Use of heated tobacco products (IQOS) causes an acute increase in arterial stiffness and platelet thrombus formation.

BACKGROUND AND AIMS: Heated tobacco products (HTPs) are novel alternative tobacco products being promoted as an alternative to cigarettes. To evaluate the impact of HTP use on vascular function, we investigated the effects of a brief HTP usage on arterial stiffness and platelet thrombus formation in healthy volunteers. METHODS: In a randomised crossover study, twenty-four healthy young adults with occasional tobacco use smoked the HTP IQOS 3 Multi (Phillip Morris Int.) and "no-exposure" was used as a control, with a wash-out period of at least one week in-between. Arterial stiffness was assessed through pulse wave velocity and pulse wave analysis. Blood samples, collected at baseline and 5 min following exposure, were analysed with the Total-Thrombus-formation analysis system evaluating platelet and fibrin-rich thrombus formation tendency. RESULTS: HTP exposure caused immediate heightened pulse wave velocity (+0.365 m/s, 95% CI: +0.188 to 0.543; p = 0.004) and enhanced augmentation index corrected to heart rate (+6.22%, 95% CI: +2.33 to 10.11; p = 0.003) compared to the no-exposure occasion. Similarly, blood pressure and heart rate transiently increased immediately following HTP inhalation. Platelet thrombus formation significantly increased following HTP exposure (area under the curve +59.5, 95% CI: +25.6 to 93.4; p < 0.001) compared to no-exposure. No effect was seen on fibrin-rich thrombus formation following HTP-exposure. CONCLUSIONS: Brief HTP use in healthy young adults had immediate adverse effects on vascular function resulting in increased arterial stiffness and platelet thrombus formation, known risk factors for the development of atherosclerosis. Further research is needed to address long term health impacts.

Ventilatory support and inflammatory peptides in hospitalised patients with COVID-19: A prospective cohort trial.

PURPOSE: Several studies have shown that SARS-CoV-2 can induce a massive release of cytokines which contributes to disease severity and mortality. Therefore, cytokine levels in the serum may help to predict disease severity and survival in COVID-19 patients. METHODS: In this prospective trial, 88 patients who were hospitalised for COVID-19 were enrolled. Blood samples for serum peptide measurements were taken at the time closest to hospitalisation, at day 5, 9 and 13 (±1). The concentrations of cytokines (IL-1α, IL-1ß, IL-1RA, IL-6, L-7, L-10, IFN-γ and TNF-α), chemokines (CCL-3, CCL-4 and CCL-7) and growth factors (G-CSF, GM-CSF and VEGF) were assessed and correlated with the type of ventilation, occurrence of consolidations on imaging and the level of care. RESULTS: COVID-19 patients (median age 68 years, IQR 55-77) stayed in hospital between 5-171 days. Compared to patients in the general care unit, patients in the intermediate care unit (IMCU) and intensive care unit (ICU) presented significantly elevated serum IL-6 (p = 0.004) and lower IFN-γ levels (p = 0.005), respectively. The peak inspiratory pressure in ventilated patients correlated positively with IL-1RA, G-CSF and inversely with IFN-γ serum levels (all p<0.05). VEGF serum levels inversely correlated with the fraction of inspired oxygen in patients receiving high-flow nasal canula oxygen therapy (p = 0.047). No significant correlation between serum concentrations of the measured peptides and the type of ventilation, occurrence of radiological consolidations or in-hospital mortality has been observed. CONCLUSION: IL1-RA, IL-6, IFN-γ, G-CSF, CCL-7 and VEGF serum levels could prove helpful as biomarkers to assess disease severity and the need for intensive care in COVID-19 patients.

Electronic Cigarette Vaping with Nicotine Causes Increased Thrombogenicity and Impaired Microvascular Function in Healthy Volunteers: A Randomised Clinical Trial.

