For over a decade, endoscopic hemostatic powders have been used to manage upper gastrointestinal bleeding (UGIB). Various preclinical benchtop and animal models have been developed to evaluate these devices. Multiple companies have released hemostatic powders to market, assessing their safety and efficacy using an established porcine gastric vessel bleed model. This model simulates an aggressive arterial bleed, allowing prototypes to be tested under challenging conditions. It requires a surgeon to insert an artery segment into the gastric lumen and puncture it to produce a bleed. In our study, we tested a control group not included in prior research. We aimed to evaluate the relationship between intragastric pressure and bleed severity by injecting gas used to deliver hemostatic powder to the bleed site, without administering hemostatic powder. Our results indicate that elevated intragastric pressures alone can cause bleed cessation. Additional findings suggest that other factors in the model can lead to false positive hemostasis. This study highlights flaws in the porcine gastric vessel bleed model and underscores the need to develop more robust models for testing hemostatic devices, as no valid endoscopic bleed model currently exists. These experiments stress the importance of vetting preclinical models before acquiring efficacy data.

The arterial network in healthy young adults is thought to be structured to minimise wave reflection in conduit arteries, producing an ascending aortic pressure waveform with three key features: early systolic peak, negative systolic augmentation, and diastolic hump. One-dimensional computer models have provided significant insights into arterial haemodynamics, but no previous models of the young adult have exhibited these three features. Since the latter was likely to be related to unrepresentative or non-optimised impedance properties of the model arterial networks, we developed a new ‘YoungAdult’ model that incorporated 1) a novel and more accurate empirical equation for approximating wave speeds, based on area and relative distance to elastic-muscular arterial transition points, 2) optimally-matched arterial junctions, and 3) an improved arterial network geometry that eliminated ‘within-segment’ taper (which causes wave reflection in conduit arteries) whilst establishing ‘impedance-preserving’ taper. These model properties led to wave reflection occurring predominantly at distal vascular beds, rather than in conduit arteries. The model predicted all three typical characteristics of an ascending aortic pressure waveform observed in young adults. When compared with non-invasively acquired pressure and velocity measurements (obtained via tonometry and Doppler ultrasound in 7 young adults), the model was also shown to reproduce the typical waveform morphology observed in the radial, brachial, carotid, temporal, femoral, and tibial arteries. The YoungAdult model provides support for the concept that the arterial tree impedance in healthy young adults is exquisitely optimised, and it provides an important baseline model for investigating cardiovascular changes in ageing and disease states.

Human arteries show structural and functional peculiarities according to the nutrient and oxygen needs of a specific vascular district. This architectural heterogeneity is reflected in the pathological setting of cardiovascular diseases (CVDs). Indeed, the responsiveness to cardiovascular risk factors, the morphological and molecular patterns are discriminating factors among CVDs affecting different vascular beds. Micro-RNAs (miRNAs) are endogenous regulators of gene expression and fine tuners of vascular cell differentiation, thus these non-coding RNAs can modulate the arterial heterogeneity. The identification of a miRNA signature artery-specific would be promising in the therapy of CVDs, especially in frail elderly patients. In the present review we will provide a concise description of the arterial tree heterogeneity on structural and cellular basis, mainly in the pathological context. Secondly, we will address the miRNA potential as crucial mediators of arterial heterogeneity focusing on abdominal aorta and femoral artery, with the final goal of strengthening the search of more targeted therapies in CVDs and stratification approaches in frail elderly patients.

Accidental arterial embolization of hyaluronic acid (HA) fillers can lead to severe complications, including skin ischemia, blindness, and stroke. Currently, the intra-arterial dispersal and fragmentation behavior of HA gels is unknown but is critical to our understanding of the pathomechanism of these injuries. This work introduces the Pulsatile Unit for the Laboratory Simulation of Arterioembolic Restrictions (PULSAR) and evaluates the intravascular behavior of different HA gels. The fragmentation and dispersal behaviors of four HA gels with distinct rheological properties were evaluated via high-resolution videography and ImageJ particle size and morphology analysis. The gels' elastic modulus (G'), loss modulus (G''), tan(δ), and HA concentration were subsequently correlated with their intra-arterial behaviors. This study effectively confirms the extensive fragmentation of HA gels upon arterial inoculation, with particle sizes ranging from <50 µm to >1 mm. Gel particle size and morphology correlate most significantly with tan(δ). Conversely, arterial flow rates do not significantly influence gel fragmentation behavior, though the probability of proximal, macrovascular obstruction is affected. Overall, this study validates the PULSAR model for simulation of arterial dynamics and the testing of intravascular filler kinematics. The findings highlight the importance of gel viscoelasticity and flow parameters in determining particle size, dispersibility, and occlusive potential.

Pulmonary hypertension (PH) is a progressive condition that affects pulmonary vessels, but its main prognostic factor is right ventricle (RV) function. Many mice/rat models are used for research in PAH, but results fail to translate in clinical trials. This study reviews studies that test interventions on pulmonary artery banding (PAB), a model of isolated RV disfunction, and PH models. Multiple tested drugs both improved pulmonary vascular hemodynamics in PH models and RV structure and function in PAB animals. PH models and PAB frequently exhibited similar results (73.1% concordance) with drugs other than endothelin receptor antagonists and phosphodiesterase inhibitors. RV systolic pressure accounted for most differences between PH models and PAB. On the other side, all results on RV fibrosis agreed (12 drugs). Macitentan, sildenafil and tadalafil improved most tested pathophysiological parameters in PH models, but almost none in PAB animals. Dapagliflozin was the only drug that improved no parameters. This review shows that many drugs currently under research for PAH have a cardioprotective effect on animals that may translate to humans. To improve the translational potential of drugs in this field, researchers should test them in multiple models, including PAB, while optimizing induction methods for human disease translation.

When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that decon-struction of the extracellular matrix is essential to the remodeling of smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of in-ternal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content is low. Outward remodeling of these vessels with a 10-20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension as demonstrated by straight-ening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an increased risk of cardiovascular diseases (CVD), leading to elevated mortality rates among patients. We aimed to evaluate the levels of cardio-ankle vascular index (CAVI), global longitudinal strain (GLS), ventricular-arterial coupling (VAC) and high-sensitivity cardiac troponin (hsTn), in SLE patients and to explore their relationship with clinical parameters. Methods: This cross-sectional study enrolled 82 SLE patients without evident cardiac or kidney impairment and 41 age- and sex matched healthy controls. We comparatively evaluated CAVI, GLS, VAC, and hsTn between SLE patients and controls, and we assessed their association among SLE patients with disease activity based on the SELENA-SLEDAI Activity Index. Multivariate regression analysis was performed to identify independent predictors of CAVI and hsTn within the SLE cohort. Results: In comparison to healthy controls, SLE patients presented with significantly higher CAVI, GLS and hsTn levels, while VAC was significantly reduced (p<0.001). Further, SLE patients with active disease (SELENA-SLEDAI≥4) exhibited higher levels of CAVI and troponin than those with inactive disease (p<0.001). SLEDAI was an independent predictor of CAVI, while VAC and SLEDAI were independent determinants of hsTn in SLE cohort. Conclusion: SLE patients displayed abnormal levels of CAVI, VAC, GLS, and troponin compared to healthy individuals. Our findings implicate the potential of those CV novel CVD risk factors to refine screening and therapeutic strategies for this specific population.

Pulmonary arterial hypertension (PAH) is a pathophysiological condition characterized by pulmonary vascular remodeling and elevated vascular resistance, which may ultimately result in cardiovascular failure and sudden cardiac death. In recent years, the occurrence of pregnancy complicated by pulmonary arterial hypertension has witnessed a notable increase, whereas the incidence of postpartum pulmonary arterial hypertension is comparatively rare. This study presents a case involving a 39-year-old female who exhibited severe pulmonary arterial hypertension, finally diagnosed as idiopathic pulmonary arterial hypertension, within 2 days postpartum. The diagnosis was made following a thorough clinical examination. This case report emphasizes the significance of promptly initiating targeted therapy as an initial step in effectively managing patients and the criticality of conducting a thorough assessment of multidisciplinary collaboration in postpartum management. Furthermore, the report has the potential to enhance awareness and education regarding the future management of similarly intricate conditions.

Arterial ageing is thought to cause a diastolic-to-systolic shift in the return time (RT) of backward waves to central arteries. However, current methods of estimating RT—inflection point, zero crossing, and foot methods—depend on a single waveform feature and produce systolic RT throughout life. We propose a novel centroid method that accounts for the entire backward pressure waveform and develop a ground truth RT (GTRT), which can be used in computational models to test the accuracy of RT estimation methods. Linear wave tracking was implemented in a one-dimensional systemic arterial tree model and GTRT was calculated as the amplitude-weighted mean RT of backward waves at the ascending aorta. Using a virtual cohort of 1200 patients, the centroid RT was closest to GTRT compared to the zero crossing, inflection point, and foot methods; mean differences (limits of agreement) were -8 (-47,30), vs -42 (-136,52), -78 (-305,149), and -197 (-379,-15) ms, respectively. The sensitivity of the methods to changes in RT was also assessed in ten sheep. A balloon catheter in the descending thoracic aorta was used to generate a backward-running pulse that arrived at the ascending aorta at different times during diastole or systole, allowing the “bulk” RT of the backward-running wave ensemble to be manipulated. Only the centroid method was sensitive to both diastolic and systolic changes in RT. We conclude that the accuracy and robustness of the centroid method make it most suitable for evaluating the diastolic-to-systolic shift in RT of backward waves with ageing.

If we accept that human body is a dissipative structure, then the recovery of the body should be considered as a redirection of the enegy flows. The recovery of vertebral cartilage through redirecting of inner dissipative flow requires the understanding of how is this case the fact of reversibility can be proven. We proposed the approach, that according to the collected data, satisfies all the scientific requirements.

Exercise training influences the risk of vascular thrombosis in patients with peripheral arterial disease (PAD). Mitochondrial functionalities in platelets involve the cellular bioenergetics and thrombogenesis. This study aimed to elucidate the effect of cycling exercise training (CET) on platelet mitochondrial bioenergetics in PAD patients. Forty randomly selected patients with PAD engaged in general rehabilitation (GR) with CET (i.e., cycling exercise at ventilation threshold for 30 min/day, 3 days/week) (GR+CET, n=20) or to a control group that only received GR course (n=20) for 12 weeks. Systemic aerobic capacity and platelet mitochondrial bioenergetics that included oxidative phosphorylation (OXPHOS) and electron transport system (ETS) were measured using automatic gas analysis and high-resolution respirometry, respectively. The experimental results demonstrated that GR+CET for 12 weeks significantly (i) elevated VO2peak and lowered VE-VCO2 slope, (ii) raised resting ankle-brachial index and enhanced cardiac output response to exercise, (iii) increased the distance in 6-minute walk test and raised the Short Form-36 physical/mental component scores, and (iv) enhanced capacities of mitochondrial OXPHOS and ETS in platelets by activating FADH2 (Complex II)-dependent pathway. Moreover, changes in VO2peak levels were positively associated with changes in platelet OXPHOS and ETS capacities. However, no significant changes in systemic aerobic capacity, platelet mitochondrial bioenergetics, and health-related quality of life (HRQoL) occurred following GR alone. Hence, we conclude that CET effectively increases the capacities of platelet mitochondrial bioenergetics by enhancing Complex II activity in patients with PAD. Moreover, the exercise regimen also enhanced functional exercise capacity, consequently improving HRQoL in PAD patients.

The current echocardiography reference values are derived primarily from populations in North America and Europe. It becomes necessary to study ethnically different groups of the population, which often have different living conditions, food habits and lifestyle. The aim of the study was to compare echocardiography indicators in urbanized patients with arterial hypertension of the Shor and non-indigenous ethnic groups living in the Gornaya Shoria region. The study included patients with arterial hypertension: 58 Shors (20 men and 38 women) and 50 non-indigenous residents (15 men and 35 women) of Gornaya Shoria. All underwent an echocardiographic study with an assessment of the left heart parameters. We assessed the left ventricular hypertrophy (LVH) severity, LV geometry and diastolic function in the ethnic and sex groups. Shor with hypertension no showed a significant difference in left ventricular dimensions compared to Caucasian. Severe abnormal LVH was associated in the Shors with glucose levels (OR 3.24, 95%CI 1.56-6.7, p=0,001), and in Caucasians with systolic (p=0.021) and diastolic (p=0.011) blood pressure, and heart rate (p=0.033). The Shor men were more likely to have normal LV diastolic function (p=0.029) and LV concentric remodeling (p=0.023), and less often to have normal LV geometry (p=0.015) compared to non-indigenous men. Thus, this study can be useful in assessing the impact of the development of arterial hypertension, as well as the impact of changing the lifestyle of the Shors when moving to the city from rural areas on ethnic differences in echocardiography.

