Whole-body non-forensic fetal virtopsy using postmortem magnetic resonance imaging at 7 Tesla vs classical autopsy.

OBJECTIVE: To determine the diagnostic accuracy of virtual autopsy using whole-body postmortem ultra-high field magnetic resonance imaging (MRI) at 7 Tesla (T), using a short T2-weighted imaging (T2-WI) protocol, compared with classical autopsy, for detecting structural abnormalities in small second-trimester fetuses. METHODS: Thirty consecutive fetuses at 13-19 weeks' gestation (weight, 17-364 g) were included following spontaneous pregnancy loss or termination of pregnancy. After fixation in 10% formaldehyde solution (48 h to 1 week), all fetuses were scanned using a two-dimensional turbo high-resolution T2-WI protocol with multislice relaxation time, followed by an invasive autopsy. The diagnostic accuracy of virtual autopsy vs classical autopsy was calculated for 990 anatomical structures (30 fetuses × 33 items). Sensitivity, specificity, positive and negative predictive values and Cohen's κ coefficient of agreement, with their 95% CIs, as well as the McNemar test, were used to evaluate the accuracy and agreement of the two diagnostic methods. Analysis was stratified by anatomical segment (nervous, pulmonary, cardiovascular, digestive, renal, facial and skeletal) and across three gestational-age intervals (13-14, 15-16 and 17-19 weeks). RESULTS: Considering classical autopsy as the gold standard, virtual autopsy had a sensitivity of 92.04% (95% CI, 85.42-96.29%) and a specificity of 97.87% (95% CI, 94.64-99.42%), with a positive predictive value of 96.30% (95% CI, 90.78-98.56%) and a negative predictive value of 95.34% (95% CI, 91.61-97.45%), achieving a diagnostic accuracy of 95.68% (95% CI, 92.73-97.68%) for detecting structural abnormalities in second-trimester fetuses. Cohen's κ for virtual vs classical autopsy was 0.907. The diagnostic ability of virtual autopsy at 7 T for malformed fetuses was superior to that of classical autopsy for analyzing the nervous system in small fetuses with pronounced autolysis, equivalent to that of classical autopsy when analyzing pulmonary, cardiovascular and renal systems and inferior when evaluating the fetal intestines. The sensitivity of virtual autopsy at 7 T for describing structural abnormalities increased with gestational age. CONCLUSION: Virtual fetal autopsy using 7-T MRI and a turbo high-resolution T2-WI protocol with multislice relaxation time is a feasible postmortem diagnostic tool for the identification of fetal structural anomalies. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

RELATIONSHIP OF OXIDATIVE STRESS TO URINARY ANGIOTENSIN CONVERTING ENZYME 2 IN TYPE 2 DIABETES MELLITUS PATIENTS.

CONTEXT: Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and cleaves angiotensin II to Angiotensin (1-7), annihilating the deleterious effects of angiotensin II which is known to be a strong activator of oxidative stress. OBJECTIVE: We aimed to evaluate the relationship of oxidative stress to urinary ACE2 (uACE2) in type 2 diabetes mellitus (T2DM) patients. DESIGN: We included consecutive normo or microalbuminuric T2DM patients in an observational transversal study. Routine laboratory investigations, plasma malondialdehyde (MDA, fluorimetric thiobarbituric method) as a marker of prooxidant capacity and superoxide dismutase (SOD, cytochrome reduction method) and catalase (CAT) activity (in erythrocyte lysate by the modification of absorbance method) as two measures of serum antioxidant capacity and uACE2 (ELISA method) were assessed. RESULTS: MDA showed a negative correlation with SOD (r=-0.44, p=0.001), CAT (r=-0.37, p=0.006), uACE2 (r=-0.33, p=0.016) and a positive correlation with glycated haemoglobin (HbA1c) (r=0.49, p<0.001) and associated cardiovascular disease (r=0.42, p=0.001). CAT as also positively correlated to uACE2 (r=0.29, p=0.037). SOD was also negatively correlated with glycemia (r=-0.71, p<0.001) and HbA1c (r=-0.53, p<0.001). Patients with lower MDA (when divided according to median value of 3.88 nmol/mL) had higher uACE2 57.15(40.3-71.2) pg/mL compared to 38.5(31.8-45.95) pg/mL in patients with higher MDA (p<0.001). In multivariate logistic regression uACE2 was the only predictor for MDA above or below its median (OR=0.94, 95%CI[0.90-0.98], p=0.002). CONCLUSION: Increased prooxidant serum capacity is associated with lower uACE2 levels in T2DM patients.

