Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Impact of Acute Kidney Injury on the COVID-19 In-Hospital Mortality in Octogenarian Patients: Insights from the COVOCA Study.

BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

An unusual cause of iron deficiency anemia in a patient with severe aortic stenosis and heart failure.

There has been an exponential increase in incidence of severe aortic stenosis partially due to the lengthening of average lifespan. Among the most disabling symptoms of aortic stenosis are chest pain, fatigue, and dyspnea up to heart failure and pulmonary edema. In some cases, to worsen this symptomatology, there are coagulation disorders linked to an alteration of functional von Willebrand factor, responsible for progressive anemia. In elderly patients with severe aortic stenosis, the simultaneous presence of an angiodysplasia of the colon can favor blood dripping, which may cause iron deficiency anemia. The coexistence of colonic angiodysplasia and acquired von Willebrand disease in patients with aortic stenosis was identified as Heyde's syndrome. In the long term, Heyde's syndrome can contribute to worsen the clinical manifestations of severe aortic stenosis leading to heart failure. Here, we describe the case of a patient suffering of severe calcific aortic stenosis who developed Heyde's syndrome achieving a condition of heart failure with mildly reduced ejection fraction. Learning objectives: Severe aortic stenosis can alter the conformation of the circulating von Willebrand glycoprotein, causing an alteration of the hemostatic balance. When angiodysplasia of the colon coexists with aortic stenosis, a gastrointestinal blood drip can occur inducing an iron deficiency anemia that worsens the symptoms of aortic valvulopathy. This condition often remains undiagnosed. We discuss the pathophysiologic and hemodynamic mechanisms responsible for acquired von Willebrand syndrome in patients with severe aortic stenosis focusing on the clinical elements useful to raise the diagnostic suspicion and analyzing different alternative tools to recognize it promptly.

Association between Renal Function at Admission and COVID-19 in-Hospital Mortality in Southern Italy: Findings from the Prospective Multicenter Italian COVOCA Study.

Background. Evidence has shown a close association between COVID-19 infection and renal complications in both individuals with previously normal renal function and those with chronic kidney disease (CKD). Methods. The aim of this study is to evaluate the in-hospital mortality of SARS-CoV-2 patients according to their clinical history of CKD or estimated glomerular filtration rate (eGFR). This is a prospective multicenter observational cohort study which involved adult patients (≥18 years old) who tested positive with SARS-CoV-2 infection and completed their hospitalization in the period between November 2020 and June 2021. Results. 1246 patients were included in the study, with a mean age of 64 years (SD 14.6) and a median duration of hospitalization of 15 days (IQR 9−22 days). Cox's multivariable regression model revealed that mortality risk was strongly associated with the stage of renal impairment and the Kaplan−Meier survival analysis showed a progressive and statistically significant difference (p < 0.0001) in mortality according to the stage of CKD. Conclusion. This study further validates the association between CKD stage at admission and mortality in patients hospitalized for COVID-19. The risk stratification based on eGFR allows clinicians to identify the subjects with the highest risk of intra-hospital mortality despite the duration of hospitalization.

Lung ultrasound for diagnosis of pneumonia in emergency department.

Lung ultrasound (LUS) in the emergency department (ED) has shown a significant role in the diagnostic workup of pulmonary edema, pneumothorax and pleural effusions. The aim of this study is to assess the reliability of LUS for the diagnosis of acute pneumonia compared to chest X-ray (CXR) study. The study was conducted from September 2013 to March 2015. 107 patients were admitted to the ED with a clinical appearance of pneumonia. All the patients underwent a CXR study, read by a radiologist, and an LUS, performed by a trained ED physician on duty. Among the 105 patients, 68 were given a final diagnosis of pneumonia. We found a sensitivity of 0.985 and a specificity of 0.649 for LUS, and a sensitivity of 0.735 and specificity of 0.595 for CXR. The positive predictive value for LUS was 0.838 against 0.7 for CXR. The negative predictive value of LUS was 0.960 versus 0.550 for CXR. This study has shown sensitivity, positive predictive value and negative predictive value of LUS compared to the CXR study for the diagnosis of acute pneumonia. These results suggest the use of bedside thoracic US first-line diagnostic tool in patients with suspected pneumonia.

