Cardiovascular outcomes and molecular targets for the cardiac effects of Sodium-Glucose Cotransporter 2 Inhibitors: A systematic review.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new class of glucose-lowering drugs traditionally used to control blood glucose levels in patients with type 2 diabetes mellitus, have been proven to reduce major adverse cardiovascular events, including cardiovascular death, in patients with heart failure irrespective of ejection fraction and independently of the hypoglycemic effect. Because of their favorable effects on the kidney and cardiovascular outcomes, their use has been expanded in all patients with any combination of diabetes mellitus type 2, chronic kidney disease and heart failure. Although mechanisms explaining the effects of these drugs on the cardiovascular system are not well understood, their effectiveness in all these conditions suggests that they act at the intersection of the metabolic, renal and cardiac axes, thus disrupting maladaptive vicious cycles while contrasting direct organ damage. In this systematic review we provide a state of the art of the randomized controlled trials investigating the effect of SGLT2i on cardiovascular outcomes in patients with chronic kidney disease and/or heart failure irrespective of ejection fraction and diabetes. We also discuss the molecular targets and signaling pathways potentially explaining the cardiac effects of these pharmacological agents, from a clinical and experimental perspective.

Chronic thromboembolic pulmonary disease: Association with exercise-induced pulmonary hypertension and right ventricle adaptation over time: Chronic thromboembolic pulmonary disease and exercise pulmonary hypertension.

BACKGROUND AND AIM: Chronic thromboembolic pulmonary disease (CTEPD) is a progressive condition caused by fibrotic thrombi and vascular remodeling in the pulmonary circulation despite prolonged anticoagulation. We evaluated clinical factors associated with CTEPD, as well as its impact on functional capacity, pulmonary haemodynamics at rest and after exercise, and right ventricle (RV) morphology and function. METHODS: We compared 33 consecutive patients with a history of acute pulmonary embolism and either normal pulmonary vascular imaging (negative Q-scan, group 1, n = 16) or persistent defects on lung perfusion scan (positive Q-scan) despite oral anticoagulation at 4 months (group 2, n = 17). Investigations included thrombotic load, the Pulmonary Embolism Severity Index (PESI) score, functional class, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), cardiopulmonary exercise test (CPET) and echocardiographic parameters at rest and after exercise (ESE), at 4 and at 24 months. RESULTS: Compared with group 1, group 2 featured a higher PESI score (p = 0.02) and a higher thrombotic load (p = 0.004) at hospital admission. At 4 months, group 2 developed exercise-induced pulmonary hypertension (Ex-PH) at CPET (p < 0.001) and ESE (p < 0.001). At 24 months group 2 showed higher NT-proBNP (p < 0.001), WHO-FC (p < 0.001), systolic (p<0.001) and diastolic (p = 0.037) RV dysfunction and worse RV-arterial coupling (p < 0.001) despite maintaining a low or intermediate echocardiographic probability of PH. CONCLUSIONS: This is the first "proof of concept" study showing that patients with a positive Q-scan frequently develop Ex-PH and RV functional deterioration as well as reduced functional capacity, generating the hypothesis that Ex-PH could help detect the progression to CTEPD.

Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.

BACKGROUND: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients. OBJECTIVES: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. METHODS: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. RESULTS: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. CONCLUSIONS: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.

Impact of Exercise-Induced Pulmonary Hypertension on Right Ventricular Function and on Worsening of Cardiovascular Risk in HIV Patients.

Background and Aim: Exercise-induced pulmonary hypertension (ExPH) predicts clinical outcomes, such as all-cause mortality and cardiovascular (CV) hospitalizations, in patients with dyspnea on effort. We investigated its prognostic significance in human immunodeficiency virus (HIV)-affected patients. Methods: In 52 consecutive HIV patients with either low (n = 47) or intermediate probability (n = 5) of PH at rest, we evaluated­at time 0 and after 2 years­the prognostic determinants of CV risk, according to the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines. Patients were classified with or without ExPH at stress echocardiography (ESE) and cardiopulmonary exercise test (CPET). We then related ExPH at time 0 with clinical worsening (CV risk score increase >20% after 2 years). Results: Right ventricle (RV) systolic function was significantly reduced in patients with ExPH compared to those without ExPH at CPET. This also occurred in patients with intermediate/high probability compared to those with low probability of ExPH at ESE. The former exhibited worse values of TAPSE and FAC (p < 0.001 and p = 0.01, respectively). A significantly higher proportion of patients with ExPH (CPET) or with intermediate/high probability of ExPH (ESE) had higher sPAP (p < 0.001), mPAP (p = 0.004) and higher TRV (p = 0.006), as well as higher right atrial area (p < 0.001) and indexed right atrial volume (p = 0.004). Total pulmonary vascular resistance (expressed by the ratio between TRV and the velocity-time integral at the level of the right ventricular outflow tract) was higher both in patients with ExPH and in those with intermediate/high probability of ExPH (p < 0.001). Patients with intermediate/high probability of ExPH at ESE showed a trend (p = 0.137) towards clinical worsening compared to those with low probability of ExPH. No patients with low probability of ExPH had a >20% increased CV risk score after 2 years. We found an association between higher NT-proBNP and the presence or intermediate/high probability of ExPH after 2 years (p = 0.048 at CPET, p = 0.033 at ESE). Conclusions: The assessment of ExPH may predict a trend of increasing CV risk score over time. If confirmed at a longer follow-up, ExPH could contribute to better risk stratification in HIV patients.

