Vascular injury such as central venous stenosis (CVS) is a common complication in hemodialysis patients with central venous catheters (CVCs), yet the impact of the microstructure and partial physic characteristics of catheter surface on the chronic injury of central vein has not been elucidated. In this study, the microscopic morphology of tips and bodies of six different brands of polyurethane CVCs was observed and their roughness was assessed. Subsequently, an in vitro model was established to measure the coefficients of friction (COF) between CVCs (tips and bodies) and the vena cava intima of Japanese rabbits under the same condition in a linear reciprocating mode, and changes in the intima of vessels after friction were observed. The study found that there was a significant variation in surface roughness among different brands of CVCs (tips P < 0.001, bodies P = 0.02), and the COF was positively correlated with the catheter surface roughness (tips P = 0.005, R = 0.945, bodies P = 0.01, R = 0.909). Besides, the endovascular roughness increased after friction. These findings suggest that the high roughness surface of CVCs may cause chronic mechanical friction injury to the central venous intima, which is one of the potential factors leading to CVS or occlusion. This provides a breakthrough for reducing complications, improving patient prognosis, and advancing catheter surface lubrication technology.

Centrally inserted central catheters (CICCs) are indispensable in modern healthcare, but unfortunately, come with complications. Catheter-related thrombosis is a well-known complication reported to occur in 5-30% of patients with CICC. There is a paucity of studies that report the incidence of catheter-related thrombosis after the introduction of real-time ultrasound insertion guidance as clinical practice. This study aimed to demonstrate any pathological macro- or microscopic changes in the vein wall associated with CICCs.
The study was approved by the Swedish Ethical Review Authority and was conducted at a large university hospital. The study included 12 patients with a short-term CICC who were subject to autopsies. Vessels with inserted catheters were macroscopically and microscopically examined.
In total, seven female and five male patients with a median age of 70 (interquartile range 63-76) were included. With one exception, all patients received routine thromboprophylaxis throughout the period with CICC. Most inserted CICCs were 9.5 French (54%) and were inserted in the internal jugular vein (92%). The median time with CICC was seven days (interquartile range 1.8-20). At autopsy, thrombi were observed in all cases (100%), macroscopically and microscopically, attached to the distal portion of the CICC and/or the adjacent vessel wall. Inflammatory changes in the vessel walls were seen in all cases, and varying degrees of fibrosis were demonstrated in eight cases (67%).
This autopsy study demonstrated that catheter-related thrombus formation with adjacent inflammatory and fibrotic vessel wall thickening was very common, despite a limited period of catheter use. The consequences of these findings are important, as thrombi may cause pulmonary embolism and possibly lead to catheter-related infections, and since inflammatory and fibrotic vessel wall thickening may evolve into chronic venous stenosis. Furthermore, the findings are a cause of concern, as CICCs are indispensable in modern healthcare and complications may be masked by the general disease that was the indication for CICC insertion.

BACKGROUND: Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF.
METHODS: This retrospective autopsy study included cases from the São Paulo (Brazil) epidemic of 2017-2019. We reviewed medical records and performed cardiac tissue histopathological evaluation, electron microscopy, immunohistochemical assays, RT-qPCR for YF virus (YFV)-RNA, and proteomics analysis on inflammatory and endothelial biomarkers.
RESULTS: Seventy-three confirmed YF cases with a median age of 48 (34-60) years were included. We observed myocardial fibrosis in 68 (93.2%) patients; cardiomyocyte hypertrophy in 68 (93.2%); endothelial alterations in 67 (91.8%); fiber necrosis in 50 (68.5%); viral myocarditis in 9 (12.3%); and secondary myocarditis in 5 (6.8%). Four out of five patients with 17DD vaccine-associated viscerotropic disease presented with myocarditis. The cardiac conduction system showed edema, hemorrhages and endothelial fibrinoid necrosis. Immunohistochemistry detected CD68-positive inflammatory interstitial cells and YFV antigens in endothelial and inflammatory cells. YFV-RNA was detected positive in 95.7% of the cardiac samples. The proteomics analysis demonstrated that YF patients had higher levels of multiple inflammatory and endothelial biomarkers in comparison to cardiovascular controls, and higher levels of interferon gamma-induced protein 10 (IP-10) in comparison to sepsis (p = 0.01) and cardiovascular controls (p < 0.001) in Dunn test.
CONCLUSIONS: Myocardial injury is frequent in severe YF, due to multifactorial mechanisms, including direct YFV-mediated damage, endothelial cell injury, and inflammatory response, with a possible prominent role for IP-10.
BACKGROUND: This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo, Bill and Melinda Gates Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

OBJECTIVE: Chronic venous disease (CVD) is a prevalent pathology, and endothelial dysfunction is recognized as a core of its physiopathology. Flow-mediated dilation (FMD) is one of the most widely used tests for evaluating endothelial function. The aim of this study is to evaluate the influence of varicose vein (VV) surgery on FMD.
METHODS: A prospective study with patients with superficial CVD and saphenous incompetence on Doppler ultrasonography that were proposed for VV surgery. The FMD test was performed before and 6 months after the procedure. The operator performing the post-operative evaluation was blinded to the pre-operative result.
RESULTS: A total of 42 patients were included in the analysis. The median pre-operative percent change of FMD was 4.20% (±1.30) and the post-operative was 4.56% (±1.25) (p = 0.819).
CONCLUSIONS: Our findings do not corroborate the presence of an overall endothelial dysfunction prone to modulation by surgery. Nevertheless, further studies are needed to confirm our findings.

