Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia.

OBJECTIVES: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19. METHODS: Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death. RESULTS: IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations. CONCLUSIONS: IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment. CLINICALTRIALS: gov, NCT04680949 and NCT04357366.

The Importance of Out-of-Office Blood Pressure Measurement, as Highlighted by the Correlation with Left Ventricular Hypertrophy in an Untreated Hypertensive Population.

Background and Objectives: Hypertensive heart disease, especially left ventricular hypertrophy (LVH), is considered to be one of the main types hypertension-mediated organ damage. Hence, the purpose of this study was to examine which method of measuring BP (office BP measurement (OBPM), 24 h ambulatory BP monitoring (ABPM), or home BP monitoring (HBPM)), can be better correlated with echocardiographic LVH in the untreated hypertensive population. Materials and Methods: This study's population consisted of 202 patients 58 ± 15 years old (40.8% males). All patients reported elevated home BP measurements for at least 3 months, but they had never been treated before for hypertension. Office and out-of-office BP measurements, including ABPM on a usual working day and seven-day HBPM, as well as 2D echocardiography, were performed. Results: In the univariate analysis, LVH was associated (p < 0.05) with a mean 24 h systolic BP (OR: 1.93, CI: 1.29-2.91), a mean 24 h diastolic BP (OR: 1.30, CI: 1.16-1.80), ambulatory daytime systolic (OR: 1.11, CI:1.01-1.82) and diastolic BP (OR: 1.13, CI:1.09-1.17), ambulatory nighttime systolic BP (OR: 2.11, CI: 1.04-4.31), and mean home systolic BP (OR: 1.05, CI:1.01-1.12). Pearson's correlation analysis showed a significant correlation between the LV mass index and the mean 24 h systolic BP (r = 0.58, p < 0.05), daytime systolic BP (r = 0.59, p < 0.05), and nighttime systolic BP (r = 0.57, p < 0.05). Most of the population with confirmed LVH presented confirmed hypertension (based on ABPM, 48.1% or HBPM, 40%). The second most dominant phenotype was masked hypertension (ABPM, 32.7% and HBPM, 23.7%). The majority (59.3%) had non-dipping status, 20.4% had a reverse dipping pattern, 13% had a dipping pattern, and only 7.3% had extreme dipping BP. Conclusions: Out-of-office BP measurement devices seemed to be superior compared to in-office. This advantage is highlighted by better correlations in the identification of LVH as well as the diagnosis of masked hypertension, a condition also highly correlated with LVH.

Association of the Common Catalase Gene Polymorphism rs1001179 With Glycated Hemoglobin and Plasma Lipids in Hyperlipidemic Patients.

Catalase represents perhaps the most effective antioxidant defense in the body under conditions of increased oxidative stress, and rs1001179 (CAT-262C >T) is its most extensively studied gene polymorphism. Using an established PCR-RFLP method for genotyping, we examined the association of rs1001179 with glycated hemoglobin (HbA1c) and plasma lipids using univariate analyses with age, sex, body mass index (BMI), smoking, and alcohol abuse as covariates, in a group of dyslipidemic patients from northern Greece. Our results suggest that the TT genotype is a risk factor for increased HbA1c and plasma triglycerides, and that this association is modulated by the BMI and/or age of the patients.

The effect of menopause on lipoprotein (a) concentrations: A systematic review and meta-analysis.

