To examine the serum irisin level in a group of Behcet’s disease patients, its association with illness parameters, and its utility in diagnosing subclinical atherosclerosis.This randomized case–control study included 50 patients and 50 age- and sex-matched controls. Carotid Doppler ultrasound for the measurement of the carotid artery intima-media thickness (CIMT) and ankle-brachial pressure index (ABPI) were performed. A clinical evaluation, lipogram, and serum irisin were also performed.r =  − 0.62, P 0.0001).Between the patients and the control group, there was a significant difference in CIMT, S. irisin level, and ankle-brachial pressure index; however, gender and BMI did not significantly affect CIMT, ABPI, or S. irisin level. CIMT demonstrated a substantial negative correlation with both S. irisin and ABPI (With a sensitivity of up to 94.30% and a specificity of 93.30%, the ROC analysis revealed that a decrease in S. irisin level in Behcet’s patients was indicative of subclinical atherosclerosis. The drop in the ABPI level demonstrated a sensitivity of up to 94.30% and a specificity of 100%.Subclinical atherosclerosis is prevalent among Egyptian Behcet’s patients, and S. irisin can be employed as a biomarker for diagnosing subclinical atherosclerosis in Behcet’s illness. Behcet’s disease (BD) is a chronic, relapsing, inflammatory disorder characterized by systemic involvement, vascular damage, and endothelial cell dysfunction , 2.Cardiovascular involvement ranges from 7 to 46% , 3, and Chronic inflammatory disorders are characterized by systemic inflammation that leads to cardiovascular disease (CVD) by well-established mechanisms: accelerated atherosclerosis, insulin resistance (IR), platelet dysfunction, hypercoagulability, hypercholesterolemia, and hyperglycemia .Endothelial dysfunction is a well-recognized indicator of subclinical vascular atherosclerosis; it is determined by the intima-media thickness of the common carotid artery (CIMT).Endothelial dysfunction is the first manifestation of BD’s vascular problems. It greatly contributes to the onset and progression of vascular damage in many body locations, resulting in metabolic disease consequences .Vasculitis and inflammations of the artery wall can increase platelet aggregation and inhibit fibrinolysis, resulting in thrombosis .Subclinical atherosclerosis is an early sign of atherosclerotic load, and its prompt diagnosis can postpone or prevent the development of overt cardiovascular disease .Irisin is a myokine secreted by the liver, kidney, heart, skeletal muscles, and skin in response to exercise . PreviouIn 2015, Lee HJ et al. established the association between circulating irisin levels, endothelial dysfunctions, and subclinical atherosclerosis in non-diabetic adult patients by finding a substantial correlation between carotid atherosclerosis and serum irisin levels in dialysis patients .Recently Altay et al. investigated the relationship between inflammation and irisin in serum samples from chronic spontaneous urticaria (CSU) patients, they observed lower irisin levels in the CSU group, and they raised a suggestion that a decrease in irisin levels may be decisive for CSU .The purpose of this study is to determine the link between serum irisin level and subclinical atherosclerosis in patients with Behcet’s illness and to compare serum irisin to other modalities for diagnosing subclinical atherosclerosis and endothelial dysfunctions.It is a case–control study that included 50 Behcet’s patients diagnosed according to 2006 classification criteria  , 14, andThe Ethics Committee of our university’s medical school approved the study under the number IBR ♯ S20-154, and all participants provided written informed permission.All subjects underwent a comprehensive clinical examination, and disease activity was assessed using the Behcet Syndrome Activity Score (BSAS) .Each participant’s 10 ml of venous blood was drawn under aseptic conditions using sterile disposable gloves for laboratory examinations.A: Routine investigations, liver function tests (LFT), kidney function tests (KFT), fasting blood glucose, lipid profile including cholesterol, triglyceride, high density lipoprotein (HDL), and low-density lipoprotein (LDL) utilizing the Cobas c311 Chemistry Analyser System .The B complete blood count was performed by CELL-DYN Abbott  and the ESR was performed using a westergren tube.C: The serum irisin concentration was determined with an irisin ELISA kit and an ELISA Thermo Fisher, Scientific Multiscan EX Microplate Reader, OY, FI-O1621, Vantaa, Finland.Step 1:prepare all reagents, working standards, blanks, and samples according to the instructions in the preceding sections.Step 2:refer to the assay layout sheet to calculate the number of wells to place any unused wells and desiccant back into the pouch, reseal the pouch, and store the wells at 4C.Step 3:add 50 mL of the standard to the testing standard well, followed by 10 mL of the testing sample . Pipette the sample to the wells, avoiding the well walls as much as possible, and mix gently.Step 4:cover with the included adhesive strip and incubate for 30 min at 37 °C.Step 5:configure liquid, 30 times dilute wash solution with distilled water to configure liquid.Step 6:washing, remove the adhesive strip, discard the liquid, and then pipette washing buffer into each well. Allow to stand for 30 s and then drain.Step 7:add enzymes, pipette 50 l of HRP-conjugate reagent into each well, excluding the well designated as a blank.Step 8:incubate, operation with fourStep 9:washing, using number 6Step 10:add 50 ml of chromogen solution A and 50 ml of chromogen solution B to each well, avoiding light for 15 min at 37 °C.Step 11:stop the reaction by pipetting 50 ml of stop solution into each well (the blue change to yellow).Calculate the value of the blank well as zero. Read absorbance at 450 nm 15 min after pipetting stop solution.A: Carotid Doppler ultrasound, for the measurement of carotid artery intima-media thickness (CIMT): CIMT is defined as a low-level echo gray band that does not project into the arterial lumen. CIMT was measured during the diastolic phase as the distance between the leading edge of the first and second echogenic lines of the far walls of the distal segment of the common carotid artery, the carotid bifurcation, and the internal using superficial multifrequency linear array transducer [5–8 MHz] with a sonographic apparatus . CIMT tests were done on artery segments devoid of plaque. To eliminate examiner bias, all examinations and measures have been conducted by the same examiner. Age-dependent normal range is used as the reference for CIMT. The identification of a carotid atherosclerotic plaque is defined as a focal IMT of 50% or > 0.5 mm relative to the adjacent artery wall, or an absolute IMT of > 1.5 mm .B: Evaluation of ankle/brachial BP index utilizing blood pressure cuff Doppler pulse volume recording (PVR) ultrasound. Grayscale duplex Doppler is used to map arterial disease and to solve problems.1.0–1.4: normal0.91–0.99 borderline ≤ 0.9: abnormal 0.4 to 0.9: moderate to mild PAD < 0.4: indicative of severe PADThe index is a ratio of the pressure in the highest ankle artery / the highest brachial artery.t-test was used to compare the means of two groups. When data distribution was not normal, the Mann–Whitney test was utilized. Using chi square, qualitative data were presented as numbers and percentages and compared. Using a Roc curve analysis, the optimal cutoff was determined. Also calculated were sensitivity, specificity, positive predicted value, and negative predictive value. Pearson’s test of correlation was employed to determine the relationship between continuous variables. Excel or the STATA application was used to create graphs. Less than 0.05 was considered significant for the P value.Quantitative data were expressed as the mean, standard deviation, median, and range. The student The study comprised 50 BD patients and 50 healthy controls with a mean age of 30.2, a mean onset age of 28.6 years, and a mean disease duration of 1.64 years, with a range of 1 to 5 years. 12 cases were female (24%) while 38 cases were male (76.6%). Regarding BSAS score, Behcet’s illness patients had a mean score of 5.6, with a range of 3 to 9.A total of 100% of the patients presented with oral ulcers, 88% with genital ulcers, 80% with skin lesions, 68% with ocular lesions, and 44% with uveitis. Vascular lesions in the form of  were present in 26% of the patients, and neurological deficits in 10%.The variables having a significant difference between patients and healthy controls are listed in Table P = 0.37) among the control, but in the patients with Behect’s disease, there was a significant increase of BMI in females.A subgroup analysis based on gender and body mass index is shown in Table P = 0.5) , whereas patients with neurological deficits had significantly lower S. irisin levels than those without neurological deficits .Comparing S. irisin levels between BD patients with and without ocular lesions and vascular events revealed no significant differences  between individuals with subclinical and non-subclinical atherosclerosis. A decrease in ankle brachial pressure index is also correlated with an increase in subclinical atherosclerosis, with a significant difference Meanwhile, our findings regarding the relationship between S. irisin, ankle brachial pressure index, and subclinical atherosclerosis in patients with Behcet’s illness revealed a significant difference in S. irisin levels , ESR (P = 0.0006), and WBCs (P = 0.04), and a significant negative relationship with S. irisin (p0.0001) and ankle brachial pressure index (P 0.0001).Univariate linear regression examination of factors influencing CIMT in Behect’s patients revealed a significant positive relationship with age (P = 0.02) and ESR level (P = 0.01) were the most significant factors increasing incidence, while S. irisin (P = 0.04) and ankle brachial pressure index (P = 0.04) were the most significant factors decreasing incidence.Multivariate linear regression analysis of factors affecting CIMT in patients with Behcet’s disease (include significant variable in univariate) revealed that age of patient . The level of ankle brachial pressure index in patients with Behcet’s illness is also indicative of preclinical atherosclerosis, as its level reduced dramatically with a sensitivity of 94.30% and a specificity of 100% (P 0.0001), indicating subclinical atherosclerosis.The ROC analysis Fig.  of S. irIncreased risk for cardiovascular lesions (CVD) in patients with pre-existing chronic inflammatory diseases at younger ages observed in some studies raised the assumption about endothelial dysfunction as a common initial lesion in the development of atherosclerosis , 17, andThere are few studies examining S. irisin as a biomarker for diagnosing subclinical atherosclerosis in Behcet’s illness. In our study, we intended to investigate this topic.We did not find a significant relationship between serum irisin level and disease activity score, nor did we find a relationship between CIMT and disease activity score. The BSAS score of the included patients had a mean value of 5.6, and a range of 3 to 9 indicates that they are in remission and have been on treatment for more than six months. These results concur with Icli et al.’s findings .Subclinical atherosclerosis can begin early in life and be unnoticed until a cardiac infarction or stroke .Hyperglycemia and hyperlipidaemia are known to accelerate the atherosclerotic process by direct endothelial dysfunction augmenting cytokine release with increasing lipid peroxidation and causing oxidative damage ; our resThere were no documented cases of Q-T dispersion; therefore, the atherosclerotic changes in our patients are asymptomatic and a sufficient narrowing of coronaries may be required for symptoms to appear; our results agreed with  Ross.199P-value = 0.88); these findings were consistent with those of Koca et al. [Obesity is a condition characterized by excessive fat buildup and is frequently accompanied with insulin resistance (IR), type 2 diabetes (T2DM), and cardiovascular diseases (CVDs) , 23. Oura et al. , who repThe non-significant difference for ankle brachial pressure index between those of BMI 25 and those of BMI > 25 was cleared by the controlled blood glucose level, controlled blood lipid, and blood pressure in our patients.P = 0.17), which may have been caused by the non-significant difference in fat mass, which is known to have a direct effect on irisin level. Our results did not concur with Moreno et al. [In the same instance, serum irisin levels did not differ significantly between those with a BMI 25 and those with a BMI > 25 (o et al. , who repo et al. , who repThe regression analysis of factors affecting CIMT in a patient with Behcet’s disease revealed that the most influential factors on the disease were the patient’s age and ESR level. The patient’s age is one of the risk factors for atherosclerosis and can be determined by CIMT level , 28, andFor characteristics that indicate subclinical atherosclerosis, male gender and decreasing S levels are predictive. Irisin, and decreasing ankle brachial pressure index agreed with Vogt et al. , who staIcli et al.  providedWe also found a very strong correlation between CIMT, an indicator of subclinical atherosclerosis, and decreased irisin levels in BD patients.With a sensitivity of 94.30% and specificity of 93.33%, the declining level of S. irisin in patients can be utilized as a predictor of subclinical atherosclerosis. This finding agreed with Ankle Brachial Index Collaboration, 2008 , which dIrisin in the serum is recommended for detecting subclinical atherosclerosis in Behcet’s disease patients.We recommend that more longitudinal studies of patients be conducted at this point.Cross-sectional study, small sample size, and low disease activity indexes in our patients are limitations of the study.


