Background: Since the 1990s, numerous investigations have assessed the diagnostic effectiveness—specifically sensitivity, specificity, and accuracy—of exercise stress testing (EST), stress echocardiography (SE), stress myocardial single-photon emission computed tomography (SPECT), and stress cardiac magnetic resonance imaging (CMR). However, the outcomes of these studies have often been inconsistent and inconclusive. To provide a clearer comparison, we conducted systematic reviews and meta-analyses aimed at quantitatively evaluating and comparing the aggregated diagnostic performance of these four commonly used techniques for detecting coronary artery disease (CAD). Methods: A comprehensive search of PubMed, Scopus, Embase, Cochrane Library, and Web of Science was conducted to identify cohort studies evaluating the diagnostic accuracy of EST, SE, stress myocardial SPECT, and stress CMR in symptomatic patients with suspected or confirmed CAD. The main goal was to compare their diagnostic value by pooling sensitivity and specificity results. Each study’s data were extracted in terms of true positives, false positives, true negatives, and false negatives. Results: A total of 104 studies, comprising 16,824 symptomatic individuals with either suspected or known CAD, met the inclusion criteria. The pooled sensitivities for CAD detection were 0.66 (95% CI: 0.59–0.72, p < 0.001) for EST, 0.81 (95% CI: 0.79–0.83, p < 0.001) for SE, 0.82 (95% CI: 0.78–0.85, p < 0.001) for stress myocardial SPECT, and 0.83 (95% CI: 0.81–0.85, p < 0.001) for stress CMR. Corresponding specificities were 0.61 (95% CI: 0.55–0.67, p < 0.001), 0.85 (95% CI: 0.82–0.87, p < 0.001), 0.74 (95% CI: 0.70–0.78, p < 0.001), and 0.89 (95% CI: 0.86–0.92, p < 0.001), respectively. Considerable heterogeneity was observed across the studies, as reflected by I² values ranging from 82.5% to 92.5%. Egger’s generalized test revealed statistically significant publication bias (p < 0.05 for all methods), likely due to the influence of smaller studies reporting more favorable results. Despite this, sensitivity analyses supported the overall robustness and reliability of the pooled findings. Conclusions: Among the diagnostic tools assessed, EST demonstrated the lowest accuracy for detecting obstructive CAD, whereas stress CMR exhibited the highest. Although stress myocardial SPECT showed strong sensitivity, its specificity was comparatively limited. SE emerged as the most balanced option, offering good diagnostic accuracy combined with advantages such as broad availability, cost-effectiveness, and the absence of ionizing radiation.

Background: During the last decades, a small number of studies reported a wide range of variability in the estimated prevalence of mitral valve prolapse (MVP) among individuals with pectus excavatum (PE). The present systematic review and meta-analysis has been primarily designed to summarize the main findings of these studies and to estimate the overall prevalence of MVP among PE individuals. Methods: All imaging studies assessing the prevalence of MVP in PE individuals vs. healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case–Control Studies. Events (presence of MVP) and nonevents (absence of MVP) in PE individuals and control groups were recorded. The main outcome was the measure of odds ratio (OR) for MVP presence pooled with 95% confidence intervals, using a fixed-effects model. Results: The full texts of eight studies with 303 PE patients (mean age 25.7 yrs) and 498 healthy controls (mean age 31 yrs) were analyzed. Three studies assessed MVP prevalence in children and early adolescents, whereas the remaining five studies examined PE adults. The prevalence of MVP in PE individuals and healthy controls was 40.6% and 12.8%, respectively. In the pooled sample, the OR for MVP presence was significantly higher in PE individuals compared to controls (OR = 5.80, 95%CI = 3.83–8.78, Z = 8.30, p < 0.001). Subgroup analysis revealed that MVP prevalence was approximately three-fold higher among PE children and early adolescents compared with PE adults. Overall, high consistency was observed in the pooled effect sizes, due to the low statistical heterogeneity among the included studies (I² = 22.7%, p = 0.25). Egger’s test for a regression intercept gave a p-value of 0.07, indicating no publication bias. The sensitivity analysis supported the robustness of the results. Conclusions: PE individuals are nearly six times more likely to have MVP than controls. MVP prevalence is three-fold higher in PE individuals during childhood and early adolescence, compared to PE adults. Given the strong association between MVP and PE, MVP should be suspected in all individuals with anterior chest wall deformity.

