Hepatic steatosis with significant fibrosis is associated with an increased 10-year estimated risk of cardiovascular disease in adults with type 1 diabetes mellitus.

BACKGROUND: We assessed whether hepatic steatosis with or without significant fibrosis (determined by validated non-invasive biomarkers) is associated with an increased 10-year estimated risk for cardiovascular disease (CVD) in people with type 1 diabetes mellitus (T1DM). METHODS: We conducted a retrospective, multicenter, cross-sectional study involving 1,254 adults with established T1DM without pre-existing CVD. We used the hepatic steatosis index (HSI) and fibrosis (FIB)-4 index for non-invasively detecting hepatic steatosis (defined as HSI > 36), with or without coexisting significant fibrosis (defined as FIB-4 index ≥ 1.3 or < 1.3). We calculated the Steno type 1 risk engine and the atherosclerotic CVD (ASCVD) risk score to estimate the 10-year risk of developing a first fatal or nonfatal CVD event. RESULTS: Using the Steno type 1 risk engine, a significantly greater proportion of patients with hepatic steatosis and significant fibrosis (n = 91) had a high 10-year estimated CVD risk compared to those with hepatic steatosis alone (n = 509) or without steatosis (n = 654) (75.8% vs. 23.2% vs. 24.9%, p < 0.001). After adjustment for sex, BMI, diabetes duration, hemoglobin A1c, chronic kidney disease, and lipid-lowering medication use, patients with hepatic steatosis and significant fibrosis had an increased 10-year estimated risk of developing a first fatal or nonfatal CVD event (adjusted-odds ratio 11.4, 95% confidence interval 3.54-36.9) than those without steatosis. We observed almost identical results using the ASCVD risk calculator. CONCLUSIONS: The 10-year estimated CVD risk is remarkably greater in T1DM adults with hepatic steatosis and significant fibrosis than in their counterparts with hepatic steatosis alone or without steatosis.

Efficacy of a training programme for the management of diabetes mellitus in the hospital: A randomized study (stage 2 of GOVEPAZ healthcare).

AIMS: To assess the efficacy of a structured educational intervention for health professionals on the appropriateness of inpatient diabetes care and on some clinical outcomes in hospitalised subjects. METHODS: A multicentre (6 regional hospitals) cluster-randomized (2:1) two parallel-group pragmatic intervention trials, as a part of the GOVEPAZ study, was conducted in three clinical settings, that is, Internal Medicine, Surgery and Intensive Care. Intervention consisted of a 2-month structured education of clinical staff to inpatient diabetes care. Twelve wards - 2 for each hospital - and 6 wards - 1 for each hospital - were randomized to usual care and to the intervention arm, respectively. Consecutively hospitalised diabetic subjects (n = 524, age 74 ± 14 years, 57% males, median HbA1C 57 mmol/mol) were included. The clinical appropriateness of inpatient diabetes management was assessed by a previously validated multi-domain performance score (PS). Clinical outcomes included hypoglycemia, glucose control biomarkers, clinical conditions at discharge and inpatient mortality rate. RESULTS: A numerically, but not statistically significant, higher PS (+0.94; 95% C.I.: -0.53 - +2.4) was achieved in the intervention than in the usual care wards. Hypoglycemias (p = 0.32), glucose control (p = 0.89) and survival rates (p = 0.71) were similar in the two experimental arms. Plasma glucose on admission (OR = 1.52 per 1 SD; C.I. 1.07-2.17; p = 0.021) and the number of hypoglycemic events per patient (OR = 1.55 per 1 SD; C.I.:1.11-2.16; p = 0.011) were independently associated with the inpatient mortality rate. CONCLUSIONS: Structured education of the clinical staff failed to improve the inpatient appropriateness of diabetes care or clinical outcomes. In-hospital hypoglycemia was confirmed to be an independent indicator of death risk.

Aqueous Humor Analysis in Overlapping Clinical Diagnosis of Cytomegalovirus and Rubella Virus Anterior Uveitis.