However, we found a significant difference in the change of diastolic BP . With all this, we conclude that an SMS-based home BP telemonitoring system is effective in reducing diastolic BP by working in conjunction with primary care centers. Our findings represent one of the first interventions of this type in our environment, being an important alternative for the control of high blood pressure.Despite being a public health problem, less than a third of hypertensive patients manage to control blood pressure (BP). In this paper, we conducted a two-arm randomized controlled trial to investigate the efficacy of an SMS-based home BP telemonitoring system compared to usual care in patients with uncontrolled hypertension from a primary care center. This study was conducted between April and August 2018. Participants in the intervention arm used a custom-designed telemonitoring device for two weeks and were followed up for two additional weeks; controls were followed for 4 weeks. The main objective of this study is to evaluate the impact on blood pressure of a telemonitoring system using a blood pressure monitor adapted to send data via SMS to health providers in primary care centers for 4 weeks. In this trial, 38 patients were included in the analysis (18 in each arm), 68% were women, and the mean age was 68.1 [SD: 10.8 years], with no differences between arms. Among the results we found was that There was no significant difference in the change in systolic BP values between the control and intervention arm (−7.2 [14.9] mmHg vs. −16.3 [16.7] mmHg;  High blood pressure is a public health problem, resulting in 15 million deaths per year worldwide ,3.In Peru, it is estimated that only 39.3% of those with hypertension are under treatment, and only 20% have their blood pressure under control , but in Home blood pressure telemonitoring is defined as the process by which blood pressure readings at home are transmitted to a central health information center or electronic medical record for use by healthcare providers and patients . There iAn alternative for the implementation of telemonitoring at home is the adaptation of blood pressure monitors for home use, enabling them to send data through text messages (SMS), a technology with wide penetration . Some stA randomized controlled trial was performed. The intervention arm received the telemonitoring system, while the control arm continued with the usual management. The main outcome was the difference in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at follow-up. The blood pressure monitors used in this study were adapted to send SMS using the services of a local mobile telecommunications provider.clinicaltrials.gov (NCT03524456).The data were obtained confidentially. Personal identifiers were stored separately in a password-protected database to which only the researchers had access. The study protocol was registered on This study included patients with uncontrolled high blood pressure treated at the Condevilla health center in the district of San Martín de Porres, in the province of Lima. Patients with uncontrolled treated hypertension were defined as those with SBP above 130 mmHg or DBP above 80 mmHg [The inclusion criteria were the following: (i) Patients older than 18 years; (ii) Diagnosis of high blood pressure for at least 3 months; (iii) Uncontrolled blood pressure; and (iv) Under treatment with antihypertensive medication. Exclusion criteria were (i) Patients on hemodialysis or peritoneal dialysis for chronic kidney disease; (ii) Pregnant women, and (iii) Patients planning to travel or change of address within a month of enrollment.Patients were referred to the study by the Condevilla health center. If they met the inclusion and exclusion criteria, they were invited to participate in the study and asked to provide informed consent. Randomization was performed in complete blocks of size 4.For a significance level of 95% and 80% power, a standard deviation of 10 and 12 mmHg for the control and intervention arm and a sample size of 20 participants per arm would be required to detect differences of at least 10 mmHg .® blood pressure monitor was used, which has USB  connectivity from the factory. The USB port built into the blood pressure monitor was used to link it to the data capture and delivery module . This platform allows users to develop, compile and upload programs to an Arduino board.Participants in the intervention arm received the telemonitoring equipment and were asked to take at least two blood pressure measurements in the mornings and two in the evenings for two weeks. The blood pressure measurements were sent to the health personnel at the Condevilla health center, who made clinical decisions based on the measurements. These decisions could be adjustments or changes in medication or calls to the patient for appointments at the center.Participants in the control arm received the status quo, consisting of monitoring based on visits to the health center for blood pressure determinations and treatment indications.The technical and process aspects of home blood pressure monitoring are important to ensure accurate and reliable readings and to allow for effective monitoring and management of the patient’s blood pressure.Patient training: The patient is trained on how to properly use the blood pressure monitor and how to accurately record the readings.Equipment: A blood pressure monitor with telemonitoring capability, such as an adapted tensiometer with SMS capability, is provided to the patient.Monitoring frequency: The frequency of monitoring was determined and agreed upon between the patient and healthcare provider in two measurements in the morning and two measurements at night spaced out by 5 min each daily, after 1 min of rest.Data transmission: The patient takes their blood pressure readings, and the telemonitoring capability of the blood pressure monitor transmits the data to their healthcare provider using via SMS.Review by a healthcare provider: The healthcare provider receives the transmitted data and reviews the readings to monitor the patient’s blood pressure and identify any potential issues.Follow-up: The healthcare provider may schedule a follow-up appointment with the patient, if necessary, based on the review of the transmitted data.Outpatients of the health center were invited to participate in the study after verifying the inclusion and exclusion criteria. The patients were informed of the study objectives, procedures, and requirements. Consenting patients were asked to sign the informed consent form.After randomization, those in the intervention arm were given a training session in the use of the telemonitoring system. They were provided with information on the proper placement of the cuff, as well as on the correct position of the body during blood pressure measurement. They were given an informative guide as well as a user manual.Study personnel delivered the monitors to participants during home visits. The most suitable place for taking blood pressure was selected to suit the patient. After choosing the place, the signal of the equipment and the reception of the message were both verified through a blood pressure measurement .Participants skipping more than two consecutive blood pressure measurements were contacted by telephone to evaluate the reasons for the discontinuation and to encourage continuous monitoring. The decision to adjust the medication or call the patient was given by the health center’s physician. The final measurement was taken two weeks after completing the telemonitoring. For participants in the control arm, baseline and follow-up measurements were taken four weeks apart .t-test for two independent samples comparing the mean change in blood pressure between intervention and control arms. The change in blood pressure was the difference between the four-week value and the baseline value. Qualitative variables have been expressed as a percentage. A Fisher’s exact test, or a Chi2 test, was used for the comparison of proportions. For normally distributed quantitative variables, means and ±standard deviations are presented. A comparison of means was performed using the Student’s t-test. Non-normally distributed quantitative variables were described with medians and interquartile ranges, and comparisons were performed using the Mann–Whitney test. Associations with p values < 0.05 were considered statistically significant. Statistical analysis was performed using the STATA 15 .The primary statistical analysis was performed using the Student’s The recruitment and follow-up of patients took place between April and August 2018. A total of 223 patients were evaluated for eligibility, of which 183 patients were excluded . A total of 40 patients were randomized: 20 to the control arm and 20 to the intervention arm. One of the patients in the control arm withdrew before the second blood pressure measurement. Likewise, one patient in the intervention arm died days before the second blood pressure measurement was performed; thus, 38 participants were included in the final analysis, 19 in each arm .2. 