Metabolomic analysis of retinopathy stages and amputation in type 2 diabetes.

BACKGROUND: Diabetic retinopathy (DR) and limb amputation are frequent complications of diabetes that cannot always be explained by blood glucose control. Metabolomics is a science that is currently being explored in the search for biomarkers or profiles that identify clinical conditions of interest. OBJECTIVE: This study aimed to analyze, using a metabolomic approach, peripheral blood samples from type 2 diabetes mellitus (DM2) individuals, compared with those with diabetic retinopathy and limb amputation. METHODS: The sample consisted of 128 participants, divided into groups: control, DM2 without DR (DM2), non-proliferative DR (DRNP), proliferative DR (DRP), and DM2 amputated (AMP). Metabolites from blood plasma were classified by spectra using nuclear magnetic resonance (NMR), and the metabolic routes of each group using metaboanalyst. RESULTS: We identified that the metabolism of phenylalanine, tyrosine, and tryptophan was discriminant for the DRP group. Histidine biosynthesis, on the other hand, was statistically associated with the AMP group. The results of this work consolidate metabolites such as glutamine and citrulline as discriminating for DRP, and the branched-chain amino acids as important for DR. CONCLUSIONS: The results demonstrate the relationship between the metabolism of ketone bodies, with acetoacetate metabolite being discriminating for the DRP group and histidine being a significant metabolite in the AMP group, when compared to the DM2 group.

MTHFR Polymorphisms and Cardiac Parameters in Patients with Diabetic Retinopathy.

BACKGROUND: Diabetes Mellitus (DM) is directly associated with cardiovascular dysfunctions and microvascular complications, such as diabetic retinopathy (DR). The association between DR and increased risks of developing cardiovascular diseases has been described. The low activity of the Methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the metabolism of homocysteine, can lead to hyperhomocysteinemia that has already been related to cardiac outcomes and resistance to insulin. The A1298C and C677T polymorphisms in the MTHFR can reduce enzyme activity. OBJECTIVE: The study aims to analyze the association between MTHFR genotypes and cardiac parameters in patients with DR. METHODS: DM patients diagnosed with DR (n=65) were categorized and compared according to MTHFR genotypes A1298C (AA and AC+CC groups) and C677T (CC and CT+TT) groups; biochemical, cardiological, anthropometric, genetic, lifestyle and vitamin B9 and B12 consumption variables. Fischer's exact test and Poisson regression were performed to assess the relationship between variables. RESULTS: Comparing echocardiographic and electrocardiogram parameters within genotypic groups, we found a significant association between left atrial dilation and C677T polymorphism. Left atrium diameter was higher in the T allele carriers (CT+TT group), with a prevalence ratio of 0.912. This association was confirmed in the regression model, including confounding variables. The other cardiac structural and functional parameters studied were not significantly associated with the A1298C or C677T genotypes. CONCLUSION: The MTHFR C677T genotype may contribute to atrial remodeling in RD patients. We found an association between the diameter of the left atrium and the T allele of the MTHFR C677T polymorphism in patients with DR.

Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants.

Diabetic cardiomyopathy (DCM) is a diabetes mellitus-induced pathophysiological condition characterized by cardiac structural, functional, and metabolic changes that can result in heart failure (HF), in the absence of coronary artery disease, hypertension, and valvular heart disease. Metabolic alterations such as hyperglycemia, insulin resistance, hyperinsulinemia, and increased metabolism of free fatty acids result in oxidative stress, inflammation, advanced glycation end products formation, abnormalities in calcium homeostasis, and apoptosis that are responsible for structural remodeling. Cardiac stiffness, hypertrophy, and fibrosis eventually lead to dysfunction and HF with preserved ejection fraction and/or HF with reduced ejection fraction. In this review, we analyzed in detail the cellular and molecular mechanisms and the metabolic pathways involved in the pathophysiology of DCM. Different phenotypes are observed in DCM, and it is not clear yet if the restrictive and the dilated phenotypes are distinct or represent an evolution of the same disease. Phenotypic differences can be observed between T1DM and T2DM DCM, possibly explained by the different myocardial insulin action. Further studies are needed in order to better understand the underlying mechanisms of DCM and to identify appropriate therapeutic targets and novel strategies to prevent and reverse the progression toward heart failure in diabetic patients.

Correlation of SpO2/FiO2 and PaO2/FiO2 in patients with symptomatic COVID-19: An observational, retrospective study.

