Mobile health diagnostics have been shown to be effective and scalable for chronic disease detection and management. By maximizing the smartphones’ optics and computational power, they could allow assessment of physiological information from the morphology of pulse waves and thus estimate cuffless blood pressure (BP). We trained the parameters of an existing pulse wave analysis algorithm (oBPM), previously validated in anaesthesia on pulse oximeter signals, by collecting optical signals from 51 patients fingertips via a smartphone while simultaneously acquiring BP measurements through an arterial catheter. We then compared smartphone-based measurements obtained on 50 participants in an ambulatory setting via the OptiBP app against simultaneously acquired auscultatory systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) measurements. Patients were normotensive (70.0% for SBP versus 61.4% for DBP), hypertensive (17.1% vs. 13.6%) or hypotensive (12.9% vs. 25.0%). The difference in BP (mean ± standard deviation) between both methods were within the ISO 81,060–2:2018 standard for SBP (− 0.7 ± 7.7 mmHg), DBP (− 0.4 ± 4.5 mmHg) and MBP (− 0.6 ± 5.2 mmHg). These results demonstrate that BP can be measured with accuracy at the finger using the OptiBP smartphone app. This may become an important tool to detect hypertension in various settings, for example in low-income countries, where the availability of smartphones is high but access to health care is low. Its complications are responsible for the deaths of approximately ten million people annually, a 50% increase over the estimates from 19902. By 2025, the number of people suffering from hypertension will reach 1.5 billion3. The impact of this disease represents a daunting burden to any healthcare system.High blood pressure (BP) remains the leading risk factor for death and disability in both high and low income countries5. Early detection and prevention of the complications of hypertension are essential but depend on accessible and accurate measurements. A recent report from the National Health Service  stated that BP from only 60% of registered hypertensive patients was controlled6 and only 50% of those starting on a new antihypertensive medications were compliant 6 months later7. Issues such as device accessibility, poor patient compliance, physicians’ inertia and the inability of healthcare systems to detect, manage and prevent cardiovascular diseases were among the consequences linked to those findings. The traditional healthcare model of hypertension management based on regular office BP measurements has been challenged, and new hypertension guidelines now strongly recommend the use of home and/or ambulatory BP monitoring for the diagnosis and follow-up of hypertensive patients, thereby motivating and empowering the patient and potentially increasing the frequency of BP measurement9.Epidemiological studies have shown that prevalence and control of hypertension plateaued since the mid-2000s in developed countries, while prevalence has increased in developing countries with low rates of awareness and control11. Mobile phones represent a widespread, readily available device for mHealth. Worldwide, over one-third of consumers own a mobile phone13. If the accuracy of reliable smartphone-based blood pressure measurements was to be demonstrated, this would be a promising tool that could improve access to more populations, medical record keeping, analysis of blood pressure measurements for hypertension management as well as medication compliance and health education. Interest in “cuffless” BP measurement, using smartphones or wearable sensor technologies that estimate BP from photoplethysmograms (PPG) is rapidly increasing14. In particular, pulse wave analysis techniques15, which derive central blood pressure from the morphology of pulse waves in peripheral tissues, are a growing area of interest16. Recently, a first wrist-worn device using Pulse Wave Transit Time (PWTT) has obtained a 510(k) clearance by the US Food and Drug Administration for tracking changes in BP following a calibration process using an oscillometric BP monitor . However, none of the smartphone-based applications has yet been clinically validated or demonstrated to be accurate17.Digital health approaches, and in particular mobile health  diagnostics, have been shown to be effective, scalable and sustainable for chronic disease prevention and management18 —previously validated in anaesthesia on pulse oximeter signals19—applied to smartphone-derived PPG signals acquired via a dedicated smartphone app (OptiBP). This was accomplished by comparing in an ambulatory setting—using the published ISO 81,060–2:2018 standard20—the smartphone-derived BP estimates to simultaneously acquired reference systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) measurements obtained using the auscultatory method with a dual-head stethoscope.The aim of