14 (36.8%) of the participants were born in Lima), 22 (57.9%) were married or cohabiting, 24 (63.2%) had only primary education, and 20 (52.6%) were housewives. The only significant difference found within the demographic and clinical variables between the two study arms was marital status (p = 0.026).The majority of participants  were female. The mean age of 68.1 ± 10.8 years, and the mean BMI was 29.5 ± 4.0 kg/mn = 24; 63.2%). Likewise, it was found that the majority of participants had a family history of hypertension . The most common comorbidity was Diabetes Mellitus . No differences were found in clinical variables between the two study arms (p > 0.05)  ( > 0.05) .In the total sample, the mean SBP at the baseline measurement was 156.7 ± 13.7 mmHg, while the DBP was 86.6 ± 9.6 mmHg; there were no differences in blood pressure between control and intervention arms at baseline. Regarding the final measurement, the mean SBP was 144.9 ± 15.8 mmHg, and the DBP was 82.3 ± 10.6 mmHg; no differences between study arms were found .p = 0.087). Similarly, the difference in DBP values was −7.2 ± 9.8 mmHg in the intervention arm, while in the control arm, it was −1.2 ± 6.4 mmHg (p = 0.032).The difference in SBP values  was −16.3 ± 16.7 mmHg in the intervention arm, while in the control arm, it was −7.2 ± 14.9 mmHg  and −2.0 mmHg (DBP), significantly higher than those in controls . AlthougOn the other hand, our results are comparable with studies that used more sophisticated telecommunication systems. A study conducted in Germany that evaluated a telemonitoring system using a blood pressure monitor connected to a mobile phone via Bluetooth found mean reductions in the intervention arm of −17.0 (SBP) and −9.0 mmHg DBP  significAge can represent a limiting factor for the use of some telecommunication systems, resulting in a barrier to the implementation of telemonitoring systems . The simRegarding the use of telemonitoring systems in primary care centers, information is scarce , and theRegarding the causal relationship of the effectiveness of the telemonitoring system, we speculate that in our study, it could be due to an improvement in adherence to treatment, but we have the limitation of not having evaluated this parameter in this study.Our study shows a reduction in SBP values and a significant reduction in DBP values in those participants who used the telemonitoring system compared to the control group. These results show the potential benefit of including telemonitoring systems in primary care centers for the control of hypertensive patients, and if scaled up, they represent an important alternative strategy for public health.The telemonitoring system helps improve adherence to treatment, also improving disease awareness. When patients see the blood pressure values, they have an objective parameter to base themselves on; likewise, knowing that there is someone on the other side continuously reviewing the values helps them to continue and not stop taking the medication.Part of the future work that could be generated from this study is to take it to rural environments where the only constant telecommunication signal is SMS, in addition to evaluating this tool for longer follow-up times and with a larger sample size.


Daytime hypersomnolence, the prime feature of obstructive sleep apnea (OSA), frequently leads to high coffee consumption. Nevertheless, some clinicians ask for patients’ caffeine avoidance. Caffeinated drinks are sometimes associated with more severe OSA. However, these effects are not consensual. Here we investigated the effect of caffeine consumption on sleep architecture and apnea/hypopnea index in OSA. Also, the impact of caffeine on variables related with dysmetabolism, dyslipidemia, and sympathetic nervous system (SNS) dysfunction were investigated. A total of 65 patients diagnosed with OSA and 32 without OSA were included after given written informed consent. Polysomnographic studies were performed. Blood was collected to quantify caffeine and its metabolites in plasma and biochemical parameters. 24 h urine samples were collected for catecholamines measurement. Statistical analyses were performed by SPSS: (1) non-parametric Mann-Whitney test to compare variables between controls and OSA; (2) multivariate logistic regression testing the effect of caffeine on sets of variables in the 2 groups; and (3) Spearmans’ correlation between caffeine levels and comorbidities in patients with OSA. As expected OSA development is associated with dyslipidemia, dysmetabolism, SNS dysfunction, and sleep fragmentation. There was also a significant increase in plasma caffeine levels in the OSA group. However, the higher consumption of caffeine by OSA patients do not alter any of these associations. These results showed that there is no apparent rationale for caffeine avoidance in chronic consumers with OSA. Obstructive sleep apnea (OSA), the most common sleep-disordered breathing, is a highly prevalent disease  characteDaytime hypersomnolence and fatigue are regular symptoms in OSA, being frequently considered the main responsible for the high coffee consumption. It was previously described that OSA patients drink, on average, nearly three times more coffee than control subjects . HoweverSeveral authors have correlated high caffeine consumption with an elevated blood pressure (BP) , suggestBesides, all of the literature that can be found regarding the association of OSA and sympathetic activity and BP, the effect of caffeine consumption in other variables closely associated with OSA, such as sleep parameters  sleep, non-REM sleep and arousals), dyslipidemia , cholesterol, high-density lipoproteins (HDL) and low-density lipoproteins (LDL) and dysmetabolism  and glycemia), has not been evaluated so far. Thus, the aim of the present study was to investigate if caffeine plasma levels affect OSA severity and OSA association with dysmetabolism and sympathetic nervous system dysfunction.ClinicalTrials.gov accessed on 17 February 2022 (NCT01803815). It was performed in accordance with the Helsinki Declaration. All volunteers gave their written informed consent.Eligible male patients with or without OSA (65 vs. 32) were recruited from the Respiratory Diseases Service of Hospital Pulido Valente (Lisbon). The diagnosis of OSA was established by the presence of typical clinical features of this disorder and confirmed by overnight polysomnography. Patients were included independently of their hypertension condition, hypertension ongoing medication and body mass index (BMI) and excluded if they had any psychiatric disorder, smoking habits, or inability to understand the information required for an informed consent. The study was approved by the Centro Hospitalar Lisboa Norte’s Ethics Committee  and by the Ethics Committee of the NOVA Medical School and registered at Sociodemographic and anthropometric data, comorbidities and ongoing medication profile were documented. Weight, and abdominal circumference using standardized protocols were assessed. Polysomnographic studies were performed using a polysomnographer . Polysomnography report included sleep parameters , respiratory events such as number and duration of apneas and hypopneas (apnea is the cessation of airflow at the nose and mouth for more than 10 s associated with oxygen desaturation of 3% and hypopnea is a discernible reduction in respiratory effort accompanied by a decrease of more than 4% of oxygen saturation) and apnea/hypopnea index (AHI). OSA was categorized according to current AHI cut-offs of less than 5 (nondiagnostic), 5≥ and <15 (mild), 15≥ and <30 (moderate), and at least 30 (severe). In all patients, blood and 24 h urine samples were collected, before and after polysomnographic studies and stored at −80° until analyzed. Xanthine’s concentrations, including caffeine, theobromine, theophylline and paraxanthine, glycemia total cholesterol, triglycerides (TG), HDL and LDL were measured in blood and epinephrine (E), norepinephrine (NE) and dopamine were measured in the 24 h urine. Quantifications of xanthines and catecholamines were carried by HPLC with UV and electrochemical detection, respectively, as previously described ,21. p < 0.05. We have used non-parametric tests since variables did not follow a normal distribution.Data were presented as median (interquartile range) with nonparametric Mann-Whitney test between two independent samples. Spearman correlations were performed between caffeine concentrations and sleep-related parameters in all subjects or in OSA patients and it was considered significantly correlated at p < 0.05 being considered statistically significant. Afterwards we have grouped the significantly different variables between the 2 groups in 4 different models  and tested its association with OSA when caffeine concentration in blood is present in each model. Each logistic regression was tested for goodness of fit by the Hosmer and Lemeshow test. Statistical analyses were performed using SPSS statistical software (vs 26.0 for Mac) .Exploring the OSA patients we have performed an exploratory data analysis by binary logistic regression for each measured parameter for the dependent variable OSA and data were presented as odds ratio (OR), interval of confidence of 95% (IC95%) and correspondent value of p, with Male patients diagnosed with OSA (65) and male patients without OSA (32) were recruited. The study and the control groups included volunteers aged 50 ± 8 and 34 ± 7 years, respectively. In Aiming to evaluate the impact of caffeine consumption on the prediction of OSA development and on disease severity we correlated caffeine plasma levels and sleep architecture-related parameters for the OSA patients’ group. We found that there is no statistically significant correlation for any of the tested parameters, showing that caffeine is not associated with disease severity .To deeply understand if OSA development is associated with dyslipidemia, dysmetabolism, SNS dysfunction and/or sleep fragmentation we performed a binary logistic regression within both groups, OSA and control patients, for all the covariables significantly different in the previous nonparametric test analysis. Blood pressure was not considered as a covariable for the statistical analysis since OSA patients presented normotensive values due to the use of anti-hypertensive medication. Also, apart from this medication no relevant drugs for the present study were taken by patients. p value in We found that all the tested covariables were associated with the development of OSA, showed by the Coffee and other beverages and foods rich in caffeine consumption has been reported to be increased in OSA condition due to the sleep privation and daily sleepiness, as shown herein in the present study by the higher caffeine concentration in blood in patients diagnosed with OSA. As such, we had interest in investigating if the associations between metabolic and sleep parameters with OSA pathology are influenced by caffeine levels.Therefore, we performed a multivariate logistic regression with OSA as dependent variable and tested the association of the pathology with dyslipidemia , dysmetabolism (BMI and glycemia), SNS dysregulation (dopamine and norepinephrine) and sleep impairment  taking in account caffeine concentration in all models. Each model followed the goodness of fit represented by a non-significative Hosmer and Lemeshow test. The results for each model tested are presented in We found that caffeine association with OSA is lost when all the other variables related with OSA comorbidities are taken in account. Moreover, we also observed that all the variables tested maintain their association with OSA even in the presence of caffeine. Regarding the dysmetabolism model we observed that BMI and glycemia associates statistically significantly with OSA independently of the higher caffeine intake in these patients a. SimilaIn the present study, we showed that the group of OSA patients studied in the present manuscript exhibit significant dysmetabolic condition with higher BMI and glycemia, dyslipidemia with high total cholesterol, LDL, TG and lower HDL levels and deregulation of the SNS assessed as high dopamine and NE levels. Moreover, we showed, as expected, that OSA patients consume more caffeinated products to compensate daytime sleepiness, this being reflected in the high caffeine plasma levels in these patients. We also found that no correlation exists between caffeine plasma levels and OSA and its severity. Finally, we have shown that metabolic dysfunction, dyslipidemia, and sleep disturbances are associated with OSA independently of caffeine plasma levels.Caffeine is one of the most widely consumed psychoactive substances in the World and it is known that this xanthine disrupts sleep, diminishing total sleep time and sleep onset in healthy volunteers ,22. AparSome studies in the past have suggested that caffeinated coffee consumption was associated with a lower metabolic control and therefore with an increased risk of type 2 diabetes and metabolic syndrome ,30, althRegarding SNS-related parameters and following the previous findings of Bardwell et al. , where aIn conclusion, caffeine consumption in OSA patients is not associated with OSA severity, as well as with dysmetabolism and sleep fragmentation although we cannot discharge a contribution of high caffeine levels to the overactivation of the SNS observed in OSA patients. While there is no apparent rationale for caffeine avoidance in chronic consumers with OSA, we believe that more studies regarding coffee/caffeine consumption in OSA patients should be performed.