Leukotrienes are proinflammatory mediators that participate in the process of atherogenesis and contribute to the development of symptomatic peripheral arterial disease. The aim was to evaluate the relationship between leukotriene E4 (LTE4) and B4 (LTB4) with parameters reflecting endothelial vascular function in patients with chronic lower limb ischemia. This prospective observational study enrolled 50 consecutive patients undergoing endovascular treatment due to chronic lower limb ischemia (Rutherford 3). All participants were followed-up for one year (after 1, 3, 6 and 12 months), with a sequential assessment of urinary LTE4 and LTB4, as well as measures of endothelial and vascular function: Flow-Mediated Dilatation (FMD), Intima-Media Thickness (IMT), corrected Augmentation Index (AI75), Shear Rate (SR), Ankle-Brachial Index (ABI), Toe-Brachial Index (TBI). There was a significant relationship between LTE4 and measures of vascular function: FMD (R2 = 0.69, P<0.001), IMT (R2=0.12, P<0.01), AI75 (R2=0.43, P<0.001), SR (R2=0.48, P<0.001). Similar findings were noted for LTB4: FMD (R2=0.47, p<0.001), IMT (R2=0.23, P<0.001), AI75 (R2=0.61, P<0.001) and SR (R2=0.33, P<0.001). Alterations in parameters were significantly related: ΔLTE4 vs ΔFMD(R2=0.63, P<0.001), ΔSR (R2=0.42, P<0.001) and ΔLTB4 vs AI75(R2=0.40, P<0.001), SR(R2=0. 29, P<0.001). We conclude, that increasing concentrations of LTE4 and LTB4 are associated with impairment of vascular and endothelial function, which may lead to worse endovascular treatment clinical outcomes.

Access to health services compromises therapeutic adherence in patients with HTN, which is a risk factor for cardiovascular disease and premature death. The aim of the research is to determine the influence of access to health services on adherence to antihypertensive treatment during the COVID-19 pandemic. We included a cross-sectional analytical study. A survey was applied to 241 hypertensive patients at the Daniel Alcides Carrión Hospital, Callao-Peru. Data were analyzed using SPSS software. Absolute and relative frequencies were reported and the chi-square test was applied with a statistical significance level of p<0.05. In addition, multiple logistic regression analysis was performed using the Stepwise method. An association was found between non-adherence to treatment and health expenses (ORa: 1.9 CI 95% 1.7-2.2), not receiving care due to lack of a doctor (ORa: 2.8 CI 95% 1.5-3.2), having difficulty with schedules (ORa: 3.7 CI 95% 2. 3-5.5), fear of receiving care at the hospital (ORa: 4.5 CI 95 % 2.7-6.8), trust in health personnel (ORa: 7.5 CI 95% 2.3-10.5) and considering that the physician does not have enough knowledge (ORa: 3.1 CI 95% 2.4-7.8). Therapeutic adherence was associated with physician availability for care, difficulty with schedules, fear of being seen in the hospital, trust in health personnel, and waiting time.

Introduction: Spinal epidural arteriovenous fistulas (SEDAVFs) are extremely rare and the pathological process still remains unclear. Nevertheless, neurofibromatosis, surgery, as well as trauma have been implicated as causes. Nevertheless, long standing chronic vertebral compression fractures (VCFs) as a cause of SEDAVFs has not been reported in literature. Case Presentation: Our cases comprised of a male and female with ages 67 and 62 year respectively. They presented with weakness of bilateral lower extremities and back pain. Their symptoms deteriorated into mild recto-bladder dysfunction as well as hypoesthesia of lower limbs. They both had history of road traffic accidents (RTAs) prior to their symptomatology. In both cases, Magnetic resonance imaging (MRI) revealed VCFs prior to the above symptomatology. Spinal digital subtraction angiography (DSA) was used to confirm SEDAVFs in both cases. We utilized the trans-arterial route with Onyx embolization agent to obliterate both fistulae and their symptom resolved after the embolization. Two-years follow-ups revealed no recurrence of their fistulae. Conclusion: The initial long standing VCFs caused by trauma resulted in perforation of the dorsal somatic branches of the radicular artery leading to the occurrences of SEDAVFs in our cases.

Pulmonary arterial hypertension is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors, and likely gene x environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 36% of pediatric-onset idiopathic PAH (IPAH) compared to ~11% of adult-onset IPAH. De novo variants are frequently associated with PAH in children, and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, the increased etiologic heterogeneity, poorer prognosis and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

Pulmonary arterial hypertension (PAH) is a complex and devastating disease that the underlying cellular and molecular mechanisms are largely remains unknown. This study aimed to elucidate the key hub genes and pathways in PAH by bioinformatics analysis. In the current study, we performed WGCNA analysis to systematically identify the hub genes for PAH using transcriptome microarray data. From the Gene Expression Omnibus (GEO) database, one microarray dataset (GSE113439) was downloaded for this study. There were 26 samples in this data set, including 15 PHA samples and 11 normal controls. Based on weighted correlation network analysis, 11 modules were identified and the MEgreenyellow module showed a significantly positive correlation with PAH (r = 0.93, P = 1e−06). The genes in greenyellow module were mainly significantly enriched in mitophagy related pathways by KEGG analyses. Combined with the protein–protein interaction (PPI) and co-expression networks, ten hub genes were identified as candidate biomarkers for PAH in the greenyellow module, including CTNNB1, NIPBL, ROCK2, ROCK1, SCAF11, JAK1, BIRC6, KIF5B, PPP1R12A and XRN1. These hub genes might be potential targets for clinical therapy against PAH. The molecular mechanisms involved in these genes that affected the prognosis of PAH should be further validated through biological and basic studies.

Objectives: To analyze the clinical characteristics and factors associated with adverse drug reactions (ADR) in liver cancer patients receiving oxaliplatin‐based hepatic arterial infusion chemotherapy (HAIC). Methods: A retrospective analysis was performed on the clinical data of 137 patients with liver cancer who received oxaliplatin‐based HAIC. Changes in baseline characteristics, inflammatory factors, and other laboratory indicators in the no‐ADR and ADR groups were analyzed. Results: The incidence of serious ADR (CTCAE ≥ 3) was 21.9% (30/137). There was no significant difference in the cumulative dose of oxaliplatin between the two groups [157.3 (80.3, 322.4) vs. 206.6 (139.1, 324.2), P=0.161]. The increase in NEUT and IL‐6 was greater in the group treated with ADR than in the group not treated with ADR. Changes in NEUT [4.1 (1.5, 6.2) vs. 2.5 (0.5, 4.9), P=0.045] and changes in NEUTIL‐6 [4.2 (‐0.2, 22.9) vs. 0.8 (‐3.9, 7.7), P=0.026]. TBIL, ALT, AST, ALP, WBC, NEUT, PCT, CRP, TNF, IL‐2R, IL‐6, and IL‐10 were significantly higher after treatment than before in the ADR group (P < 0.05). In contrast, ALB and AFP were decreased. Conclusions: The severe ADR (CTCAE ≥ 3) associated with oxaliplatin‐based HAIC may be closely related to increased inflammatory factors such as NEUT and IL‐6. We should be vigilant for allergic reactions to oxaliplatin and increase monitoring during treatment

This study aimed to compare the effects of a permanent ischemic stroke model (focal ischemia by thermocoagulation of pial vessels) on sensorimotor function (cylinder test and adhesive removal test), behavioral tasks (novelty habituation memory-open field task), and cerebral infarct size in adult male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats over 42 days after the occurrence of stroke. We observed that the stroke caused asymmetry in the front paws and delayed adhesive removal. These effects were spontaneously reduced in WKY rats, but not in SHR. Short- and long-term novelty habituation memories were abolished by stroke in WYK and SHR. On the 3rd day after stroke, the size of the focal cerebral infarct was the same in WKY and SHR. However, on the 7th day, the infarct size decreased in WKY rats, but not SHR. These results suggested that SAH impairment of sensorimotor recovery in rats subjected to cerebral ischemia could be related to augmented focal cerebral infarct size. Moreover, the behavioral tasks used in this study were unaffected by Systemic Arterial Hypertension. Our results highlight the need for animal models of comorbidities in stroke research.

Background: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. There is a growing recognition of the causal interplay between arterial stiffness and HFpEF. We recently reported that phosphate retention is a trigger for arterial stiffness. This study focuses on whether arterial stiffness due to phosphate retention could be a predictor for HFpEF. Methods: The study subjects were 158 patients (68 males and 90 females, mean age 74.8±11.2). HFpEF was defined according to the guidelines of the ESC 2019. Pulse wave velocity (PWV) and central systolic blood pressure (CSBP) were used as markers for arterial stiffness and afterload, respectively. We measured serum levels of fibroblast growth factor 23 (FGF23) as a marker of phosphate retention. Results: The serum levels of FGF23 had significant relationship with PWV. PWV had significant relationships with LV mass index, plasma BNP levels, and relative wall thickness, e’ and E/e’ (p<0.001, respectively). Multivariate logistic regression analysis revealed that PWV higher values and hypertension were significant predictors for the dependent factor (HFpEF). Conclusions: Arterial stiffness amplified LV afterload, leading to LV concentric hypertrophy and LV diastolic dysfunction. This study presents that arterial stiffness due to phosphate retention, and hypertension are important predictors of HFpEF.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal „C” loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, associated usually with long-term alcohol and tobacco misuse and being more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66 year old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast enhanced computed tomography revealed the existence of a chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since there was no indication for endoscopic retrograde cholangiopancreatography, we decided to perform a pancreatoduodenectomy, as surgery appears to be the single effective treatment.

Introduction: The predictive value of the risk stratification scales in elderly patients with IPAH might differ from that in younger. It is unknown whether young and older IPAH patients have the same survival dependence on PAH-specific therapy numbers. The aim of the study was to evaluate the prognostic relevance of risk stratification scales and PAH medication numbers in elderly in comparison with young IPAH patients. Material and methods: 119 patients from a prospective single-center PAH registry were divided on to group I <60 years old (n=89) and group II ≥60 years old (n=30). ESC/ERS, REVEAL, and REVEAL 2.0 risk stratification scores were assessed at baseline, as well as H2FpEF- score and survival at follow-up. Results: During a mean follow-up period of 2.9 years (1.63; 6.0) 42 (35.3%) patients died; at 1, 2, 3, 5, 7, and 10 years survival was 95%, 88.6%, 78.5%, 61.7%, 48.5% and 33.7%, respectively. No survival difference was observed between the two groups despite the use of monotherapy in elderly patients. The best predictive value exhibited the REVEAL in group II (IPAH patients ≥60 years) - AUC 0.73 (0.56-0.91), p = 0.03; and in patients with LHD comorbidities in the entire cohort - AUC 0.73 (0.59-0.87), p<0.009. Factors independently associated with death in the entire cohort were CKD (p=0.01, HR 0.2), the right-to-left ventricle dimension ratio (p=0.0047, HR 5.97), and NT-proBNP >1400 pg/ml (p=0.008, HR 3.18). Conclusion: Risk stratification in elderly IPAH patients requires a fundamentally different approach than that of younger patients, taking into account the initial limitations in physical performance and comorbidities that interfere with current assessment scores. The REVEAL score reliably stratifies patients at any age and LHD comorbidities. The initial monotherapy seems to be reasonable in patients over 60 years. Selection tools for initial combination PAH therapy in older IPAH patients with comorbidities need to be validated in prospective observational studies.

Antioxidants reduce arterial stiffness but the effects previously reported are weak. The present study evaluated the effects of 2 weeks of therapy with a combination of antioxidants (l-cysteine, thiamine, pyridoxine and ascorbic acid) compared to placebo on stiffness index (SI) a measure of arterial stiffness that is strongly correlated with central pulse wave velocity (PWV), using a Pulse Trace recorder in a diverse group of 78 volunteers. SI fell by 1.7 m/sec relative to placebo (95% confidence intervals 0.6 to 2.7 m/sec), a reduction of 19% (95% confidence intervals 9% to 31%). The Glass effect size was 1.4, indicating a very strong treatment effect which was substantially greater than found in previous studies of the effects of antioxidant therapy on arterial stiffness. The magnitude of reduction in SI was positively correlated with increasing age (r = 0.362 P = 0.02). The change in RI, a measure of compliance of small to medium size arteries, did not differ between the antioxidant and placebo groups The combination of antioxidants studied reduced PWV to a much greater extent than reported for other antioxidants. This combination may be of value in the treatment of cardiovascular disease.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.

Purpose: To analyze the clinical efficacy of superselective renal artery embolization and retroperitoneal laparoscopic partial nephrectomy for the treatment of ruptured hemorrhagic renal angiomyolipoma and to provide a reference for the selection of treatment methods for ruptured hemorrhagic renal angiomyolipoma. Methods: A retrospective analysis was conducted on the clinical data of 24 patients who were diagnosed with ruptured hemorrhagic renal angiomyolipoma at the Second Hospital of Tianjin Medical University between January 2019 and December 2021. Among them, 10 patients were treated with superselective arterial embolization (SAE), and 14 patients were treated with retroperitoneal laparoscopic part nephrectomy (RLPN). The differences between the two treatment methods in terms of hospital stay, hospital costs, anesthesia method, operation time, intraoperative blood loss, postoperative bed rest time, antibiotic dosage, postoperative complication rate, tumor diameter changes, creatinine value changes, hemoglobin value changes, tumor recurrence rate, and reoperation rate were compared. Results: All patients completed the treatment and were discharged. There were no significant differences in length of hospital stay, hospital costs, creatinine change values, or postoperative complication rates between the two groups (P > 0.05). However, there were statistically significant differences (P < 0.05) in surgical time (85.50±19.94 min vs. 141.07±76.33 min), intraoperative blood loss (21.50±14.72 ml vs. 153.57±97.00 ml), postoperative bed rest time (22.7±1.56 h vs. 41.21±3.57 h), preoperative hemoglobin levels (94.7 ±23.62 g/L vs. 113.79 ±17.83 g/L), and hemoglobin changes (-6.60 ±10.36 g/L vs. -15.21 ±8.79 g/L) between the two groups. Both groups of patients had an average follow-up period of 22 months, and patients in the SAE group had a mean reduction of 3.33 cm in tumor diameter within the follow-up period compared with the preembolization period (P < 0.05). None of the patients in the SAE group experienced rebleeding, and there was no tumor recurrence in either group. Conclusion: SAE and RLPN are effective treatments for ruptured renal angiomyolipoma with good outcomes. Furthermore, compared to RLPN, SAE offers advantages such as simplicity of operation, minimal trauma, shorter surgical time, minimal impact on hemoglobin levels, shorter bed rest time, faster postoperative recovery, and maximal preservation of renal units.