OBJECTIVE: Transition to menopause has been associated with an increased risk of cardiovascular disease (CVD), attributed mainly to atherogenic dyslipidemia. Whether lipoprotein (a) [Lp(a)], an independent cardiovascular risk factor, also contributes to menopause-associated CVD has not yet been clarified. The aim of this study was to systematically investigate and meta-analyze the best available evidence regarding the effect of menopause on Lp(a) concentrations. METHODS: A comprehensive search was conducted in PubMed and Scopus databases up to March 8th, 2022. Data were expressed as weighted mean difference (WMD) with 95 % confidence intervals (CI). The I2 index was employed to assess heterogeneity. RESULTS: Seventeen studies were included in the qualitative and 15 in the quantitative analysis, yielding 4686 premenopausal and 8274 postmenopausal women. Lp(a) concentrations were lower in premenopausal than in postmenopausal women [WMD -3.77 (95 % CI -5.37, -2.18) mg/dl, p < 0.001; I2 99%, p < 0.001]. This difference was maintained when the analysis was restrained to good-quality studies (n = 9). Four studies included pre- and postmenopausal women, matched for age, and these found no difference in Lp(a) concentrations between groups [WMD -1.22 (95 % CI -3.15, 0.72) mg/dl, p < 0.001; I2 99%, p < 0.001]. Three studies provided data for Lp(a) in women before and after bilateral oophorectomy, and these found no difference between them [WMD -3.38 (95 % CI -7.29, 0.54) mg/dl, p = 0.09; I2 0%, p < 0.44]. CONCLUSIONS: Transition to menopause may increase Lp(a) concentrations, although the effect of aging cannot be excluded by current data.

Microvascular and Endothelial Dysfunction in Prediabetes.

Prediabetes is a significant metabolic status since there is high potential for future progression of diabetes mellitus (DM). People with prediabetes are at increased risk of cardiovascular disease (CVD) and mortality. Endothelial and microvascular dysfunction is considered a key step towards the development and progression of CVD. Importantly, endothelial and microvascular dysfunction can be detected and monitored using non-invasive procedures in peripheral organs and tissues, including the retina, kidney, skin and skeletal muscle. Structural and functional alterations of the microvasculature have been consistently documented in the above microvascular beds in patients with diabetes mellitus. In contrast, such alterations remain understudied in prediabetes, but are currently receiving attention as markers of subclinical and future CVD. The aim of this review is to summarize available evidence regarding the presence of subclinical microvascular and endothelial dysfunction in prediabetes and their impact on cardiovascular risk.

Development and validation of SCOPE score: A clinical score to predict COVID-19 pneumonia progression to severe respiratory failure.

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.

Impact of Obesity in Kidney Diseases.

The clinical consequences of obesity on the kidneys, with or without metabolic abnormalities, involve both renal function and structures. The mechanisms linking obesity and renal damage are well understood, including several effector mechanisms with interconnected pathways. Higher prevalence of urinary albumin excretion, sub-nephrotic syndrome, nephrolithiasis, increased risk of developing CKD, and progression to ESKD have been identified as being associated with obesity and having a relevant clinical impact. Moreover, renal replacement therapy and kidney transplantation are also influenced by obesity. Losing weight is key in limiting the impact that obesity produces on the kidneys by reducing albuminuria/proteinuria, declining rate of eGFR deterioration, delaying the development of CKD and ESKD, and improving the outcome of a renal transplant. Weight reduction may also contribute to appropriate control of cardiometabolic risk factors such as hypertension, metabolic syndrome, diabetes, and dyslipidemia which may be protective not only in renal damage but also cardiovascular disease. Lifestyle changes, some drugs, and bariatric surgery have demonstrated the benefits.

Knowledge and Perceptions about COVID-19 among Health Care Workers: Evidence from COVID-19 Hospitals during the Second Pandemic Wave.

Health care workers (HCWs) face a higher risk of infection, since they work at the front line of COVID-19 patients' management. Misinterpretations of current scientific evidence among HCWs may impact the delivery of appropriate care to COVID-19 patients and increase the risk of SARS-CoV-2 transmission in the hospital setting. Moreover, knowledge may affect HCWs perceptions depending on their broad beliefs and past experiences. The aim of this study was to explore the knowledge and perceptions of HCWs regarding COVID-19 issues during the second wave of the pandemic. A cross-sectional survey, involving a printed questionnaire, was conducted from 21 October 2020 to 31 January 2021 in four tertiary care hospitals located at four distant geographical regions in Greece. In total, 294 HCWs participated in this study. The majority of HCWs provided precise responses regarding general knowledge, perceptions, and practices concerning the COVID-19 pandemic. However, responses on hand hygiene and antimicrobial use in HCWs with COVID-19 were mistaken. This study reveals a certain degree of misconceptions and knowledge gaps in HCWs everyday practice, especially regarding hand hygiene and antimicrobial use in COVID-19 patients.