P < .001), history of stroke , and typical nodules  were all relevant factors in unilateral primary aldosteronism (UPA). In the unilateral nodule group, multivariate logistic regression analysis suggested that maximum systolic blood pressure  and typical nodules  were the related factors for UPA. However, the consistency between adrenal CT and AVS was only 40.68%, while maximum systolic blood pressure  and plasma aldosterone renin ratio  were the relevant consistent factors between AVS and CT results. Maximum systolic blood pressure, typical nodules, and history of stroke are important factors to consider when screening for UPA. It is recommended to combine medical history and imaging findings when looking at different subgroups before a clinical decision is made. Patients with PA in the absence of lesions or bilateral lesions on CT should be diagnosed by AVS as far as possible.To determine factors associated with lateralization in primary aldosteronism (PA). The clinical data for PA patients hospitalized at the First Affiliated Hospital of Guangxi Medical University from October 2016 to March 2021 were included in this study. They were classified according to results derived from computed tomography (CT): bilaterally normal nodules , unilateral nodules  and bilateral nodules . Multivariate logistic regression and receiver operating characteristic (ROC) were used to analyze the factors associated with lateralization of PA and consistencies between adrenal CT images and adrenal venous sampling (AVS) results. A total of 269 patients with PA were recruited, with an average age of 46 years and 112 cases had typical nodules. Results from CT scans revealed that there were 49 bilateral normal cases, 177 cases were unilateral abnormal and 43 cases were bilateral abnormal. In all of the PA patients, multifactorial logistic regression analysis showed that the maximum systolic blood pressure (OR = 1.03,  It is mainly characterized as the spontaneous production of excess aldosterone, resulting in sodium retention, plasma renin inhibition, increased K + excretion, and elevated blood pressure. Aldosteronoma is a kind of mineralocorticoid synthesized by the glomerular zone (ZG) of the adrenal cortex, which regulates the electrolyte balance through the reabsorption of water and sodium by the kidney. Its biosynthesis is controlled by two main factors: angiotensin II (Ang II) and extracellular potassium concentration (K+).,4 Unilateral primary aldosteronism (UPA) is mainly caused by aldosteronogenic adenomas, due to the mutations in potassium and calcium channels or ion pumps. This may lead to membrane depolarization, an elevation of intracellular calcium, disruption of intracellular ion homeostasis and increased adrenal cortical hormone secretion and CYP11B2  transcription.–7 The incidence of PA in patients with hypertension is greater than 10% and approximately 65.6% of secondary hypertension is caused by PA, which is the most common cause of secondary hypertension.–10 According to the 2020 European Society of Hypertension expert consensus on primary aldosteronism, the risk of cardiac, renal and cerebrovascular complications and major cardiovascular events in PA patients without good treatment, is significantly higher than that those with primary hypertension, metabolic abnormalities or bone disease.Primary aldosteronism (PA) is a disorder of the endocrine system caused by increased secretion of aldosterone in the globular region of the adrenal cortex.,12,13 Adrenal vein sampling (AVS) was first performed in the 1960s, and has been further improved in recent years with the development of imaging. AVS can be performed by cannulating a femoral or upper limb vein and placing the catheter port in bilateral adrenal veins to collect blood and measure aldosterone levels in both adrenal veins, which is used to determine whether aldosterone hypersecretion is unilateral or bilateral. At present, it is considered as the gold standard for the diagnosis of PA subtypes, and its accuracy is reported to be as high as 79% to 100%. However, AVS has only been performed in a limited number of centers and adrenal CT is often used as an alternative method for functional diagnosis. Previous studies have shown that there are numerous differences in results between adrenal CT and AVS and clinical decisions based only on CT imaging may lead to an increased risk of misdiagnoses. However, AVS is invasive, expensive, and requires a high level of technology. Therefore, to perform an accurate and targeted diagnosis and classification of the disease has become the focus of clinical research in this area. This study retrospectively analyzed the clinical data from patients with PA diagnosed at the First Affiliated Hospital of Guangxi Medical University, in order to explore the relationship between AVS lateralization and consistency between CT and AVS results to assist clinicians in the early screening of UPA, which is conducive to the diagnosis and treatment of functional typing of PA patients.In order to prevent aldosterone mediated end organ injury, it is necessary to improve the ability to diagnose subtypes of PA. This will help to optimize treatment methods and assist clinical management. The two subtypes of PA mainly include unilateral primary aldosteronism (UPA) caused by aldosteronoma and bilateral primary aldosteronism (BPA), which account for more than 95% of all PA cases.The corresponding clinical treatment is unilateral adrenalectomy or surgery combined with pharmacological and antihypertensive drug therapy using salt corticosteroid receptor antagonists.,19: using plasma aldosterone-to-renin ratio (ARR) > 20 (ng/dL)/(ng/mL/h) , and the diagnosis of PA was confirmed by the Saline infusion test (SIT),or Captopril Challenge test (CCT). SIT: patients started at 8:00 am. and kept sitting for at least 1 hour before and during intravenous infusion of 2 L of 0.9% normal saline within 4 hours. The blood samples for detection of renin, aldosterone, cortisol and plasma potassium were taken at zero time and 4 hours later. During the test, the patient remained seated and monitored blood pressure and heart rate every hour. CCT: Patients received 25 to 50 mg of captopril orally from 8:00 to 9:00 am after sitting or standing for at least 1 hour. Blood samples were withdrawn for PRC and PAC measurement at baseline and 2 hours after provocation, with patients remaining seated during this time. Both SIT and CCT were used to confirm the diagnosis of PA. The 2016 TES guidelines recommend PAC > 10 ng/dL after SIT in the recumbent position as more likely to be PA, <5 ng/dL to exclude PA; PAC > 11 ng/dL after CCT with renin at suppressed levels or ARR > 20 (ng/dL)/[μg/(L/h)] to confirm the diagnosis of PA. For patients diagnosed with PA, AVS and sequential cannulation were performed, and successful catheter insertion was defined as a selectivity index  ≥ 2. If they showed lateralization of aldosterone secretion during AVS, they were further classified into the UPA group, which showed a lateralization index  ≥ 2. Meanwhile, patients with a lateralization index < 2 were classified into the BPA group. AVS was performed according to the consensus from adrenal vein sampling experts, and during hospitalization, adrenal CT enhancement scanning was improved. Patients with unsuccessful AVS blood collection, inability to obtain CT imaging results, or imaging considerations, or pathology confirming a non-adrenocortical origin of the tumor were excluded.In this study, patients with PA treated with AVS were selected as research subjects, and patients hospitalized in the First Affiliated Hospital of Guangxi Medical University from October 2016 to March 2021 were retrospectively included. This study was reviewed by the Medical Ethics Review Committee of the First Affiliated Hospital of Guangxi Medical University, all patients signed written informed consent. The diagnosis of PA was based on criteria from expert consensus on PA in 2020According to the CT findings, patients were divided into: bilateral normal , unilateral nodule  and bilateral nodule  at the same time, according to AVS results. The results from AVS, were divided into two groups: the group with a secretory dominant side and the group with no secretory dominant side.Detailed data of all patients were collected, including sex, age, body mass index (BMI) ≥ 24, maximum systolic blood pressure, maximum diastolic blood pressure, duration of hypertension, family history of hypertension, dyslipidemia, hyperuricemia, history of stroke, lowest serum potassium, glomerular filtration rate (GFR), endogenous creatinine clearance rate (Ccr), aldosterone at screening, plasma renin activity (PRA) at