Background: Myocardial infarction is increasing at a young age. New tools are needed to evaluate the risk population of young patients. GDF-15 has been implicated in several key mechanisms of atherogenesis and also is associated with increased mortality and cardiovascular events in patients with coronary artery disease. Arterial stiffness parameters, including pulse wave velocity, can also be measured using peripheral arterial tonometry and can indicate the presence or progression of atherosclerotic changes. The aim of this study is to evaluate the GDF-15 level and arterial stiffness parameters in patients with premature myocardial infarction Method: Thirty patients who recovered from a myocardial infarction were consecutively included. Fifteen age-sex-matched subjects were included as controls. The patients’ serum GDF-15 concentration levels were measured using relevant kits. Measurements of arterial stiffness [pulse-wave velocity (PWV) and augmentation index (AIx)] were performed using a Mobil-O-Graph arteriography system. Results: GDF-15 concentration levels were significantly higher in the patients with premature myocardial infarction when compared to controls. PWV and AIx were similar between the groups. GDF-15 level was negatively correlated with high-density cholesterol (HDL) and positively correlated with uric acid levels in all study populations. Conclusions: GDF-15 levels may be a risk factor for patients with premature myocardial infarction. This pilot study may trigger further studies to elucidate the central role of GDF-15 in the pathophysiology of early atherosclerosis in the young population.

Introduction: Hemostatic dysfunction during extracorporeal membrane oxygenation (ECMO) due to blood-circuit interaction and the consequences of shear stress by flow rates lead to rapid activation of the coagulation cascade and thrombus formation in the ECMO system and blood vessels. In this study, we aimed to identify the incidence and risk factors for cannula-associated arterial thrombosis (CaAT) post-decannulation. Methods: A retrospective study of patients undergoing arterial cannula removal following ECMO. We evaluated the incidence of CaAT and compared clinical characteristics, pre-ECMO severity, and daily hemostasis parameters in patients with and without CaAT. Multivariate analysis revealed the risk factors for CaAT. Results: Forty-seven patients requiring venoarterial ECMO or hybrid methods were recruited to be screened for thrombosis. The median SOFA score was 11 (8-13). CaAT occurred in 29 patients (61.7%), with thrombosis in the superficial femoral artery accounting for 51.7%. Limb ischemia complications in the group with CaAT was 17.2%. In multivariate analysis, an ECMO flow rate of 100 mL/min was determined to be the independent factor for CaAT with an OR of 0.84 (95% CI, 0.73–0.95, p=0.008). Conclusion: In patients successfully weaned from ECMO, the incidence of CaAT was 61.7%. Our study found that a low-flow rate of ECMO was an independent risk factor for CaAT.

Objectives The most severe type of peripheral arterial disease (PAD) is critical limb ischaemia (CLI). In CLI, calcification of the vessel wall plays an important role in symptoms, amputation rate and mortality. However, calcified arteries are also found in asymptomatic persons (non-PAD patients). We investigated whether the calcification pattern in CLI patients and non- PAD patients are different and could possibly explain the symptoms in CLI patients. Materials and Methods 130 CLI and 204 non-PAD patients underwent a CT of the lower extremities. This resulted in 118 CLI patients (mean age 72±12, 70.3% male) that were age-matched with 118 non-PAD patients (mean age 71±11, 51.7% male). The characteristics severity, annularity, thickness and continuity were assessed in the femoral and crural arteries and analysed by binary multiple logistic regression. Results Nearly all CLI patients have calcifications and these are equally frequent in the femoropopliteal (98.3%) and crural arteries (97.5%), while the non-PAD patients had in just 67% any calcifications with more calcifications in the femoropopliteal (70.3%) than in the crural arteries (55.9%, p<0.005). The crural arteries of the CLI patients had significantly more complete annular calcifications (OR 2.92, p=0.001.) while in the non-PAD patients dot-like calcifications dominated. In CLI patients, the femoropopliteal arteries had more severe, irregular / patchy and thick calcifications (OR 2.40, 3.27, 1.81, p≤0.05, respectively) while in non-PAD patients, thin continuous calcifications prevailed. Conclusions Compared with non-PAD patients CLI patients are more frequently and extensively calcified. Annular calcifications were found in the crural arteries of CLI patients while dot-like calcifications were mostly present in the non-PAD patients. These different patterns of calcifications in CLI point at different etiology and can have prognostic and eventually therapeutic consequences.

Background: Epidemiological surveillance of nursing diagnosis is an approach anchored on a post-modern epidemiology focused on persons health-disease responses. Regarding to public health priorities, the population where our study occurred had as priority problem the arterial hypertension. Related to this chronical disease, nursing diagnoses about health-disease responses in primary healthcare has as major focus Therapeutic Regime Management. Our aim was to study the nursing diagnosis in this issue, from an epidemiological approach. Methods: A descriptive study from an epidemiological approach was developed, analyzing nursing diagnoses in hypertensive patients. Results: We found 17,7% of undiagnosed patients and better diagnoses in patients with complications than in those without complications. Conclusions: nursing records need to be improved in order to promote more robust studies in the post-modern epidemiology defended for the future.

The Wnt/β-catenin signaling deregulation is associated with the pathogenesis of many human diseases, including hypertension and heart disease. The aim of the study was to immunohisto-chemically evaluate and compare the expression of Fzd8, WNT1, GSK-3ß and β-catenin genes in the hearts of rats with spontaneous hypertension (SHR) and DOCA-salt- induced hypertension. The myocardial expression Fzd8, WNT1, GSK-3ß and β-catenin was detected by immunohisto-chemistry and the gene expression was assessed with real-time PCR method. In SHR immunore-activity of Fzd8, WNT1, GSK-3β and β-catenin was attenuated in comparison to normotensive animals. In DOCA-salt immunoreactivity of Fzd8, WNT1, GSK-3β and β-catenin was enhanced. In SHR, decrease in the expression of genes encoding Fzd8, WNT1, GSK-3ß and β-catenin was observed compared to the control group. Increased expression of genes encoding Fzd8, WNT1, GSK-3ß and β-catenin was demonstrated in the hearts of rats DOCA-salt. Wnt signaling may play an essential role in the pathogenesis of arterial hypertension and the accompanying heart damage. Obtained results may constitute the basis for further research aimed at better under-standing the role of the Wnt/β-catenin pathway in the functioning of the heart.

Background: Myocardial infarction (MI) is a major cause of mortality worldwide. Its presentation as ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI) is influence by atherosclerosis risk factors. Aim: To assess the patterns of presentation and predicting risk factors of acute MI in Kosovo. Methods: This is a cross sectional study from the Clinic of Cardiology of the University Clinical Center of Kosovo, which included all patients hospitalized with acute MI over a period of 7 years (January 1st, 2014 to December 31st, 2020). Data was collected using a structured questionnaire and epidemiological patterns and risk factors were analyzed. Results: Among 7353 patients admitted with acute MI (age 63 ± 12 years, 29% female), 4366 (59.4%) patients had STEMI, and 2987 (40.6%) NSTEMI. Patients age was not different between the two groups (p=0.077). NSTEMI patients smoked less (48.3% vs. 54%, p<0.001), but were more diabetics (37.8% vs. 33.6%, p<0.001), more hypertensives (69.6% vs. 63%, p<0.001), frequently had family history for coronary artery disease (CAD) (40% vs 38%, p=0.009), and included more females compared to STEMI patients (32% vs 27%, p<0.001). The two groups of patients, did not differ in the prevalence of significant CAD on angiography (66.8% vs. 67.8%, p = 0.396), but NSTEMI patients underwent less primary percutaneous interventions compared with STEMI patients (43.6% vs. 55.2%, p < 0.001). Conclusion: In Kosovo, STEMI is commoner than NSTEMI, who were mostly males, more likely to have diabetes, hypertension and family history for CAD compared to those with NSTEMI. Smoking and arterial hypertension proved the strongest predictors of acute MI, in Kosovo, thus highlighting the urgent need for better atherosclerosis risk control and education strategy.

Aim. Atherosclerotic complex femoropopliteal lesions have traditionally been treated with bypass surgery. A prosthetic graft is used to save the vein graft for more distal revascularization or when unavailable. However, the endovascular approach has gained popularity and is offered as first-line strategy for complex lesions. This study aimed to evaluate whether endovascular procedures for complex femoropopliteal native lesions can be a first-line treatment strategy over open surgery with prosthetic bypass in patients with peripheral arterial disease (PAD). Methods. A retrospective study was conducted between 2013 and 2021 to identify patients with symptomatic PAD who required limb revascularization at the femoropopliteal segment and complex lesions (TASC II C and D). Primary endpoints were technical success, primary patency, freedom from clinically driven target lesion revascularization (cdTLR), freedom from major adverse limb and cardiovascular events (MALE and MACE), freedom from limb loss, and survival. Secondary endpoints were length of in-hospital stay, duration of the procedure, and costs. Results. We identified 185 limbs among 174 suitable candidates for comparison, wherein 105 were treated with endovascular procedure and 80 with femoral popliteal prosthetic bypass. Most patients in both groups presented with chronic limb-threatening limb ischemia, and all were ASA >3. There were more octogenarians (p = 0.02) and patients with coronary disease (p = 0.004) in the endovascular group. Median follow-up was 30 months. Technical failure rate for endovascular procedures was 4.8% vs 0% in the open group (p 0.003). Freedom from MACE was similar in both groups. The endovascular group showed superior primary patency (p<0.0001), cdTLR (p<0.0001), MALE (p<0.0001), and freedom from limb loss (p = 0.0018) at 24 months. Further analysis performed for the open above-the-knee subgroup showed that the aforementioned endpoints were similar at 12 months, and favoured the endovascular group at 24 months. Procedural time and in-hospital stay were longer in the open group (p<0.0001 and p<0.001). Finally, procedural cost was 10-fold lower in the endovascular bypass group than in the prosthetic bypass group. Conclusion. Endovascular procedures for complex femoropopliteal lesions are safe in patients at high risk for surgery and show better outcomes at 24 months than prosthetic bypasses. The latter may be considered as an alternative in cases of endovascular failure.

Peripheral arterial diseases (PAD) are complex cardiovascular conditions influenced by environmental factors and somatic mutations in multiple genes involved in hematopoiesis and inflammation. While traditional risk factors such as smoking, hypercholesterolemia, and hypertension have been extensively studied, the role of somatic mutations in PAD progression remains underexplored. This article aims to provide a comprehensive review of the molecular mechanisms, genetic landscape, prognostic significance, and clinical implications of somatic mutations in PAD. The expansion of clonal hematopoiesis of indeterminate potential (CHIP) clones in the circulating blood, named clonal hematopoiesis (CH), leads to the infiltration of these clones into atherosclerotic plaques and the production of inflammatory cytokines, increasing the risk of cardiovascular diseases including PAD. Furthermore, recent experimental evidence has demonstrated the involvement of somatically mutated TP53 genes with a high variant allele frequency (VAF) in PAD development and prognosis. The review delves into the relationship between CH and PAD, elucidating the prevalence, impact, and underlying mechanisms of this association. This understanding paves the way for novel therapeutic approaches targeting CHIP to promote tissue regeneration and improve outcomes in PAD patients. It emphasizes the need for further re-search to fully unravel the genetic footprint of the disease and highlights potential clinical implications. The findings presented in this article lay the foundation for personalized medicine approaches and open avenues for the development of targeted therapies based on somatic mutation profiling.

Physical exercise is the greatest stress on the cardiovascular system, not only in humans but also in all vertebrates. Consequently, the cardiovascular response cannot be thought of as having only one "anthropocentric" interpretation. The modulation of cardiac output (Q) in response to exercise in the five major groups of vertebrates exhibits considerable variability. Moreover, the response of the heart rate (HR) and the stroke volume (SV), the fundamental factors that cause the rise in Q, is also highly variable. The difference in the range of HR is difficult to determine in many vertebrates, both at rest and at maximal effort. Additionally, the increase in SV varies among vertebrates. For example, while rainbow trout and leopards increase their SV by increasing end diastolic volume (EDV), humans do so at the expense of both increasing EDV and reducing end systolic volume (ESV). The variation in arterial pressure that arises during exercise varies notably among vertebrates, such as amphibians, whose blood pressure values do not increase as significantly as in mammals. Such differences in cardiovascular response among vertebrates may be linked to their habitat or living environment. This review aims to analyze the cardiovascular response of vertebrates to physical exercise as the most common stressor.