First Report of Diabetes Phenotype due to a Loss-of-Function ABCC8 Mutation Previously Known to Cause Congenital Hyperinsulinism.

Monogenic Diabetes is relatively rare, representing only 1-2% of total diabetes cases; nevertheless, it is often misdiagnosed primarily as type 1 diabetes, leading to unnecessary insulin therapy and delayed recognition of affected family members. In the present article, we describe a case of a young, male patient who presented with hyperglycemia in the absence of ketosis and following genetic testing; he proved to harbor the loss-of-function p.Arg1353His (c.4058G>A) mutation in the ABCC8 gene, inherited from his mother. This mutation has been previously described in patients with Congenital Hyperinsulinism. Furthermore, different mutations in the ABCC8 gene have been linked with MODY 12, type 2, and gestational diabetes; however, to the best of our knowledge, this is the first report that associates this specific mutation with diabetes phenotype. ABCC8-related diabetes is characterized by remarkable heterogeneity in terms of clinical presentation and therapeutic approach. Early diagnosis and individualized treatment are essential to achieving metabolic targets and avoiding long-term diabetes complications.

Early Vascular Aging Risk Assessment From Ambulatory Blood Pressure Monitoring: The Early Vascular Aging Ambulatory Score.

BACKGROUND: This study compared the diagnostic accuracy of blood pressure (BP) measurement methods, office BP, ambulatory BP monitoring (ABPM), and home BP, in the identification of early vascular aging (EVA) and developed a score to predict the risk of EVA in hypertensive patients. METHODS: Two-hundred eighty-two consecutive subjects (39.7% male) aged 56.8  ±â€Š 15.8 years were included. Office and out-of-office BP measurements including ABPM on a usual working day and 7 days home BP monitoring were performed. Carotid-femoral pulse wave velocity (c-f PWV) was measured in all patients. EVA was defined as c-f PWV values higher than the expected for age average values according to European population data. RESULTS: In univariate analysis, EVA was significantly correlated with office systolic BP, average 24-hour systolic and diastolic BP, and average 24-hour and office heart rates. The area under the curve for predicting EVA was 0.624 (95% CI 0.551 to 0.697), 0.559 (95% CI 0.484 to 0.635) and 0.565 (95% CI 0.49 to 0.641), for daytime, home, and office systolic BP, respectively. Ambulatory BP variables, age, sex, body mass index, diabetes mellitus (yes/no), and estimated glomerular filtration rate were used to develop a new score for EVA providing a total accuracy of 0.82, 0.84 sensitivity, and 0.78 specificity. CONCLUSIONS: In conclusion, the new risk score, Early Vascular Aging Ambulatory score, may accurately identify hypertensive patients with EVA using ABPM values and classic cardiovascular risk factors.

The role of telenursing in the management of Diabetes Type 1: A randomized controlled trial.

BACKGROUND: Diabetes Mellitus type 1 (T1DM) is a chronic disease that requires patients' self-monitoring and self-management to achieve glucose targets and prevent complications. Telenursing implicates technology in the interaction of a specialized nurse with patients with chronic diseases in order to provide personalized care and support. OBJECTIVE: To evaluate the effect of telenursing on T1DM patients' compliance with glucose self-monitoring and glycemic control. DESIGN: Randomized controlled study. SETTINGS: Outpatient Department of Diabetes, Endocrinology and Metabolism of a University Hospital in Northern Greece. METHODS: Ninety-four T1DM patients were recruited and randomized in two groups by a random number generator. The intervention group (N = 48) was provided with telenursing services. A specialized nurse made a weekly contact via telephone motivating patients to frequently measure blood glucose and adopt a healthy lifestyle. The control group (N = 46) received standard diabetes advice and care in the clinic. The primary outcome was the effect of the intervention in glucose control and glucose variability. The secondary outcome was the effect on frequency of self-monitoring. SPSS 20.0 was used for data analysis. RESULTS: The two groups did not differ in age, sex, physical activity or initial HbA1c. In the intervention group, blood glucose significantly decreased at the end of the study in all predefined measurements, compared to control group: morning (93.18 ±â€¯13.30 mg/dl vs. 105.17 ±â€¯13.74 mg/dl, p < 0.005), pre-prandial (114.76 ±â€¯9.54 mg/dl vs. 120.84 ±â€¯4.05 mg/dl, p < 0.005), post-prandial (193.35 ±â€¯25.36 mg/dl vs. 207.84 ±â€¯18.80 mg/dl, p < 0.005), and HbA1c decreased significantly over time in the intervention group (8.3 ±â€¯0.6% at the beginning of the study vs. 7.8 ±â€¯1% at the end of the study, p = 0.03). In the intervention group there were also fewer omitted glucose measurements than in the control group. CONCLUSIONS: Patients in the intervention group achieved better glucose control and more frequent self-monitoring than patients in routine care in the clinic. The findings of our study indicate that telenursing can motivate T1DM patients to better control their disease.