screening, ARR at screening, and left ventricular mass index (LVMI). Thin slice CT enhanced scanning of the adrenal gland used in this study was interpreted by two professional imaging doctors and a typical adenoma was defined as a unilateral nodule of at least 8 mm in diameter with a smooth contralateral gland without enlargement.t test and reported as mean ± standard deviation (SD). Non normally distributed variables were analyzed by Mann–Whitney test and expressed as median (quartile range). Counts data was analyzed by chi square test and expressed in frequency (percentage). Taking the existence of the dominant side as the dependent variable and the variable with P < .05 in univariate analysis as the independent variable, the related factors associated with UPA were analyzed by multivariate logistic regression. In the adrenal CT scan results of unilateral typical nodules, the dependent variable was whether it represented UPA and whether the discriminatory results from the CT scan and AVS were consistent. The variable with a P < .1 in univariate analysis represented the independent variable. The factors associated with the concordance between UPA, CT and AVS were analyzed by multifactorial logistic regression. A receiver operating characteristic (ROC) curve was used for analysis and expressed as the area under the curve (AUC) and 95% confidence interval (95% CI). All the above analyses were analyzed using SPSS  and Medcalc .Data distribution was assessed using the Shapiro–Wilk test and the variables whose measurement data conformed a normal distribution were analyzed by independent sample We included 269 patients with PA, aged 46.24 ± 10.64, into the study, including 113 males (42.01%) and 156 females (57.99%), with a maximum systolic blood pressure of 184 (172–200); lowest serum potassium 3.38 (2.96–3.69) and 112 (41.64%) cases had typical nodular changes and 152 cases had UPA diagnosed by AVS. CT imaging results showed that 49, 177, and 43 cases were bilateral normal, unilateral abnormal and bilateral abnormal respectively.P = .047), maximum systolic blood pressure , history of stroke , lowest serum potassium , and typical nodules  and these correlation showed statistically significant differences. The proportion of both male and female patients with UPA was higher than those with BPA and there were proportionately more female patients, overweight patients [(103 (67.76%) vs (77 (65.81%)] and family history of hypertension [85 (55.92%) vs 71 (60.68%)]. There was no significant difference in the maximum diastolic blood pressure between the two groups. In terms of renal function, the glomerular filtration and endogenous creatinine clearance rates in patients with BPA were slightly higher than those in patients with UPA. In terms of left ventricular mass index, UPA is relatively high. There was no significant difference in screening aldosterone and renin, while the ARR value of patients with UPA was higher than BPA. For the CT scan results, the proportion of bilateral abnormalities in UPA patients was higher [104 (68.42%) vs 73 (62.40%)].In Table P < .001), stroke history  and the presence of typical nodules  represented the independent related factors of UPA , stroke history (P = .004) and typical nodules (P = .002) in UPA patients. Furthermore, multivariate logistic regression analysis showed that patients with a higher maximum systolic blood pressure  and typical nodules  were more likely to be diagnosed with UPA , history of stroke (P = .01) and lowest potassium (P < .001) between the consistent group and the inconsistent group. In addition. There was a greater ARR  in patients with unilateral nodules with a higher likelihood of concordance between CT and AVS findings , and the nodal side contralateral to the occurrence of lateralization was determined to be inconsistent in 105 of the cases . There were significant differences in the maximum systolic blood pressure  cases developing cerebrovascular injury and myocardial infarction over a mean observation period of 5 to 7 years. Tomaschitz et al showed that higher plasma aldosterone concentrations (PAC) were strongly associated with increased stroke mortality, even in the absence of primary aldosteronism. However, their study was only focused on a specific population (patients who underwent coronary angiography). Takeda et al demonstrated that, in a prospective study of 883 cases, 45 cases of stroke occurred during the average follow-up of 10.9 years. The study found that high ARR, or relative aldosterone excess, was a predictor of stroke in conditions of high sodium intake. In recent years, Tang et al conducted a survey of the prevalence and clinical characteristics of PA in 116 young adults with acute stroke, and found that the prevalence of PA was at least 12.9% among adults with stroke under 45 years old. Among young patients with a history of hypertension and stroke, the prevalence of PA was 21.2%, which was far higher than the general population and stubborn hypertension according to previous reports. Compared to patients without PA, patients with PA have higher blood pressure levels and an increased incidence of hypertension and hypokalemia. This suggests the need for more rigorous screening for PA in adults with acute stroke episodes under 45 years of age, especially in those with severe hypertension and hypokalemia. Interestingly, relevant experiments and human studies have confirmed that excessive aldosterone can promote cerebrovascular oxidative stress, inflammation, and endothelial dysfunction, thereby increasing the risk of stroke, independent of blood pressure and other risk factors.–27It has been reported that the clinical scores from Kupers et al on the diagnosis of proto aldehyde subtypes are related to typical adenomas, which is consistent with the results of our study. Previous studies however, have shown that AVS is an unnecessary investigation for patients with typical unilateral imaging manifestations in younger age cohorts,30Our findings suggest that UPA is closely associated with stroke and maximum systolic blood pressure, especially in moderate to severe hypertension. This may be due to sodium retention, and hypertension due to increased secretion of aldosterone. It has been shown that biochemical treatment of hypokalemia and normalization of aldosterone levels after adrenalectomy is almost certainly involved. However, not all patients are completely cured of hypertension after adrenalectomy. Unfortunately, ARR was not an independent correlate when discriminating for UPA.Patients with unilateral nodal PA requiring surgical resection represent the most challenging clinical decisions. In our study, multivariate logistic regression analysis in the unilateral nodule group showed that patients with PA and a higher maximum systolic blood pressure and typical nodules were more likely to be diagnosed as UPA. Moreover, multivariate logistic regression analysis showed that there was significant difference in the highest systolic blood pressure and ARR between CT and AVS. It has been reported that the score regarding the prediction for the use of procedural subtypes consisted of serum potassium, plasma aldosterone, and ARR.Our study also has some limitations: firstly, similar to almost all other studies on PA, retrospective designs may limit the universality of our results, and further prospective studies are needed to confirm our findings. Secondly, the research object comes from a single center research in Guangxi, China, and large sample data are needed to further verify the research results in the future.In conclusion, the maximum systolic blood pressure, stroke history and typical nodules are important related factors for the diagnosis of different PA subtype. When diagnosing of subtypes of patients with PA, a combination of medical history and imaging data is recommended. At the same time, patients with PA with no obvious CT lesions or bilateral lesions are recommended to be divided into different subgroups for clinical decision-making according to the imaging results. Centers that are eligible for AVS should perform it to clarify the functional staging and diagnosis of PA where possible.https://www.editsprings.cn/) for the expert linguistic services provided.The authors thank the participants and participating doctors from the First Affiliated Hospital of Guangxi Medical University. Also, the authors would like to express their gratitude to EditSprings (YM, KC, AX, and YL are responsible for data collection. YM conducted data sorting, statistical analysis and manuscript composition. JH contributed to the study conception and design. All authors read and approved the final version of the manuscript.