Background and Objectives: A cross-sectional single-center study was conducted to investigate the etiology in hypertensive anterior uveitis whose clinical features are not fully distinctive from cytomegalovirus or from rubella virus and to demonstrate the possible coexistence of both these viruses in causing anterior uveitis. Materials and Methods: The clinical charts of a cohort of patients with hypertensive viral anterior uveitis of uncertain origin consecutively seen in a single center from 2019 to 2022 were retrospectively reviewed; data on the clinical features, aqueous polymerase chain reaction, and antibody response to cytomegalovirus and rubella virus were collected. Results: Forty-three eyes of as many subjects with viral anterior uveitis of uncertain origin were included. Thirty-two patients had an aqueous polymerase chain reaction or antibody index positive to cytomegalovirus only, while 11 cases had an aqueous antibody response to both cytomegalovirus and rubella virus. This latter overlapping group had a statistically significant higher rate of hypochromia and anterior vitritis (p-value: 0.02 and < 0.001, respectively). Conclusions: The simultaneous presence of intraocular antibodies against cytomegalovirus and rubella virus could redefine the differential diagnosis of hypertensive viral anterior uveitis, demonstrating a possible "converged" immune pathway consisting in a variety of stimuli.

A performance score of the quality of inpatient diabetes care is a marker of clinical outcomes and suggests a cause-effect relationship between hypoglycaemia and the risk of in-hospital mortality.

AIMS: To build a tool to assess the management of inpatients with diabetes mellitus and to investigate its relationship, if any, with clinical outcomes. MATERIALS AND METHODS: A total of 678 patients from different settings, Internal Medicine (IMU, n = 255), General Surgery (GSU, n = 230) and Intensive Care (ICU, n = 193) Units, were enrolled. A work-flow of clinical care of diabetes was created according to guidelines. The workflow was divided into five different domains: (a) initial assessment; (b) glucose monitoring; (c) medical therapy; (d) consultancies; (e) discharge. Each domain was assessed by a performance score (PS), computed as the sum of the scores achieved in a set of indicators of clinical appropriateness, management and patient empowerment. Appropriate glucose goals were included as intermediate phenotypes. Clinical outcomes included: hypoglycaemia, survival rate and clinical conditions at discharge. RESULTS: The total PS and those of initial assessment and glucose monitoring were significantly lower in GSU with respect to IMU and ICU (P < .0001). The glucose monitoring PS was associated with lower risk of hypoglycaemia (OR = 0.55; P < .0001), whereas both the PSs of glucose monitoring and medical therapy resulted associated with higher in-hospital survival only in the IMU ward (OR = 6.67 P = .001 and OR = 2.38 P = .03, respectively). Instrumental variable analysis with the aid of PS of glucose monitoring showed that hypoglycaemia may play a causal role in in-hospital mortality (P = .04). CONCLUSIONS: The quality of in-hospital care of diabetes may affect patient outcomes, including glucose control and the risk of hypoglycaemia, and through the latter it may influence the risk of in-hospital mortality.

Acute-phase reactants during tocilizumab therapy for severe COVID-19 pneumonia.

OBJECTIVES: To identify predictors of clinical improvement and intubation/death in tocilizumab-treated severe COVID19, focusing on IL6 and CRP longitudinal monitoring. METHODS: 173 consecutive patients with severe COVID-19 pneumonia receiving tocilizumab in Reggio Emilia province Hospitals between 11 March and 3 June 2020 were enrolled in a prospective cohort study. Clinical improvement was defined as status improvement on a six-category ordinal scale or discharge from the hospital, whichever came first. A composite outcome of intubation/death was also evaluated. CRP and IL-6 levels were determined before TCZ administration (T0) and after 3 (T3), and 7 (T7) days. RESULTS: At multivariate analysis T0 and T3 CRP levels were negatively associated with clinical improvement (OR 0.13, CI 0.03-0.55 and OR 0.11, CI 0.0-0.46) (p=0.006 and p=0.003) and positively associated with intubation/death (OR 17.66, CI 2.47-126.14 and OR 5.34, CI: 1.49-19.12) (p=0.01 and p=0.004). No significant associations with IL-6 values were observed. General linear model analyses for repeated measures showed significantly different trends for CRP from day 3 to day 7 between patients who improved and those who did not, and between patients who were intubated or died and those who were not (p<0.0001 for both). ROC analysis identified a baseline CRP level of 15.8 mg/dl as the best cut-off to predict intubation/death (AUC = 0.711, sensitivity = 0.67, specificity = 0.71). CONCLUSIONS: CRP serial measurements in the first week of TCZ therapy are useful in identifying patients developing poor outcomes.