Assessment of telomerase activity in leukocytes of type 2 diabetes mellitus patients having or not foot ulcer: Possible correlation with other clinical parameters.

Telomerase is the enzyme that maintains telomere length by adding telomeric repeats after each cell division. Numerous metabolic factors such as obesity, insulin resistance or physical inactivity have been associated with shortened telomeres. In the present study, we assessed telomerase activity in diabetic patients having or not foot ulcer. A total of 90 adult patients with type 2 diabetes mellitus (T2DM) were studied. Patients were allocated into two groups according to the absence or presence of active foot ulcers as follows: Νon-ulcer group (N=58) and ulcer group (N=32). Our data revealed that the patients with diabetic ulcers had significantly greater waist circumference and neuropathy disability score, while exhibiting lower telomerase activity, indicating the possible existence of a common clinical profile among ulcer-bearing diabetic patients. Validation of our findings by extending the study in larger patient groups may contribute to the understanding of T2DM pathophysiology and its main clinical implications.

Obese Patients with Type 2 Diabetes on Conventional Versus Intensive Insulin Therapy: Efficacy of Low-Calorie Dietary Intervention.

INTRODUCTION: The aim of this prospective study was to assess the results of a standard low-calorie dietary intervention (7.5 MJ/day) on body weight (BW) and the metabolic profile of obese patients with type 2 diabetes mellitus (T2DM) on intensive insulin therapy (IIT: 4 insulin injections/day) versus conventional insulin therapy (CIT: 2/3 insulin injections/day). METHODS: A total of 60 patients (n = 60, 23 males and 37 postmenopausal females) were recruited and categorized into two groups according to the scheme of insulin treatment. Thirty were on IIT (13 males and 17 females) and an equal number on CIT (10 males and 20 females). BW, body mass index (BMI), HbA1c, and metabolic parameters were compared at 6 and 12 months after baseline. RESULTS: Significant reductions were observed in the BW, BMI, HbA1c (p ≤ 0.001 for all) and cholesterol (p ≤ 0.05) at 6 months post-intervention. At 1 year, median BW reduction was 4.5 kg (3.3, 5.8) for patients on IIT and 4.8 kg (3.6, 7.0) for those on CIT. The 12-month dietary intervention increased prevalence of normoglycemia in the IIT group and reduced the prevalence of obesity prevalence among the CIT participants (all p < 0.001). CIT patients with BW reduction ≥5.0% demonstrated 11-fold greater chances of being normoglycemic (odds ratio 11.3, 95% CI 1.1-110.5). BW reduction ≥7.0% was associated with CIT, being overweight, and having normal HDLc, LDLc, and cholesterol levels. A reduction in BW between 5.0% and 6.9% was associated with IIT, normoglycemia, and obesity. CONCLUSION: A 12-month 1800-kcal dietary intervention achieved significant BW and HbA1c reductions irrespectively of insulin regimen. CIT was associated with BW reduction greater than 8.0%, whereas IIT was associated with higher rates of normoglycemia.

Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis.

PURPOSE: The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. METHODS: A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. RESULTS: Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). CONCLUSIONS: Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials.