blood pressure (BP)-lowering effects, reduction of insulin levels and weight loss. Clinical benefits of GLP-1R agonists were acknowledged due to data from large randomized phase III clinical trials conducted to assess their cardiovascular(CV) safety. These drugs improved renal biomarkers in placebo-controlled clinical studies, with effects supposed to be independent of the actions on glycemic control. In this review, we will focus on the actions of GLP-1R agonists on glucose metabolism and kidney physiology, and evaluate direct and indirect mechanisms through which these drugs may confer renal protection.

Objective. We studied the prevalence of nonalcoholic fatty liver disease (NAFLD) and its clinical correlates in a population of patients with type 2 diabetes mellitus (T2DM). Methods. Clinical data of 94,577 T2DM patients were retrieved from 160 diabetes clinics in Italy in a standardized format and centrally analyzed anonymously. After exclusion of 5967 cases (high or uncertain alcohol intake), in 38,880 the Fatty Liver Index (FLI) was used as a proxy for the diagnosis of NAFLD. Factors associated with FLI assessed NAFLD (FLI-NAFLD) were evaluated through multivariate analysis. Results. FLI-NAFLD was present in 59.6% of patients. Compared to non-NAFLD, FLI-NAFLD was associated with impairment in renal function, higher albumin excretion, HbA1c and blood pressure, lower HDL cholesterol, and poorer quality of care. ALT was within normal limits in 73.6% of FLI-NAFLD patients (45.6% if the updated reference values were used). The prevalence of FLI-NAFLD did not differ if the whole sample (94,577 cases) was examined, irrespective of alcohol intake. Conclusions. FLI-NAFLD was present in the majority of T2DM patients of our sample and metabolic derangement, not alcohol consumption, was mainly associated with the disease. FLI-NAFLD patients have a worse metabolic profile. ALT levels are not predictive of NAFLD.

BackgroundTo investigate prospectively the relationship between target values of glycated hemoglobin, blood pressure and LDL-cholesterol, as considered in a combined fashion, and all-cause mortality in patients with type 2 diabetes mellitus.MethodsTwo cohorts of patients with type 2 diabetes mellitus, the Gargano Mortality Study (n=810) and the Foggia Mortality Study (n=929), were investigated. A weighted target risk score was built as a weight linear combination of the recommended targets reached by each patient.ResultsIn the Gargano Mortality Study and in the Foggia Mortality Study (mean follow up=7.4 and 5.5 years, respectively), 161 (19.9%) and 220 (23.7%) patients died, with an age and sex adjusted annual incidence rate of 2.1 and 2.8 per 100 person-years, respectively. In both study samples the weighted target risk score tended to be linearly associated with all-cause mortality (HR for one point increment=1.30, 95% CI: 1.11-1.53, p=0.001, and HR=1.08, 95% CI: 0.95-1.24, p=0.243, respectively). When the two cohorts were pooled and analyzed together, a clear association between weighted target risk score and all-cause mortality was observed (HR for one point increment=1.17, 95% CI:1.05-1.30, p=0.004). This counterintuitive association was no longer observable in a model including age, sex, body mass index, smoking habit, estimated glomerular filtration rate, albuminuria and anti-diabetic, anti-hypertensive and anti-dyslipidemic treatment as covariates (HR for one point increment=0.99, 95% CI: 0.87-1.12, p=0.852).ConclusionsIn a real life clinical set of patients with type 2 diabetes mellitus, the combination of recommended target values of established cardiovascular risk factors is not associated with all-cause mortality.

High serum adiponectin has been increased in several conditions of kidney disease. Only sparse and conflicting results have been reported in patients with type 2 diabetes (T2D), a subgroup of individuals who are at high risk for renal dysfunction. The aim of this study was to fill up this gap of knowledge by investigating such association in a large sample of Italian diabetic patients. The association between serum adiponectin levels and estimated glomerular filtration rate (eGFR by Chronic Kidney Disease-Epidemiology Collaboration CKD-EPI equation) was investigated in 1,243 patients with T2D from two cross-sectional Italian studies: 878 from San Giovanni Rotondo (SGR) and 365 from Foggia (FG). Serum adiponectin was inversely associated with eGFR in SGR [β (standard error, SE) for 1 standard deviation (SD) of adiponectin = -3.26 (0.64)] and in FG [β(SE)=-5.70(1.28)] sample, as well as in the two studies combined [β(SE)=-3.99(0.59)];(p