Clinical, Electrocardiographic, and Echocardiographic Features in Hospitalized Nonagenarians (90+): Comparison between the Genders.

OBJECTIVES: We investigated the clinical, electrocardiographic, and echocardiographic determinants of the cardiac status in nonagenarian patients. METHODS: We consecutively examined 654 Caucasian patients (232 males and 422 females) aged ≥90 years. All patients underwent clinical examination, ECG, and transthoracic echocardiography. RESULTS: Their average age was 92.5 ± 2.5 years. Patients were predominately female of older age (p < 0.0001 and p = 0.02, respectively). A history of cardiovascular disease was present in 78.4% of the participants. One third of the patients was hospitalized for cardiovascular causes, with females being twice as many (p < 0.0001). Females showed higher levels of serum cholesterol, triglycerides, and glycemia (p < 0.0001, p< 0.0001, and p = 0.04 respectively). Sinus rhythm was detected in 65%, and atrial fibrillation in 31% of the overall population. Heart rate, PR and corrected QT (QTc) intervals, right bundle branch block (RBBB) and RBBB associated with left anterior fascicular block (LAFB) were higher in males (p < 0.0001, p = 0.036, p = 0.009, p = 0.001, and p = 0.004, respectively). Aortic root dimension, left ventricular (LV) mass index, and indexed LV systolic-diastolic volumes were higher in males (p < 0.001, p < 0.0001, p < 0.001, and p < 0.0001, respectively). Women showed fewer LV segmental kinetic disorders (p = 0009) and higher LV ejection fraction (LVEF; p< 0.0001). Hyperuricemia was positively associated with a history of cardiovascular disease (r = 0.15), glycemia (r = 19), creatininemia (r = 0.50), uremia (r = 0.51), triglycerides (r = 0.19), PR interval (r = 0.14), and left bundle branch block (r = 0.11), and inversely associated with sinus rhythm (r = -0.14) and LVEF (r = -0.17). Diabetes was positively correlated with PR and QTc intervals (r = 0.14 and r = 0.10, respectively), and RBBB with LFAB (r = 0.10), and inversely correlated with LVEF (r = -0.10). CONCLUSIONS: We found a remarkable presence of cardiovascular risk factors, ECG, and structural alterations in hospitalized nonagenarians, which presents more commonly in males.

Distribution patterns of 18F-fluorodeoxyglucose in large vessels of Takayasu's and giant cell arteritis using positron emission tomography.

OBJECTIVES: To compare patterns of vascular involvement using 18F-fluorodeoxyglucose-positron emission tomography computed tomography (FDG PET/CT) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK). METHODS: A total of 130 consecutive 18F-FDG PET/CT scans performed during the disease course for evaluating disease activity in 15 GCA and 13 TAK patients were retrospectively examined by two nuclear physicians blinded to clinical data. Standardised uptake values (SUVmax) in 14 vascular districts including all the aortic segments and the main tributaries were measured. The average SUVmax value for each vascular district was also calculated. Principal component analysis (PCA) and agglomerative hierarchical cluster analysis (CA) were used to explore distribution patterns of vascular FDG uptake. RESULTS: The aortic segments showed the highest SUV max values among the different districts in both GCA and TAK. SUV max values measured in the different districts were significantly higher in GCA compared to TAK, except for the axillary arteries. Regarding thoracic and abdominal aorta, ascending aorta and aortic arch had the highest correlation in both vasculitis (p<0.0001). CA confirmed that carotid, axillary, subclavian, iliac and femoral arteries clustered with their contralateral counterpart in both vasculitis. The 3 components of thoracic aorta clustered with abdominal aorta in TAK, while aortic arch clustered only with ascending aorta, and descending and abdominal aorta grouped together with iliac and femoral arteries in GCA. PCA analysis identified 3 different components for TAK and GCA explaining 72% and 71% of the total variance respectively in these two vasculitis. Confirming CA, a component including the entire aortic district was identified in TAK, but not in GCA. Similar results in PCA using averaged data were observed. CONCLUSIONS: Strong similarities, but also a subtle skewing in terms of distribution patterns of arterial involvement assessed by SUVmax values were observed between GCA and TAK.