High cardiovascular risk in patients with Type 2 diabetic nephropathy: the predictive role of albuminuria and glomerular filtration rate. The NID-2 Prospective Cohort Study.

BACKGROUND: In Type 2 diabetic patients, clinical diagnosis of diabetic nephropathy (DN) is generally based on the concomitant presence of abnormal albuminuria and severe retinopathy. In this high-risk population, cardiovascular (CV) outcome has never been evaluated. METHODS: A cohort of 742 Type 2 diabetic patients with DN from 17 national centres was selected by the presence of persistent albuminuria ≥ 30 mg/day and severe diabetic retinopathy and was followed prospectively. Time to CV event (CV death, non-fatal myocardial infarction, non-fatal stroke, revascularization, major amputation) was the primary composite end point and it was analysed by multivariable Cox's proportional hazards model. The interaction between albuminuria and glomerular filtration rate (GFR) was specifically investigated. RESULTS: Median follow-up was 4.6 years. Overall 242 events (26% of which fatal) were observed in 202 patients. The proportion of CV events increased from 19 to 40% as GFR declined from the highest (≥ 90 mL/min/1.73 m(2)) to the lowest (<45 mL/min/1.73 m(2)) category and was equal to 25 and 33% in microalbuminuria and macroalbuminuria, respectively. In multivariable analysis, the interaction between albuminuria and GFR was statistically significant (P = 0.012). Albuminuria, indeed, had a remarkable prognostic effect in subjects with high GFR that virtually disappeared as GFR became <30 mL/min/1.73 m(2). Age, smoking habit, previous occurrence of myocardial infarction or stroke and proliferative retinopathy were all found to have a statistically significant prognostic effect on CV outcome. CONCLUSIONS: A clinically based diagnosis of DN in Type 2 diabetes allows the identification of subjects with high CV risk. Albuminuria has a relevant prognostic effect on CV morbidity and mortality; its effect is especially pronounced when GFR is normal or near normal.

Coronary artery disease is detectable by multi-slice computed tomography in most asymptomatic type 2 diabetic patients at high cardiovascular risk.

OBJECTIVE: Non-invasive testing often does not identify coronary artery disease (CAD) in diabetic subjects. This study was designed in order to examine the prevalence of CAD in a cohort of asymptomatic type 2 diabetic patients at high cardiovascular risk and negative nuclear imaging, using multi-slice computed tomography (MSCT) angiography. METHODS: In total, 770 type 2 diabetic patients were screened from January 2008 through July 2010. Of these, 132 Caucasians with diabetic nephropathy and asymptomatic for angina were eligible for a cross-sectional study. Patients underwent MSCT after ischaemia was excluded by myocardial Single Photon Emission Computed Tomography (SPECT) at rest and after dynamic exercise. When obstructive plaques were found (≥ 50% lumen narrowing), patients were sent to conventional coronary angiography (CCA). RESULTS: Six subjects were not included in the analysis because of motion artefacts. MSCT was positive for CAD in 114 patients (90%). Within patients with positive MSCT, 60 (48% of all) showed one or more obstructive plaques. CCA confirmed significant stenosis (≥ 50%) in 48 of these 60 patients (80%). Some 21 (35%) showed stenosis ≥ 75% and were submitted to the revascularisation procedure. CONCLUSION: MSCT seems to better identify CAD than myocardial SPECT in asymptomatic patients with type 2 diabetes and diabetic nephropathy.

Kidney in diabetes: from organ damage target to therapeutic target.