The comparative efficacy and safety between lenvatinib and hepatic artery infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC) are still unclear. This multicenter historical cohort study enrolled 244 patients who were treated with HAIC (n = 173) or lenvatinib (n = 71) between 2012 and 2020. Propensity score matching (PSM) was performed, and 52 patients were selected per group. Clinical outcomes and safety were compared. Objective response rate (ORR) was not different between the two groups (26.0% vs. 23.1%, P = 0.736). Before PSM, HAIC group had a higher proportion of Child-Pugh B and portal vein tumor, whereas lenvatinib group had more patients with extrahepatic metastases, which was adjusted after PSM. There were no differences in progression-free survival (PFS) and overall survival (OS) after PSM (HAIC vs. lenvatinib, median PFS, 3.6 vs. 4.0 months, P = 0.706; median OS 10.8 vs. 7.9 months, P = 0.106). Multivariate Cox-regression showed that alpha-fetoprotein ≤ 1000 ng/mL was only associated factor for OS after PSM in all patients (hazard ratio = 0.421, P = 0.011). Subgroup analysis for patients with high tumor burden beyond the REFLECT eligibility criteria revealed that HAIC group (n = 29) had a significantly longer OS than did lenvatinib group (n = 30) (10.0 vs. 5.4 months, P=0.004). More patients in HAIC group achieved better liver function than those in lenvatinib group at the time of best responses. There was no difference in the incidence of grade 3 and 4 adverse events between the two groups. Therefore, lenvatinib is comparable to HAIC in terms of ORR and OS in unresectable HCC meeting REFLECT eligibility criteria.

Photoplethysmography (PPG) is a simple-to-perform vascular optics measurement technique that can detect changes in blood volume in the microvascular tissue bed. Beat-to-beat analysis of the PPG waveform enables the study of the variability of pulse features such as amplitude and pulse arrival time (PAT), and when quantified in the time and frequency domains, has considerable potential to shed light on perfusion changes associated with peripheral arterial disease (PAD). In this pilot study innovative multi-site bilateral finger and toe PPG recordings from 43 healthy control subjects and 31 PAD subjects were compared (recordings each at least 5 minutes, collected in a warm temperature-controlled room). Beat-to-beat normalized amplitude and PAT variability was then quantified in the time-domain using SD and IQR measures and in the frequency-domain bilaterally using Magnitude Squared Coherence (MSC). Significantly reduced normalized amplitude variability (healthy control 0.0384 (IQR 0.0217-0.0744) vs PAD 0.0160 (0.0080-0.0338) (p<0.001) and significantly increased PAT variability (healthy control 0.0063 (0.0052-0.0086) vs PAD 0.0093 (0.0078-0.0144) (p<0.001) was demonstrated in PAD using the time-domain analysis. Frequency-domain analysis demonstrated significantly lower MSC values across a range of frequency bands for PAD patients. These changes suggest a loss of right-to-left body side coherence and cardiovascular control in PAD. This study has also demonstrated the feasibility of using these measurement and analysis methods in studies investigating multi-site PPG variability for a wide range of cardiac and vascular patient groups.

Experimental and clinical data indicates that the initiation and progress of atherosclerosis, and its clinical manifestations, are caused first by circulating apoB-100 lipoproteins that enter and are retained in the arterial intima. Extracellular sulfated proteoglycans (PGs) of the intima are the retention agents. The PGs also initiate physical and biochemical lipoprotein degradation with the production of bioactive, lipid products that trigger an inflammatory response that leads to atherosclerosis. There are many simple methods for measuring abnormalities of circulating lipoproteins and their relation to atherosclerotic cardiovascular disease (ACVD). However, limited research has been aimed to evaluate procedures that could report quantitatively about the contribution of the apo-100 lipoprotein-arterial intima PGs interaction to clinical manifestation of ACVD. In the present review we will discuss observations indicating that simple ex vivo evaluation of the affinity of apoB-100 lipoproteins for arterial PGs and glycosaminoglycans (GAGs) can give indication of its association with clinical manifestations of atherosclerosis. In addition, we will discuss molecular and cellular aspect of the apoB-100 lipoproteins association with arterial PGs that are related to atherogenesis and that support the experimental framework behind the current “Response-to-Retention” hypothesis of atherosclerosis

Purpose: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in present study. In DIACRT group, 25 patients had T2, 20 patients had T3. A total of 9 patients had T2 and 2 had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months respectively. The 5-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for DIACRT group, 60.6% and 63.6% for WIACRT group respectively. The LC rate and OS of DIACRT group were significantly higher than that of WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods both in two groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

Summary: Hypertension is a public health problem with serious social, economic, and health consequences. The World Health Organisation (WHO) estimates that 1 in 3 adults worldwide suffers from hypertension. In Cameroon, the prevalence of hypertension is estimated at 35%, with nearly 17,000 deaths recorded each year. This study aimed to determine the factors associated with the occurrence and complications of hypertension at the Sangmélima Referral Hospital (HRS). A total of 528 patients treated in the cardiology department of the HRS were identified between January and December 2023. The data were analyzed using SPSS 28 software. Binary logistic regression determined the odds ratios and 95% confidence intervals associated with each variable. Differences were statistically significant for a p-value &lt; 0.05. At the HRS, the annual incidence of hypertension was 16.13%. Hypertension was present in 78.8% of patients. The factors associated with the occurrence and complications of hypertension were age (OR=1.028; p=0.003 ), level of education (OR=15.49; p=0.023), marital status (OR=3.859; p=0.04), hypercholesterolemia (OR=2.856; p=0.01), monthly income (OR=0.882; p=0.026), number of dependents (OR=1.231; p=0.025), food security (OR=16.666; p&lt;0.001), tobacco consumption (OR=8.592; p=0.041), fruit and vegetable consumption (OR=0.027; p=0.031), salt/sugar consumption (OR=8.129; p&lt;0.001), place of residence (OR=4.794; p=0.005), access to essential technologies (OR=8.851; p=0.002), and use of traditional care (OR=3.137; np=0.032). HTA at the HRS is associated with several factors. In order to limit the impact of hypertension, it is crucial to emphasize improving socioeconomic and health conditions.

Background: Cardiovascular (CV) morbidity and mortality are many times higher in chronic kidney disease (CKD), as well as IgA nephropathy (IgAN), than in the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease and renal progression. The study aimed to determine the prognostic role of metabolic profiles in a homogenous group of CKD patients. Methods: One hundred and forty-five IgA nephropathy patients (92 male, 53 female, age 54.7 ± 13 years) with CKD stage 1-4 were investigated and followed for a median of 190 months. The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularization (CV), end-stage renal disease, and renal replacement therapy (renal). Results: Patients with MetS had significantly more endpoint events (16/27 patients vs. 15/98 patients, p = 0.001) compared to the nonMetS group. Of the secondary endpoints (CV or renal separately), the rate of the renal and CV endpoints was significantly higher in the MetS group (p = 0.001 and p = 0.029). The primary endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus, as determined by Cox regression analysis. Independent predictors of secondary renal endpoint were dyslipidemia, hemoglobin, urine albumin, and eGFR. Predictors of secondary cardiovascular endpoints were gender, BMI, and diabetes. Kaplan-Meier curves showed significant differences in MetS and non-MetS when examined at the combined endpoints (CV and renal) or at each endpoint separately. The primary endpoint rate increased significantly with the increased number of MetS components (MetS comp. 0 vs. MetS comp. 2+, primary endpoints, p = 0.012). Conclusion: Our results showed that the metabolic profile has a prognostic role not only for renal endpoints but also for CV endpoints in IgAN. BMI, hyperuricemia, hypertension, and diabetes have a predictive value for the prognosis of IgA nephropathy.

Chronic hemodialysis (HD) patients have very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. Aim: To study acute vascular changes during HD. In 29 consecutive chronic HD patients (age: 65.6±10.4 years) pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. SDC-1 levels increased during HD (p=0.004). Males had higher ET-1 levels. Patients were divided into 2 groups based on pulse wave velocity (PWV): PWV≥12 m/s and PWV<12 m/s. Pre-HD and mid-HD SDC-1 levels were higher in the group with PWV≥12 m/s (10.174±2.568 vs. 7.928±1.794 ng/ml, p=0.013, and 10.319±3.482 vs. 8.248±1.793 ng/ml, p=0.044, respectively). Post-HD ET-1 levels were higher in the patient group having PWV≥12 m/s (10.88±3.00 vs. 8.05±3.48 pg/l, p=0.027). Patients having PWV≥12 m/s had higher pre-HD peripheral and aortic systolic blood pressure (p<0.05). Total cholesterol correlated with the SDC-1 decrease during HD (r=0.539; p=0.008). Pre-, mid-, and post-HD SDC-1 correlated with the ultrafiltration (r=0.432, p=0.019; r=0.377, p=0.044; and r=0.401, p=0.012, respectively). SDC-1 and ET-1 contribute to vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.

It has been reported that prostaglandin I2, such as epoprostenol, develops Grave's disease. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she started complaining of neck swelling and was diagnosed with Grave’s disease. Thyroid function was controlled by thiamazole and levothyroxine. Nevertheless, her thyroid gland enlargement worsened as epoprostenol dose was titrated. After 23 years of treatment with epoprostenol, she suddenly experienced respiratory failure with a giant goiter leading to airway stenosis and passed away. The autopsy confirmed a giant goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

Background The prognostic value of estimated pulse wave velocity (ePWV) has been infrequently explored in high-risk patient groups. Our study aimed to evaluate the prognostic significance of ePWV among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Methods A total of 4,119 consecutive subjects who underwent PCI with DES (mean age, 67.1 ± 11.6 years and 33.1% were female) were retrospectively analyzed. ePWV was calculated based on the patient’s age and mean blood pressure. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization, and ischemic stroke, were evaluated. Reults During a median follow-up duration of 3.51 years (interquartile range, 1.35 ~ 6.37 years), there were 746 MACE (18.1%). Multivariable analysis showed that higher ePWV was associated with higher MACE incidence (middle tertile vs. the lowest tertile: hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.81-3.42; P < 0.001; the highest tertile vs. the lowest tertile: HR, 6.18; 95% CI, 4.33-8.80; P < 0.001) The inclusion of ePWV data significantly increased the global chi-square values when added to the clinical information (from 96 to 128; P < 0.001). Conclusion ePWV demonstrated a significant association with MACE in patients who underwent DES implantation. Given its relative simplicity to calculate, ePWV could potentially serve as a valuable instrument for stratifying cardiovascular risk within this high-risk patient population.

In this paper, the feasibility of automated and accurate in vivo measurements of vascular parameters continuously and non-invasively using ultrasound sensor is presented. Vascular parameters such as pulse wave velocity (PWV), blood pressure (BP), arterial compliance (AC) and stiffness index (SI) are affluent indicators of cardiovascular disorders and needs to be monitored non-invasively and continuously during surgeries and follow-up procedures. Cuff based or invasive catheter techniques are considered as gold standard to measure BP and are fed manually to compute AC and SI which employ imaging algorithms. In this context, a Continuous and Non-Invasive Vascular Stiffness and Arterial Compliance Screener (CaNVAS) is developed to measure said parameters continuously and non-invasively using ultrasound sensor. Acoustic waves of 5 MHz (2.2 – 10 MHz) are driven through target arterial walls, reflected echoes captured, pre-processed and frequency shift is used to calculate PWV. It is observed that PWV measured using CaNVAS varies exponentially with BP values obtained from sphygmomanometer (BPMR-120) and this relationship is used to compute instantaneous values of BP. The proposed device is validated by performing measurements on 250 subjects in pre and post exercise conditions and found to have 95% accuracy and an average of 12.5% coefficient of variation.

This article introduces new method using ANN to control SVC in order to correct the source power factor of low voltage network. Two ANN approaches are investigated to design accurate and fast power factor correction (PFC) controller. First approach uses simple ANN (SANNA). Second approach uses cascaded ANN (CANNA). ANN regression, performance and the calculated error for both approaches are investigated to select between the two approaches. CANNA is selected as a better solution and it used to build the ANN PFFC controller using database, generated by MATLAB-Simulink, for standard three low voltage levels (240V, 220V and 110V). Nine test cases are carried out to validate the performance of proposed ANN PFC controller with a network has variable loads and low power factor (0.6 approximately). In order to extend the use of the controller to other voltage levels not included in the training process of the cascaded ANN, only the SVC is resized. Another nine cases are carried out with the same loads using the same ANN controller, as it is, to test its performance with the extended voltage level range (415V, 230V and 120V). The results show accurate and fast response in all test cases.

Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverses established arterial wall thickening, stiffening and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from better understanding of pulmonary vascular gene expression programs. In this review potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. Progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized.

This study aimed to identify the utility of diffusion-weighted magnetic resonance (MR) imaging with an apparent diffusion coefficient (ADC) map as a predictor of the intrahepatic response of hepatocellular carcinoma (HCC) to cisplatin-based hepatic arterial infusion chemotherapy (HAIC). We retrospectively evaluated 113 consecutive patients with HCC who underwent gadoxetic acid-enhanced and diffusion-weighted MR imaging. The appropriate cutoff for the tumor-to-liver ADC ratio was determined to be 0.741. Of the 113 patients, 51 (45%) presented with a tumor-to-liver ADC ratio < 0.741. Evaluation of the intrahepatic treatment response after 2-3 cycles of HAIC in these 51 patients revealed that 20 patients (39%) experienced an objective response to HAIC. On the other hand, only 10 of the 62 patients with a tumor-to-liver ADC ratio ≥ 0.741 (16%) experienced an objective response. Thus, the objective response rate was significantly higher in patients with a tumor-to-liver ADC ratio < 0.741 than in those with a tumor-to-liver ADC ratio ≥ 0.741 (P = 0.006). Multivariate logistic regression analysis using parameters including perfusion alteration, percentage of a non-enhancing portion, and tumor-to-liver ADC ratio revealed that a tumor-to-liver ADC ratio < 0.741 (odds ratio 3.03; P = 0.015) is the sole predictor of an objective response to HAIC. Overall survival rates were significantly higher in patients with objective responses to HAIC than in those without objective responses (P = 0.001 by log-rank test). In conclusion, patients with unresectable HCC with a tumor-to-liver ADC ratio < 0.741 showed a favorable intrahepatic response to HAIC. Therefore, diffusion-weighted MR imaging can play a critical role as a predictor of response to cisplatin-based HAIC in unresectable HCC.