Long-term remission in biopsy proven giant cell arteritis: A retrospective cohort study.

OBJECTIVE: To evaluate the frequency of long-term remission after glucocorticoids (GCs) suspension in an Italian cohort of patients with biopsy-proven GCA and to identify factors that may predict long-term remission. METHODS: We evaluated 131 patients with biopsy-proven transmural GCA diagnosed and followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 18 months of follow-up. Long-term remission was defined as complete clinical remission without elevation of inflammatory markers for at least one year after the GC withdrawal. RESULTS: 73 patients (56%) experienced long-term remission. Disease flares were less frequently observed in patients with long-term remission compared to those without (p = 0.002). The cumulative doses of prednisone at 1 year and for the entire followup duration were significantly lower (p < 0.0001 for both parameters) in patients with long-term remission; similarly, the duration of prednisone treatment was also significantly lower (p < 0.0001). The presence of PMR at diagnosis (HR 0.46) was significantly negatively associated with long-term remission (p = 0.008), while hemoglobin levels (HR 1.48) were significantly positively associated (p < 0.0001). Patients with long-term remission were able to reach 10 mg/day and 5 mg/day of prednisone sooner than the patients without (p = 0.02 and p < 0.0001, respectively). CONCLUSION: In our cohort of GCA patients around half of the patients were able to attain long-term remission. Recognition of findings which predict disease course may aid decisions regarding therapy.

Objective Quantification of Anterior Chamber Inflammation: Measuring Cells and Flare by Anterior Segment Optical Coherence Tomography.

PURPOSE: To assess the ability of swept-source (SS) optical coherence tomography (OCT) of the anterior segment (AS) to measure anterior chamber (AC) inflammation (both flare and cells) objectively. To compare OCT-derived inflammatory indices with standard techniques. DESIGN: Prospective evaluation of a diagnostic test. PARTICIPANTS: Patients diagnosed with anterior uveitis (active or inactive) and controls. METHODS: Participants underwent an AC inflammation evaluation including: clinical cell and flare grading and laser flare photometry (LFP). Uveitis patients were divided into active or inactive uveitis status according to clinical grading. Anterior segment SS-OCT scans were obtained for each participant. Tomographic images were analyzed to count the AC cells, and to calculate to absolute measurements of aqueous signal intensity. The absolute values were compared with the signal measured by the scan outside the eye, generating an optical density ratio (aqueous-to-air relative intensity [ARI] index). Correlations between OCT-derived AC inflammatory indexes and LFP, clinical grading, participant category (active or inactive uveitis, control), age, gender, and central corneal thickness (CCT) were assessed. MAIN OUTCOME MEASURES: Correlation between OCT-derived AC inflammatory indexes (ARI index and AC cells on OCT) and standard clinical techniques (LFP, clinical cell grading). RESULTS: Two hundred thirty-seven eyes (70 active uveitis, 97 inactive uveitis, and 70 controls) were included. Anterior chamber cells count on OCT did not differ between inactive uveitis and controls, but was significantly higher in active uveitis compared to the other categories (both P < 0.0001). All groups had different LFP (all P < 0.0001). Active uveitis had significantly higher ARI index compared with inactive uveitis and controls (both P < 0.0001). Interobserver agreement (intraclass correlation coefficient) for ARI index was 0.78. The ARI index correlated positively with age (P = 0.043) and negatively with CCT (P = 0.006). The ARI index correlated with LFP in the active uveitis group (P < 0.0001), but not in the others. Anterior chamber cells on OCT increased among all cell clinical grades (P < 0.0001). The ARI index increased among all flare clinical grades (P < 0.005). CONCLUSIONS: Anterior segment SS-OCT could be used for a comprehensive assessment of AC inflammation, providing objective measurements of inflammatory cells and aqueous flare.

Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes.