Despite the growing of pharmacological options for the treatment of diabetes, epidemiological studies suggest that a substantial proportion of patients does not achieve glycemic goals and so suffers from the risk of chronic complications. This review explores the inhibition of renal glucose reabsorption as a novel approach to treat hyperglycemia. Sodium-glucose cotransporter 2 (SGLT2), a low-affinity high-capacity transporter located in the brush-border membrane of the early segment (S1) of the proximal renal tubule, accounts for about 90% of the reabsorption of glucose from tubular fluid. Competitive inhibitors of SGLT2 that are responsible for renal excretion of glucose provide a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. They act independently of insulin secretion, thereby minimizing the risk of hypoglycemia and weight gain, to control energy balance in a negative direction, a distinctive advantage of this class of drugs over existing oral hypoglycemic agents. Although this group of medications is still under investigation, it appears to be safe and generally well tolerated and it would be expected to improve the treatment of type 2 diabetes as monotherapy or in combination with other oral or parenteral agents. Dapagliflozin is the first agent within this class, which induces clinically meaningful reductions in FPG, PPG, HbA1c, and body weight in type 2 diabetes.

Cardiovascular risk factors and disease management in type 2 diabetic patients with diabetic nephropathy.

OBJECTIVE: The purpose of this study was to assess the prevalence of cardiorenal risk factors, their management in a routine clinical setting, and the actual achievement of international guideline targets in a large cohort of type 2 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: A multicentric cross-sectional study was performed in the Campania region in Italy to evaluate cardiorenal risk factors and their management in light of international guidelines. Overall, 28,550 diabetic patients were screened in the 21 participating centers; 847 (348 male and 449 female) patients with type 2 diabetes and a clinical diagnosis of diabetic nephropathy were recruited. RESULTS: Of these subjects, 749 had microalbuminuria and 98 had macroalbuminuria. Targets for blood pressure, HbA(1c), LDL cholesterol, HDL cholesterol, and triglycerides were reached in, respectively, 17.5, 32.3, 30.7, 47, and 55.2% of the patients. Chronic renal failure (glomerular filtration rate <60 ml/min) was revealed in 41% and anemia in 23.8% of the patients. CONCLUSIONS: This is the first study to investigate a large cohort of type 2 diabetic patients with early and moderate diabetic nephropathy strictu sensu. Notably, impaired renal function can be often diagnosed in these patients even in the presence of microalbuminuria. Thus, clinical diagnosis of diabetic nephopathy allows us to identify a group of patients at very high cardiorenal risk, for whom care is really difficult. We suggest that a correct diagnosis of diabetic nephropathy should always be made and that sodium intake and anemia should be routinely evaluated in these patients.

Increased vascular endothelial growth factor expression but impaired vascular endothelial growth factor receptor signaling in the myocardium of type 2 diabetic patients with chronic coronary heart disease.

OBJECTIVES: The aim of the present study was to evaluate the expression and the activity of vascular endothelial growth factor (VEGF) in the hearts of diabetic patients with chronic coronary heart disease (CHD). BACKGROUND: Diabetes is characterized by a decreased collateral vessel formation in response to coronary ischemic events, although the role of VEGF in human diabetic macroangiopathy has not been fully investigated. METHODS: Biopsies of left ventricular (LV) myocardium were obtained from 10 patients with type 2 diabetes and 10 non-diabetic patients with chronic CHD, all undergoing surgical coronary revascularization. Right ventricle myocardial samples taken from normal hearts were used as control specimens. Vascular endothelial growth factor and VEGF-receptors (flt-1 and flk-1) were evaluated by Western blot, reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR. Akt and endothelial nitric oxide synthase (eNOS) protein expression and their phosphorylated forms were also evaluated by Western blot. RESULTS: Vascular endothelial growth factor, flt-1, and flk-1 messenger ribonucleic acid (mRNA) and protein expressions were increased in non-diabetic patients with CHD compared with control subjects. Remarkably, in diabetic patients, VEGF mRNA and protein levels were significantly higher, whereas flt-1, flk-1 mRNA, and protein were lower when compared with non-diabetic patients. Interestingly, phospho-flk-1 was reduced in diabetic patients compared with non-diabetic patients. As a consequence, Akt phosphorylation, eNOS protein and its phosphorylated form were significantly higher in the samples from non-diabetic patients compared with diabetic patients. CONCLUSIONS: Chronic CHD in diabetic patients is characterized by an increased VEGF myocardial expression and a decreased expression of its receptors along with a down-regulation of its signal transduction. The latter could be partially responsible for the reduced neoangiogenesis in diabetic patients with ischemic cardiomyopathy.