Some patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience acute hypoxemic respiratory failure progressing toward atypical acute respiratory distress syndrome (ARDS). The aim of the study is to evaluate whether a correlation between ratio of peripheral saturation of oxygen (SpO2) and fraction of inspired oxygen (S/F) and ratio of arterial partial pressure of oxygen and fraction of inspired oxygen (P/F) exists in COVID-19-related ARDS as already known in classical ARDS. In this multicenter, retrospective, observational study, consecutive, adult (≥ 18 years) patients with symptomatic coronavirus disease 2019 (COVID-19) admitted to different COVID-19 divisions in Italy between March and December 2020 were included. Patients with SpO2 > 97% or missing information were excluded. We included 1,028 patients (median age 72 years, prevalence of males [62.2%]). A positive correlation was found between P/F and S/F (r = 0.938, p < 0.0001). A receiver operating characteristic (ROC) curve analysis showed that S/F accurately recognizes the presence of ARDS (P/F ≤ 300 mmHg) in COVID-19 patients, with a cut-off of ≤ 433% showing good sensitivity and specificity. S/F was also tested against P/F values ≤ 200 and ≤ 100 mmHg (suggestive for moderate and severe ARDS, respectively), the latter showing great accuracy for S/F ≤ 178%. S/F was accurate in predicting ARDS for SpO2 ≥ 92%. In conclusion, our findings support the routine use of S/F as a reliable surrogate of P/F in patients with COVID-19-related ARDS.

Clinical, Laboratory and Lung Ultrasound Assessment of Congestion in Patients with Acute Heart Failure.

Congestion is the main cause of hospitalization in patients with acute heart failure (AHF), however its precise assessment by simple clinical evaluation remains elusive. The recent introduction of the lung ultrasound scan (LUS) allowed to physicians to more precisely quantify pulmonary congestion. The aim of this study was to compare clinical congestion (CC) with LUS and B-type natriuretic peptide (BNP) in order to achieve a more complete evaluation and to evaluate the prognostic power of each measurement. Methods: All patients were submitted to clinical evaluation for blood sample analysis and LUS at admission and before discharge. LUS protocol evaluated the number of B-lines for each chest zone by standardized eight site protocol. CC was measured following ESC criteria. The mean difference between admission and discharge congestion logBNP and B-lines values were calculated. Combined end points of death and rehospitalization was calculated over 180 days. Results: 213 patients were included in the protocol; 133 experienced heart failure with reduced ejection fraction (HFrEF), and 83 presented with heart failure with preserved ejection fraction (HFpEF). Patients with HFrEF had a more increased level of BNP (1150 (812−1790) vs. 851 (694−1196); p = 0.002) and B lines total number (32 (27−38) vs. 30 (25−36); p = 0.05). A positive correlation was found between log BNP and Blines number in both HFrEF (r = 0.57; p < 0.001) and HFpEF (r = 0.36; p = 0.001). Similarly, dividing B-lines among tertiles the upper group (B-lines ≥ 36) had an increased clinical congestion score. Among three variables at admission only B-lines were predictive for outcome (AUC 0.68 p < 0.001) but not LogBNP and CC score. During 180 days of follow-up, univariate analysis showed that persistent ΔB-lines <−32.3% (HR 6.54 (4.19−10.20); p < 0.001), persistent ΔBNP < −43.8% (HR 2.48 (1.69−3.63); p < 0.001) and persistent ΔCC < 50% (HR 4.25 (2.90−6.21); p < 0.001) were all significantly related to adverse outcome. Multivariable analysis confirmed that persistent ΔB-lines (HR 4.38 (2.64−7.29); p < 0.001), ΔBNP (HR 1.74 (1.11−2.74); p = 0.016) and ΔCC (HR 3.38 (2.10−5.44); p < 0.001 were associated with the combined end point. Conclusions: a complete clinical laboratory and LUS assessment better recognized different congestion occurrence in AHF. The difference between admission and discharge B-lines provides useful prognostic information compared to traditional clinical evaluation.

Metabolic impact of the VDR rs1544410 in diabetic retinopathy.

AIMS: To investigate the association between BsmI and DM2 in patients with and without DR and to correlate with clinical parameters in a population in northeastern Brazil. METHODS: Cross-sectional case-control study in which data were collected from 285 individuals, including 128 patients with DM2 and 157 with DR. Clinical, biochemical and anthropometric parameters were analyzed, in addition to the single nucleotide polymorphism (SNP) BsmI of the VDR gene (rs1544410), genotyped by PCR-RFLP. RESULTS: In the DR group we found a greater number of patients using insulin therapy (p = 0.000) and with longer duration of DM2 (p = 0.000), in addition to higher serum creatinine values (p = 0.001). Higher fasting glucose levels and higher frequency of insulinoterapy were independently observed in patients with DR and b allele carriers, when compared to BB. CONCLUSION: The association of the bb/Bb genotypes (rs1544410) of the VDR gene with increased blood glucose levels and insulinoterapy may represent worse glicemic control in rs1544410 b allele carriers in DR Latin American individuals.