In the last years, research proofs have confirmed that hydrogen sulfide (H2S) plays an important role in various physio-pathological processes, such as oxidation, inflammation, neurophysiology, and cardiovascular protection; in particular, the protective effects of H2S in cardiovascular diseases were demonstrated. The interest in H2S-donating molecules as tools for biological and pharmacological studies has grown, together with the understanding of H2S importance. Here we performed a comparative study of a series of H2S donor molecules with different chemical scaffolds and H2S release mechanisms. The compounds were tested in human serum for their stability and ability to generate H2S. Their vasorelaxant properties were studied on rat aorta strips, and the capacity of the selected compounds to protect NO-dependent endothelium reactivity in an acute oxidative stress model was tested. H2S donors showed different H2S-releasing kinetic and produced amounts and vasodilating profiles; in particular, compound 6 was able to attenuate the dysfunction of relaxation induced by pyrogallol exposure, showing endothelial protective effects. These results may represent a useful basis for the rational development of promising H2S-releasing agents also conjugated with other pharmacophores.

UNASSIGNED: Dual pathway inhibition (DPI) by combining acetylsalicylic acid (ASA) with low-dose rivaroxaban has been shown to reduce cardiovascular events in patients with peripheral arterial disease (PAD) when compared to ASA monotherapy. A potential explanation is that inhibition of factor Xa improves endothelial function through crosstalk between coagulation and inflammatory pathways, subsequently attenuating the occurrence of cardiovascular events. We hypothesize that the addition of rivaroxaban to ASA in PAD patients leads to improved endothelial function.
UNASSIGNED: An investigator-initiated, multicentre trial investigating the effect of DPI on endothelial function.
UNASSIGNED: Patients, diagnosed with PAD, were enrolled in two cohorts: cohort A (Rutherford I-III) and cohort B (Rutherford IV-VI). Participants received ASA monotherapy for a 4-weeks run-in period, followed by 12 weeks of DPI. Macro- and microvascular endothelial dysfunction were studied by measuring carotid artery reactivity upon sympathetic stimulus and by measuring plasma endothelin-1 concentrations, respectively. All measurements were performed during the use of ASA (baseline) and after 12 weeks of DPI.
UNASSIGNED: 159 PAD patients (111 cohort A, 48 cohort B) were enrolled. Twenty patients discontinued study drugs early. Carotid artery constriction upon sympathetic stimulation at baseline (ASA) and after 12 weeks of DPI was similar in the total group, 22.0 vs. 22.7% (p = 1.000), and in the subgroups (Cohort A 22.6 vs. 23.7%, p = 1.000; cohort B 20.5 vs. 20.5%, p = 1.000), respectively. The mean concentration of plasma endothelin-1 at baseline and after 12 weeks of DPI did not differ, 1.70 ± 0.5 vs. 1.66 ± 0.64 pmol/L (p = 0.440) in the total group, 1.69 ± 0.59 vs. 1.62 ± 0.55 pmol/L in cohort A (p = 0.202), and 1.73 ± 0.53 vs. 1.77 ± 0.82 pmol/L in cohort B (p = 0.682), respectively.
UNASSIGNED: Macro- and microvascular endothelial dysfunction, as reflected by carotid artery reactivity and plasma endothelin-1 concentrations, are not influenced in PAD patients by addition of low-dose rivaroxaban to ASA monotherapy for 12 weeks.
UNASSIGNED: https://clinicaltrials.gov/ct2/show/NCT04218656.

Vascular endothelium insults caused by high serum glucose levels affect the oxygen supply to tissues, via the microvascular endothelium, resulting in an increased perfusion heterogeneity. These insults may lead to the underuse of blood capillaries, while other vessels are overused and effectively overload their oxygen supply capacity, which eventually causes damages to distal parts of the peripheral nervous system. Therefore, the proprioceptive and exteroceptive feedback information will be gradually lost and contribute to a mobility reduction. This study aims to assess the efficacy of whole-body vibration (WBV) associated with strength training (ST) on lower-limb blood flow and mobility in older adults with type 2 diabetes (DM2). Methods and analyses: This is a protocol (1st version) for Pa single-blind, randomized, controlled clinical trial guided by the SPIRIT guidelines. Our sample will consist of 51 older adults with DM2 randomly allocated to three groups: low frequency WBV (16−26 Hz) associated to ST (G1), WBV sham (G2) and nonintervention control (G3). The study protocol is set for a 12-week (three times per week) schedule. Primary outcomes: skin temperature using infrared thermographic imaging (ITI); mean peripheral arterial blood flow velocity (MBF) by a handheld Doppler ultrasound (DU), and functional mobility by Timed Up and Go (TUG) test. Secondary outcomes: quasi-static posture using the DX100 BTS Smart optoelectronic system, and plantar pressure and body balance using the MPS stabilometric platform. Data will be collected and analyzed at baseline and post-intervention, considering p-value < 0.05 level of significance. The analyses will also be conducted with an intention-to-treat method and effect size. Dissemination: All results will be published in peer-reviewed journals as well as presented in conferences.