this study was to assess the performance of a pulse wave analysis-based BP estimation technique19 (oBPM) originally designed to estimate BP values from transmission PPG signals18 to reflectance PPG signals acquired by a smartphone camera. The validation part was designed to assess the accuracy of the OptiBP smartphone app on patients using the trained algorithm compared with reference measurements acquired through the classic auscultatory method at the upper arm in an ambulatory setting. This clinical investigation was conducted in compliance with the European Directive 93/42/EEC on medical devices21, with international standards ISO 14,155:2011 and the Declaration of Helsinki. The protocol was designed in accordance with the AAMI/ESH/ISO consensus for the validation of BP measuring devices20.The protocol consisted of two parts: a training part and a validation part. The training part was designed to collect optical signals via the embedded camera of a smartphone running a dedicated mobile app, while simultaneously acquiring invasive intra-arterial BP values. The purpose of this part was to train and further develop an existing algorithmwww.clinicaltrials.gov on March 14 2019.The study was approved by the local ethics committee  and registered under number NCT03875248 at For the training part, written informed consent was obtained from 51 patients aged 18 years or older, who were scheduled for elective surgery necessitating general anaesthesia and invasive arterial BP monitoring at CHUV  or HUG . Exclusion criteria were patient refusal, arrhythmia and inability to give informed consent.20.For the validation part, written informed consent was obtained from 50 participants (hypertensive or not) aged 18 years or older and scheduled for an elective visit at the outpatient hypertension clinic at CHUV . Exclusion criteria were patient refusal, inability to give informed consent, dysrhythmia or an arterial disease leading to a SBP difference > 15 mmHg or DBP difference > 10 mmHg between arms22. The continuous invasive SBP, DBP, and MBP, were recorded before and during induction of general anaesthesia for one minute followed by an average per-patient duration of 20 min with the ixTrend express software version 2.1.0  installed on a laptop computer connected to the monitor. Each minute of recording generated one average BP value. Simultaneously, a customized app installed on a Samsung Galaxy S7  recorded a raw optical signal consisting of a sequence of images at 30 Hz. Each session encompassed 10 series of recordings of 1 min, each separated by a 1-min interval free of recording. The procedure included the positioning of the patient’s middle or index finger on the phone camera lens . A 20-gauge, 4.5 cm length arterial catheter  was inserted under local anaesthesia predominantly into the left or right radial artery. The transducer for the intra-arterial catheter was kept at the level of the left ventricle of the heart. A flush test was performed to rule out over- or under-damping18 as illustrated in Fig. All smartphone data were analysed and post-processed offline using MATLAB . For each 1-min sequence of images acquired with the smartphone, a BP estimate . The reference device was a validated non-invasive (auscultatory) sphygmomanometer , which was calibrated before the study, allowing intermittent BP measurements operated by two independent trained observers using a dual-head stethoscope. The two healthcare professionals formed a trained team that was validated before the onset of the study. The ISO specification requires the two observers to have a maximal difference in the measure of systolic and diastolic BP of 4 mmHg and successive recordings to have variations of at most 12 mmHg SBP and 8 mmHg DBP. In case of failure of the above, the measurements were discarded. The protocol included 7 sequential measurements of BP every 2 min. After four valid measurements, the devices were interchanged. The starting arm side for the reference reading was alternated between subjects: odd-numbered subjects started with the reference device on the right arm and even-numbered subjects on the left arm , DBP (DBPoBPM) and MBP (MBPoBPM) estimates to their corresponding auscultatory-derived reference values . MBPAusc was estimated as 2/3 DBPAusc + 1/3 SBPAusc. We computed the mean and standard deviation (SD) of the estimation error both at a cohort-wise and patient-wise level to determine group and within-patient accuracy. We also computed the percentage errors in order to assess the performance of each pressure measurement  independently of their absolute values. In the absence of standards applicable to our cuffless approach, we evaluated the performance of the smartphone-based BP estimations in an ambulatory setting using the standards of the ISO 81060–2:2018 norm25. This standard requires the mean value of the errors of the individual paired determinations of the