Upper extremity deep vein thrombosis in COVID-19: Incidence and correlated risk factors in a cohort of non-ICU patients.

BACKGROUND: Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. METHODS: We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. RESULTS: 257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1-14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33-26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41-9.78). CONCLUSIONS: UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.

Superior vena cava syndrome after pacemaker implantation treated with direct oral anticoagulation.

BACKGROUND: Superior Vena Cava (SVC) syndrome, is a quite rare but serious complication after pacemaker lead implantation; most patients are asymptomatic due to the development of adequate venous collateral circulation. CASE PRESENTATION: We report a case of a 75-year-old woman who developed SVC syndrome after transvenous pacemaker implantation with complete resolution of the thrombosis after 3 months of oral anticoagulation. CONCLUSIONS: Generally other causes as malignancy are considered to be the most common etiology of SVC syndrome, but benign iatrogenic causes, mainly intravascular devices (central vein catheters, cardiac defibrillators and pacemaker wires), are becoming increasingly common. Procedures performed on venous vasculature, causing a possible intimal injury or vein stenosis, provoked by transvenous leads, seem to be the most reasonable explanation for the observed complication.

Suspected myocarditis in patients with COVID-19: A multicenter case series.

ABSTRACT: Although myocarditis can be a severe cardiac complication of COVID-19 patients, few data are available in the literature about the incidence and clinical significance in patients affected by SARS-CoV-2. This study aims to describe the prevalence and the clinical features of suspected myocarditis in 3 cohorts of patients hospitalized for COVID-19. We retrospectively evaluated all the consecutive patients admitted for COVID-19 without exclusion criteria. Suspect myocarditis was defined according to current guidelines. Age, sex, in-hospital death, length of stay, comorbidities, serum cardiac markers, interleukin-6, electrocardiogram, echocardiogram, and therapy were recorded. Between March 4 to May 20, 2020, 1169 patients with COVID-19 were admitted in 3 Italian Medicine wards. 12 patients (1%) had suspected acute myocarditis; 5 (41.7%) were men, mean age was 76 (SD 11.34; median 78.5 years); length of stay was 38 days on average (SD 8, median value 37.5); 3 (25%) patients died. 8 (66.7%) had a history of cardiac disease; 7 (58.33%) patients had other comorbidities like diabetes, chronic obstructive pulmonary disease, or renal insufficiency. Myocarditis patients had no difference in sex prevalence, rate of death, comorbidities, elevations in serum cardiac markers as compared with patients without myocardial involvement. Otherwise, there was a significantly higher need for oxygen-support and a higher prevalence of cardiac disease in the myocarditis group. Patients with suspected myocarditis were older, had a higher frequency of previous cardiac disease, and significantly more prolonged hospitalization and a lower value of interleukin-6 than other COVID-19 patients. Further studies, specifically designed on this issue, are warranted.

Palliative care in a COVID-19 Internal Medicine ward: A preliminary report.

BACKGROUND: in the current pandemic emergency, increased attention has given to treating symptoms that cause suffering in patients with COVID-19. This study aims to describe the role of palliative care in the management of these patients. METHODS: palliative consultation was requested by the staff as per protocol. In brief, the criteria for referring patients to a palliative care physician or to undergo palliative care were left to the discretion of the physician in charge. We recorded data regarding age, gender, length of stay, type of discharge (dead or alive, and transfer to long-term or hospice facilities). RESULTS: Between March 18 to May 8, 2020, 412 patients with COVID-19 were admitted to the Internal Medicine wards of Magenta Hospital, Italy. The palliative care physician was directly involved in 105 cases (25.5%) and performed 236 consultations. Of the 105 patients who received palliative care counselling, 66 (63%) died. The average number of days in care was 2.26 days. The principal reason for counseling was controlling symptoms (54%) and 12% deal with the end of life management. The prevalent symptom, among those which led to the counseling, was restlessness/agitation (41%), followed by emotional issues (26%) such as anxiety, fear, and demoralization. In only 20% of cases, dyspnoea was the reason for symptomatic treatment. CONCLUSIONS: A large number of hospitalized Covid-19 patients are at high risk of clinical deterioration and death. This leads to the opportunity to integrate a palliative physician into the staff, who treat these patients. There is an urgent need for protocol standardization and formal trials to verify the effectiveness of this approach.

Methylation Profile of miR-9-1 and miR-9-1/-9-3 as Potential Biomarkers of Diabetic Retinopathy.