Effects of insulin on left ventricular function during dynamic exercise in overweight and obese subjects.

AIMS: We designed this study in order to determine the effect of insulin on cardiac function in overweight and obese subjects during exercise. METHODS AND RESULTS: The cardiac function of 62 normal glucose tolerant subjects, aged 30-40 and divided into normal weight (group 1, n=22, BMI 20-24.9 kg/m(2)), overweight (group 2, n=20, BMI 25-29.9 kg/m(2)), and obesity (group 3, n=20, BMI 30-35 kg/m(2)) was evaluated at rest and during dynamic exercise through angiocardioscintigraphy, when on hyperinsulinaemic euglycaemic clamp (test A) and when on normal saline infusion (test B). Left ventricular function at rest was statistically greater (P<0.05) in both tests in overweight and obese subjects compared with normal weight controls, with no statistical difference (P=0.057) within groups between insulin and normal saline infusion. During exercise, cardiac function improved in all the subjects in both tests. The increase was lower in overweight and obese patients, even if statistically significant only in obese vs. control subjects in both tests (P<0.05). Insulin sensitivity showed a significant correlation (P< or =0.001) with left ventricular ejection fraction (LVEF) at rest and with change in LVEF during clamp. CONCLUSION: Our findings suggest a metabolic pathogenesis for the impaired LV function in obesity.

Glucose metabolism and coronary heart disease in patients with normal glucose tolerance.

CONTEXT: Several investigations as well as prospective studies have shown a significant correlation between glucose metabolism and atherosclerosis in patients without diabetes, but differences in parameters of glucose metabolism among the various degrees of coronary disease in such patients have not been specifically evaluated. OBJECTIVE: To investigate glucose metabolism in patients with normal glucose tolerance (NGT) and coronary heart disease (CHD). DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 234 men (mean [SD] age, 56.2 [6.1] years) with NGT and suspected CHD who were admitted from January 1 through June 30, 2001, to an academic medical center in Italy for coronary angiography. MAIN OUTCOME MEASURES: Correlation of glucose metabolic factors and extent of atherosclerosis determined by coronary angiography. Factors included levels of fasting and postload glucose and insulin, glycosylated hemoglobin (HbA1c), and lipids, as well as insulin resistance measured by homeostasis model assessment (HOMA-IR). RESULTS: Patients were divided into 4 groups based on coronary angiography: no significant stenosis (n = 42), 1-vessel disease (n = 72), 2-vessel disease (n = 64), and 3-vessel disease (n = 56). Simple correlation analysis showed that the factors correlated with the extent of atherosclerosis were levels of postload glucose (r = 0.667), HbA1c (r = 0.561), postload insulin (r = 0.221), and fasting insulin (r = 0.297), as well as HOMA-IR (r = 0.278) (P<.001 for all). Multiple stepwise regression analysis suggested that the factors independently associated with the number of stenosed coronary arteries were levels of postload plasma glucose (r = 0.572), HbA1c (r = 0.413), postload insulin (r = 0.267), and fasting insulin (r = 0.174), as well as HOMA-IR (r = 0.250) (P<.001 for all). Similar results were obtained after grouping patients by Duke Myocardial Jeopardy Score. CONCLUSIONS: For patients with NGT and different extents of atherosclerotic disease, postload glycemia and HbA1c level are not equally distributed but are significantly higher in those with more severe disease. This suggests that the glycemic milieu correlates with the cardiovascular risk according to a linear model.