BACKGROUND: Fewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cell-derived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality. Short-term/acute treatment with DPP-4 inhibitors improve EPC bioavailability; however, long-term effects of DPP-4i on EPCs bioavailability/plasma (C-term) SDF-1α are unknown. METHODS: Randomized (2:1) open-label trial to compare the effects of vildagliptin (V) (100 mg/day) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC levels at 4 and 12 months of treatment in 64 patients with type 2 diabetes in metformin failure. At baseline, and after 4 and 12 months, main clinical/biohumoral parameters, inflammatory biomarkers, concomitant therapies, EPC number (CD34+/CD133+/KDR+/106 cytometric events) and plasma (C-term) SDF-1α (R&D system) were assessed. RESULTS: Baseline characteristics were comparable in the two groups. V and G similarly and significantly (p < 0.0001) improved glucose control. At 12 months, V significantly increased EPC number (p < 0.05) and significantly reduced (C-term) SDF-1α plasma levels (p < 0.01) compared to G, with no differences in inflammatory biomarkers. CONCLUSIONS: V exerts a long-term favorable effect on EPC and (C-term) SDF-1α levels at glucose equipoise, thereby implying a putative beneficial effect on vascular integrity. Trial registration Clinical Trials number: NCT01822548; name: Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes. Registered 28 March, 2013.

Effects of a New Nutraceutical Formulation (Berberine, Red Yeast Rice and Chitosan) on Non-HDL Cholesterol Levels in Individuals with Dyslipidemia: Results from a Randomized, Double Blind, Placebo-Controlled Study.

Increased non high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol levels are independent risk factors for cardiovascular (CV) mortality with no documented threshold. A new combination of nutraceuticals (berberine 200 mg, monacolin K 3 mg, chitosan 10 mg and coenzyme Q 10 mg) with additive lipid-lowering properties has become available. The aim of the study is to test the efficacy of the nutraceutical formulation (one daily) in lowering non-HDL cholesterol vs. placebo at 12 weeks in individuals with non-HDL-cholesterol levels ≥160 mg/dL. 39 subjects (age 52 ± 11 years; 54% females; body mass index 27 ± 4 kg/m²) were randomized (3:1) in a double blind phase II placebo-controlled study. At baseline, 4 and 12 weeks main clinical/biohumoral parameters, pro-inflammatory cytokines, (gut)-hormones, proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and endothelial progenitor cell (EPC) number were assessed. Baseline characteristics were comparable in the two groups. The intervention significantly decreased non-HDL cholesterol (-30 ± 20 mg/dL; p = 0.012), LDL cholesterol (-31 ± 18 mg/dL, p = 0.011) and apolipoprotein (Apo) B (-14 ± 12 mg/dL, p = 0.030) levels compared to the placebo. Pro-inflammatory, hormonal, PCSK9 and EPC levels remained stable throughout the study in both groups. The intervention was well tolerated. Three adverse events occurred: Epstein Barr virus infection, duodenitis and asymptomatic but significant increase in creatine phosphokinase (following intense physical exercise) which required hospitalization. The tested nutraceutical formulation may represent a possible therapeutic strategy in dyslipidemic individuals in primary prevention.

Correlations between histopathological findings and clinical manifestations in biopsy-proven giant cell arteritis.

OBJECTIVE: To correlate histopathological features of positive temporal artery biopsy (TAB) and clinical manifestations of the disease in a large single-center population-based cohort of patients with biopsy-proven giant cell arteritis (GCA). METHODS: A pathologist with expertise in vasculitis and blinded to clinical data and final diagnosis reviewed all TABs performed for suspected GCA at our hospital between January 1986 and December 2013. Histopathologic features evaluated were: the severity of inflammation and intimal hyperplasia, both graded on a semiquantitative scale (mild = 1, moderate = 2, severe = 3), the presence of intraluminal acute thrombosis, calcifications, giant cells, fibrinoid necrosis and laminar necrosis. RESULTS: 274 patients had a final diagnosis of biopsy-proven GCA and were included in the study. Cranial ischemic events (CIEs) were observed in 161 (58.8%), visual manifestations in 79 (28.8%) and permanent (partial or complete) visual loss in 51 (18.6%) patients. Predictors for the development of CIEs were older age (OR = 1.057, 95% CI 1.019-1.097, p = 0.003), lower ESR values (OR = 0.990, 95% CI 0.981-0.999, p = 0.026) as well as the presence of giant cells (OR = 1.848, 95% CI 1.045-3.269, p = 0.035) and laminar necrosis at TAB (OR = 2.334, 95% CI 1.187-4.587, p = 0.014). Predictors for the development of permanent visual loss were lower CRP values (OR = 0.906, 95% CI 0.827-0.992, p = 0.033) and the presence of calcifications at TAB (OR = 3.672, 95% CI 1.479-9.121, p = 0.005). Fibrinoid necrosis was not observed in any of the TABs evaluated. CONCLUSION: Pathological features of TAB may predict some manifestations of GCA. These findings may have implications for patients' management.