device-under-test to be less than or equal to ± 5.0 mmHg with an experimental standard deviation (SD) no greater than 8.0 mmHg.The accuracy of our approach to estimate absolute BP values was assessed by comparing the oBPM-derived SBP  was a BP-measuring app that was available on the iTunes store from June 2014 through July 2015 and claimed to estimate BP by placing the smartphone on the chest while the user placed his right index finger over the smartphone’s camera. The BP measurements of this popular app was demonstrated as highly inaccurate with a mean (standard deviation) absolute difference between IBP and the reference device to be 12.4 (10.5) mmHg for systolic BP and 10.1 (8.1) mmHg for diastolic BP26 demonstrated that a watch-based wearable monitor, consisting of an oscillometric cuff-based automatic BP monitor integrated in a wrist band, fulfilled the ISO81060-2:2013 validation criteria in a standard sitting position with the watch at heart level. Its small size and silent measurement functions were interesting advantages compared to existing cuff devices and would allow access to measure BP in specific situations and settings27. However, due to the automatic cuff-based BP measurement, the accuracy under real-world conditions and how it might be affected by body, palm position or wrist size must be assessed. Furthermore, it requires the acquisition of a specific device and might represent similar burdens as the automatic cuff, including discomfort and occlusive blood pressure measurement.Kuwabara et al.28 described a cuffless BP estimation device including a photoplethysmographic sensor, coupled to an algorithmic transformation of the optical signal, and used it on 35 patients. Changes in light absorption at the participant’s right index correlated to changes in peripheral blood volume and were transformed by their algorithm into BP estimates after initial calibration. Although they were able to demonstrate agreement of their sensor assemblies coupled to an algorithm with standard cuff-based measurements under static and dynamic conditions, the applicability to a commercially available device is not yet realized and reproducibility has yet to be established in various settings. Based on the measurement of a pulse transit time from an electrocardiogram and a PPG signal at the fingertip, the Checkme Pro Health Monitor  has been compared with the measurement of SBP from a classic home BP monitor29. Although the device was complex to use and the success rate of the SBP measurement was low, it is noteworthy that participants indicated an increased willingness to take their BP measurement. The small study sample size and the restriction to the sole value of SBP limits its validity, particularly in young hypertensive patients30.Watanabe et al.31. This technology uses state-of-the-art remote PPG32 with extractions of raw signals and estimation of plethysmography signal (band pass filtering). Using a machine learning-based algorithm from a FDA-cleared BP measurement system, TOI extracts haemoglobin-rich signals that are recombined and linked to represent facial blood flow oscillations. BP was measured on normotensive patients in an experimental setting after an individual calibration. The system needs to be validated with changing blood pressures before its usefulness can be assessed.Transdermal optical imaging (TOI) allowing detection of facial blood flow changes with a smartphone camera in combination with advanced machine learning techniques has been shown to be capable of determining BP values33. The public’s interest in downloading smartphone applications for hypertension management is suggested by the fact that some apps for BP measurement, despite not disclosing the methodology nor the accuracy of the measurements, were downloaded more than one million times in 201534.Our research protocol was designed according to the ISO81060:2-2018 norm and conducted in an ambulatory setting in a leading Swiss hypertension University clinic by specifically trained personnel on 50 patients. The parameters of our oBPM algorithm were trained in challenging operating room conditions (large BP variations) against an invasive reference, thereby ensuring its sensitivity to such changes. Our results demonstrate that a smartphone-model unveiled 4 years ago, without any additional hardware, can be used to measure BP accurately with 70% of the optical signals of sufficient quality to be interpreted. While no cut-off values have been defined to declare the device reliable, future improvement in technology and signal processing will further increase the acceptance rate. Our results suggest that smartphones offer a high potential to improve the accessibility of BP measurements to a broad population, since there is deep penetration of such devices in almost all geographical areas of the world35. Smartphones and mHealth could play a promising role in both high-income and developing countries to reduce the adverse effects of hypertension33, by maximizing the synergies of mHealth and eHealth as demonstrated in various settings36.Although the prevalence of hypertension in developed countries has remained stable in recent years, its increase in low- and middle-income countries represents a future burden to any healthcare system. In many parts of the world, health care services are limited and can provide only occasional and unstructured care for blood pressure related diseases. Cuffless blood pressure measurement is receiving increased attention since it has the potential to overcome some of the shortcomings related to cuff based blood pressure measurements, mainly accessibility of the device37. In 2018, the Association for the Advancement of Medical Instrumentation (AAMI), the European Society of Hypertension (ESH) working group on BP monitoring and the International Organization for Standardization (ISO) presented principles and key elements of a universal validation procedure. With this publication, the basis to enforce regulatory requirements over apps that diagnose, treat or prevent a medical condition may become clearer38. The existing IEEE Std 1708 establishes a normative definition of wearable cuffless blood pressure measuring devices and the objective performance evaluation of such devices39. While this is not a fundamental deficiency of new systems and this only reflects the “first-to-market” advantage of cuff devices, issues in practicality and maintenance remain to be studied regarding oBPM technology.Finally, although no universally accepted standards for the validation of the cuffless BP measurement currently exist, groups of experts have participated in the development of International standardsIn the current study, we present the preliminary blood pressure results based on the analysis of the first 50 patients. Further data collection is ongoing and additional work needs to be conducted on various subpopulations and larger groups of patients where accuracy might be different. Furthermore, in our study, the population recruited so far does not correspond to the distribution of blood pressure values requested by the ISO standards.40. A similar longitudinal study must now validate those findings in a hypertensive population. The cuff-based devices that have been validated using the static ISO norms are based on the assumption that the rested device is capable of measuring BP without an initial calibration reference measurement. In real life, a cuffless BP monitor should operate accurately over a range of pressure after being calibrated at a known pressure. Further explorations related to the cuffless-BP measure must be undertaken to better report specifics related to this new technology.A second seeming limitation is that a calibration procedure was established for every patient individually in our study, as could be happening at a clinic or at the patients’ general practitioner. A preliminary longitudinal study in healthy subjects was able to demonstrate calibration stability for 3 months with a standard deviation of 8% on systolic and diastolic BPThis study demonstrates the high accuracy of the OptiBP smartphone app to estimate blood pressure in a subset of 40 patients with a mean and SD of the error of − 0.7 ± 7.7 mmHg for SBP, − 0.4 ± 4.5 mmHg for DBP and − 0.6 ± 5.2 mmHg for MBP and complied with the requirements of the ISO81060-2:2018 norm. This widely-available device could impact health assessment capabilities in developed and third world countries.


Patients presented to hypertension clinic were included. Each patient had his blood pressure recorded by three methods: OBP using a digital sphygmomanometer device, unattended ASqBP using sequential BP devices with recording of the readings over 30 min, and ABPM that was performed within 48 h of office visit using portable BP devices with BP recording over 24 h.Office blood pressure (OBP) measurement is the most common method of blood pressure measurement. However, it is associated with several pitfalls as white coat effect and masked hypertension. Ambulatory blood pressure monitoring (ABPM) is usually used for diagnosis of hypertension and elimination of white coat effect. This study aimed to assess the correlation and degree of agreement of the automated sequential blood pressure (ASqBP) with OBP and ABPMr 0.81 for SBP and 0.83 for DBP, p < 0.001). We also found a strong positive correlation between ASqBP and ABPM readings . The ASqBP readings were lower than OBP (137.0 ± 16.8/86.4 ± 13.8 vs. 142.7 ± 15.5/88.5 ± 12.3) and close to ABPM readings . For SBP readings, there was moderate agreement between ASqBP and AMBP (both average and daytime). For DBP readings, there was fair agreement between ASqBP and AMBP (both average and daytime).We recruited 64 patients . We found a strong positive correlation between ASqBP and OBP readings (ASqBP measurement has good correlation