Adiponectin predicts cardiovascular events in diabetes dialysis patients.

OBJECTIVES: Adiponectin is an insulin-sensitizing, anti-inflammatory adipokine with anti-atherogenic actions in the general population. In dialysis patients it is unclear whether adiponectin conserves its protective value or is, on the contrary, associated to worse prognosis. We assessed the predictive value of adiponectin for atherosclerosis related cardiovascular events in type 2 diabetic dialysis patients. DESIGN AND METHODS: Prevalent diabetic dialysis patients from three dialysis units (n=77) were enrolled in a 3years' prospective observational study. Serum adiponectin, clinical and laboratory parameters were determined at baseline; new occurrence of atherosclerosis related events (coronary events, atherosclerosis obliterans, and stroke) was recorded. RESULTS: Baseline adiponectin was 17.25(9.53-31.97) µg/mL and significantly correlated to HDL cholesterol (r=0.29, p=0.01), triglycerides (r=-0.40, p=0.0004), ferritin (r=-0.29, p=0.02), transferrin (r=-0.28, p=0.02), and uric acid (r=-0.24, p=0.04). In multivariate analysis association to triglycerides (p=0.001), HDL cholesterol (p=0.01) and ferritin (p=0.04) remained significant. 36 new fatal and non-fatal new cardiovascular events occurred, 29 patient died. Cox proportional regression analysis showed that adiponectin below or above a ROC-derived cut-off of 27.33µg/mL significantly influenced event-free survival: hazard ratio (HR) 2.48, 95% confidence interval (CI) (1.09-5.66), p=0.031 along with fasting glucose HR 1.01, 95%CI(1.00-1.02), p=0.01 and history of cardiovascular events at inclusion HR 3.16, 95%CI(1.36-7.32), p=0.007. In multivariate analysis baseline adiponectin HR 5.02, 95%CI(0.98-25.06), p=0.05 and glycemia HR 1.01, 95%CI(1.00-1.02), p=0.01 influenced event-free survival. Adiponectin also predicted cardiovascular events in patients without cardiovascular disease at inclusion but was not associated to overall mortality. CONCLUSIONS: In diabetes dialysis patients low adiponectin favors occurrence of atherosclerosis related cardiovascular events.

Bone metabolism regulators and arterial stiffness in postmenopausal women.

BACKGROUND: Osteoprotegerin (OPG), osteopontin (OPN) and matrix Gla protein (MGP) are markers of bone metabolism but they are also involved in vascular calcification. However, their precise role is not completely understood. Arterial stiffness is considered an independent predictor of cardiovascular events and it may be one of the causes of the increased cardiovascular risk associated with postmenopausal status. Medial and intimal calcification may increase arterial stiffness. The aim of our study was to assess the relationship of OPG, OPN and MGP with aortic pulse wave velocity (aPWV) as a marker of arterial stiffness in postmenopausal women. MATERIALS AND METHODS: Circulating OPG, OPN and serum total MGP were measured in 144 postmenopausal women using the enzyme-linked immunosorbent assay method. Aortic PWV was determined by an oscillometric method. RESULTS: Osteoprotegerin correlated with age (p<0.001, r=0.27), aPWV (p<0.001, r=0.32) and hypersensitive C reactive protein (hsCRP) (p<0.001, r=0.37), OPN correlated directly with hsCRP (p<0.001, r=0.39) and inversely with high density lipoprotein cholesterol (p=0.02, r=-0.02). No significant association was found between total MGP and clinical, biochemical and vascular parameters. The correlation between OPG and aPWV persisted even after the adjustment for various potential confounders (p=0.02, r=0.19). In multiple regression analysis in the whole study population the most important predictors of aPWV were OPG (ß=0.230, p=0.006), hsCRP (ß=0.212, p=0.01) and systolic blood pressure (ß=0.163, p=0.04). After exclusion of patients treated with statins the independent predictors were hsCRP (ß=0.275, p=0.005) and OPG (ß=0.199, p=0.04). CONCLUSION: Circulating OPG, but not OPN and total MGP, is associated with aPWV and may be a marker of the increased arterial stiffness and cardiovascular risk in postmenopausal women.