Exercise-Induced Pulmonary Hypertension Is Associated with High Cardiovascular Risk in Patients with HIV.

Background and Aim: Pulmonary hypertension (PH) at rest can be preceded by the onset of exercise-induced PH (ExPH). We investigated its association with the cardiovascular (CV) risk score in patients with human immunodeficiency virus (HIV). Methods: In 46 consecutive patients with HIV with low (n = 43) or intermediate (n = 3) probability of resting PH, we evaluated the CV risk score based on prognostic determinants of CV risk. Diagnosis of ExPH was made by cardiopulmonary exercise test (CPET) and exercise stress echocardiogram (ESE). Results: Twenty-eight % (n = 13) of the enrolled patients had ExPH at both CPET and ESE, with good agreement between the two methods (Cohen's kappa = 0.678). ExPH correlated directly with a higher CV score (p < 0.001). Patients with a higher CV score also had lower CD4+ T-cell counts (p = 0.001), a faster progression to acquired immunodeficiency syndrome (p < 0.001), a poor immunological response to antiretroviral therapy (p = 0.035), higher pulmonary vascular resistance (p = 0.003) and a higher right atrial area (p = 0.006). Conclusions: Isolated ExPH is associated with a high CV risk score in patients with HIV. Assessment of ExPH may better stratify CV risk in patients with HIV.

Temporal Convolutional Neural Networks for Radar Micro-Doppler Based Gait Recognition.

The capability of sensors to identify individuals in a specific scenario is a topic of high relevance for sensitive sectors such as public security. A traditional approach involves cameras; however, camera-based surveillance systems lack discretion and have high computational and storing requirements in order to perform human identification. Moreover, they are strongly influenced by external factors (e.g., light and weather). This paper proposes an approach based on a temporal convolutional deep neural networks classifier applied to radar micro-Doppler signatures in order to identify individuals. Both sensor and processing requirements ensure a low size weight and power profile, enabling large scale deployment of discrete human identification systems. The proposed approach is assessed on real data concerning 106 individuals. The results show good accuracy of the classifier (the best obtained accuracy is 0.89 with an F1-score of 0.885) and improved performance when compared to other standard approaches.

Space geodetic monitoring of engineered structures: The ongoing destabilization of the Mosul dam, Iraq.

We present a detailed survey of the ongoing destabilization process of the Mosul dam. The dam is located on the Tigris river and is the biggest hydraulic structure in Iraq. From a geological point of view the dam foundation is poor due to a site geology formed by alternating strata of highly soluble materials including gypsum, anhydrite, marl and limestone. Here we present the first multi-sensor cumulative deformation map for the dam generated from space-based interferometric synthetic aperture radar measurements from the Italian constellation COSMO-SkyMed and the European sensor Sentinel-1a over the period 2014-2016 that we compare to an older dataset spanning 2004-2010 acquired with the European Envisat satellite. We found that deformation was rapid during 2004-2010, slowed in 2012-2014 and increased since August 2014 when grouting operations stopped due to the temporary capture of the dam by the self proclaimed Islamic State. We model the inferred deformation using a Markov chain Monte Carlo approach to solve for change in volume for simple tensile dislocations. Results from recent and historical geodetic datasets suggests that the volume dissolution rate remains constant when the equivalent volume of total concrete injected during re-grouting operations is included in the calculations.

The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients.

BACKGROUND: Tacrolimus is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCB1. We have investigated the effects of possible relevant CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) present in both donors and recipients on tacrolimus blood levels achieved in a population of 32 Caucasian liver transplant patients. MATERIAL/METHODS: At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C(0)) were determined. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*3 [6986A>G] as well as ABCB1 at exons 21 [2677G>T] and 26 [3435C>T]. RESULTS: 87.5% of the population showed a CYP3A5*3/*3 genotype. For the ABCB1 SNPs, in the case of 3435C>T the total frequency observed for the allelic variant was 50%. For the 2677G>T, the total frequency of the allelic variant was 12.5%, lower than in other Caucasian populations and without any significant linkage with 3435C>T. At 3 and 6 months after transplantation, tacrolimus dose requirements were significantly higher in patients receiving a liver with one copy of the *1 allele compared to those homozygous for the *3 allele (0.111+/-0.057 vs. 0.057+/-0.030 [P<0.05] at 3 month and 0.086+/-0.051 vs. 0.044+/-0.025 [P<0.05] at 6 month). For the recipients' genotypes, the presence of at least one *1 copy tended, though not statistically significantly, to increase tacrolimus doses. With regard to the ABCB1 SNPs, they did not show any influence on tacrolimus dosing requirements. CONCLUSIONS: Pharmacogenetic analysis of CYP3A5 in the donor could contribute to determine the appropriate initial dosage of tacrolimus in liver transplant patients.