Electronic cigarette (EC) vaping is increasingly popular, despite growing evidence of adverse health effects. To further evaluate the impact of EC use on vascular health, we investigated the effects of brief EC inhalation on flow-dependent thrombus formation and microcirculation in healthy volunteers. The study was performed with a randomised double-blind crossover design. Twenty-two healthy subjects aged between 18 and 45 years with occasional tobacco use were recruited. Subjects inhaled 30 puffs of EC aerosol with and without nicotine on two occasions separated by a wash-out period of at least 1 week. Blood samples were collected at baseline and at 15 and 60 min following exposure and analysed with the Total-Thrombus-formation analysis system evaluating fibrin-rich thrombus formation and platelet thrombus formation in whole blood under flow. Microvascular function was assessed at baseline and 30 min after exposure by laser speckle contrast imaging and iontophoresis of acetylcholine and sodium nitroprusside (SNP) to evaluate the endothelium-dependent and independent pathways of vasodilation. Compared with nicotine free EC aerosol, exposure to EC aerosol with nicotine significantly increased platelet thrombus formation and fibrin-rich thrombus formation at 15 min (p = 0.017 and p = 0.037, respectively) with normalisation after 60 min. Peak SNP-mediated microvascular perfusion, i.e. endothelium-independent vasodilation, was reduced following EC vaping with nicotine compared with baseline (p = 0.006). Thirty puffs of EC aerosol with nicotine increased platelet and fibrin-dependent thrombus formation and reduced microvascular dilatation capacity. No compelling effects of EC vaping without nicotine were observed, indicating nicotine as the main effector. Trial registration: ClinicalTrials.gov Identifier: NCT04175457 URL: https://clinicaltrials.gov/ct2/show/NCT04175457.

Associations of hyponatremia and SIADH with increased mortality, young age and infection parameters in patients with tuberculosis.

BACKGROUND AND OBJECTIVE: Hyponatremia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) are associated with and can be caused by tuberculosis (TB) through meningitis by locally invading the hypothalamus, adrenal, or pituitary glands or possibly through ectopic ADH production. This study assessed the association of TB mortality with hyponatremia and SIADH in a large cohort of a university hospital in Austria. METHODS: This retrospective study enrolled patients with hyponatremia and patients diagnosed with TB from 01/2001-11/2019 to assess the prevalence of TB in hyponatremia and TB morbidity and mortality in patients with and without hyponatremia. Sex, age, microbiological results, laboratory tests and comorbidities were analysed and used to calculate survival rates. RESULTS: Of 107.532 patients with hyponatremia (0.07%) and 186 patients with TB (43%), 80 patients were diagnosed with both-hyponatremia and TB. Only three TB patients had SIADH, precluding further SIADH analysis. In hyponatremia, young age and high CRP levels showed significant associations with TB diagnosis (p<0.0001). Survival rates of patients diagnosed with TB with moderate to profound hyponatremia were significantly lower than those without hyponatremia (p = 0.002). CONCLUSION: In this study of a large cohort from a tertiary care hospital in a non-endemic area of TB, 0.07% of patients presenting with hyponatremia, but especially younger patients and patients with high CRP values, were diagnosed with TB. Crucially, patients with moderate to profound hyponatremia had a significantly higher mortality rate and thus required increased medical care.

Chronic snus use in healthy males alters endothelial function and increases arterial stiffness.

BACKGROUND: Snus usage is commonly touted as a safer alternative to cigarette smoking. However, recent studies have demonstrated possible adverse cardiovascular effects in chronic snus users. The present study evaluates the effects of chronic snus use on vascular function by assessing central arterial stiffness and endothelial vasodilatory function in healthy chronic snus users as compared to matched non-users. METHODS AND RESULTS: Fifty healthy males (24 snus users, 26 age-matched controls) with a mean age of 44 years were included in the study. Arterial stiffness was assessed employing both pulse wave velocity and pulse wave analysis. Endothelial vasodilatory function was measured by venous occlusion plethysmography, utilizing intra-arterial administration of acetylcholine, glyceryl trinitrate and bradykinin to further gauge endothelium-dependent and -independent vasodilatory function. Arterial stiffness was significantly higher in chronic snus users as compared to controls: pulse wave velocity [m/s]: 6.6±0.8 vs 7.1±0.9 resp. (p = 0.026), augmentation index corrected for heart rate [%]: 0.1±13.2 vs 7.3±7.8 resp. (p = 0.023). Endothelial independent vasodilation, i.e. the reaction to glyceryl trinitrate, was significantly lower in snus users as measured by venous occlusion plethysmography. CONCLUSIONS: The results of this study show an increased arterial stiffness and an underlying endothelial dysfunction in daily snus users as compared to matched non-tobacco controls. These findings indicate that long-term use of snus may alter the function of the endothelium and therefore reinforces the assertion that chronic snus use is correlated to an increased risk of development of cardiovascular disease.