Arterial stiffness, carotid atherosclerosis and left ventricular diastolic dysfunction in postmenopausal women.

BACKGROUND: Postmenopausal women have an increased cardiovascular morbidity that may be due to the increase in classical cardiovascular risk factors and also to the arterial structure and function alterations. The aim of our study was to evaluate the association of aortic pulse wave velocity (PWV), and carotid intima-media thickness (IMT), with left ventricular diastolic dysfunction (LVDD) in postmenopausal women. PATIENTS AND METHODS: In 96 women without overt cardiovascular disease (age 62±7.7 years), and with normal left ventricular systolic function, aortic PWV was assessed by using an oscillometric device, intima-media thickness was measured by B-mode ultrasonography and the parameters of left ventricular diastolic function were evaluated by a transthoracic echocardiographic study. RESULTS: LVDD, defined as an E/A ratio≤1 was found in 50 patients (52%). All of them had mild LVDD. In these patients we found significant increase in age (p<0.001), aortic PWV (p<0.001), carotid IMT (p=0.002) and plaque score (p=0.004) when compared with patients without LVDD. In a logistic regression analyzed, after adjusting for age, only aortic PWV was a significant predictor of LVDD (2.15, 95% CI 1.39-3.31, p=0.0006). CONCLUSIONS: This study among postmenopausal women provides evidence that increased arterial stiffness as measured by aortic PWV and not carotid IMT may be a marker or a risk factor for LVDD, independent of other classical risk factors.

Low plasma adiponectin levels predict increased urinary albumin/creatinine ratio in type 2 diabetes patients.

BACKGROUND: Experimental studies have shown that adiponectin has antiproteinuric and nephroprotective effects. The purpose of the study was to assess the value of plasma adiponectin as a predictor of proteinuria in type 2 diabetes (T2D) patients. METHODS: In this one-year prospective follow-up study, we included T2D patients with positive visual test for microalbuminuria (Micral) and negative visual test for proteinuria. Exclusion criteria were: glomerular filtration ratio (GFR) < 30 ml/min, acute infection/inflammation, uncontrolled hypertension, and atherosclerotic complications. The main outcome measure was the change in urinary albumin/creatinine ratio (UACR) after 1 year follow-up (Δ UACR). RESULTS: Fifty-six patients (66% males) completed the study. Their initial mean UACR was 81.58 ± 26.42 mg/g and mean GFR was 81.15 ± 3.96 ml/min. At baseline, simple regression disclosed significant correlations between UACR and plasma adiponectin (r = 0.54, P = 0.00002) and GFR (r = -0.28, P = 0.03); in multiple regression analysis, plasma adiponectin remained the only predictor of UACR (P = 0.00007). Baseline plasma adiponectin was significantly correlated to body mass index (r = -0.28, P = 0.04), waist circumference (r = -0.27, P = 0.05), HDL cholesterol (r = 0.35, P = 0.01), and LDL cholesterol (r = 0.27, P = 0.04). Baseline plasma adiponectin significantly correlated in simple (r = -0.38, P = 0.004) and multiple regression (P = 0.04) to Δ UACR. When patients were divided according to Δ UACR in nonprogressors (Δ UACR < 0) and progressors (Δ UACR > 0), logistic regression showed that baseline GFR (OR = 1.04, CI95%: 1.00-1.09, P = 0.04) and plasma adiponectin (OR = 1.16, CI95%: 1.02-1.32, P = 0.02) were the only factors that predicted whether the patient would be a progressor or not. CONCLUSION: In T2D patients, lower plasma adiponectin levels seem to be predictive of increased UACR.