Background In SILIUS (NCT01214343), combination of sorafenib and hepatic arterial infusion chemotherapy did not significantly improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib alone. In this study, we explored the relationship between objective response by mRECIST and overall survival (OS) in the sorafenib group, in the combination group and in all patients in the SILIUS trial. Methods Association between objective response and OS in patients treated with sorafenib (n=103), combination (n=102) and all patients (n=205) were analyzed. The median OS of responders was compared with that of non-responders. Landmark analyses were performed according to objective response at several fixed time points, as sensitivity analyses, and the effect on OS was evaluated by Cox regression analysis with objective response as a time-dependent covariate, with other prognostic factors was performed. Results In the sorafenib group, OS of responders (n = 18) was significantly better than that of non-responders (n = 78) (p < 0.0001), where median OS was 27.2 (95% CI, 16.0–not reached) months for responders and 8.9 (95% CI, 6.5–12.6) months for non-responders. HRs from landmark analyses at 4, 6, and 8 months were 0.45 (p=0.0330), 0.37 (p=0.0053), and 0.36 (p=0.0083), respectively. Objective response was an independent predictor of OS based on unstratified Cox regression analyses. In the all patients and the combination group, similar results were obtained. Conclusion In the SILIUS trial, objective response was an independent prognostic factor for OS in patients with HCC.

Purpose: A number of imaging readout schemes have been proposed for renal arterial spin labelling (ASL) to quantify kidney cortex perfusion, including gradient echo based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo based schemes of spin-echo echo planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T. Methods: Ten healthy volunteers with normal renal function were scanned using each 2D multislice imaging scheme, in combination with a respiratory triggered FAIR (flow-sensitive alternating inversion recovery) ASL scheme on a 3 T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability. Results: For each imaging scheme, renal cortex perfusion was calculated (bFFE: 276 ± 29 mL/100 g/min, GE-EPI: 222 ± 18 mL/100 g/min, SE-EPI: 201 ± 36 mL/100 g/min, TSE: 200 ± 20 mL/100 g/min). Perfusion was found to be higher for GE based readouts compared to SE based readouts, with significantly higher measured perfusion for the bFFE readout compared to all other schemes (P < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI compared to all other schemes (P < 0.05), the SE-EPI readout gave the highest tSNR and was found to be the most reproducible scheme for the assessment of kidney cortex, with a CoV of 17.2%, whilst minimizing variability of the perfusion weighted signal across slices for whole kidney perfusion assessment. Conclusion: For the assessment of kidney cortex perfusion, SE-EPI provides optimal tSNR, minimal variability across slices and repeatable data acquired in a short scan time with low specific absorption rate.

Abstract: This paper outlines the methodology and results for a two species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA) ) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two species (free-drug and bound-drug) mass transport setup including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of drug between the free and bound-drug states. The model is solved by a 2-D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over our previously developed model using the finite-difference method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 hours (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug.

This retrospective study examines 248 test-bolus examinations preceding contrast-enhanced magnetic resonance angiography (CE-MRA) to extract clinically relevant data for critical limb ischemia (CLI) management. Methods involved a retrospective review of test-bolus exams, analysing 60 graphs for time-to-peak (TTP), full-width half-maximum (FWHM) time, and time to continual rise in signal intensity. These values were correlated with heart function parameters (ejection fraction, ASA-Classification, Lee-Index, and MET-Score). Results indicate a mean TTP of 31.2 ± 7.3s, showing a correlation between ejection fraction and ASA classification. Patients with atrial fibrillation exhibited prolonged TTP compared to those without. Despite population heterogeneity, findings facilitate risk stratification for limb-saving interventions in CLI. TTP emerges as a potential clinical cardiovascular parameter and a risk factor for vascular interventions. Given the variation in injection protocols across centres, this study underscores the importance of precise bolus arrival time documentation for future multicentre studies.

The right heart catheterisation constitutes the gold standard for pulmonary hypertension (PH) diagnosis. However, echocardiography remains a reliable, non-invasive, inexpensive, convenient, and easily reproducible modality not only for the preliminary screening of PH but also for PH prognosis. The aim of this review is to describe a cluster of echocardiographic parameters for the detection and prognosis of PH and analyse the challenges of echocardiography implementation in patients with suspected or established PH. The most important echocardiographic index is the calculation of pulmonary arterial systolic pressure (PASP) through the tricuspid regurgitation (TR). It has shown high correlation with invasive measurement of pulmonary pressure, but several drawbacks have questioned its accuracy. Besides this, the right ventricular outflow track acceleration time (RVOT-AT) has been proposed for PH diagnosis. A plethora of echocardiographic indices: right atrial area, pericardial effusion, the tricuspid annular plane systolic excursion (TAPSE), the TAPSE/PASP ratio, tricuspid annular systolic velocity (s′) and recently, can reflect the severity and prognosis of PH. Recent advances in echocardiography with 3-dimensional right ventricular (RV) ejection fraction, RV free wall strain and right atrial strain may further assist the prognostication of PH.

This analytical cross-sectional study was designed to evaluate the association between glycemic control and peripheral arterial disease in patients with diabetic foot with more than ten years of evolution of diabetes mellitus who attended the diabetic foot outpatient clinic of the Guillermo Almenara National Hospital between June 2015 and February 2017. Glycosylated hemoglobin (HbA1C) and ankle-brachial index (ABI) were used to diagnose glycemic control and peripheral arterial disease, respectively. A generalized Poisson log-linear regression model was used to calculate the crude (cPR) and adjusted (aPR) prevalence ratios, with 95% confidence intervals, and a significance level of p < 0.05. 226 patients were included in the study, finding 23% (n=52) with good glycemic control, and 44.7% (n=101) with peripheral arterial disease. The adjusted model found statistically significant associations for glycemic control, age, and sedentary lifestyle with peripheral arterial disease. Compared with patients with good glycemic control, those with poor glycemic control had a 34% higher probability of presenting peripheral arterial disease (aPR: 1.34, 95%CI: 1.01-1.79, p=0.045). The prevalence of good glycemic control in the population with diabetic foot is low. Poor glycemic control was found to be independently associated with the presence of peripheral arterial disease.

Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant to treat partial seizures and neuropathic pain. While a majority of the side effects are associated with the nervous system, emerging evidence suggests a high risk for heart diseases in the patients taking GBP. In the present study, we used a preclinical model of rats to investigate (1) the acute cardiovascular responses to GBP (bolus i.v. injection, 50 mg/kg) and (2) the effects of chronic GBP treatment (i.p. 100 mg/kg/day x 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane-anesthesia, rat blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics were measured using Millar pressure transducers. The LV myocardium and brain cortex were analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction. In experiment (1), we found that i.v. GBP significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (*p < 0.05 and **p < 0.01 vs baseline; n = 4/group). In experiment (2), we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium, we identified 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Particularly, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function.

The purpose of this study was to determine the effects of aerobic exercise on carotid to femoral pulse wave velocity (cf-PWV), cell adhesion molecules (intracellular adhesion molecules (ICAM-1), vascular cell adhesion molecules (VCAM-1), and endothelial selectin (E-selectin), and oxidized-LDL in elderly women aged 70–85 years, and to identify the effect of and correlation with vascular stiffness. Forty participants were recruited and divided into three groups; vascular stiffness (VSG, n=14), obesity (OG, n=14), and normal (NG, n=12). All groups were given a 16-week intervention of aerobic exercise, and the data collected before and after exercise were analyzed using SPSS Ver. 23.0. Two-way repeated-measures ANOVA was used to evaluate between-group and time-dependent interaction effects. One-way ANOVA was used to evaluate between-group variations. In addition, the significance was tested using a post-hoc test (Scheffe). The within-group variations by time before and after exercise were examined using a paired t-test, and correlation analysis was performed using Pearson correlation coefficients. Simple regression analysis was performed for variables showing significant differences. The results indicated interaction effects for cf-PWV (p<.001), VCAM-1 (p<.01), E-selectin (p<.05) and oxidized LDL (p<.001). The rate of change of cf-PWV was positively correlated with that of VCAM-1 (r=.352, p<.05) and that of oxidized-LDL (r=.325, p<.05) with statistical significance. To determine the effect of the rate of change of cf-PWV on the rate of change of VCAM-1, the variables were tested, and the coefficient of determination in the regression analysis was .124, indicating that 12.4% of the tested variables fit the standard regression line. The variables for the effect of the rate of change of cf-PWV on the rate of change of oxidized LDL were also tested, and the coefficient of determination in the regression analysis was .106, indicating that 10.6% of the tested variables fit the standard regression line. Thus, the 16-week regular and consistent aerobic exercise program had significant effects on the cf-PWV, ICAM-1, VCAM-1, E-selectin, and oxidized-LDL in elderly Korean women with vascular stiffness, suggesting improvements in vascular stiffness, based on which the intervention is predicted to contribute to the prevention of vascular dysfunction by lowering the risk of cardiovascular disease due to atherosclerosis, as well as having a positive effect in the prevention of impairment of vascular endothelial cells.

Initially, renal resistive index (RRI) was investigated to improve diagnosis in kidney diseases, but failed to meet this goal. Recently many papers highlighted the prognostic significance of RRI in chronic kidney disease, in the estimation of revascularization success of renal artery stenoses or the evolution of the graft and recipients in renal transplantation. Moreover, RRI gained importance in prediction of acute kidney injury in critically ill patients. Along with RRI study in renal pathology have been revealed correlations of this index with parameters of systemic circulation. The theoretical and experimental premises of this connection were reconsidered, and studies for analyzing the link between RRI and arterial stiffness, central and peripheral pressure or left ventricular flow were conducted with this purpose. A high amount of data is currently indicating that RRI is influenced more by pulse pressure and vascular compliance than by renal vascular resistance – assuming that RRI reflects the complex interplay between systemic circulation and renal microcirculation and should be considered as a marker of systemic cardiovascular risk beyond its prognostic relevance for kidney disease. In this review we will go through clinical research that revealed the implications of RRI in renal and cardiovascular disease.

Reliable quantification of pulmonary arterial pressure is essential in the diagnostic and prognostic assessment of a range of cardiovascular pathologies including rheumatic heart disease, yet an accurate and routinely available method for its quantification remains elusive. This work proposes an approach to infer pulmonary arterial pressure based on scientific machine learning techniques and non-invasive, clinically available measurements. A 0-D multicompartment model of the cardiovascular system was optimized using several optimization algorithms, subject to forward-mode automatic differentiation. Measurement data were synthesized from known parameters to represent the healthy, mitral regurgitant, aortic stenosed and combined valvular disease situations with and without pulmonary hypertension. Eleven model parameters were selected for optimization based on 95 % explained variation in mean pulmonary arterial pressure. A hybrid Adam and limited-memory Broyden-Fletcher-Goldfarb-Shanno optimizer yielded the best results with input data including valvular flow rates, heart chamber volume changes and systematic arterial pressure. Mean absolute percentage errors ranged from 1.8 % to 3.78 % over the simulated test cases. The model was able to capture pressure dynamics under hypertensive conditions with pulmonary arterial systole, diastole, and mean pressure average percentage errors of 1.12 %, 2.49 % and 2.14 %, respectively. The relatively low errors highlight the potential of the proposed model to recover pulmonary pressures for diseased heart valve and pulmonary hypertensive conditions.

The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines, however, has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease alongside the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out with the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms from thrombosis following vaccination was also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.

Circulating tumor cells (CTCs) enumeration is a promising technique to predict cancer prognosis and treatment response. CTCs were evaluated in healthy subjects, cirrhotic controls and hepatocarcinoma (HCC) patients. CTCs were isolated using microfluidic system based on the expression of EpCAM, EGFR and three epithelial to mesenchymal transition (EMT) markers. Patients were stratified according to disease progression and exitus. Although counts of individual CTCs, clustered CTCs and α-fetoprotein (AFP) at basal level in patients with HCC were significantly increased compared with the values obtained in cirrhotic patients and control subjects, only individual CTCs (p=0.027), but not clustered CTCs (p=0.063) and AFP (p=0.072), were independent predictors of HCC development. The univariate regression model showed that basal levels of CTCs46 were related to high risk of HCC (Odds Ratio 3.467, p=0.011). The stratification of our cohort according to disease progression and death showed that basal individual CTCs 76 (Hazard Ratio 5.131, p=0.004) were related to disease progression, as well as the difference of clustered CTCs between 1-month and baseline levels 1.5 were related to death (Hazard Ratio 10.204, p=0.036). In conclusion, the preoperative and 1-month measurements of CTCs in blood constitute useful markers to predict the outcome of patients under TACE treatment.

Background: Although transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be more favourable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. Methods: This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected for the study. Propensity score matching was used to adjust for patient demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). Conclusion: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides more favorable outcome than TACE.