OBJECTIVE: The aim of the study was to assess the relationship between the improvement of the clinical condition of patients with the first episode of psychosis (FEP) and changes in - nitric oxide (NO) plasma concentration based on the level of its metabolites NO2- and NO3, as well as changes in lipid profile and biomarkers of systemic inflammation.
METHODS: The study was carried out in agroup of 25 young patients with FEP (aged 14-35). Blood samples were collected in the 1st and 12th week after admission to the hospital to assess NO metabolites, lipid profile and inflammatory biomarkers. Demographic and clinical data were also analysed.
RESULTS: In the study group, three months after admission to the hospital, an improvement in the clinical symptoms was observed, as evidenced by a decrease in the Positive and Negative Syndrome Scale (PANSS) scores. This improvement was associated with a decrease in the plasma nitrite concentration, a deterioration of the lipid profile and the activation of systemic inflammation. Interestingly, in the 1st week after the hospital admission, a longer duration of untreated psychosis (DUP) was associated with a lower NO2- plasma concentration, and a higher intensity of positive symptoms (PANSS Positive Symptoms Scale) was associated with higher CRP plasma level.
CONCLUSIONS: Our results suggest that adverse metabolic response, systemic inflammation and a fall in systemic NO bioavailability represent early systemic manifestations of FEP that are not controlled by short-term anti-psychotic treatment and may pose cardiovascular risk.

UNASSIGNED: Glucose variability (GV) is considered an important factor for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). High GV causes endothelial dysfunction and increased oxidative stress. Dipeptidyl peptidase-4 (DPP-4) inhibitors may improve endothelial function and decrease GV. The aim of this study was to investigate the effects of vildagliptin, a DPP-4 inhibitor, compared with glibenclamide in GV and endothelial function in patients with T2DM and arterial hypertension.
UNASSIGNED: This is a prospective, randomized, open and drug-controlled study. Fifty patients older than 35 years with T2DM and hypertension without CVD were randomized to receive vildagliptin (n=25) or glibenclamide (n=25), both in added-on metformin. Laboratory tests and analysis of endothelial function were performed before and 12 weeks after treatment. Endothelial function, defined by reactive hyperemia index (RHI), was analyzed by peripheral artery tonometry (endo-PAT2000). GV was evaluated by capillary glucose with intermittent monitoring device, six measurements per day, for three days, before and after treatment. The median of standard deviation (SD) of mean blood glucose (MBG) was used to evaluate GV.
UNASSIGNED: GV decreased in the vildagliptin group (35.2 to 30.7, P=0.037) but did not change with glibenclamide (37.6 to 37.5, P=0.765). Glycated hemoglobin was similar in both groups. MBG decreased only in glibenclamide group, without difference with vildagliptin group (P=0.374). There were no changes in the RHI in both groups and there was no correlation between GV and RHI (P=0.658).
UNASSIGNED: Vildagliptin reduces GV; however, the action on endothelial function was not demonstrated. In addition, there was no correlation between GV and endothelial function.

OBJECTIVE: To assess the effects of periodontal treatment on endothelial function in patients with coronary artery disease.
METHODS: A randomized controlled trial was conducted with 69 patients with stable coronary disease and severe periodontitis. The test group received nonsurgical periodontal therapy consisting of personalized oral hygiene instructions, subgingival scaling, and root planing per quadrant, whereas the control group received equal treatment after the study period. Endothelial function was assessed by measurement of brachial artery flow-mediated dilation, concentrations of sVCAM-1, sICAM-1, and P-selectin in serum before and 3 months after periodontal therapy.
RESULTS: The test group exhibited statistically better periodontal parameters-plaque, probing depth, periodontal attachment loss, and bleeding on probing. No significant improvements were observed in the control (1.37%) and test (1.39%) groups in flow-mediated dilation, with no significant between-group difference. sVCAM-1 concentration increased in the control group (997.6 ± 384.4-1201.8 ± 412.5; p = 0.03), whereas in the test group, no significant changes were observed (915.1 ± 303.8-1050.3 ± 492.3; p = 0.17), resulting in a significant difference between the two groups (p = 0.04). The same pattern was observed for concentrations of sICAM-1.
CONCLUSIONS: Periodontal treatment did not provide better vasodilation in patients with coronary disease in a short-term follow-up period, although it maintained blood concentrations of markers of vascular inflammation.