Adjunctive use of oral MAF is associated with no disease progression or mortality in hospitalized patients with COVID-19 pneumonia: The single-arm COral-MAF1 prospective trial.

Based on a growing body of evidence that a dysregulated innate immune response mediated by monocytes/macrophages plays a key role in the pathogenesis of COVID-19, a clinical trial was conducted to investigate the therapeutic potential and safety of oral macrophage activating factor (MAF) plus standard of care (SoC) in the treatment of hospitalized patients with COVID-19 pneumonia. Ninety-seven hospitalized patients with confirmed COVID-19 pneumonia were treated with oral MAF and a vitamin D3 supplement, in combination with SoC, in a single-arm, open label, multicentre, phase II clinical trial. The primary outcome measure was a reduction in an intensive care unit transfer rate below 13% after MAF administration. At the end of the study, an additional propensity score matching (PSM) analysis was performed to compare the MAF group with a control group treated with SoC alone. Out of 97 patients treated with MAF, none needed care in the ICU and/or intubation with mechanical ventilation or died during hospitalization. Oxygen therapy was discontinued after a median of nine days of MAF treatment. The median length of viral shedding and hospital stay was 14 days and 18 days, respectively. After PSM, statistically significant differences were found in all of the in-hospital outcomes between the two groups. No mild to serious adverse events were recorded during the study. Notwithstanding the limitations of a single-arm study, which prevented definitive conclusions, a 21-day course of MAF treatment plus SoC was found to be safe and promising in the treatment of hospitalized adult patients with COVID-19 pneumonia. Further research will be needed to confirm these preliminary findings.

Successful Treatment of Iron Deficiency Anemia with Ferric Carboxymaltose in an Elderly Patient with Multiple Comorbidities and COVID-19.

Anemia is frequently associated with older age and comorbidities. Also, anemia is a frequent finding in patients hospitalized for Coronavirus infectious disease 2019 (COVID-19), where it has been associated with poor outcomes. Management of anemia is thus crucial in this setting. We present the case of an elderly woman with chronic iron deficiency anemia and multiple comorbidities, hospitalized for COVID-19, whose iron deficiency was successfully treated with ferric carboxymaltose. Hemoglobin and iron stores were replenished, and transferrin saturation increased to average values. Ferric carboxymaltose was well tolerated, and there were no safety concerns. The patient recovered from COVID-19 was discharged 25 days after admission.

A Triad of Ketoacidosis, Hypertriglyceridemia, and Acute Pancreatitis Associated With Sugar-Sweetened Soft Drinks Abuse in a Caucasian Patient With Undiagnosed Type 2 Diabetes Mellitus.

A 24-year-old obese Caucasian male, without relevant anamnesis, who was admitted to the ER presented with abdominal pain, nausea and vomiting, hyperglycemia, and diabetic ketoacidosis (DKA). The diagnosis of acute pancreatitis (AP) was supported by increased serum levels of triglycerides and lipase associated with abdominal CT scans. The patient was treated for five days with IV regular insulin, hydration, electrolytes replacement, and statin/fibrate therapy with clinical improvement. Some 10% hemoglobin A1c value, normal C-peptide level and negative glutamic acid decarboxylase (GAD-65), and islet cell autoantibodies suggested the diagnosis of a new-onset type 2 diabetes mellitus (DM) presenting with an uncommon triad of DKA and hypertriglyceridemia (HTG)-induced AP. Anamnestic history suggested that DKA was dependent on sugar-sweetened soft drinks abuse (soft drink ketosis), a clinical association more frequent in Asian than in Western patients.

Peripheral Vascular Function in Dilated Cardiomyopathy of Different Etiology.

Vascular function in dilated cardiomyopathy of different etiology has been poorly investigated. Moreover, reference values of flow-mediated dilation (FMD) in chronic heart failure (CHF) need to be updated according to the new standardized protocols. We characterized the vascular impairment in different stages of post-ischemic dilated cardiomyopathy (PI-DC) or idiopathic dilated cardiomyopathy (I-DC). Eighty consecutive outpatients with CHF in different New York Heart Association (NYHA) classes (45 PI-DC, 35 I-DC) and 50 control subjects underwent FMD and brachial distensibility coefficient measurement. Patients with CHF showed a marked impairment in FMD compared with controls that worsened from classes NYHA I-II to III-IV, independently of etiology (P < .05). New York Heart Association I-II PI-DC patients showed a worse FMD compared with NYHA I-II I-DC patients (P < .05). Brachial distensibility coefficient values were significantly lower in patients with CHF compared with controls (P < .001) without differences between PI-DC and I-DC. In conclusion, advanced CHF is characterized by vascular impairment that is independent of etiology. In the early stages of CHF, endothelial dysfunction is more severe in patients with PI-DC compared with I-DC probably due to the high cardiovascular risk profile. In I-DC, vascular function impairment is independent of cardiovascular risk factors and could participate in the pathogenesis of I-DC.

Long-term follow-up in high risk hypertensive patients with carotid dolicoarteriopathies.