Artificial Intelligence (AI) made its first appearance in 1956, and since then it has progressively introduced itself in healthcare system and patients’ information and care. AI functions can be grouped under the following headings: Machine Learning (ML), Deep Learning (DL), Artificial Neural Network (ANN), Convolutional Neural Network (CNN), Computer Vision (CV). Chronic limb-threatening ischemia (CLTI) represents the last stage of peripheral artery disease (PAD), and has increased over recent years, together with the rise in prevalence of diabetes and population ageing. Nowadays AI grants the possibility of developing new diagnostic and treatment solutions in the vascular field, given the possibility of accessing clinical, biological, and imaging data. By assessing the vascular anatomy in every patient, as well as the burden of atherosclerosis, and classifying the level and degree of disease, sizing and planning the best endovascular treatment, defining the perioperative complications risk, integrating experiences and resources between different specialties, identifying latent PAD, thus offering evidence-based solutions and guiding surgeons in the choice of the best surgical technique, AI challenges the role of the physician’s experience in PAD treatment.

Oxidative stress driven by several environmental and local airway factors associated with chronic obstructive bronchiolitis, a hallmark feature of COPD, plays a crucial role in the disease pathomechanism. Unbalance between oxidants and antioxidant defense mechanisms not only amplifies the local inflammatory processes, but it also worsens cardiovascular health and contribute to the COPD related cardiovascular dysfunctions and mortality. The current review summarizes recent developments in our understanding of different mechanisms contributing to oxidative stress and its countermeasures with special attention to those that link local and systemic processes. Major regulatory mechanisms orchestrating these pathways are also introduced together with some suggestions for further research on the field.

Background: Brachial-ankle pulse wave velocity (baPWV) is widely used as a marker of arterial stiffness. It has been suggested as a simple method for detecting arterial loads that can trigger left ventricular hypertrophy in the heart. Increased left ventricular hypertrophy in hypertensive patients is a predictor that will have an impact on increasing morbidity and mortality. Objective: This study aimed to evaluate the correlation between the baPWV and the left ventricular mass index (LVMI) in hypertensive patients. Methods: This cross-sectional study was conducted by collecting secondary data from hypertensive patients at the Heart Outpatient Clinic, with inclusion: aged more than 40 years old, suffering hypertension more than one year, and had baPWV and echocardiography data. Correlation between baPWV and LVMI was evaluated using the Pearson correlation test. Results: A total of 40 hypertensive patients were enrolled in this study. 60% were women. The mean age was 52.92 ± 9.50 years. Mean LVMI was 107.20 + 21.01 gram/m2. LVMI showed a significant association with age and systolic blood pressure (p=0.001 and 0.019, respectively). Mean baPWV was 1832.90 + 336.22 cm/sec. A significant association was found between baPWV and age and systolic blood pressure (p=0.000 and 0.049, respectively). There was a significant positive correlation between baPWV and LVMI (r=0.493, p=0.001); and between baPWV and Relative Wall Thickness (RWT) (r=0.404, p=0.01). Conclusion: This study shows that elevated baPWV is an indicator of increased LVMI in hypertensive patients. Examination of baPWV should be carried out routinely to detect earlier arterial stiffness as a morbidity and mortality prevention strategy in hypertensive patients.

This study aimed to investigate the potential correlations and differences between patients with Acute Coronary Syndrome (ACS) and controls. Emphasis was placed on examining the relationship between arterial blood gas PH value and arterial blood gas lactate value as well as assessing the utility of the Peripheral Perfusion Index (PI) in ACS management. Materials and Methods: A prospective observational study was conducted between January 1, 2023, and July 1, 2023, involving 60 ACS patients and 30 control subjects in an emergency department. The diagnosis of ACS was confirmed by experienced emergency physicians, and various parameters, such as peripheral perfusion index, blood gas values, and cardiac biomarker values, were collected. The statistical analyses included Pearson’s chi-square test, Mann-Whitney U test, Student’s t-test, and others, using SPSS version 18.0. There were significant differences in the mean age, perfusion index, and lactate levels between the patient and control groups. A robust negative correlation was found between age and PI, and a moderate negative correlation was observed between pH and lactate levels (r = -0.301, p=0.004). The perfusion index in the patient group was significantly lower, indicating its potential diagnostic utility. The findings demonstrate the importance of arterial blood gas pH and lactate values in understanding ACS patient profiles, emphasizing the potential of PI as a noninvasive diagnostic method. The negative correlation between pH and lactate levels may offer valuable insights into risk stratification and treatment strategies for patients with ACS.

Chronic Limb Threatening Ischemia (CLTI) represents the end stage form of peripheral arterial disease (PAD) and is associated to very poor prognosis with high risk of limb loss and mortality. It can be considered very similar to a terminal cancer disease reflecting a large impact on quality of life and healthcare costs. The aim of this study is to offer an overview of the relationship between CLTI, limb salvage and mortality with a focus on the need of a fast-track team-based management, that’s a driver to achieve better survival results. This review can be useful to improve management of this growing impact disease, and promote standardisation of care and communication between specialist and non-specialist health care professionals.

The influence of cuff inflations on nighttime measurements during 24h ambulatory blood pressure (BP) measurements is unknown. We investigated the potential effect of cuff-inflations on asleep parameters using measurements taken simultaneously with a cuffless device using pulse-transit-time (PTT). On the first day of measurement, standard cuff-based 24h BP and cuf-fless measurements were simultaneously performed on right and left arms (CUFF/PTT-D). 1-2 days after the first measurement, the cuffless device was worn alone (PTT-D). Only data from the cuffless device was analyzed. The following mean asleep parameters were analyzed: systolic and diastolic BP, arousals, sleep efficiency, total arousals, arousal per hour and desaturations. 21 in-dividuals were prospectively enrolled. Mean (SD) age was 47(±15) years and 57% were female. Mean systolic asleep BP for the during CUFF/PTT-D and during PTT-D were 131(±21) and 131(±26) mmHg respectively. Mean diastolic asleep BP values during CUFF/PTT-D and during PTT-D were 80(±14) and 84(±14) mmHg respectively (p=0.860, p=0.100 respectively). Systolic and diastolic asleep mean difference was 0.1 (±18.0) and -3.6 (±9.8) mmHg, respectively. There were significantly more total arousals during PTT-D (p=0.042). There was no significant difference seen in sleep efficiency (p=0.339) or desaturations (p=0.896) between the two measurements. We could not show any significant impact from cuff inflations during asleep PTT-D measurements.

Pulmonary hypertension (PH) is a severe vascular complication of connective tissue diseases (CTD). Patients with CTD may develop PH belonging to different groups: 1) pulmonary arterial hypertension (PAH), 2) PH secondary to lung disease and/or hypoxia, 3) PH due to left heart disease, and 4) chronic thromboembolic pulmonary hypertension (CTEPH). PAH most often develops in systemic scleroderma (SSc), mostly in its limited variant. PAH-CTD is a progressive disease characterized by poor prognosis, therefore the early diagnosis should be established A specific treatment for PAH-CTD is currently available and recommended: prostacyclin derivative (treprostinil, epoprostenol, iloprost, selexipag), nitric oxide and natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase 5 inhibitors (PDE5i: sildenafil, tadalafil), endothelin receptor antagonists (ERA: bosentan, macitentan, ambrisentan). Moreover, novel drugs e.g. sotatercept are intensively investigated in the clinical trials. The aim of this paper is to review the literature on the recent advances in treatment strategy and prognosis of patients with PAH-CTD.

A key feature of pulmonary arterial hypertension (PAH) is the hyperplastic proliferation exhibited by the vascular smooth muscle cells from patients (HPASMC). The growth inducers FOXM1 and PLK1 are highly upregulated in these cells. The mechanism by which these two proteins direct aberrant growth in these cells is not clear. Herein we identify cyclin dependent kinase 1 (CDK1) also termed cell division cycle protein 2 (CDC2), as having a primary role in promoting progress of the cell cycle leading to proliferation in HPASMC. HPASMC obtained from PAH patients and pulmonary arteries from Sugen/hypoxia rats were investigated for their expression of CDC2. Protein levels of CDC2 were much higher in PAH than in cells from normal donors. Knocking down FOXM1 or PLK1 protein expression with siRNA or pharmacological inhibitors lowered the cellular expression of CDC2 considerably. However, knockdown of CDC2 with siRNA or inhibiting its activity with RO-3306 did not reduce the protein expression of FOXM1 or PLK1. Expression of CDC2 and FOXM1 reached its maximum at G1/S, while PLK1 reached its maximum at G2/M phase of the cell cycle. The expression of other CDKs such as CDK2, CDK4, CDK6, CDK7 and CDK9 did not change in PAH HPASMC. Moreover, inhibition via Wee1 inhibitor adavosertib or siRNAs targeting Wee1, Myt1, CDC25A, CDC25B, or CDC25C led to dramatic decreases in CDC2 protein expression. Lastly, we found CDC2 expression at the RNA and protein level to be upregulated in pulmonary arteries during disease progression Sugen/hypoxia rats. In sum, our present results illustrate that the increased expression of FOXM1 and PLK1 in PAH leads directly to increased expression of CDC2 resulting in a potentiated growth hyperactivity of PASMC from patients with pulmonary hypertension. Our results further suggest that the regulation of CDC2, or associated regulatory proteins, will prove beneficial in the treatment of this disease.

The aims of the study were to analyze the relationship between the Mediterranean diet (MD) and arterial stiffness and metabolic syndrome (MetS) and its components in individuals aged over 65, overall and by sex. Subjects were people over 65 years of age with a full record of all variables analyzed from the EVA, MARK and EVIDENT studies. Data from 1,280 subjects with a mean age of 69.52±3.58 years (57.5% men) were analyzed. MD was recorded with the validated 14-item MEDAS questionnaire used in the PREDIMED study. MetS was defined following the guidelines of the joint scientific statement from the Programa Nacional de Educación sobre el Colesterol III. Arterial stiffness was assessed with the VaSera VS-1500® device by measuring the cardio-ankle vascular index (CAVI) and the brachial-ankle pulse wave velocity (baPWV). Results: The mean MEDAS score was 6.00 ± 1.90, (5.92 ± 1.92 in men, 6.11 ± 1.88 in women; p = 0.036). The mean CAVI value was 9.30 ± 1.11 (9.49 ± 1.05 men, 9.03 ± 1.13 women; p = &lt;0.001). The mean baPWV value was 15.82 ± 2.56 (15.75 ± 2.46 men, 15.92 ± 2.68 women; p = &lt;0.001). MetS was found in 51% (49% men, 54% women; p = 0.036). Subjects with MetS had lower MD adherence and higher arterial stiffness values than subjects without MetS. Overall, we found a negative association of MD score with the number of MetS components (β = -0.168), with glycemia (β = -0.007), triglycerides (β = -0.003), waist circumference (β = -0.018), CAVI (β = -0.196) and baPWV (β = -0.065), and a positive association with HDL cholesterol (β = 0.013). By sex, associations followed the same direction but without reaching statistical significance with blood glucose and triglycerides in women and with HDL cholesterol and waist circumference in men. Conclusion: Results indicate that greater adherence to the Mediterranean diet decreases arterial stiffness and the percentage of subjects with MetS, although results differed in the association with MetS components by sex.

Traumatic vascular injuries consist in direct or indirect damage to arteries and/or veins and accounts for 3% of all traumatic injuries. Typical consequences are hemorrhage and ischemia. Extremities vascular injuries can occur isolated or in association in major trauma with other organ injuries. They account for 1-2% of patients admitted to Emergency Department, for approximately 50% of all arterial injuries. Lower extremities are more frequently injured than the upper ones in adult population. The outcome of vascular injuries is strictly correlated to the environment and the time background. Treatment can be challenging notably in polytrauma because of the dilemma of which injury should be prioritized and treatment delay can cause disability or even death especially for limb vascular injury. Our purposes are to discuss the role of Computed Tomography Angiography (CTA) in the diagnosis of vascular trauma and its optimized protocol to achieve the definitive diagnosis, and to assess the radiological signs of vascular injuries and the possible pitfalls.

Introduction: Postpartum hypertension (PPHT) is hypertension that persists or develops directly after pregnancy. PPHT affects 10% of pregnancies and is the most common cause for re-hospitalization after giving birth. In general, PPHT stems from hypertensive disorders of pregnancy (HDP). The aim of the current interim report of the Basel PPHT registry is to describe the cohort, and to determine feasibility and acceptance of a home-based telemonitoring management strategy (HBTMS) in women with PPHT. Methods: Enrollment in the cohort began in June 2020 during the SARS-CoV-2 pandemic at the University Hospital Basel. Women in the maternity ward were screened for preexisting hypertension, HDP, and de novo postpartum hypertension and after consenting, were enrolled. In this pragmatic non-randomized prospective trial, women in the PPHT cohort could choose, between a HBTMS or usual care which consisted of in-hospital appointments at the hypertension clinic. HBTMS was defined as a smartphone application or a programmed spreadsheet to report blood pressure followed by telephone consultations. Standard of care was hospital-based visits as clinically needed after discharge. All participants were assessed three months after delivery with a standardized clinical visit including a 24-hour blood pressure measurement, blood, biomarker, and urine analysis. Results: 311 participants were enrolled from 06/20-08/23. Mean age was 34±5.3 years. Regarding pregnancy-related medical history: 10 % had preexisting hypertension, 27.3 % gestational hypertension, 53% preeclampsia (PE), 0.3% eclampsia, 6% HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) and 18.3% had de novo PPHT. More than one diagnosis was possible. Family history of cardiovascular disease was seen in 49.5%, 7.5% had a family history of PE. 23.3% were determined as high risk for PE during pregnancy. The most common type of delivery was C-Section (68.5%), mean hospital stay was 6.3 days (±3.9) and IUGR (intrauterine growth restriction) was seen in 21% of the newborns. 99% of participants chose a home-based management strategy. Conclusion: This first description of the Basel PPHT Cohort showed that a HBTMS is well accepted. This is particularly relevant in the direct postpartum period and even more pertinent when the exposure of hospital visits should be avoided when possible.