with OBP and ABPM readings. Unattended automated office pressure has moderate degree of agreement with ABPM for the SBP& fair degree of agreement for the DBP. It can be used in the hypertension clinics to eliminate the problems of white coat effect and marked BP variability. For decades, office blood pressure (OBP) has been used for diagnosis and follow-up of hypertension. However, the use of ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) for diagnosis of hypertension is now recommended . This isAutomated sequential blood pressure (ASqBP) then came to action with its fully automated electronic sphygmomanometer that helps to record multiple BP readings without the need for physician while the patient is resting in a quiet place . In 2011Our study aimed to compare ASqBP measurement to AMBP measurement and OBP measurement in the diagnosis and monitoring of hypertensive patients in the Egyptian hypertension clinic.This was a cross-sectional observational study that was conducted from January 2017 to May 2017. We included patients who attended the Hypertension Specialized Clinics—settled by the Egyptian Society of Hypertension—at Cairo University Hospital, to check their medical status, and/or control their blood pressure. Written informed consent was obtained from all subjects enrolled in the study. The study was approved by the local ethics committee. We excluded patient who refused to sign informed consent and failed to perform or denied the use of ASqBP.Medical history including age; gender; cardiovascular risk factors, e.g., smoking, dyslipidemia, and diabetes mellitus; medical illness, e.g., chronic kidney disease (CKD); and current antihypertensive medications.Body mass index (BMI) and waist circumference (WC).Blood pressure measurements.All patients were subjected to:Office BP (OBP) measurement according to the European Society Guidelines for the Management of Hypertension [rtension  using a Automated Sequential BP measurements (ASqBP): The Mobil-O-Graph ®, PWA, was used to measure the unattended sequential blood pressure over a period of half an hour in a quiet room. The measurements were taken every 2 min, and the results were averaged, after excluding the first and final ones [nal ones .Ambulatory BP measurements (ABPM): ABPM was performed with the patient wearing a portable BP measuring device, usually on the non-dominant arm using  every half an hour in daytime and every hour during the night according to patient sleep and awake time for a 24-h period. The test was done within 48 h of clinic visit. For each patient, a cuff containing an inflatable bladder of correct length and width appropriate for him is used. The measurements were downloaded to a computer and at least 70% of the readings during daytime and night-time periods should be satisfactory, or else the monitoring should be repeated [Labs including lipid profile, urea, and creatinine; urine analysis for microalbuminuria; and blood sugar measurement .Systolic and diastolic blood pressure readings were obtained through the following methods:.To assess the correlation and degree of agreement of the automated sequential blood pressure (ASqBP) with OBP and ABPMt test while categorical variables were compared using chi-square and Fischer’s exact tests. Degree of agreement between sequential and ambulatory blood pressure measurements was evaluated using kappa test and interpreted according to the result into none to slight (0.01–0.20), fair (0.21–0.40), moderate (0.41–0.60), substantial (0.61–0.80), or perfect (0.81–1.00) [p value of less than 0.05 was considered significant.Statistical analysis was performed using S-Plus Statistical Software (SPSS) for Windows . Continuous variables were presented as mean ± standard deviation. Categorical variables were presented as numbers and percentages. Continuous variables were compared using Student’s 81–1.00) . CorrelaSixty-four patients were included in this study. Table Table For SBP readings, there was moderate agreement between ASqBP and AMBP (both average and daytime). For DBP readings, there was fair agreement between ASqBP and AMBP (both average and daytime) Table .Table 3Our study shows that ASqBP showed good correlation with AMBP and OBP when it is used for BP measurement in the Egyptian Hypertension Clinics. There was moderate degree of agreement between ASqBP and ambulatory SBP (24 h and daytime) and fair degree of agreement between ASqBP and ambulatory DBP (24 h and daytime).Hypertension is very common medical problem affecting 26.3% of adult Egyptians with only 38% of them were aware of having high blood pressure. It was found that only 24% of hypertensive patients were receiving the antihypertensive medications, with control rates  were 8% .Office BP measurement is the routine in clinical evaluation of patients and follow-up. Because of the white coat effect, several patients have been labeled hypertensive and were prescribed