Carotid arterial stiffness in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality.Patients with COPD have a cardiovascular risk three times greater than the normal population and cardiac disease accounts for about 50% of deaths in these patients. Arterial stiffness is a marker of increased cardiovascular risk and a predictor for cardiovascular morbidity and mortality. There is evidence of increased aortic stiffness in COPD. The aim of our study is to determine parameters of carotid arterial stiffness in patients with stable COPD. PATIENTS AND METHODS: We enrolled 38 patients with COPD and 36 matched controls. All subjects were evaluated by clinical history and spirometry; parameters of carotid stiffness (beta stiffness index - 13 stiffness index, arterial compliance - AC, pulse wave velocity - PWV, augmentation index - AIx) were determined using an ultrasound device (ALOKA ProSound a 10). RESULTS: Patients with COPD have increased markers of arterial stiffness compared to controls (B stiffness index,p=0.03; AC, p=0.002; carotid PWV, p<0.001; Alx, p<0.001). There were no differences between the two groups regarding the classical cardiovascular risk factors with the exception of smoking history. Patients with severe pulmonary disease had more increased 13 stiffness index and PWV than those with mild and moderate disease(p=0.03, respectively p=0.004). CONCLUSIONS: Patients with COPD had increased carotid arterial stiffness. In severe forms of COPD, arterial stiffness seems to be more important than in mild and moderate pulmonary disease.

Assessment of the correlation between two defining criteria for bidirectional isthmic block in the ablation of typical atrial flutter.

BACKGROUND: A complete, bidirectional conduction block in the cavotricuspid isthmus (CTI) represents the end-point of the typical atrial flutter ablation. We investigated the correlation between two criteria for successful ablation, one based on the atrial bipolar electrogram morphology before and after complete CTI conduction block, compared to the standard criteria of differential pacing and reversal in the right atrial depolarization sequence during coronary sinus (CS) pacing. METHOD: We conducted a retrospective study in 111 patients (81 males, average age 62±10 years) who underwent an atrial flutter ablation during September 2007 - July 2009 in the Cardiology - Rehabilitation Hospital, UMF Cluj-Napoca. We assessed the presence of a bidirectional block at the end of the procedure using the standard criteria. We then analyzed the morphology of the bipolar atrial electrograms adjacent to the ablation line, before and after CTI conduction block. RESULTS: A change from a qRs morphology to a rSr' morphology when pacing from the coronary sinus and from a rsr' morphology to a QRS morphology when pacing from the low-lateral right atrium was associated with a CTI conduction block. Sensitivity (Se), specificity(Sp), positive predictive value (PPV), negative predictive value (NPV) were 96%, 89%, 99% and 67% respectively. CONCLUSION: Our study suggests that the analysis of the atrial bipolar electrogram next to the ablation line before and after CTI ablation may be used as a reliable criterion to validate CTI conduction block due to its high sensitivity, specificity and positive predictive value.

Factors influencing the onset of diabetes mellitus after kidney transplantation: a single French center experience.

Posttransplantation diabetes mellitus (PTDM) is a complication arising mostly during the first 6 months after kidney transplantation. Considering the serious outcomes of chronic hyperglycemia in kidney transplant patients, the recognition of factors that contribute to the onset of PTDM is of particular relevance. A retrospective analysis was performed to document the incidence of and the risk factors for diabetes mellitus occurring in the first year after kidney transplantation among 177 adult patients, without previously known diabetes transplanted between January 1998 and December 2000. PTDM, defined as fasting plasma glucose > or = 126 mg/dL confirmed by repeat testing on a different day, occurred in 48 (27.12%) patients of whom 36 showed transient changes during the first year after transplantation. Univariate analysis identified variables to be associated with the onset of PTDM: older recipient age (P = .05), male gender (P = .03), family history of diabetes (P = .04), advanced donor age (P = .008), absence of induction immunosuppression (P = .04), use of tacrolimus (vs cyclosporine; P = .01), one or more than one (steroid-treated) acute rejection episode(s) (P = .000001), cytomegalovirus infection (P = .02), and use of beta-blockers or diuretics (P = .05). By multivariate analysis, five factors were independently associated with the onset of PTDM: two episodes of rejection (odds ratio = 42.69, P = .000025), one episode of rejection (5.01, P = .007), older recipient age (1.06, P = .017), family history of diabetes (7.24, P = .011), and weight at transplantation (1.03, P = .048). Tacrolimus treatment remained of borderline significance (2.77, P = .05). In addition to traditional risk factors predisposing to the development of type 2 diabetes in the general population, episodes of acute rejection significantly influence the incidence of PTDM.