Electronic cigarettes containing nicotine increase endothelial and platelet derived extracellular vesicles in healthy volunteers.

BACKGROUND AND AIMS: E-cigarette use is increasingly common. Whether e-cigarettes are harmful to human health is an intensely debated subject. In order to investigate whether e-cigarettes with and without nicotine cause different vascular responses, we obtained blood samples from healthy young volunteers who performed brief active e-cigarette inhalations. Extracellular vesicles (EVs) of endothelial and platelet origin were measured to determine vascular changes. METHODS: Using a randomized, double-blind, crossover design, 17 healthy occasional smokers inhaled 30 puffs of e-cigarette vapor during 30 min. Blood samples were collected at baseline, as well as at 0, 2, 4 and 6 h post-exposure. EVs from platelets and endothelial cells were measured by flow cytometry. RESULTS: Platelet and endothelial derived EVs were significantly increased with peak levels seen at 4 h following exposure to active inhalation of e-cigarette vapor with nicotine. Moreover, platelet derived EVs, expressing platelet activation marker P-selectin and the inflammation marker, CD40 ligand, were also significantly increased following inhalation of e-cigarette vapor with nicotine. In addition, platelet derived EVs expressing CD40 ligand was increased after inhalation of e-cigarette vapor without nicotine. CONCLUSION: As few as 30 puffs of nicotine-containing e-cigarette vapor caused an increase in levels of circulating EVs of endothelial and platelet origin, which may signify underlying vascular changes. Although e-cigarette vapor without nicotine caused an increase in platelet EVs expressing CD40 ligand, nicotine, as a component in the vapor, seems to have a more compelling effect on extracellular vesicle formation and protein composition.

Polymerase chain reaction for the diagnosis of herpesvirus infections in dermatology : Analysis of clinical data.

BACKGROUND: Rapid identification of human herpesviruses from lesion swabs is necessary for timely initiation of antiviral treatment, especially with infections involving neonates and immunocompromised individuals. The aim of the study was to investigate the results of an in-house polymerase chain reaction (PCR) test for herpesviruses in patients with symptoms suggestive for a herpesvirus infection. PATIENTS AND METHODS: In this single center retrospective study the results of 3677 lesion swab specimens tested for human herpes simplex virus 1 and 2 (HSV 1 and 2) and varicella zoster virus (VZV) were analyzed in the context of data sheets giving details of the suspected diagnosis, medical history as well as the demographic data of the patients. The PCR procedures for cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpes virus 8 (HHV-8) were applied on special occasions. RESULTS: Of the samples 3369 (91.6%) were swabs and a minority were tissue or blood samples. Of the 3015 samples tested for HSV­1, HSV­2 and VZV concomitantly, 52.3% were positive for at least one of these viruses. Clinically distinct conditions, such as herpes zoster and varicella had a high rate of positive PCR results, ranging from 81% to 88%, respectively. Among HSV­2 positive samples, 23.7% derived from human immunodeficiency virus (HIV) positive patients, in contrast to the 10.8% originating from immunocompetent patients, the difference being statistically significant (p < 0.002). The HSV­2 was detected more often in women than in men. CONCLUSION: Distinct clinical diagnoses have a high correlation rate with positive PCR results. A significantly higher number of HSV­2 positive results were found in HIV positive patients and in women.

Acute Effects of Electronic Cigarette Inhalation on the Vasculature and the Conducting Airways.