Endovascular techniques are currently considered as a first line treatment options for lower limb chronic limb-threatening ischemia (CLTI), defined by the presence of ischemic rest pain and severe tissue loss such as ulcers or gangrene. Although the technical success rate of endovascular revascularization is high, in specific patients with advanced infrapopliteal disease and absence of run-off tibial vessels ("desert foot"), the chance of successful revascularization is minimal. In order to avoid primary amputation several treatment option are currently being investigated, including different strategies such as gene therapy or venous arterialization techniques. This review focuses on the percutaneous deep venous arterialization technique, recently introduced in everyday clinical practice, as a promising, minimally invasive treatment option for limb salvage in CLTI patients presenting with “desert foot”.

Transarterial embolization (TAE) for high-flow pancreaticoduodenal artery (PDA) aneurysms in patients with celiac-trunk stenosis by the median arcuate ligament (MAL) has been found effective both after rupturing and to prevent rupture. The objective was to describe the TAE techniques used and their effectiveness in excluding PDA aneurysms due to MAL syndrome. This single-center retrospective study done at the Dijon-Bourgogne University Hospital included all patients treated by TAE in 2010–2022 for ruptured or unruptured high-flow PDA aneurysms caused by MAL syndrome. We identified 14 patients (7 women and 7 men; mean age, 64 years). Packing and trapping techniques were used alone or together. Occlusion was with microcoils, co-polymer, or cyanoacrylate glue, used separately or combined. Technical success was achieved in 13 (93%) patients. Clinical success was achieved in 12 (86%) patients. One major and two minor complications were recorded within the first 30 days. No complications occurred after 30 days. Follow-up ranged from 1 to 84 months. No cases of aneurysm recanalization were recorded to date. TAE had high technical and clinical success rates in our patients with unruptured or ruptured PDA aneurysms due to MAL syndrome.

The purpose of this work was to evaluate a novel methodology developed by Digital Blood Corporation (DBC) to calculate critical blood values using four non-invasive measured values as input. The values obtained using a point-of-care testing (POCT) device were utilized for comparison and reference. Radial arterial blood was collected for the POCT comparator analysis using the Abbott i-STAT^® device. The non-invasive methodology from DBC requires four parameters to be directly measured: temperature, hemoglobin, pO2, and pCO2. Subsequently, sodium, potassium, chloride, ionized calcium, total carbon dioxide, pH, bicarbonate, and oxygen saturation are calculated using an algorithm. The agreement between the POCT and DBC’s methodology was analyzed using Bland-Altman difference plots. For a second data set, pO2 and pCO2 values collected with the POCT were used as input for DBC’s algorithm to test its robustness. Data from 37 healthy ambulatory individuals, mean age: 42.4 + 13 years; range: 18-64 years, were included in the primary analysis. In the case of the non-invasive gained four input values the greatest variation between POCT and DBC’s approach was observed for pO2 and consequently for algorithm values that depend upon pO2 precision. Replacing transcutaneous pO2 and pCO2 with POCT values demonstrates the principal ability of DBC’s algorithm to predict the additional 8 blood values in sufficient agreement with a standard POCT device in healthy patients. The algorithm developed by DBC appears to be robust in the case of healthy patients but does need the four measured input values with preciseness comparable to a POCT device to give reliable and clinically relevant results. The present study thus serves as a proof of concept to facilitate future study and further development of this methodology into a non-invasive device.

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassemia and 14,3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization, were included in the study. The patients were divided into three groups according to haemodynamics and overall diagnostic approach: 42,9% had precapillary PH (Pulmonary Arterial Hypertension -PAH group), 25% post-capillary PH and 32.1% Chronic Thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics was recorded. PAH-specific drug therapy received 82.1% of patients and Balloon Pulmonary Angioplasty (BPA) was performed in 6 patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for PAH-group. Patients who underwent BPA improved Pulmonary Haemodynamics. Median survival time was 162 months and the survival rate was 1yr-100%, 2,3,4,5,6 years 96%, 9yrs 90% and 13yrs 78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlights the importance of a correct diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies, however the management should be offered in expert PH centers under patients’ individualized approach.

The aim of the present study was to investigate whether chronic undernutrition modifies the response to rostafuroxin in juvenile rats. Chronic undernutrition was induced in male rats using a multideficient diet known as Regional Basic Diet (RBD), mimicking alimentary habits in impoverished regions worldwide. Animals were given RBD – or a control/CTRL normal diet for rodents – from weaning to 90 days, and rostafuroxin (1 mg/kg body mass) or vehicle were orally administered during the last 30 days. Undernourished rats became hypertensive at 55–60 days of age (tail-cuff recording). During the last two days, the rats were hosted in metabolic cages to measure food/energy, water, Na⁺ ingestion, and urinary volume. Blood and kidneys were collected after euthanasia. Rostafuroxin increased food/energy and Na⁺ intake in CTRL and RBD rats but had opposite effects on Na⁺ balance (intake minus urinary excretion): negative in CTRL and positive in RBD. The drug normalized the decreased plasma Na⁺ concentration found in RBD rats, increased urinary volume in RBD but not in CTRL, and decreased and increased urinary Na⁺ concentration in the RBD and CTRL groups, respectively. Rostafuroxin decreased the ouabain-sensitive (Na⁺+K⁺)ATPase and increased the ouabain-resistant, furosemide-sensitive Na⁺-ATPase from proximal tubule cells in both groups, and normalized the systolic blood pressure in RBD without effect in CTRL rats. We conclude that chronic undernutrition modifies the response of blood pressure, caloric metabolism, Na⁺ distribution in liquid compartments, mobilization of Na⁺ from non-osmotic compartments, Na⁺ and water balance, and activity of renal Na⁺-transporting ATPases to rostafuroxin.

Several noninvasive vascular biomarkers have been suggested for improving the risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment (L-LT) in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and free of diabetes and L-LT. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score =0 (OR 0.67; 95%CI 0.48-0.92, P=0.01), CAC score >100 (1.59; 1.08-2.39, P=0.01) and with high femoral IMT (1.89; 1.19-3.06, P<0.01), but not with other biomarkers. Our data confirm that in the presence of CAC score =0 in individuals at intermediate risk, L-LT can be avoided, while it should be used in those with CAC score >100. Femoral artery IMT could represent a useful biomarker for decision regarding L-LT, however the reference values according to sex and age should be established in a large healthy population

The aim of the present study was to investigate whether chronic undernutrition modifies the response to rostafuroxin in juvenile rats. Chronic undernutrition was induced in male rats using a multideficient diet known as Regional Basic Diet (RBD), mimicking alimentary habits in impoverished regions worldwide. Animals were given RBD – or a control/CTRL normal diet for rodents – from weaning to 90 days, and rostafuroxin (1 mg/kg body mass) or vehicle were orally administered during the last 30 days. Undernourished rats became hypertensive at 55–60 days of age (tail-cuff recording). During the last two days, the rats were hosted in metabolic cages to measure food/energy, water, Na+ ingestion, and urinary volume. Blood and kidneys were collected after euthanasia. Rostafuroxin increased food/energy and Na+ intake in CTRL and RBD rats but had opposite effects on Na+ balance (intake minus urinary excretion): negative in CTRL and positive in RBD. The drug normalized the decreased plasma Na+ concentration found in RBD rats, increased urinary volume in RBD but not in CTRL, and decreased and increased urinary Na+ concentration in the RBD and CTRL groups, respectively. Rostafuroxin decreased the ouabain-sensitive (Na++K+)ATPase and increased the ouabain-resistant, furosemide-sensitive Na+-ATPase from proximal tubule cells in both groups, and normalized the systolic blood pressure in RBD without effect in CTRL rats. We conclude that chronic undernutrition modifies the response of blood pressure, caloric metabolism, Na+ distribution in liquid compartments, mobilization of Na+ from non-osmotic compartments, Na+ and water balance, and activity of renal Na+-transporting ATPases to rostafuroxin.

Overweight/obesity is a growing pandemic nowadays that affects many organs and tissues. We have investigated whether a high-lipid diet provokes an imbalance between type 1 and type 2 angiotensin II (Ang II) receptors signaling, leading to liver alterations associated with previously described cardiovascular and kidney disturbances. Chronic administration of a high-lipid diet can provoke an hepatocardiorenal syndrome as the result of activation of the Ang II→type 1 receptor axis, which is completely counteracted by Ang-(3–4) the allosteric enhancer of the Ang II→type 2 receptor pathway.

Given that the outcome of hepatic arterial infusion chemotherapy (HAIC) with cisplatin for intrahepatic advanced hepatocellular carcinoma (HCC) is unclear, we aimed to compare prognostic factors for overall survival (OS) following HAIC with cisplatin versus sorafenib for intrahepatic advanced HCC using propensity score-matched analysis. We enrolled 348 patients with intrahepatic advanced HCC who received HAIC with cisplatin (n = 97) or sorafenib (n = 251) between June 2006 and March 2020. No significant difference was observed in OS between HAIC with cisplatin and sorafenib cohorts (median survival time [MST]: 13.9 vs. 12.7 months; p = 0.0989). To reduce confounding effects, 176 patients were selected using propensity score-matched analysis (n = 88 for each treatment). HAIC with cisplatin significantly prolonged OS compared with sorafenib (MST: 16.2 vs. 12.2 months; p = 0.0060). Following stratification according to the Child–Pugh classification, for both patients with class A (MST: 24.0 vs. 15.6 months; p = 0.0097) and class B (MST: 8.5 vs. 6.9 months; p = 0.0391), HAIC with cisplatin rather than sorafenib significantly prolonged OS. Our findings suggest that HAIC with cisplatin demonstrates longer prognostic effects than sorafenib in intrahepatic advanced HCC, regardless of the hepatic reserve.

Background: The treatment of peripheral arterial disease (PAD) is focused on improving perfusion and oxygenation in the affected limb. Standard revascularization methods include bypass surgery, endovascular interventional procedures, or hybrid revascularization. Cell-based therapy can be an alternative strategy for patients with no-option critical limb ischemia who are not eligible for endovascular or surgical procedures. Aims: This review offers an up-to-date critical overview of the knowledge and data of evidence-based medicine on the position of cell therapy in the treatment of PAD. It provides an overview of current evidence and appraises the future perspectives of cell-based therapy, emphasizing the potential of exosomal cell-free approaches in patients with critical limb ischemia. Results: Meta-analyses focused on cell therapy problems in PAD treatment confirm a significantly greater chance of limb salvage in the first year after the cell therapy administration. The opportunity of defect healing is at least two times higher when compared with the standard conservative therapy. Secondary endpoints of the available meta-analyses are also included in this review. Improvement of perfusion and oxygenation parameters in the affected limb, pain regression, and claudication interval prolongation are discussed. Conclusions: The available evidence-based medicine data show that this technique is safe, associated with minimum complications or adverse events, and effective.

Despite the important role that the GH/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium has turned to be considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effect, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, it will be described the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy. It will be analyzed all those elements triggering the local and systemic production of GH/IGF-I and their possible role both in physiological and pathological conditions. The whole evidence will be combined with important data from the GHAS trial, in which GH or placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of the ischemic disease.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

Contrast-enhanced ultrasonography (CEUS) is useful for evaluation of the hemodynamics of hepatic tumors and surrounding he-patic parenchyma in real time. CEUS with intravenous contrast administration is well established for evaluation of hepatocellular carcinoma (HCC). On the other hand, intra-arterial (transcatheter) CEUS (IAUS) is an emerging technique that allows more selective evaluation of the arterial supply to the tumor. IAUS was performed by administration of Sonazoid® through the microcatheter and imaging of the area of the target lesion with a dedicated, contrast-specific technique. Sonazoid® (0.5 ml diluted with 49.5 ml of distilled water) was used as the contrast medium in IAUS. The diluted Sonazoid® was introduced into the feeding artery by in-termittent injection of 0.3-1.0 ml through a microcatheter placed in the artery and flushing with saline at the same flow rate. We report the three cases in which IAUS was useful in transarterial chemoembolization (TACE) for HCC. Two cases were performed TACE for hepatic metastasis. In any cases, plain computed tomography (CT) after TACE showed accumulation of Lipiodol® only in the metastases. One case was suspected having HCC rupture and urgent abdominal angiography was performed. IAUS was performed frequently to reduce the amount of iodinated contrast agent as much as possible because of renal failure. Concomitant use of IAUS enabled reduction of the amount of contrast agent.

Cardiovascular surgeries, though lifesaving, can lead to complications requiring further interventions, including amputations. This study uses Sankey diagrams, Sunburst plots, and Icicle plots to analyze treatment pathways in patients with peripheral artery disease (PAD), focusing on those that lead to amputation versus those that do not. We found that non-amputation outcomes commonly involve anti-platelet and lipid-lowering medications, while amputation pathways, although less frequent, often share similar initial treatments but diverge later, suggesting areas for early intervention. These visualizations highlight patterns in patient care and emphasize the importance of tailored treatment strategies to reduce amputations, offering insights to predict likely outcomes based on treatment sequences.