No difference was found in the retinal venular caliber or vascular oxygen saturation. These results indicate that GCA and PMR patients differ similarly in the retinal arteriolar diameter compared to controls. Further studies are needed in order to clarify the underlying inflammatory mechanisms in retinal arteriolar vessels and if these parameters can be used to predict clinical outcomes.Giant cell arteritis (GCA) is a potential sight-threatening disease. Although it is associated with polymyalgia rheumatica (PMR), visual loss is not common in PMR. A retinal oximeter can be used to conduct a direct, non-invasive, in vivo assessment of the vascular system. In a cross-sectional study, we measured the retinal oxygen saturation and retinal vessel calibers in GCA patients, PMR patients, and control participants. Twenty GCA patients (38 eyes), 19 PMR patients (33 eyes), and 12 controls (20 eyes) were investigated. Images were analyzed using Oxymap Analyzer software 2.5.0 . Groups were compared using an age- and sex-adjusted linear mixed model regression. The median (IQR) age for GCA patients was 69.0 (66.5–76.5) years, for PMR 69.0 (67.0–72.0) years, and for the controls 75.5 (71.5–81.0) years, respectively. As compared to the controls (115.3 µm), the retinal arterioles were significantly wider in patients with GCA (124.4 µm;  Giant cell arteritis (GCA) is a type of medium and large blood vessel vasculitis with a high risk of ocular morbidities, such as visual impairment . In contA direct, non-invasive, in vivo assessment of the retinal metabolism ,5,6,7,8 In newly diagnosed GCA patients, retinal oximetry has shown an altered venular oxygen saturation and differences in arterio-venular oxygen saturation, even in GCA patients with no ocular symptoms . HoweverThus, we aimed to investigate the vascular system in terms of the retinal metabolism and retinal vascular calibers in GCA and PMR patients at 6–24 months after diagnosis. Our objectives were to examine if (a) the retinal arteriolar oxygen saturation, (b) retinal venular oxygen saturation, (c) difference in retinal arterio-venular oxygen saturation, (d) retinal arteriolar vessel diameter, and (e) retinal venular vessel diameter differed similarly between GCA and PMR patients, on one hand, and control participants, on the other hand. M315, M315A, M316, M316A (GCA), and M353 (PMR) were identified in medical journal files from the Department of Rheumatology at Odense University Hospital, Odense, Denmark, or Svendborg Sygehus, Svendborg, Denmark, and invited to participate in the study via e-mail.This clinical cross-sectional study was conducted between March 2021 and January 2022. GCA and PMR patients with the International Classification of Diseases (10th revision) and Related Health Problems (ICD-10) codes We divided patients into a group of GCA patients and a group of PMR patients.GCA patients were included if a positive temporal artery biopsy, positive positron emission tomography/computer tomography scans, or positive ultrasonography were obtained, as described in the 2018 European League Against Rheumatism recommendations . PMR patients with a score of four or above on the European League Against Rheumatism 2012 classification criteria were included. Age above 50 years, bilateral shoulder pain, and elevated C-reactive protein (CRP) were mandatory, while negative anti-citrullinated protein antibodies (Anti-CCP) and IgM rheumatoid factor (IgM-RF) scored two points and morning stiffness >45 min scored two points. Pelvic pain and no swollen or painful distal joints each scored one point . FurtherControl participants were invited the Department of Ophthalmology, Odense University Hospital, Odense, Denmark, prior to cataract surgery and recruited after surgery if no rheumatologic, cancer or relevant retinal or optic nerve diseases were present at the time of inclusion. Minimal small retinal drusen and minor epiretinal fibrosis were not considered ophthalmologic diseases. Our predictors were the study groups .The outcomes of the study comprise retinal arteriolar oxygen saturation, a measure of the mean saturation in the largest arteriole of each quadrant of the retina, given as a percentage; retinal venular oxygen saturation, a measure of the mean saturation in the largest venule of each quadrant of the retina, given as a percentage; the difference in retinal arterio-venular oxygen saturation, a measure of the difference between the mean arteriolar oxygen saturation and the mean venular oxygen saturation, given as a percentage; retinal arteriolar vessel diameter, a measure of the mean vessel diameter in the largest arteriole of each quadrant of the retina, given in micrometers; and retinal venular vessel diameter, a measure of the mean vessel diameter in the largest venule of each quadrant of the retina. All means are based on three or four quadrants.Confounders include age and sex, which were adjusted for in the linear mixed regression model. We do not believe that any variable had a different effect on the GCA group compared to PMR group, respectively. Thus, we assume that no effect modifiers were present in this study.We carried out all clinical examinations at the Department of Ophthalmology at Odense University Hospital, Odense, Denmark. The CRP value closest to inclusion was defined as the latest blood sample drawn before the study visit.We obtained medical history for diagnoses with giant cell arteritis and polymyalgia rheumatica. Moreover, based on medical journals over a period of five years prior to inclusion, participants were scored according to the Charlson comorbidity index (CCI), using ICD-10 . The CCIDBP + 1/3(SBP − DBP). Height was measured in meters. Weight was measured in kilograms with clothes. Body mass index (BMI) was calculated as height/(meters2). The ophthalmological examination consisted of ophthalmoscopy, with the best-corrected visual acuity tested using the Early Treatment Diabetic Retinopathy Study chart at four meters . Intraocular pressure was measured using Goldmann applanation tonometry and was provided in mmHg. Pupils were dilated using tropicamide 1% and supplemented with phenylephrine 10% if required for optimal dilation. Upon the hospital visit, the blood pressure was obtained in mmHg and measured three consecutive times from the left arm using the same monitor. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) was calculated. Mean arterial blood pressure (MAP) was defined as We used Oxymap T1  to detect the retinal arteriolar, venular oxygen saturation, and retinal blood vessel calibers. The Oxymap T1 device comprises two digital cameras and an optical adapter attached to a TRC-50DX fundus camera . Fundus images were captured using a 50° view at wavelengths of 570 nm and 600 nm of light simultaneously. The fact that light absorbance by the blood affects the brightness in the blood vessels, but not the sides of the blood vessels, is useful for finding the optical density at each wavelength. The ratio between the optical densities of each wavelength is inversely and linearly related to the retinal oxygen saturation . The optic disc was centered in the image, and at least two pictures were captured of each eye, starting with the right eye. The image with the highest overall quality was chosen for further analysis. The image quality was automatically graded on a scale from 0 to 10 by the Oxymap T1 (Oxymap ehf.). The pictures were taken at different light intensities, starting with no light and gradually building up the light intensity for each image. A circle was manually fitted to the optic disc, and two more circles were semi-automatically enlarged to 0.5 times and 3.0 times the size of the circle surrounding the optic disc, respectively. The circle surrounding the optic disc was deleted, and blood vessel measurements were performed manually in the space between the two remaining circles. The required length of the blood vessels for inclusion was between ≥50 pixels and ≤200 pixels. The retinal arteriole and venule with the most considerable length and diameter were chosen from each quadrant, starting with the upper nasal quadrant, and followed by the lower nasal quadrant, the lower temporal quadrant, and the upper temporal quadrant. Mean values for the retinal arteriolar and venular oxygen saturation and blood vessel diameters were calculated.All images were captured and analyzed by S.J.L. For their conversion from pixels to µm, a conversion factor of 9.3 was used . A retinThe tenets of the Declaration of Helsinki were followed, and the study was approved by the Record of Data Processing Activities in the Region of Southern Denmark (20/61779) and by the Research Ethics Committee in the Region of Southern Denmark (20200189). All participants in this study gave informed consent and were allowed to withdraw their consent at any time. Participation in the study was non-invasive and without risk for the participants. However, the dilation of the pupils could burden the participants with blurred vision for 4–6 h afterwards.For the presentation of the demographic data, categorical variables are presented as counts (n) and proportions (%). Continuous variables are reported as medians with interquartile ranges (IQR). For the comparison of the continuous variables, the Kruskal–Wallis test and Wilcoxon rank sum test were used, as the data were not normally distributed. Pearson’s chi-squared test was used for the categorical data. p-values of <0.05 and 95% confidence intervals that were not null were considered statistically significant. Regarding the regression analysis, there were no missing data among the outcome-variables, including the mean retinal arteriolar and venular oxygen saturation, arterio-venular difference, and mean retinal arteriolar and venular vessel diameters .As every participant could contribute two eyes, the cluster robust standard error was used in a linear mixed model regression analysis, adjusted for age and sex, to determine the retinal arteriolar and venular oxygen saturation, the arteriolar–venular difference, and the retinal arteriolar and venular vessel diameter. All tests were two-sided, and Statistical analyses were carried out in Stata 17 . The sample size was estimated from the findings by Türksever et al. , accordiWe invited 194 patients with either GCA (n = 40) or PMR (n = 154) to participate in the study . The reaOf the control participants, thirty-three responded to the invitation, of whom eleven rejected participation and ten were excluded due to highly suspected glaucoma (n = 1), large retinal oedema (n = 1), dry age-related macular degeneration (n = 2), pseudovitelliform macular degeneration (n = 2), a former PMR diagnosis (n = 1), diabetic retinopathy (n = 1), disseminated colon cancer (n = 1), and small lymphocytic lymphoma (n = 1). Of the remaining 12, four participated with a single eye due to poor image quality (n = 1), highly suspected glaucoma (n = 1), severe epiretinal fibrosis (n = 1), and postoperative cystoid macular edema after cataract surgery (n = 1). Thus, we included 20 participants (38 eyes) with GCA, 19 participants (35 eyes) with PMR, and 12 control participants (20 eyes). p = 0.039), higher image quality (p = 0.002), higher best-corrected visual acuity (p = 0.017), and lower intraocular pressure (p = 0.008). Additionally, a difference in the Charlson comorbidity index (p < 0.001) was found between all groups but not in the adjusted Charlson comorbidity index (p = 0.54). While patients with GCA and PMR did not differ in any of the parameters, the controls had a higher age .An overview of the linear mixed regression model analysis adjusted for age and sex is found in There were no differences between any of the groups with respect to the retinal arteriolar oxygen saturation, retinal venular oxygen saturation, arterio-venular difference, or retinal venular diameter.This cross-sectional study aimed to investigate whether the vascular system in patients with GCA and PMR differed similarly in terms of the retinal metabolism and retinal vascular calibers compared to control participants. The results showed a significantly wider arteriolar diameter in GCA patients compared to control participants and in PMR-patients compared to control participants. This may indicate a microvascular overlap between GCA and PMR. The retinal vessel diameter can be adjusted by a complex autoregulatory system  and has Patients with ocular and central nervous system sarcoidosis showed a difference in the retinal arterio-venular oxygen saturation compared to sarcoidosis patients whose ocular and central nervous systems were not affected. However, no difference was found in the retinal venular vessel diameter or arteriolar vessel diameter . AccordiThe dilation of the retinal venular diameters has previously been linked to inflammation . AlthougIn patients with Voigt–Koyanagi–Harada disease, immunosuppressive treatment decreased the retinal arteriolar and venular diameter at follow-up compared to the baseline . The majStrengths can be found in this study. Firstly, retinal examinations were conducted to eliminate the risk of significant ocular disease. Secondly, this was, to our knowledge, the first study to investigate retinal metabolism and the retinal structure in patients with GCA and PMR at 6–24 months after diagnosis. Finally, the image capturing and analysis were performed by the same investigator (SJL). Limitations can also be found within this study. Firstly, it was a cross-sectional study and, hence, causality cannot be determined. Secondly, we were only able to include a limited number of patients and, thus, the risk of type-2 errors must be considered when interpreting the results. Thirdly, some clinical characteristics differed between the control participants and GCA and PMR patients, potentially affecting the results. Finally, we cannot conclude whether the same patterns would emerge in newly diagnosed treatment-naïve patients. In conclusion, we found a wider arteriolar diameter comparing the GCA and PMR patients to the controls. These results suggest that GCA and PMR patients differ similarly in terms of their retinal structure compared to controls at 6–24 months after diagnosis. Prospective studies on newly diagnosed treatment-naïve patients could help us to determine whether changes in the retinal metabolism and structure can be used predictively or whether they simply reflect the initiated treatment.