High serum levels of the pro-inflammatory adipokine resistin have been associated with decreased renal function in the general population. The goal of this study was to investigate whether such association is also present among diabetic subjects, who are at increased risk of renal function loss.The cross-sectional association between serum resistin levels and estimated glomerular filtration rate (eGFR) was investigated in 1,560 type 2 diabetic (T2D) patients of European ancestry comprised in two different cohorts: 762 patients from San Giovanni Rotondo (SGR; Italy) and 798 patients from Boston (US).Serum resistin was inversely associated with eGFR in SGR [β (SE) for one SD of resistin increment = -1.01 (0.70) ml/min/1.73 m(2), p = 0.019] and in Boston [β (SE) = -5.31 (0.74) ml/min/1.73 m(2), p < 0.001] samples, as well as in the two studies combined [β (SE) = -3.42 (0.52) ml/min/1.73 m(2), p < 0.001]. The association was unaffected by adjustment for smoking habits, BMI, waist circumference, diabetes duration, HbA1c, insulin treatment, hypertension and lipid-lowering therapy: β (SE) for one SD of resistin increment = -1.07 (0.70), p = 0.02; -5.50 (0.88), p < 0.001; and -2.81 (0.55) ml/min/1.73 m(2), p < .001, in SGR, Boston and the two studies combined, respectively. The association was significantly stronger in men than in women (p for resistin-by-gender interaction = 0.003). For each resistin SD increment, the odds of having eGFR < 0 ml/min/1.7 3m(2) increased by 22% (OR = 1.22; 95% CI 1.02-1.44; p = 0.025) in SGR sample, 69% (OR = 1.69; 95% CI 1.38-2.07; p < 0.001) in Boston sample, and 47% (OR = 1.47; 95% CI 1.29-1.68; p < 0.001) in the two studies considered together. Similar associations were observed in the adjusted model: OR 95% CI for each SD resistin increment being 1.23 (1.03-1.46), p = 0.021; 1.52 (1.20-1.92), p < 0.001; 1.33 (1.16-1.53), p < 0.001, in SGR, Boston and the two studies combined, respectively.This is the first report of an association between high serum resistin and low eGFR in patients with T2D of European ancestry.

Some patients diagnosed as having type 2 diabetes mellitus (T2DM) are, instead, affected by multigenerational diabetes whose clinical characteristics are mostly undefined.1. To identify among patients who had been previously defined as affected by T2DM those, in fact, affected by multigenerational diabetes; 2. After excluding patients carrying the most common MODY genes and mitochondrial mutations, we compared clinical features of remaining patients with those of patients with T2DM.Among 2,583 consecutive adult patients who had been defined as affected by T2DM, we looked for those with diabetes in ≥3 consecutive generations. All probands were screened for mutations in six MODY genes (HNF4A, GCK, HNF1A, PDX1, HNF1B and NeuroD1) and for the A3243G mitochondrial mutation. After excluding patients with mutations in one of such genes, we compared clinical features of the remaining 67 patients (2.6% of the whole initial sample) affected by multigenerational "familial diabetes of the adulthood" (FDA) and of their diabetic relatives (n = 63) to those with T2DM (n = 1,028) by generalized hierarchical linear models followed by pairwise comparisons.Age, age at diagnosis, proportion of hypertension (all p

BackgroundHigh serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes.MethodsWe tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies. In addition, the expression of resistin gene (RETN) was measured in blood cells of 68 diabetic patients and correlated with their serum resistin levels.ResultsIn a model comprising age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies, serum resistin was associated with coronary artery disease in both cross-sectional studies: OR (95%CI) per SD increment = 1.35 (1.10-1.64) and 1.99 (1.55-2.55). Additionally, serum resistin predicted incident major cardiovascular events (HR per SD increment = 1.31; 1.10-1.56) and all-cause mortality (HR per SD increment = 1.16; 1.06-1.26). Adjusting also for fibrinogen levels affected the association with coronary artery disease and incident cardiovascular events, but not that with all cause-mortality. Finally, serum resistin was positively correlated with RETN mRNA expression (rho = 0.343).ConclusionsThis is the first study showing that high serum resistin (a likely consequence, at least partly, of increased RETN expression) is a risk factor for cardiovascular disease and all-cause mortality in diabetic patients of European ancestry.

High serum resistin levels have been associated with kidney dysfunction. Most of these studies have been carried out in individuals with severe kidney impairment, diabetes, cardiovascular disease and related treatments. Thus, the observed association might have been influenced by these confounders. Our aim was to study the relationship between serum resistin, urinary albumin/creatinine ratio (ACR) and glomerular filtration rate (GFR) in a family-based sample, the Gargano Family Study (GFS) of 635 non diabetic, untreated Whites.A linear mixed effects model and bivariate analyses were used to evaluate the phenotypic and genetic relations between serum resistin and both ACR and eGFR. All analyses were adjusted for sex, age, age squared, BMI, systolic blood pressure, smoking habits and physical exercise.After adjustments, resistin levels were slightly positively associated with ACR (β±SE = 0.049±0.023, p = 0.035) and inversely related to eGFR (β±SE = -1.43±0.61, p = 0.018) levels. These associations remained significant when either eGFR or ACR were, reciprocally, added as covariates. A genetic correlation (ρg = -0.31±0.12; adjusted p = 0.013) was observed between resistin and eGFR (but not ACR) levels.Serum resistin levels are independently associated with ACR and eGFR in untreated non-diabetic individuals. Serum resistin and eGFR share also some common genetic background. Our data strongly suggest that resistin plays a role in modulating kidney function.