anti-hypertensive medications for life, with subsequent hypotensive episodes. The use of ambulatory BP monitoring has solved to a great extent this problem of labile hypertension, and/or white coat effect. However, it is troublesome as usually disturbed by the effect of inflating cuffs. Therefore, the measurements might not reflect the basal conditions.Theoretically, ASqBP eliminates the human error as well as attenuates the white coat effect, since it allows for multiple readings to be taken in unattended fashion. The Canadian guidelines recommended the use of automated devices as the method of choice for office BP measurement . In the In the current study, we aimed at comparing sequential blood pressure measurement with both OBP and ambulatory monitoring, to correlate between their readings, and whether automated sequential BP can eliminate the pitfalls of blood pressure measurement as white coat effect.Our results showed that ASqBP measurement is significantly lower than the OBP measurement. Scherpbier-de Haan et al. revealed in their study, on 83 adult patients, that 30-min ASqBP measurements better reflects the patient’s true BP than standardized OBP does. Their mean 30-min ASqBP readings were 7.6/2.5 mmHg  lower than OBP readings .n = 238) of this population [Leenen et al.  used ASqpulation . ASqBP rpulation  reproducr = 0.571 and r = 0.145, respectively) [p < 0.001 for both). However, there was good correlation between ASqBP (both systolic and diastolic) and daytime ABPM measurements .Beckett and Godwin compared BpTRU automatic blood pressure monitor to mean daytime 24-h ambulatory blood pressure monitoring in the assessment of BP in 481 patients with hypertension. The group mean of the average of five BpTRU readings was not statistically different from the 24-h daytime mean on ABPM with mean ± SD of 140.0 ± 17.71/79.8 ± 10.46 vs 141.5 ± 13.25/79.7 ± 7.79 mmHg, respectively. Within patients, BpTRU average correlated significantly better with daytime ambulatory pressure than did clinic averages (ctively) . These rr = 0.591 and 0.587 respectively) and for daytime ABPM vs mean OBP systolic/diastolic (r = 0.173 and 0.306 respectively) [Godwin et al. studied the manual and automated office measurements in relation to awake ambulatory blood pressure monitoring by taking single automated sequential BP measurement and the mean of three OBP on different sets for 654 hypertensive patients; their results showed that the single ASqBP correlates better than the three mean OBP with the daytime ABPM which is similar to the results of the present study. In this study, Pearson correlations were as following: daytime ABPM vs ASqBP systolic/diastolic . For DBP readings, there was fair agreement between ASqBP and AMBP (both average and daytime). Unattended sequential BP measurement could overcome the problem of white coat effect that is frequently encountered with office blood pressure measurement.


There were also significant Δ in BP, RAAS components, adipokines and inflammatory biomarkers. Multiple linear regression adjusted models showed that Δaldosterone was an independent variable (B coeff.95%CI) for final PWV . Angiotensin-converting enzyme (ACE)/ACE2 and ACE were independent variables for final AIx@75  and PP , respectively. There was no correlation between ΔAS and anthropometric changes nor with Δ of adipokines or inflammatory markers except high-sensitivity C-reactive protein (hs-CRP). Patients with PWV below median decreased PWV  and both AIx@75 and PP at 1-month, but not those with PWV above median. In conclusion, there is an improvement in AS 1-month post-BS that correlates with ΔBP and Δrenin-angiotensin-aldosterone components. The benefit is reduced in those with higher PWV.Arterial stiffness (AS) is an independent predictor of cardiovascular risk. We aimed to analyze changes (Δ) in AS 1-month post-bariatric surgery (BS) and search for possible pathophysiological mechanisms. Patients with severe obesity (43% hypertensives) were prospectively evaluated before and 1-month post-BS, with AS assessed by pulse-wave velocity (PWV), augmentation index (AIx@75) and pulse pressure (PP). Ambulatory 24 h blood pressure (BP), anthropometric data, renin-angiotensin-aldosterone system (RAAS) components and several adipokines and inflammatory markers were also analyzed. Overall reduction in body weight was mean (interquartile range (IQR)) = 11.0% (9.6–13.1). A decrease in PWV, AIx@75 and PP was observed 1-month post-BS (all,  The World Health Organization reported that more than 1.9 billion adults were overweight and, of these, over 650 million were obese ,3. BariaArterial stiffness (AS), considered as an independent cardiovascular risk factor , is a deExcess body weight is associated with higher aortic stiffness in young and older adults . TherefoThe previously published BARIHTA  study  analysesThe BARIHTA study is a prospective observational trial in a cohort of