AIMS: Analysis of the relationship between the methylation profile of miR-9-1 or miRs -9-1 / -9-3 and diabetic retinopathy. BACKGROUND: Diabetic Retinopathy (DR) is a frequent complication of Diabetes mellitus and it has a decisive impact on the quality of life, as it is one of the biggest causes of blindness in the adult population. Levels of microRNA-9 have been shown to be related to diabetes but little is known about its involvement with DR in humans. OBJECTIVE: To analyze the relationship between the methylation profile of miR-9-1 or miRs -9-1/-9-3 and DR. METHODS: 103 patients diagnosed with diabetes for 5 to 10 years were analyzed. The data were categorized according to clinical, biochemical, lifestyle and anthropometric parameters. DNA extracted from leukocyte samples was used to determine the methylation profile of miRs-9-1 and -9-3 using a specific methylation PCR assay. RESULTS: miR-9-1 methylation was related to diabetic retinopathy, indicating that methylation of this miR increases the chances of presenting retinopathy up to 5 times. In our analyses, diabetics with lower levels of creatinine and CRP showed significant reductions (99% and 97%) in presenting DR. Methylation of both miRs-9-1 and 9-3 methylated increases the chances of presenting DR by 8 times; in addition, a sedentary lifestyle can increase the risk for the same complication by up to 6 times. CONCLUSION: Our results suggest that both methylation of miR-9-1 and e miRs-9-1 / 9-3 favors DR in patients with diabetes in a period of 5 to 10 years of diagnosis.

Ultrasound indices of congestion in patients with acute heart failure according to body mass index.

BACKGROUND: The inverse relationship between body mass index (BMI) and natriuretic peptide levels complicates the diagnosis of heart failure (HF) in obese patients. Assessment of congestion with ultrasound could facilitate HF diagnosis but it is unclear if any relationship exists amongst BMI, inferior vena cava (IVC) diameter and the number of B-lines. METHODS: We performed a comprehensive echocardiographic evaluation within 24 h from hospital admission in patients with HF, including lung B-lines and IVC diameter, and studied their relationship with BMI and outcome. RESULTS: 216 patients (median age 81 (77-86) years) were enrolled. Median number of B-lines was 31 (IQR 26-38), median IVC diameter was 23 (22-25) mm and median BNP 991 (727-1601) pg/mL. BMI was inversely correlated with B-lines (r = - 0.50, p < 0.001), but not with IVC diameter (r = - 0.04, p = 0.58). Compared to overweight patients (BMI 25-29.9 kg/m2; n = 100) or with a normal BMI (BMI < 25 kg/m2; n = 59), obese patients (BMI ≥ 30 kg/m2; n = 57) had lower B-lines [28 (24-33) vs 30 (26-35), and vs 38 (32-42), respectively; p < 0.001] but similar IVC diameter. During the first 60 days of follow-up, there were 53 primary events: 29 patients died and 24 had a HF-related hospitalisation. B-lines and IVC diameter were independently associated with an increased risk. However, B-lines were less likely to predict outcome in the subgroup of patients with a BMI ≥ 30 kg/m2. CONCLUSIONS: Assessment of IVC diameter or B-lines in patients admitted with AHF identifies those at greater risk of death or HF readmission. However, assessment of B-lines might be influenced by BMI.

Prognostic Significance of an Early Echocardiographic Evaluation of Right Ventricular Dimension and Function in Acute Heart Failure.

OBJECTIVE: Sparse and contradictory data are available on the prognostic role of an early echocardiographic examination in patients with acute decompensated heart failure (ADHF). We planned a prospective study to illustrate which early echocardiographic parameter would be better related to prognosis in such patients. METHODS: In a consecutive series of patients with ADHF with either reduced (n=209) or preserved (n=172) left ventricular ejection fraction (LVEF), a complete echocardiographic examination was performed within 12 hours of admission. The endpoint of the study was death or rehospitalization at 6 months from hospital discharge. RESULTS: After 6 months from discharge, 73 died and 96 were rehospitalized due to cardiovascular causes. In multivariable analysis, a right ventricular end-diastolic diameter (RVEDD) >40 mm (P = .02), a tricuspid annular plane systolic excursion (TAPSE) <19 mm (P= .004), and an inferior vena cava diameter >22 mm (P = .02) were associated with 6-month events. LVEF and LV diastolic function were not predictive of events. Pulmonary artery systolic pressure (PASP) >45 mmHg and TAPSE/PASP <0.425 were associated with prognosis in univariate but not in multivariable analysis. Conversely, the TAPSE/RVEDD ratio (dichotomized at its median value of 0.461) was an independent predictor of outcome in multivariable analysis (P< .001). CONCLUSIONS: In patients hospitalized for ADHF, early echocardiographic identification of right ventricular dilatation and dysfunction predicts a poor outcome better than LV systolic and/or diastolic dysfunction.