The use of electronic cigarettes has increased exponentially since its introduction onto the global market in 2006. However, short- and long-term health effects remain largely unknown due to the novelty of this product. The present study examines the acute effects of e-cigarette aerosol inhalation, with and without nicotine, on vascular and pulmonary function in healthy volunteers. Seventeen healthy subjects inhaled electronic cigarette aerosol with and without nicotine on two separate occasions in a double-blinded crossover fashion. Blood pressure, heart rate, and arterial stiffness measured by pulse wave velocity and pulse wave analysis were assessed at baseline, and then at 0 h, 2 h, and 4 h following exposure. Dynamic spirometry and impulse oscillometry were measured following vascular assessments at these time points, as well as at 6 h following exposure. e-Cigarette aerosol with nicotine caused a significant increase in heart rate and arterial stiffness. Furthermore, e-cigarette aerosol-containing nicotine caused a sudden increase in flow resistance as measured by impulse oscillometry, indicating obstruction of the conducting airways. Both aerosols caused an increase in blood pressure. The present study indicates that inhaled e-cigarette aerosol with nicotine has an acute impact on vascular and pulmonary function. Thus, chronic usage may lead to long-term adverse health effects. Further investigation is warranted.

Brief exposure to Swedish snus causes divergent vascular responses in healthy male and female volunteers.

INTRODUCTION: The use of Swedish oral moist snuff, known as snus, has for a long time been limited to the Scandinavian countries. With declining cigarette sales in the western world, tobacco companies have looked to the development of alternative tobacco products. In 2006 snus products were launched in the US. Even though several studies have demonstrated negative health effects, snus is often depicted as harmless. The aim of the present study was to investigate acute vascular effects of snus as measured by arterial stiffness as well as blood pressure and heart rate. METHODS: Two separate randomized double-blind crossover studies with the same study design were pooled for analysis. Twenty-nine healthy snus-users (17 females, 12 males) were included. Snus (Göteborgs Rapé) and tobacco free snus (Onico) were administered in a randomized order at two separate visits. Arterial stiffness, blood pressure and heart rate were measured at baseline as well as every five minutes for 40 minutes during exposure. Following snus removal, measurements continued for 30 minutes post exposure. Arterial stiffness was measured using pulse wave velocity (Vicorder) and pulse wave analysis (Sphygmocor). RESULTS: Compared to placebo, snus significantly increased systolic and diastolic blood pressure as well as heart rate, however, only in females (p = 0.004, p = 0.006 and p<0.001 respectively). No changes were seen in arterial stiffness measurements in either gender. CONCLUSION: We observed an increase in blood pressure and heart rate only in females, but not in males due to snus usage as compared to placebo. This novel finding was surprising and needs to be further investigated considering most of the earlier studies have mainly focused on male snus users and the increasing usage of snus among females.

Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers.

BACKGROUND AND AIMS: The use of electronic cigarettes is increasing dramatically on a global scale and its effects on human health remain uncertain. In the present study, we measured endothelial progenitor cells (EPCs) and microvesicles (MVs) in healthy young volunteers following short-term exposure to inhalation of e-cigarette vapor (ECV) to determine vascular changes. METHODS: Sixteen healthy seldom smokers were randomized into two groups either exposed or not exposed to 10 puffs of ECV for 10 min, in a crossover design. Blood samples were obtained at baseline and 1, 4 and 24 h following exposure. EPCs (CD34 + CD309) and MVs were analyzed by flow cytometry. MVs were phenotyped according to origin (platelet (CD41), endothelial (CD144), leukocytes (CD45), monocytes (CD14)) and nuclear content (SYTO 13 dye). In addition, expression of inflammation markers such P-selectin (CD62P), E-selectin (CD62E), CD40-ligand (CD154) and HMGB1 was investigated. Fractional exhaled nitric oxide (FeNO) was also measured at baseline and after 24 h. RESULTS: EPC levels in blood were significantly increased 1 h following exposure to ECV and returned to baseline values after 24 h. Only E-selectin positive MVs (endothelial origin) were slightly elevated (p < 0.038). FeNO was unaffected by exposure to ECV. CONCLUSIONS: In healthy volunteers, ten puffs of e-cigarette vapor inhalation caused an increase in EPCs. This increase was of the same magnitude as following smoking of one traditional cigarette, as we previously demonstrated. Taken together, these results may represent signs of possible vascular changes after short e-cigarette inhalation. Further studies analyzing potential cardiovascular health effects are critical as the e-cigarette market continues to burgeon.

In vitro susceptibility of Candida isolates from organ transplant recipients to newer antifungals.