consecutively recruited patients with severe obesity scheduled to undergo BS . Details about BARIHTA trial have been published elsewhere . In brieHere, we report additional analysis focused on the effect of BS on AS and its relationship with several renin-angiotensin-aldosterone system (RAAS) components, as well as with inflammatory markers and adipokines, according to pre-specified secondary endpoints.Demographic and clinical data were recorded from all participants in the inclusion visit. Anthropometric characteristics, pharmacological treatment and 24 h blood pressure (BP) recordings, including data on PWV and AIx, and laboratory tests were obtained at baseline and 1, 3, 6 and 12 months after surgery. Hypertension was considered if patient received antihypertensive drugs and/or if the baseline 24 h-BP was ≥130/80 mmHg. Diabetes mellitus (DM) was diagnosed if the patient was under antidiabetic treatment or had ≥2 fasting plasma glucose determinations ≥7.0 mmol/L or if glycosylated haemoglobin A1c was >6.5%.® NG-ambulatory blood pressure (NG-ABPM) by IEM, Stolberg, Germany device was used to measure brachial-BP and indirectly calculate aortic-BP and other arterial parameters through the oscillometric method . Several studies have validated this device for estimating PWV and AIx [A Mobil-O-Graph and AIx ,20. Usin and AIx ,21,22. TAll patients had recordings of good technical quality . Otherwise, a new ambulatory-BP-monitoring (ABPM) was repeated within 1-week and used as the valid one.Plasma renin activity (PRA) and plasma aldosterone concentration, as well as angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme-2 (ACE2) activities, were measured by validated laboratory methods . DetailsLeptin, adiponectin, and some cytokines and inflammatory markers, i.e., resistin, angiopoietin-2, MCP-1 and high-sensitivity C-reactive protein (hs-CRP) were also determined. See 2, as a first-step treatment in cases with a body mass index (BMI) > 50 kg/m2 and when drug malabsorption was to be avoided [Either laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) were chosen for each patient based on clinical criteria and the consensus of the Bariatric Surgery Unit. Thus, LSG was preferred in younger patients, in those with BMI ranged 35–40 kg/m avoided . The LRYt-tests in continuous normally distributed data or by Wilcoxon-test in non-normally distributed continuous data. Multiple linear regression models were constructed for the resulting 1-month value of each AS parameter (dependent variable) adjusting for age, sex, variation (Δ) of body weight, Δ 24 h-systolic BP, Δ cardiac output, the baseline value of the correspondent AS marker and Δ of each assessed RAAS components (independent variables). Results are shown by the B coefficient and corresponding 95% confidence intervals (95%CI). Pearson’s or Spearman’s correlation coefficients, when appropriate, were obtained to measure the association between AS indexes and BP estimates, RAAS components, adipokines, inflammatory markers and glucose homeostasis parameters.Descriptive data are presented as mean ± standard deviation (S.D.) for those normally distributed variables or summarized as median  in case of a non-normal distribution according to the Kolmogorov–Smirnov test. Categorical and dichotomous variables are presented as frequencies and percentages. Comparisons of variables between two periods were carried out by paired t-test for the variable Δ 24 h-PWV (1-month after BS vs. baseline), the secondary endpoint analyzed here, having a sample size of 47 patients. Since we have a mean difference of −0.26 and a standard deviation of 0.40 (effect size = −0.65), for an α = 0.05, a power of 99.4% was found.A sample size calculation was initially calculated and 61 subjects were assumed as needed to answer the primary outcome . A post-Statistical package SPSS for Windows version 25.0  was used. A change was considered significant if the two-side alpha level was ≤0.05.A quarter of the study population received treatment with one or more drugs that interfered with RAAS, being modified within the first month post-BS. For this reason, the main analyses, especially those which include BP and/or RAAS parameters, were performed separately in both the whole cohort and in the normotensive patients.Sixty-two patients completed the BARIHTA study. Complete data on AS were available for 47 subjects, and these comprise the cohort reported here  of −4.4 mmHg (−8.3 to −0.5) and −4.0 mmHg (−7.8 to −0.2) respectively.Changes (Δ) in AS were statistically significant 1-month post-BS .p = 0.042. Since our goal was to analyze changes in AS and their potential mechanisms, most of the analyses shown from now on are referred to the evaluation 1-month post-BS. Thus, 1-month changes in anthropometric and hemodynamic parameters and arterial stiffness estimates are shown in p < 0.01 for all).Although there was a trend towards a decrease in all AS