CEA serum level as early predictive marker of outcome during EGFR-TKI therapy in advanced NSCLC patients.

Considering the role of carcinoembryonic antigen (CEA) serum levels as potential useful predictive marker during chemotherapy treatment, we studied its applicability in advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). Our retrospective cohort consists of 79 patients (33 EGFR mutated and 46 EGFR wild type or unknown) affected by advanced NSCLC, for whom CEA serum values at the beginning of TKI therapy and after the first month of treatment were available, regardless of treatment line. Baseline CEA value, percentage of CEA reduction after 1 month, and percentage of patients with ≥20 % CEA decrease after 1 month (CEA response) were correlated with disease control rate (DCR), progression-free (PFS), and overall (OS) survival, according to EGFR mutational status. Median baseline CEA levels were significantly higher in EGFR mutated (40.9 ng/ml; interquartile range (IQR) 8.9-197.6) than in wild-type cases (6.2 ng/ml; IQR 2.8-12.8; p = 0.003). Both percentage reduction in CEA levels (-10.7 vs. +13.4 %) and percentage of cases with CEA response (42 vs. 20 %) were significantly higher in mutated vs. wild-type/unknown patients (p = 0.007 and p = 0.027, respectively). In wild-type/unknown patients, CEA response was significantly correlated with DCR (p = 0.001) and resulted as a significant predictor of PFS both in univariate (p = 0.002) and in multivariate analyses (hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.11-0.66; p = 0.004); only a trend was found for OS prediction (p = 0.082). In EGFR-mutated group, CEA reduction did not show any correlation either with PFS or OS. CEA response after 1 month of EGFR-TKI therapy could be a useful marker, worthy to further studies, as early predictor of treatment outcome in EGFR wild-type/unknown unselected NSCLC cases for which no molecular predictor is yet available.

MASLD, hepatic steatosis and fibrosis are associated with the prevalence of chronic kidney disease and retinopathy in adults with type 1 diabetes mellitus.

AIM: We examined whether metabolic dysfunction-associated steatotic liver disease (MASLD) with or without significant fibrosis (assessed by validated non-invasive biomarkers) was associated with an increased risk of prevalent chronic kidney disease (CKD) or diabetic retinopathy in people with type 1 diabetes mellitus (T1DM). METHODS: We performed a retrospective multicenter cross-sectional study involving 1,409 adult outpatients with T1DM, in whom hepatic steatosis index (HSI) and fibrosis (FIB)-4 index were calculated for non-invasively detecting hepatic steatosis (defined by HSI > 36), with or without coexisting significant fibrosis (FIB-4 index ≥ 1.3 or < 1.3). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin/creatinine ratio ≥ 3.0 mg/mmol. The presence of diabetic retinopathy was also recorded in all participants. RESULTS: Patients with MASLD and significant fibrosis (n = 93) had a remarkably higher prevalence of CKD and diabetic retinopathy than their counterparts with MASLD without fibrosis (n = 578) and those without steatosis (n = 738). After adjustment for sex, diabetes duration, hemoglobin A1c, hypertension, and use of antihypertensive or lipid-lowering medications, patients with SLD and significant fibrosis had a higher risk of prevalent CKD (adjusted-odds ratio 1.76, 95 % confidence interval 1.05-2.96) than those without steatosis. Patients with MASLD without fibrosis had a higher risk of prevalent retinopathy (adjusted-odds ratio 1.49, 95 % CI 1.13-1.46) than those without steatosis. CONCLUSION: This is the largest cross-sectional study showing that MASLD with and without coexisting significant fibrosis was associated, independently of potential confounders, with an increased risk of prevalent CKD and retinopathy in adults with T1DM.

Effectiveness of the flash glucose monitoring system in preventing severe hypoglycemic episodes and in improving glucose metrics and quality of life in subjects with type 1 diabetes at high risk of acute diabetes complications.