Organ transplant recipients (OTR) are at higher risk of developing life-threatening infections. In this study, we tested 527 Candida isolates obtained from the oral and genital mucosa from OTR and healthy controls in order to monitor antifungal susceptibility patterns in this particular risk group. Testing was carried out in parallel for already marketed azoles and anidulafungin. Minimal inhibitory concentrations (MICs) were determined using the E-test(®) for azoles and CLSI broth microdilution for anidulafungin. Overall, there was no difference in the distribution of Candida spp. for both groups, C. albicans being the most frequently isolated Candida sp. followed by C. glabrata. Also, there were only minor differences in the susceptibility patterns to all antifungal agents. All C. albicans isolates were fully susceptible to fluconazole and voriconazole. In C. glabrata, 2.2% (n = 1) were resistant to fluconazole, and 82.6% (n = 38) to itraconazole, and in C. krusei, 66.7% (n = 2) were resistant in itraconazole. All strains were susceptible to voriconazole. Only fluconazole showed a higher rate of resistant C. glabrata isolates for OTR (3.7%), whereas the control group showed only intermediate susceptible and no resistant isolates. As there are no breakpoints established for posaconazole by CLSI, breakpoints determined by EUCAST were used. A total of 87.9% of C. albicans, 81.3% of C. parapsilosis and 66.7% of C. tropicalis were considered susceptible. C. glabrata and C. krusei showed higher MIC values and thus lesser susceptibility than the other Candida species. There were no differences observed between OTR and control groups. For anidulafungin, 99.8% of C. albicans isolates were susceptible, 0.2% were intermediate, whereas for C. glabrata, only 95.3% were susceptible, 0.2% were resistant and 4.5% were interpreted as intermediate. Interestingly, the two resistant isolates were found in the control group. Also, the controls showed a marginally higher percentage of intermediate strains compared to the transplant patients. All in all, resistant isolates were only observed for C. glabrata of the control group.

The effects of smoking on levels of endothelial progenitor cells and microparticles in the blood of healthy volunteers.

BACKGROUND: Cigarette smoking, both active and passive, is one of the leading causes of morbidity and mortality in cardiovascular disease. To assess the impact of brief smoking on the vasculature, we determined levels of circulating endothelial progenitor cells (EPCs) and circulating microparticles (MPs) following the smoking of one cigarette by young, healthy intermittent smokers. MATERIALS AND METHODS: 12 healthy volunteers were randomized to either smoking or not smoking in a crossover fashion. Blood sampling was performed at baseline, 1, 4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were determined by flow cytometry. MPs were measured from platelets, leukocytes and endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13 to assess the content of nuclear molecules. RESULTS: Active smoking of one cigarette caused an immediate and significant increase in the numbers of circulating EPCs and MPs of platelet-, endothelial- and leukocyte origin. Levels of MPs containing nuclear molecules were increased, of which the majority were positive for CD41 and CD45 (platelet- and leukocyte origin). CD144 (VE-cadherin) or HMGB1 release did not significantly change during active smoking. CONCLUSION: Brief active smoking of one cigarette generated an acute release of EPC and MPs, of which the latter contained nuclear matter. Together, these results demonstrate acute effects of cigarette smoke on endothelial, platelet and leukocyte function as well as injury to the vascular wall.

Enhanced therapy for primary and secondary syphilis: a longitudinal retrospective analysis of cure rates and associated factors.

For the treatment of early infectious syphilis, enhanced therapy with three dosages of benzathine penicillin G has been under consideration, particularly in the human immunodeficiency virus type 1 infected population (HIV-1). The serological outcome of 249 patients with primary and secondary syphilis treated with standard or enhanced therapy was analyzed retrospectively; 98% (139/142) achieved serological cure with a single dosage and 92% with enhanced therapy (P=0.033). In HIV-1 infected individuals, cure rates were 88% after a single dosage compared to 97% after three dosages (P=0.18). A fourfold decrease of Venereal Disease Research Laboratory (VDRL) titres was achieved within a median of 102 days after treatment initiation (SD=2; 95% CI=98-106). Patients aged over 40 years were 5.5 times (OR=5.52; 95% CI=1.43-21.32; P=0.013) and patients with low baseline VDRL titres (≤ 1:32) were 4 times (OR=4.25; 95% CI=1.21-14.87; P=0.024) more likely to experience serological failure.