BACKGROUND: Carotid dolicoarteriopathies (CDA) are a common finding during the carotid ultrasound or angiography, but their potential role in the development of cerebrovascular diseases is still unclear. Aim of this study is to clarify the possible relationship between CDA and the occurrence of cerebral events. METHODS: We performed a retrospective analysis on 2124 hypertensive patients with high cardiovascular risk that underwent carotid ultrasound from January 2000 to December 2008. Follow-up data on cerebrovascular events (transient ischemic attack and/or stroke occurrence) at 10 years were collected. RESULTS: The global prevalence of CDA in the study population was 12.9% (274/2124), and carotid kinking was more frequent in females and in the left carotid axis. The percentage of cerebrovascular events among hypertensive patients with CDA was similar to those occurred in the group of patients without CDA (10.94% vs. 10.97%, P=NS), with no differences in the number of strokes (8.39% vs. 8.38% P=NS) and TIA (2.55% vs. 2.59% P=NS). CONCLUSIONS: CDA are not associated with a major occurrence of cerebrovascular events in a high-risk population of hypertensives.

Mesoglycan improves vascular reactivity and insulin sensitivity in patients with metabolic syndrome.

OBJECTIVES: The aim of this study was to evaluate the acute and chronic effects of mesoglycan on the endothelial function and arterial elastic properties in patients with metabolic syndrome (MetS). BACKGROUND: MetS is defined by a clustering of vascular risk factors that demand both pharmacologic and non-pharmacologic interventions, including body weight reductions and physical activity. The correction of endothelial dysfunction and arterial wall distensibility associated with MetS have lately received increasing interest. METHODS: Thirty consecutive ambulatory patients affected by MetS were 2:1 randomized in a double-blind fashion to receive mesoglycan or placebo, respectively. In the first phase of the study, we evaluated the acute effects of a single i.m. administration of mesoglycan (60 mg) or placebo on vascular reactivity, as assessed by brachial flow-mediated dilation (FMD). Then, patients were chronically treated with mesoglycan per os (50 mg twice a day) or placebo for 90 days. At the end of this period, vascular reactivity and the arterial wall elastic properties were evaluated. RESULTS: In the mesoglycan group, FMD increased above baseline after acute administration, with a maximum increment of 52% after 2 h. FMD was also significantly greater than baseline after 90 days of chronic treatment. In the placebo group, FMD was unaffected by both acute and chronic mesoglycan administration. Moreover, after 90 days of mesoglycan treatment, a marked improvement in arterial distensibility and compliance was detected and arterial stiffness reduced significantly. CONCLUSIONS: This small, preliminary study shows that mesoglycan exerts relevant effects on vascular physiology, both in an acute setting as well as after prolonged, three-month treatment, in patients affected by metabolic syndrome.

Management of chronic heart failure: Role of home echocardiography in monitoring care programs.

AIM: To identify a possible role of home echocardiography for monitoring chronic heart failure (CHF) patients. METHODS: We prospectively investigated 118 patients hospitalized during the last year for CHF who could not easily reach the pertaining District Healthcare Center. The patients were followed up with 2 home management programs: one including clinical and electrocardiographic evaluations and also periodic home echocardiographic examinations (group A), the other including clinical and electrocardiographic evaluations only (group B). RESULTS: At the end of the 18-mo follow-up no signi-ficant differences were observed between the 2 groups as regards the primary endpoint: rehospitalization occurred in 4 patients of the group A and in 6 patients of the group B; major cardiovascular events occurred in 2 and in 3 patients, respectively. No significant differences were observed with respect to the secondary endpoints: one vascular event appeared in both the groups, 3 cardiovascular deaths occurred in group A and 2 in group B. No significant differences were observed between the 2 groups as regards the composite endpoint of death plus hospitalization. CONCLUSION: Home echocardiography for monitoring of CHF patients does not improve the cardiovascular endpoints. In our CHF patients, a low incidence of vascular events was observed.

Impaired diastolic function in naïve untreated human immunodeficiency virus infected patients.

AIM: To evaluate cardiac function and structure in untreated human immunodeficiency virus (HIV) patients without clinical evidence of cardiovascular disease. METHODS: Fifty-three naïve untreated HIV-infected patients and 56 healthy control subjects underwent clinical assessment, electrocardiography (ECG) and echocardiography, including tissue doppler imaging. Moreover, a set of laboratory parameters was obtained from all subjects, including HIV-RNA plasma levels, CD4 cell counts and tumor necrosis factor-α levels. RESULTS: The two groups showed normal ECG traces and no differences regarding systolic morphologic parameters. In contrast, a higher prevalence of left ventricular diastolic dysfunction (abnormal relaxation or pseudonormal filling pattern) was found in the HIV patients (36% vs 9% in patients and controls, respectively, P <0.001). CONCLUSION: Subclinical cardiac abnormalities appear in an early stage of the HIV infection, independent of antiretroviral therapy. The data suggest that HIV per se plays a role in the genesis of diastolic dysfunction.