AIMS: To assess the effectiveness of the intermittent-scanned continuous glucose monitoring (isCGM) system in preventing severe hypoglycemic episodes and in improving glucose parameters and quality of life. METHODS: Four hundred T1D individuals were enrolled in a prospective real-word study with an intermittently scanned continuous glucose monitoring device during the 12-months follow-up. The primary endpoint was the incidence of severe hypoglycemic events. RESULTS: 82% of subjects were naïve to the use of the device (group A) and 18% were already wearing the system (group B). The cumulative incidence of severe hypoglycemia (SH) at 12 months was 12.06 per 100 person-year (95% CI: 8.35-16.85) in group A and 10.14 (95% CI: 4.08-20.90) in group B without inter-group differences. In group A there was a significant decrease in SH at 12 months compared to 3 months period (p = 0.005). Time in glucose range significantly increased in both groups accompanied with a significant decrease in glucose variability. HbA1c showed a progressive significant time-dependent decrease in group A. The use of the device significantly improved the perceived quality of life. CONCLUSION: This study confirmed the effectiveness of the isCGM in reducing hypoglycemic risk without glucose deterioration, with potential benefits on adverse outcomes in T1D individuals. TRIAL REGISTRATION: ClinicalTrials.gov registration no. NCT04060732.

Chronic consumption of a bergamot-based beverage does not affect glucose, lipid and inflammatory biomarkers of cardiometabolic risk in healthy subjects: a randomised controlled intervention study.

Background: Pure bergamot juice exerts lipid lowering effects in dyslipidemic subjects. It is unknown whether bergamot-based beverages exert similar effects in healthy subjects. Aim: To assess the effects, if any, of a bergamot-based beverage (BBB, bergamot juice ≤25%) on lipid, metabolic and inflammatory biomarkers. Methods: Forty-five healthy subjects were randomised 1 : 1 to BBB intake (400 mL day-1) (55.5%) or control (44.5%) for 12 weeks. Anthropometric (waist circumference, body mass index (BMI)) and clinical (blood pressure) parameters, blood samples (glucose, glycated haemoglobin, insulinemia, lipid profile, liver and renal function, inflammatory biomarkers) and 24-h urine for the analysis of (poly)phenol metabolites were collected at the baseline and at 12 weeks. Intakes of energy, nutrients and food groups were assessed by a 7-day dietary record. Results: Both groups exhibited a time-related significant decrease in total cholesterol (p = 0.02), fasting plasma glucose (p = 0.016), insulin (p = 0.034), BMI (p < 0.001) and waist circumference (p = 0.04), but with no significant between-arm difference. The urinary profile of metabolites from the BBB-derived (poly)phenols well discriminated the two study groups, documenting good compliance in the intervention arm. Notably, urinary bergamot 3-hydroxy-3-methylglutaryl (HMG) -containing flavanones or derived HMG-containing metabolites were not detectable. BBB was well tolerated and no adverse events were recorded. Conclusion: This first randomized controlled trial of BBB consumption in healthy subjects showed no effects of BBB on the cardiometabolic risk profile. BBB consumption is a safe nutritional adjunct in the context of a well balanced diet.

Searching for viral antibodies and genome in intraocular fluids of patients with Fuchs uveitis and non-infectious uveitis.

BACKGROUND: To characterise the polyspecific intraocular antibody synthesis in aqueous humor of patients with Fuchs uveitis and other types of non-infectious uveitis. METHODS: Aqueous and serum samples collected from 24 patients with Fuchs uveitis, 21 patients with non-infectious uveitis, and 27 healthy subjects undergoing elective cataract surgery (control group) were analysed. In addition, vitreous samples, collected from seven uveitis patients (five Fuchs and two panuveitis) during retinal surgery, were examined. Specific immunoglobulin G antibodies against cytomegalovirus (CMV), rubella virus, herpes simplex virus (HSV), and varicella zoster virus (VZV) were investigated, and Goldmann-Witmer coefficients (GWCs) were calculated. Real-time PCR was performed to detect viral genome for HSV, VZV, and CMV, while nested PCR was conducted to detect rubella RNA. RESULTS: None of the control samples tested positive for any of the viral antibodies investigated. Intraocular antibody production was found in eight samples of patients affected by Fuchs uveitis (6/8 positive for rubella virus and 2/8 positive for herpes virus). Among patients with non-infectious uveitis, three tested positive for intraocular antibody production (one RV, one HSV and one for VZV). PCR was positive for RV in two patients with Fuchs uveitis, in three patients with non-infectious uveitis (one for RV and two for HSV), and in three control subjects (one for CMV and one for HSV). CONCLUSIONS: Our series confirmed the presence of specific viral antibodies, especially against rubella virus, in the subgroup of patients affected by Fuchs uveitis, suggesting that this virus may be responsible for this chronic inflammatory condition. Rubella virus is probably the main causative agent of Fuchs uveitis, but other viruses may also be involved in the pathogenesis of this disease.