Maximal hyperemia is a key element of invasive physiological examination. The aim of this study was to investigate the efficacy and safety of intracoronary (IC) nicorandil in comparison with adenosine 5′-triphosphate (ATP) intravenous (i.v.) injection for fractional flow reserve (FFR) measurement in coronary artery lesions.In this study, 46 patients who had their FFR measured were enrolled, including 51 lesions. Hyperemia was induced by bolus 2 mg nicorandil and ATP  for FFR measurement. The safety and efficacy of IC nicorandil were evaluated.p < 0.001, respectively. There was a strong correlation between FFR measured by nicorandil and ATP . The rate of FFR ≤ 0.75 in the nicorandil and ATP groups was 31.37 vs. 35.29%, respectively (p = 0.841), the consistency rate was 96.08%; the FFR ≤ 0.8 rate was 41.18 and 43.14%, respectively (p = 0.674), and the consistency rate was 90.20%. In five lesions, the FFR value measured by nicorandil ranged between 0.79 and 0.82, indicating inconsistency according to FFR ≤ 0.8. The blood pressure changes caused by nicorandil and ATP were 12.96 ± 6.83 and 22.22 ± 11.44 mmHg (p < 0.001); the heart rate changes were 2.43 ± 1.31 and 6.52 ± 2.87 beats/min, respectively (p < 0.001); and the PR interval changes were 6.0 (1.0–11.0) and 9.0 (2.0–19.0) ms, respectively (p < 0.001). Visual analog scale (VAS) scores in the nicorandil group were all in the range 0–2, while in the ATP group were mostly in the range of 3–5.The mean FFR values measured by nicorandil and ATP were 0.810 ± 0.013 and 0.799 ± 0.099, Intracoronary bolus of nicorandil (2 mg) infusion induces stable hyperemia, and it could be considered as an alternative drug to ATP for FFR measurement with a lower side effect profile in most patients. Coronary angiography has limitations in evaluating functional ischemia in coronary artery stenosis. In cardiac catheterization, fractional flow reserve (FFR) has been proven to be a reliable method for assessing the severity of coronary stenosis. Several clinical studies have shown that invasive coronary physiology examinations could improve patient outcomes and provide a more appropriate selection of patients who may benefit from percutaneous coronary interventions (PCI) –4. This Despite compelling evidence and recommendations from guidelines, the use of FFR is not frequent in the real world. In addition to its cost, some patients present contraindications to adenosine or ATP infusion. When an FFR examination is performed after adenosine or ATP infusion, more than 85% of patients experience discomfort, such as chest pain or dyspnea. In a few patients, adenosine or ATP infusion will cause severe side effects, such as atrioventricular block (AVB) or ventricular tachycardia, which may require the interruption of FFR assessment , 10.In addition, some food and drink intake may affect the FFR value and the stability of ATP or adenosine. Recent studies mentioned that the consumption of caffeine, which is commonly consumed in 48 h before coronary angiography, may cause clinical data to be unbelievable .Therefore, a more convenient and safer hyperemic agent may facilitate the use of FFR measurement in the cardiac catheterization laboratory.Nicorandil , a coronary vasodilator that acts on both macro- and micro-vascular circulations, has been reported to be safe and cardio-protective when administered intracoronary (IC) in patients with coronary artery disease (CAD) . Some smWe performed this study to evaluate the feasibility and efficacy of IC nicorandil  compared with i.v. ATP infusion for FFR measurement in Chinese patients.Patients with angiographic epicardial coronary artery stenosis (50–90%) who agreed to have an FFR test were enrolled prospectively. Patients with acute myocardial infarction (within 7 days), regional wall motion abnormalities, reduced left ventricular systolic function [left ventricular ejection fraction (LVEF) < 40%], primary valvular or myocardial disease, severe liver insufficiency or renal dysfunction [estimated glomerular filtration rate (eGFR) < 30 ml/min], history of asthma/chronic obstructive pulmonary disease, and contraindication to ATP or nicorandil were excluded in this study. The angiographic exclusion criteria were left main (LM) lesion, right coronary artery (RCA) ostial lesion, and very distal lesion, which the pressure wire sensor could not cross. Patient’s clinical data, such as age, gender, diagnosis, CAD risk factors, LVEF, and medication utility histories were collected. The study protocol was approved by the institutional ethics committee board. All patients were properly informed prior to the procedure and gave their written consent to participate in the study. All patients must abandon caffeine 48 h after signing the consent willingly.All procedures were performed through the right radial artery using 6F guiding catheters without side holes. The guiding catheter and pressure-sensing guidewire are zero, respectively. After i.v. administration of heparin 100 IU/kg and IC nitroglycerin 200 mcg, a 0.014-inch pressure monitoring guidewire  was calibrated and introduced into the guiding catheter. The pressure transducer was advanced just outside the tip of a 6 Fr guiding catheter, and the pressure measured by the sensor was then equalized (EQ) to that of the guiding catheter. If the EQ value is between 1 and ±9, the wire was then advanced distally to the target coronary stenosis. If the EQ value is not in the range of 1 to ±9, then pull back the wire and zero again till the EQ value is reasonable. Special attention was paid to avoid arterial pressure wave damping, unselective catheterization of the coronary ostia, and variation in the position of the pressure wire. FFR was calculated as the ratio of distal coronary pressure divided by aortic pressure obtained after the achievement of maximal hyperemia . After baseline Pd/Pa was recorded, the hyperemic efficacy of the following two successive methods was used: continuous i.v. ATP  and an IC bolus injection of nicorandil (2 mg). A continuous i.v. infusion of ATP was performed The visual analog scale (VAS) pain score was assessed during an i.v. infusion of ATP and an IC bolus of nicorandil . Using aThe quantitative coronary angiography (QCA) was performed by an independent analyzer blinded to the results of the FFR. All images were obtained using a 6F guiding catheter after IC nitroglycerin 200 mcg. Each target lesion had at least two orthogonal views. The external diameter of the contrast-filled guide catheter was used as a calibration standard. Using an edge detection system , the minimal lumen diameter and the reference diameter were measured and the percentage diameter stenosis was calculated. The reference diameter was defined as the average value of the proximal and distal reference diameters.r and r2) and regression analysis. A p-value of 0.05 (two-sided) was considered statistically significant.All statistical analyses were performed using STATA 11. Discrete variables were expressed as a frequency and a percentage and analyzed by Fisher’s exact test. Continuous variables were expressed as the mean standard deviation or median and interquartile range (IQR) (25–75th) and analyzed by the paired t-test or the non-parametric Wilcoxon test, as appropriate. Using the SK-test method to determine whether sample data are normally distributed or not. The relationship between the two groups was quantified with a coefficient of determination ; guiding catheter pressure instability in one patient; and pressure drift in one patient. FFR comparisons were finally available in 46 patients with 51 lesions. The clinical and angiographic characteristics of study subjects are summarized in p-values < 0.001). Transient AVB occurred in 2 (4.34%) patients with an infusion of ATP, and none with an IC bolus of nicorandil. Patients complained of more chest pain with ATP infusion than with nicorandil IC bolus (p < 0.001). VSA scores in the nicorandil group were 0–2, while in the ATP group, 89.13% of VSA scores were 3–5, and 4.34% were 6–8. About 97.5% of patients complained of chest discomfort.The effects of two different hyperemia methods on blood pressure, heart rate, and heart conduction are shown in p < 0.001; r = 0.983, R2 = 0.966, p < 0.001; p < 0.001), and the plateau time of an IC bolus of nicorandil was 25.4 s (15.6–32.8 s).According to baseline Pd/Pa values, ATP, and nicorandil, all caused significant hyperemia and lowered hyperemic Pd/Pa values. FFR values with nicorandil 2 mg IC were commonly higher than those with ATP infusion  was seen in 16 (31.37%) patients with an IC bolus of nicorandil 2 mg and 18 (35.29%) patients with an infusion of ATP. The patients with FFR < 0.80 were 21 (41.18%) patients with an IC bolus of nicorandil 2 mg and 22 (43.14%) patients with an infusion of ATP.The agreement rate of FFR ≤ 0.75 for an IC bolus of 2 mg nicorandil and an infusion of ATP was 96.08%; the agreement rate of FFR ≤ 0.8 was 90.20%, and there was a discrepancy in which the FFR value with nicorandil was between 0.79 and 0.82 in five lesions.Fractional flow reserve is the most accurate method for discriminating which lesions are associated with ischemia in the catheterization laboratory, and current guidelines recommend its use when evidence of ischemia at non-invasive stress tests is not available –8. NeverTo avoid the disadvantage of adenosine or ATP, some studies have suggested the method without adenosine. In particular, Davies