Effects of long-term L-thyroxine treatment on endothelial function and arterial distensibility in young adults with congenital hypothyroidism.

OBJECTIVE: Patients with congenital hypothyroidism (CH) display subclinical abnormalities of the cardiovascular system that are related to unphysiological fluctuations of TSH levels and occur despite careful replacement therapy. DESIGN: The aim of the present case-control study was to evaluate the effects of long-term levothyroxine (l-T(4)) replacement therapy on the vascular district in CH patients by assessing endothelial function with flow-mediated dilation (FMD) and brachial artery distensibility with the measurement of the coefficient of distensibility (DC). METHODS: Thirty-two young adults with CH aged 18.9+/-0.2 years and 32 age- and sex-matched controls underwent brachial Doppler ultrasound examination to measure FMD and DC at the time of the study. Hypothyroidism was diagnosed by neonatal screening, and l-T(4) treatment was initiated within the first month of life. RESULTS: Compared to healthy controls, CH patients had significantly reduced brachial artery reactivity with lower FMD values (8.9+/-5.7 vs 14.1+/-5.1% P=0.003) and decreased vascular distensibility (24.6+/-1.6 vs 27.3+/-3 kPa(-1)x10(-3), P<0.0002). Linear regression analysis revealed that both total and pubertal mean TSH and number of episodes of undertreatment were independent determinants of FMD and DC. Pubertal mean TSH was the best predictor of both FMD and DC (r=0.81 and r=0.87 respectively, P<0.001). CONCLUSIONS: Young adults with CH treated with long-term l-T(4) replacement therapy may have significant impairment of both FMD and DC. Our data suggest that high TSH levels, inadequately corrected by l-T(4) replacement therapy in CH patients especially during puberty, can exert significant effects on the elastic and functional vessel properties.

Recombinant human thyrotropin enhances endothelial-mediated vasodilation of conduit arteries.

CONTEXT: Endothelial cells possess receptors to TSH. Their role is largely unknown. OBJECTIVES: The objective of the study was to determine whether elevated serum TSH levels, as occur in hypothyroidism, affect endothelial function of large arteries and vascular risk biomarkers. SUBJECTS AND METHODS: Thirty-four consecutively recruited patients, who had undergone thyroidectomy for thyroid carcinoma, were studied in connection with one of the monitoring procedures based on recombinant human (rh) TSH administration. Flow-mediated dilation (FMD) of the brachial artery and serum vascular risk markers were measured at baseline and for 5 d after the administration of rhTSH (0.9 mg im on d 1 and 2). Holter electrocardiogram and echocardiography were performed on d 2. RESULTS: rhTSH caused a rapid increase in flow-mediated dilation from the basal value of 10.2 to 15.6% at 6 h (P < 0.0000001), to 16.1% on d 2 (P < 0.0000001), and to 14.9% on d 6 (P = 0.0015). The results were identical when the analysis was made in a subgroup of 19 patients free of vascular risk conditions. Vascular cell adhesion molecule-1, TNFalpha, IL-6, and high sensitive C-reactive protein were unaffected by rhTSH, whereas homocysteine was decreased. Arterial blood pressure, mean 24-h heart rate, and left ventricular function were unaffected by rhTSH. CONCLUSIONS: rhTSH causes marked and persistent activation of the endothelial mediated vasodilation, independent of systemic hemodynamic changes.

Human immunodeficiency virus per se exerts atherogenic effects.

OBJECTIVE: Premature atherosclerosis in HIV-infected patients has been attributed to highly active antiretroviral therapy (HAART) and the associated metabolic complications. Whether HIV per se plays a role is an unresolved issue. The purpose of this study was to evaluate whether HIV per se exerts atherogenic effects. METHODS: We measured carotid intima-media thickness (IMT) and brachial endothelial-dependent (FMD) and endothelial-independent (NMD) vasodilation in 38 naïve untreated HIV-infected patients and 41 healthy control subjects. RESULTS: Control subjects were selected as to match the HIV patients for metabolic risk factors. Mean carotid IMT was higher in HIV patients (0.85+/-0.2mm; p<0.001) than in controls (0.63+/-0.1mm). In a stepwise multiple regression model, the changes in carotid IMT were predicted by the duration of HIV infection (p<0.001) and CD4 T-cells (p=0.035). Brachial FMD was impaired in HIV patients (8.8+/-3% versus 12.2+/-3% in controls; p<0.001). In contrast, NMD values practically overlapped in the HIV patients and controls. Analysis of the data in relation to viral load showed that FMD was significantly more impaired in the subgroup of patients with viral load values above the median (p<0.001). In addition, there was a highly significant, inverse correlation between FMD and the HIV-RNA copies (p<0.001). CONCLUSION: HIV infection causes functional and structural vascular alterations in a very early stage of the infection independent of HAART and metabolic factors. The data lend support to the viral infectious theory of atherosclerosis. Early assessment of the vascular status in HIV-infected patients is suggested.