Sex Differences in Cardiovascular Disease and Cardiovascular Risk Estimation in Patients With Type 1 Diabetes.

CONTEXT: Patients with type 1 diabetes (T1D) have higher cardiovascular disease (CVD) risk than the general population. OBJECTIVE: This observational study aims to evaluate sex-related differences in CVD prevalence and CVD risk estimates in a large cohort of T1D adults. METHODS: We conducted a multicenter, cross-sectional study involving 2041 patients with T1D (mean age 46 years; 44.9% women). In patients without pre-existing CVD (primary prevention), we used the Steno type 1 risk engine to estimate the 10-year risk of developing CVD events. RESULTS: CVD prevalence (n = 116) was higher in men than in women aged ≥55 years (19.2 vs 12.8%, P = .036), but comparable between the 2 sexes in those aged <55 years (P = .91). In patients without pre-existing CVD (n = 1925), mean 10-year estimated CVD risk was 15.4 ± 0.4% without any significant sex difference. However, stratifying this patient group by age, the 10-year estimated CVD risk was significantly higher in men than in women until age 55 years (P < .001), but this risk equalized after this age. Carotid artery plaque burden was significantly associated with age ≥55 years and with a medium and high 10-year estimated CVD risk, without any significant sex difference. Diabetic retinopathy and sensory-motor neuropathy were also associated with higher 10-year CVD risk and female sex. CONCLUSION: Both men and women with T1D are at high CVD risk. The 10-year estimated CVD risk was higher in men aged <55 years than in women of similar age, but these sex differences disappeared at age ≥55 years, suggesting that female sex was no longer protective.

Association between different modalities of insulin administration and metabolic dysfunction-associated fatty liver disease in adults with type 1 diabetes mellitus.

AIM: We examined whether different insulin administration modalities, i.e., multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII by insulin pumps), are differently associated with the risk of having metabolic dysfunction-associated fatty liver disease (MAFLD), with or without coexisting significant liver fibrosis (assessed by validated non-invasive biomarkers), in adults with type 1 diabetes mellitus (T1DM). METHODS: We conducted a retrospective, multicenter, cross-sectional study involving 1,417 adult individuals with established T1DM treated with MDI or CSII. We calculated hepatic steatosis index (HSI) and fibrosis (FIB)-4 index for non-invasively detecting MAFLD (defined by HSI >36), with or without coexisting significant fibrosis (defined by FIB-4 index ≥ 1.3 or <1.3, respectively). RESULTS: Compared to the MDI group (n = 1,161), insulin-pump users (n = 256; 18.1%) were more likely to be younger (mean age: 40 vs. 48 years, P < 0.001), had better glycemic control (mean hemoglobin A1c: 7.7%  vs. 7.9%, P = 0.025) and a markedly lower prevalence of MAFLD with coexisting significant fibrosis (2.7%  vs. 8.1%, P = 0.010), but a comparable prevalence of MAFLD without fibrosis. In multinomial logistic regression analysis, CSII therapy was associated with a ∼70%-lower risk of MAFLD with significant fibrosis (unadjusted odds ratio 0.32, 95% confidence interval 0.14-0.70; P = 0.004), but this association was no longer significant after adjustment for age, hemoglobin A1c and other potential confounders. CONCLUSION: The lower prevalence of MAFLD with coexisting significant fibrosis we observed in adults with T1DM using CSII therapy, compared to those using MDI therapy, is primarily mediated by inter-group differences in age.