et al. proposed the instantaneous wave-free ratio (iFR) as a novel adenosine-free index of stenosis severity in the ADVISE study . The iFRIn China, it is difficult to acquire adenosine in clinics because it is not domestic and imported products are also very scarce. The price of ATP is cheaper than adenosine. Most cardiologists only use ATP as a hyperemia medication instead of adenosine, with the same effectiveness and side effects. The drawbacks of ATP also include chest pain, dyspnea, and sinus bradycardia up to AVB, which may require interruption of FFR measurement. A more convenient and safer hyperemic agent may facilitate the use of FFR measurement in the cardiac catheterization laboratory.via intracoronary administration . Maybe it is partially because of a little bit higher dose of ATP infusion in this study. Adenosine or ATP is usually administered at 140 mcg/kg/min, and will be increased to 180 mcg/kg/min in some cases to obtain a more satisfying hyperemia effect. In this study, the ATP was given at a dose of 167 mcg/kg/min, the same dose as our routine clinical practice, 4 mg ATP dissolved in saline to make 40 ml ATP saline liquid, and was given at weight (kg) × 10 ml/h. This method saves the trouble of calculating the infusion speed (ml/h) according to different weights to obtain the 140–180 mcg/kg/min dose.In other studies, there was no difference between hyperemic efficacies with nicorandil and adenosine, while in this study, FFR values with nicorandil 2 mg IC were commonly a little bit higher than those with ATP infusion (p < 0.001). Additionally, Takashima noted significant (p < 0.001) fluctuations in FFR after ATP administration. This phenomenon may be explained by the different pharmacological mechanisms of nicorandil and ATP. A larger sample and multi-center studies are looking forward to perform and discover the principle.It is known that the use of ATP has the potential to induce transient AVB regardless of IV or IC administration. IV ATP infusion caused more prolongation of the PR interval than IC NIC administration . In thisr = 0.983, FFRnicorandil = 0.937 × FFRATP + 0.061, R2 = 0.966). The two methods have a similarity of identifying functionally significant stenosis. If functionally significant stenosis was defined as FFR value ≤ 0.75, the consistency rate for IC nicorandil and infusion ATP was 96.08%; while if defined as FFR value ≤ 0.8, the consistency rate was 90.20%. In 5 lesions with the discrepancy, FFR values with ATP were all between 0.79 and 0.82. Therefore, the IC bolus of nicorandil can be used for FFR measurement.In this study, a strong and linear correlation was observed between them with an infusion of ATP and an IC bolus of nicorandil 2 mg  IC nicorandil bolus did not cause much discomfort; while nearly all infusions of ATP caused chest pain or dyspnea; (2) the influence on blood pressure, heart rate, and cardiac conduction was smaller with IC nicorandil than with ATP, and could be used in some patients with contraindications to ATP; (3) An IC bolus injection method is easy and simple, does not require an additional procedure for deep vein access; and (4) IC bolus nicorandil also has evidence of its benefit in patients with the slow flow or myocardial infarction.First, multicenter studies with a larger population and with clinical endpoints are required to confirm the promising findings observed in this study. Second, we did not investigate the hyperemic efficacy of higher doses (>2 mg) of nicorandil. Third, as this was not a blinded study, there could have been a small amount of subjectivity in the interpretation of pressure tracings.This study suggests that an IC bolus injection of nicorandil is a simple, safe, and effective way to induce a stable hyperemia state for invasive physiological evaluation in patients undergoing angiography in a cardiac catheterization laboratory. The use of this novel agent may encourage interventional cardiologists to perform FFR measurements in their patients to optimize interventional procedures. While if FFR with nicorandil 2 mg lies between 0.79 and 0.82, it is better to reevaluate with ATP or adenosine.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by The First Medical Center, Chinese PLA General Hospital. The patients/participants provided their written informed consent to participate in this study.All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.


Cerebral resuscitation determines the prognosis for patients who have experienced sudden death, and brain protection is the focus of clinical treatment. Cerebral resuscitation depends on the timing and quality of cardiopulmonary resuscitation (CPR). At present, cerebral oxygen monitoring is used mainly to monitor the quality of external cardiac compression and provide a prognosis for the nervous system. However, after the return of autonomous circulation, it is necessary to conduct continuous monitoring to ensure measures are taken timeously since hemodynamic instability, brain edema, and other factors may cause occult brain injury, and invasive arterial pressure cannot represent cerebral perfusion.By using continuous cerebral oxygen monitoring after CPR and the return of spontaneous circulation, a patient who was witnessed to have experienced sudden death in the hospital was found to have insufficient cerebral perfusion; he underwent timely intra-aortic balloon counterpulsation to improve his hemodynamics and cerebral perfusion. The patient went on to achieve a good neurological prognosis.Cerebral oxygen monitoring should be conducted throughout the treatment period; physicians should understand cerebral perfusion in real time and implement timely intervention measures to reduce occult brain injury and improve the neurological prognosis of patients. After successful cardiopulmonary resuscitation (CPR), the overall prognosis of patients who have experienced sudden death is poor. The success rate of CPR for out-of-hospital sudden death is 7.6% in Europe, 6.8% in North America, 3.0% in Asia, and 9.7% in Australia . The mai™ 5100 C Cerebral/Somatic Oximeter, Medtronic) was started. An ROSC occurred 8 min later, and an electrocardiogram indicated extensive ST-segment elevation in leads V2–V5. The regional cerebral oxygen saturation (rSO2) levels were 70–80%. Cardiologists performed a coronary artery balloon dilation and administered 300-mg aspirin, 180-mg ticagrelor, and 5,500-IU heparin within 3 h of admission. However, the patient’s pupils became dilated, and they reacted slowly to light. His consciousness deteriorated. The rSO2 showed a continuous decline from 80 to 21%, with little change in the arterial blood gas analysis, but the heart rate, blood pressure, and ejection fraction (EF) measured by ultrasound cardiogram decreased from 130 to 90 bpm, 180/90 to 99/58 mmHg, and 46–33%, respectively. A left ventricular aneurysm was observed. An intra-aortic balloon pump (IABP) was fitted to maintain the patient’s blood pressure at 130–140/70–90 mmHg.Herein, we report a case in which cerebral oximetry was used to optimize brain perfusion in a patient with a return of spontaneous circulation (ROSC) after cardiac arrest (CA). A 67-year-old man  suffered a CA secondary to acute myocardial infarction. His past medical history included hypertension, diabetes mellitus, and chronic renal failure (stage 5). The patient had a 15-min history of chest distress and sweating, and CA occurred as the ambulance arrived at the emergency department. Mechanical CPR was started using the LUCAS 2 Chest Compression System , an intravenous infusion of various drugs was administered, and monitoring of frontal oxygenation using near-infrared spectrophotometry .At present, the static value of brain oxygenation as an indicator of neurological prognosis is an important research topic .In the past, cerebral resuscitation treatment has primarily consisted of providing treatment and observing the outcome without conducting any monitoring. At present, brain oxygen monitoring is not implemented routinely. A mean arterial pressure of > 65 mmHg does not represent good cerebral perfusion [Currently, brain damage is the most important cause of morbidity and mortality in survivors of CA, and an rSO2 level of < 25% increases the likelihood of death and poor neurological outcome –8. DespiSome studies have shown that increased extracorporeal membrane oxygenation (ECMO) blood flow and sweep gas flow are effective at correcting low rSO2 . HoweverTherefore, we recommend that the rSO2 of patients who are in a coma should be monitored routinely and continuously. An IABP may be an effective means of ensuring adequate brain oxygenation in patients who have experienced CA .Further studies are needed to explore the application of cerebral oxygen monitoring.In this case study, cerebral oxygen monitoring, which was conducted throughout the treatment period after resuscitation, helped the doctors understand the patient’s cerebral perfusion in real time. This facilitated timely interventions, resulting in reduced occult brain injury and a good prognosis. The approach creates possible routes for treatment after resuscitation in patients who have experienced sudden death. Furthermore, hemodynamics should be optimized based on rSO2 levels to improve patients’ neurological prognoses. The limitation of this study is that it lacks sufficient data to reveal the characteristics and influencing factors of dynamic changes in cerebral oxygenation.