Harms of combustible cigarette (CC) use in pregnancy for fetal development are well-studied. Less understood is potential impacts of newer non-combustible cigarette alternatives, including electronic cigarettes (EC). Our goal was to examine whether EC use during pregnancy predicts increased risk of adverse birth outcomes. This retrospective cohort study used data from the Obstetrics Initiative (OBI), a statewide collaborative of 70 maternity hospitals. OBI’s clinical registry of data on nulliparous, term, singleton, vertex fetal presentation pregnancies were from medical records. Three groups of pregnancy cigarette users (Controls (n=26,394), CC (n=2,216), EC (n=493) were compared on birth outcomes, controlling for background differences. Compared to controls, the EC group had significantly lower birth weight, while CC had reduced birthweight and greater rates of arterial cord pH < 7.1. Compared to EC, CC users had higher rates of neonates requiring antibiotics and NICU admission. Growing evidence suggests EC are not safer alternatives to CC, and use during pregnancy should be discouraged. Additional research is needed, as non-significant trends for increased risk of several adverse neonatal outcomes following EC use were found, potentially significant in larger studies with average-risk for adverse pregnancy outcomes and when frequency and timing of EC exposure are considered.

People with diabetic foot frequently exhibit poor gait and balance. However, there is no review to inform digital biomarkers of poor gait and balance related to diabetic foot, measurable by wearables outside traditional gait laboratories. Such information could assist in designing remote patient monitoring platform to track changes in gait and balance dysfunction among people with diabetic foot for timely referral and intervention. Accordingly, we conducted a web-based review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified 20 papers in this review. We found preliminary evidence of digital biomarkers of gait and balance dysfunction in people with diabetic foot, measured by wearables, such as slow gait speed, large gait variability, unstable gait initiation, and large body sway. However, due to heterogeneities in included papers in terms of study design, movement tasks, and small sample size, more studies are recommended to confirm this preliminary evidence. Additionally, based on our review, we recommend establishing appropriate strategies to successfully implement wearable-based assessment into clinical practice for diabetic foot care.

Background: Cytomegalovirus (CMV) infection has been associated with venous thromboembolism (VTE) and acute coronary syndromes (ACS). Methods: A retrospective study was conducted within the OSF HealthCare System in Peoria, Illinois. The objectives were to determine the incidence of acute VTE and ACS within one year of CMV testing. The “study group” included patients with positive CMV IgM or positive CMV Polymerase Chain Reaction (PCR). The “seropositive control” group included patients with positive CMV IgG and negative IgM. The “seronegative control” group included patients with negative CMV IgG and IgM, or negative PCR. Results: Within one year of CMV infection, 38 of 379 patients (10.0%) developed VTE in the study group compared to 41 of 1334 patients (3.1%) in the seropositive control and 37 of 1249 (3.0%) in the seronegative control. Adjusting for age and gender, both control groups were less likely to have VTE than the study group within one year (Seropositive Control: OR = 0.3, 95% CI 0.2-0.5, p <0.0001; Seronegative Control: OR = 0.4, 95% CI 0.2-0.6, p <0.0001). ACS was more likely to occur in the study group, with incidence of 7.7% compared to 4.7% (p <0.0001) in the seropositive control and 1.9% (p <0.0001) in the seronegative control. Adjusting for age and gender, the seronegative control was less likely to develop ACS than the study group within one year (OR = 0.4, 95% CI 0.2-0.7, p = 0.003). Conclusions: This retrospective study demonstrates that CMV infection may be a significant risk factor for VTE and ACS.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including but not limited to imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neu-rostimulation including acupuncture. Lastly, we also touch upon the disease’s different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

This study aimed on evaluating the potential diagnostic value of a novel, sonographic, B-Flow Imaging (BFI)-based sign (“flashlight sign”, FLS) for the detection of wall-adherent, floating arterial structures (WAFAS). The FLS, characterized by a fast moving, very bright, intraluminal signal was detected in 28 patients with WAFAS. We divided this cohort into three subgroups, depending on the affected vascular segments: (1) peripheral arteries (n = 10), (2) native abdominal aorta (n = 8), and (3) abdominal aorta after endovascular aortic repair (EVAR; n = 10). Clinical characteristics were analyzed and BFI-findings were compared with contrast enhanced ultrasound (CEUS) and computed tomography angiography (CTA). Seven patients (25%) suffered from arterial embolism downstream to the FLS (EVAR, n = 4; native abdominal aorta, n = 1; peripheral arteries, n = 2). WAFAS of the abdominal aorta (native or after EVAR), as indicated by the FLS, were visible by CEUS and CTA in 60% and 93.3%, respectively. Based on the so far largest cohort of patients with WAFAS, we propose a clinically useful, BFI-based sonographic sign for detection of these so far underrated arterial pathologies in the abdominal aorta and the peripheral arteries.

The coexistence of SAH with T2DM is a common comorbidity. In this present study, we investigated the link between altered plasma antioxidant trace elements (ATE: Manganese, Selenium, Zinc and Copper) and fatty acids ratio (FAR: polyunsaturated/saturated) imbalance as transition biomarkers between vascular pathology (SAH) to metabolic pathology (T2DM). Our data revealed strong correlation between plasma ATE and FAR profile which is modified during SAH-T2DM association compared to healthy group. This relationship is mediated by lipotoxicity (simultaneously prominent visceral adipose tissue lipolysis, significant flow of non-esterified free fatty acids release, TG-Chol-dyslipidemia, high association of Total SFA, Palmitic acid, Arachidonic acid and PUFA 6/ PUFA 3; drop in tandem of PUFA / SFA and EPA+DHA); oxidative stress (lipid peroxidation confirmed by TAS depletion and MDA raise, concurrently drop of Zn/Cu-SOD, GPx, GSH, Se, Zn, Se/Mn, Zn/Cu; concomitantly enhance Cu, Mn and Fe); endothelial dysfunction (endotheline-1 increase); athero-thrombogenesis risk (concomitantly raise of ApoB100/ApoA1, Ox-LDL, tHcy and Lp(a)) and inflammation (higher of Hs-CRP, Fibrinogen and Ferritin). Our study open to new therapeutic targets and to better dietary management, such as to establish dietary ATE and PUFA 6 / PUFA 3 or PUFA / SFA reference values for atherosclerotic risk prevention in hypertensive-diabetics patients.

Middle-aged adults can start to be affected by some arterial diseases, such as abdominal aortic or popliteal artery aneurysms, lower extremity arterial disease, internal carotid or renal artery or subclavian artery stenosis. These vasculopathies are often paucisymptomatic before manifesting themselves with dramatic complications. Therefore, early detection of peripheral artery disease (PAD) and aneurysmal disease is fundamental to reduce the risk of major adverse cardiovascular and limb events. Furthermore, PAD carries a high correlation with silent coronary artery disease (CAD). This study focuses on the most common PADs and aneurysmal diseases, in the attempt to summarize some key points which should selectively drive screen. Since it is evident how we are not in the human and economic possibilities to instrumentally screening wide populations, deep knowledge of semeiotics and careful anamnesis must play a central role in our daily activity as physician. The presence of some risk factors for atherosclerosis, or an already known history of CAD, can raise the clinical suspecion of PAD or aneurysmal disease after a careful clinical history and a deep physical examination. The clinical suspicion must then be confirmed by a first-level ultrasound investigation and, if so, adequate treatments can be adopted to prevent dreadful complications.

Blood gas analysis is a diagnostic tool to evaluate the partial pressures of gas in blood and acid-base content. The use of blood gas analysis enables to clear understanding the respiratory, circulatory, and metabolic disorders. The arterial blood gas (ABG) explicitly analyzes blood taken from an artery, assessing the patient's partial pressure of oxygen (PaO2), carbon dioxide (PaCO2) pH (acid/base). PaO2 indicates the oxygenation status, and PaCO2 indicates the ventilation status (chronic or acute respiratory failure). PaCO2 is affected by hyperventilation characterized by rapid or deep breathing, and hypoventilation characterized by slow or shallow breathing. The acid-base balance tested by the ABG procedure measures the pH and PaCO2 directly while the use of the Hasselbach equation gives the serum bicarbonate (HCO3) and base deficit or excess. The measured HCO3is based on strong alkali that frees all CO2 in serum, including dissolved CO2, carbamino compounds, and carbonic acid the calculation uses a standard chemistry analysis giving the amount of "total CO2", the difference will amount to around 1.2 mmol/L. Though ABG is frequently ordered in emergency medicine contests for acute conditions it may also be needed in other clinical settings. The ABG analysis shows to be an exceptional diagnostic tool including the group of those diseases known as acid-base diseases (ABDs) which include a great variety of conditions as such severe sepsis, septic shock, hypovolemic shock, diabetic ketoacidosis, renal tubular acidosis, chronic respiratory failure, chronic heart failure, and diverse metabolic diseases.

Abstract: Type A acute aortic dissection is a serious condition within the acute aortic syndromes that demands immediate treatment. Despite advancements in diagnostic and referral pathways, the survival rate post-surgery currently sits at almost 20%. Our objective was to pinpoint clinical indicators for mortality and morbidity, particularly raised arterial lactate as a key factor for negative outcomes. Methods: All patients referred to the three cardiovascular centres between January 2005 and December 2022 were included in the study. The inclusion criteria required the presence of a lesion involving the ascending aorta, symptoms within 7 days of surgery, and referral for primary surgical repair of TAAAD based on recommendations, with consideration for other concomitant major cardiac surgical procedures needed during TAAAD and retrograde extension of TAAAD. We conducted an analysis of both continuous and categorical variables and utilized predictive mean matching to fill in missing numeric features. For missing binary variables, we used logistic regression to impute values. We specifically targeted early postoperative mortality and employed LASSO regression to minimize potential collinearity of over-fitting variables and variables measured from the same patient. Results: 633 patients were recruited for the study, out of which 449 patients had complete preoperative arterial lactate data. The average age of the patients was 64 years, and 304 patients were male (67.6%). The crude early postoperative mortality rate was 24.5% (110 out of 449 patients). The mortality rate did not show any significant difference when comparing conservative and extensive surgeries. However, malperfusion had a significant impact on mortality [48/131 (36.6%) vs 62/318 (19.5%), p<0.001]. Preoperative arterial lactates were significantly elevated in patients with malperfusion. The optimal prognostic threshold of arterial lactate for predicting early postoperative mortality in our cohort was ≥ 2.6 mmol/L. Conclusion: The arterial lactate concentration in patients referred for TAAAD is an independent factor for both operative mortality and postoperative complications. In addition to mortality, patients with an upper arterial lactate cut-off of ≥2.6 mmol/L face significant risks of VA ECMO and the need for dialysis within the first 48 hours after surgery. To improve recognition and facilitate rapid transfer and surgical treatment protocol, more diligent efforts are required in the management of malperfusion in TAAAD.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, including in Croatia. Since most patients have multiple disorders and diseases caused largely by the same risk factors, and as it is essential to approach each patient as a person with all disorders, today we are talking about a new paradigm - cardio-renal-metabolic (CKM) syndrome and cardio-renal-metabolic health, which necessarily includes brain health. Elevated systolic blood pressure, LDL cholesterol, smoking, obesity, diabetes, impaired renal function or chronic kidney disease, which all stem from insufficient physical activity, unhealthy diet with excessive intake of table salt, and air pollution, are the leading causes of overall morbidity and mortality from CKM diseases, especially mortality from CVD. Experts from various fields key to CKM health have written this document with the aim of integrating it as part of the national plan for the prevention of chronic non-communicable diseases with a focus on CVD, which should become mandatory and be based on the existing guidelines of professional societies.

Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analy-sis was performed by using univariate (Spearman, t-Student, X2) and multivariate (multiple lo-gistic regression) tests. Results: 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age:71.4±12.4 (79.4% male); TNF-α:10.7±4.9; hs-CRP:1.6±2.2; Neutrophil-to-lymphocyte ratio (NLR):3.5±2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hs-CRP (≥0.5) in 60.5%. Diabetic patients with high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p=0.0346). Plasma TNF-α had a negative correlation with eNOS expression (-0.5, p=0.015) and hs-CRP with VEGF-A (-0.63, p=0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p=0.037), especial-ly in DM. Cumulative mortality at 12-month was related to NLR ≥3 (p=0.019) and TNF-α ≥8.1 (p=0.048). The best cut-off point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hs-CRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suita-ble markers of mortality in CLTI. These results are novel because they connect muscle gene expres-sion and plasma information in patients with advanced PAD, deepening the search of new and ac-curate targets for this condition.

Mild traumatic brain injury mTBI is a common occurrence around the world, associated with a variety of blunt force and torsion injuries affecting all age groups. Most never reach medical attention, and identification of acute injury and later clearance to return to usual activities is relegated to clinical evaluation particularly in sports injuries. Advanced structural imaging is rarely performed due to the usual absence of associated acute anatomic/hemorrhagic changes. This review targets physiologic imaging techniques available to identify subtle blood brain barrier dysfunction and white matter tract shear injury, and their association with chronic traumatic encephalopathy. These techniques provide needed objective measures to assure recovery from injury in those patients with persistent cognitive/emotional symptoms and in the face of repetitive mTBI.