The presence of unilateral vesicoureteral reflux (VUR), and renal dysplasia associated with posterior urethral valves (PUV) (VURD syndrome) was believed to represent a pressure-released pop-off mechanism protecting kidney function. We aimed to investigate its role with respect to long-term kidney function in a cross-sectional and longitudinal analysis. We compared the iohexol glomerular filtration rate (GFR) measured at 5 (GFR₅) and 10 (GFR₁₀) years of age in children with (Group A) and without (Group B) VURD syndrome, who underwent PUV resection under 2 years of age. VURD syndrome was diagnosed in cases of unilateral loss of kidney function (<15% on nuclear medicine test) associated with ipsilateral grade IV-V VUR. VURD syndrome was diagnosed in 16 (12.8%) out of 125 patients who met the inclusion criteria. While the median GFR₅ was similar in the 2 groups [Group A: 87.3 (74.7–101.2) mL/min/1.73 m² vs. Group B: 99.6 (77–113) mL/min/1.73 m², p-value: 0.181], the median GFR₁₀ values were significantly lower in children with VURD syndrome [Group A: 75.7 (71.2–85.9) mL/min/1.73 m² vs. Group B: 95.1 (81.2–114.2) mL/min/1.73 m², p-value: 0.009]. Similar results were obtained in a longitudinal analysis of the children with GFR measurement available both at 5 and 10 years of age [GFR₅ in Group A: 93.1 (76.9–103.5) mL/min/1.73 m² vs. Group B: 97.5 (80–113) mL/min/1.73 m², p-value: 0.460; GFR₁₀: Group A: 71.9 (71.9–85.9) mL/min/1.73 m² vs. Group B: 94.8 (81.5–110.6) mL/min/1.73 m², p-value: 0.024]. In conclusion, VURD syndrome does not show a protective role in kidney function preservation. On the contrary, it seems to be associated with a deterioration of the kidney function on a long-term follow-up.

Untargeted metabolomics faces significant challenges in standardization due to variability introduced by sample preparation and analytical workflows. We systematically evaluated the impact of biological matrices, extraction protocols, and chromatographic configurations to establish a mechanism-informed framework aimed at improving reproducibility in large-scale clinical and epidemiological studies. Three extraction protocols were compared using an in-house pooled heparin plasma: monophasic protein precipitation with isopropanol (IPA), methanol:acetonitrile (MeOH:ACN), and a modified Matyash biphasic method. The most reproducible protocol was then applied to four blood matrices. Samples were analysed using untargeted metabolomics on hydrophilic interaction liquid chromatography (HILIC) and reversed-phase (RP) HPLC columns, with mass spectrometry data processed using Compound Discoverer. Both IPA and MeOH:ACN extractions achieved over 80% of features with coefficient of variation (CV%) ≤ 30% for both RP and HILIC, whereas the Matyash method showed higher variability, with a larger proportion of metabolites exhibiting CV% > 30%. Across matrices, RP chromatography detected over 80% of metabolites with CV% < 30%, while HILIC showed higher variability, with at least 20% of metabolites above this threshold. Among matrices, serum and heparin plasma outperformed EDTA and citrate in reproducibility. We propose a standardized workflow in which monophasic extractions combined with RP chromatography maximize reproducibility and metabolite coverage, minimizing methodological artefacts and providing a reliable framework for robust biological discovery in large-scale untargeted metabolomics studies.

Background: During the last two decades, a limited number of studies have provided echocardiographic details regarding the cardiac structure and function of individuals aged ≥100 years. These studies analyzed limited sample sizes of centenarians using different methodologies. The present systematic review was primarily designed to summarize the main findings of these studies and to examine the overall influence of extremely advanced age on cardiac structure and function. Methods: All echocardiographic studies that evaluated the cardiac structure and function in individuals aged ≥100 years, selected from the PubMed, Embase, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases, were included. There was no limitation on the time period. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: A total of eight studies with 1340 centenarians [median age 101.4 years (IQR 101–103 years)] met the eligibility criteria and were analyzed. The centenarians were predominantly females [76.3% (IQR 60–85%)] with a small body surface area, long history of hypertension and slightly impaired renal functional reserve. The centenarian population showed a reduced burden of cardiovascular disease but an increased comorbidity burden, as assessed using the Charlson [median value 3.7 (IQR 1.8–5.5)] and Katz [median value 2.1 (IQR 1.1–3.1)] indexes. The echocardiographic findings comprised left ventricular (LV) concentric remodeling, with first-degree diastolic dysfunction [median E/A ratio 0.8 (IQR 0.7–0.9)], a moderate increase in LV filling pressure [median E/e’ ratio 16.8 (IQR 16.2–17)], normal LV systolic function [median left ventricular ejection fraction (LVEF) 60.9% (IQR 55–84%)] and mild-to-moderate pulmonary hypertension [median systolic pulmonary artery pressure 42.1 mmHg (IQR 37–54 mmHg)]. The pooled prevalence of LV systolic dysfunction (LVEF < 50%) was 15.8%. Moderate-to-severe valvular heart diseases were detected in less than one-third of the centenarians. Compared with the outpatient and in-home cohorts, hospitalized centenarians were less commonly females and were more likely to be affected by significant LV hypertrophy with a supra-normal LVEF, higher degrees of valvulopathies and impaired pulmonary hemodynamics. Conclusions: The evidence currently suggests that centenarians have typical LV concentric remodeling with increased myocardial stiffness and diastolic dysfunction, which predispose them to heart failure with a preserved ejection fraction (HFpEF). Cardioprotective treatment should be considered for personalized implementation and uptitration in this special population.