markers from baseline to 3, 6 and 12 months , only thStatistically significant decreases in body weight and waist circumference are also shown in p < 0.001)  .When analyzing anthropometrics, arterial stiffness and hemodynamic changes according to the surgical technique , to haviMultiple linear regression models were built for each of the statistically significant change in AS markers .In all tested models for final (1-month post-BS) 24 h PP and final PWV, Δ 24 h systolic BP and baseline values of each correspondent AS marker were statistically significant independent variables. Another independent variable for 24 h PP post-BS was Δ ACE. On the other hand, Δ aldosterone was an independent variable for the final PWV value. As regards final AIx@75, age and baseline AIx@75 value were statistically significant independent variables in all models. In addition, the ratio ACE/ACE2 was also an independent variable for the final AIx@75 value in this cohort. Neither Δ body weight nor Δ cardiac output influenced the final value of any AS marker. Equivalent results were found when the same models were tested including Δ waist circumference instead of Δ body weight . In addition, Pearson’s or Spearman’s correlation coefficients, as appropriate, were obtained to measure the association between the observed changes.At 1-month, there was no statistically significant correlation between changes in PWV, AIx@75 or PP with changes in body weight or waist circumference. When the correlations between the variation of each of these three AS markers with changes in fasting glucose, fasting insulin or the HOMA-IR index were explored, again no correlation was found.p = 0.041 [In addition, none of the changes in any of the analyzed adipokines or inflammatory markers showed a statistically significant correlation with changes in PWV, AIx@75 or PP. except between variation of 24 h PP and variation of hs-CRP: Rho = 0.382;  = 0.041 .p = 0.036. No statistically significant correlation was observed between ΔAIx@75 and any BP estimate.Variation of 24 h-PWV A correlap = 0.013). There was also a direct correlation between Δ AIx@75 and Δ ACE   B. At 1-mFinally, given the fact that some authors  reportedPatients with higher baseline 24 h PWV only showed a statistically significant decrease in PWV and AIx@75 1-month post-BS, but not in the PP. In contrast, those with 24 h-PWV below the median showed a decrease in all AS markers at 1-month. Conversely, patients with lower AIx@75 and lower PP only showed an improvement in 24 h PWV at 1-month. Remarkably, for patients with AIx@75 or PP above the median, statistically significant decreases were observed in all AS markers at 1-month.Arterial stiffness, assessed by three different methods, i.e., PWV, AIx@75 and PP, improved significantly as early as 1-month after BS in this cohort of patients with severe obesity. These changes were confirmed in the subset of patients strictly normotensives, as confirmed by the 24 h -ABPM, or who did not experience changes in their antihypertensive treatment regimen. In fact, it has been suggested that AS may precede elevations in systolic BP and incident hypertension in obese individuals . MoreoveWhat is relevant is the finding that changes in several RAAS components were also independent variables for the final values of each AS markers, after adjusting for confounding factors, relationships that were confirmed in correlation analyses. Some studies have previously suggested that the RAAS is an important determinant of AS, in addition to BP and other factors. Multiple mechanisms are responsible for the RAAS activation in obesity, including adipose tissue-derived RAAS components that might be involved in regulation of BP and AS through local production of angiotensin (Ang) II and aldosterone, conversion of adipocyte-derived angiotensinogen by systemic renin and ACE-activity, or forming Ang via alternative routes due to the presence of cathepsins and chymase in human adipose tissue ,30. The Our study has some limitations and several strengths. First, there is some debate about the reliability or not of the Mobile-O-Graph device for measuring AS in the general population and in patients with obesity or with Marfan’s syndrome . RecentlSeverely obese patients, including normotensives, have some degree of AS that improves one-month post-BS. Patients with the highest baseline PWV are less likely to improve, but improvement of AS in those with higher baseline AIx@75 maintains over time. AS changes are probably related to modifications in the RAAS, specifically to ACE and ACE2 activities, although this possibility deserves further investigation.


In women presenting for caesarean section under spinal anesthesia, continuous measurement of circulatory aspects, such as blood pressure and cardiac output, is often needed. At present, invasive techniques are used almost exclusively. Reliable non-invasive monitoring would be welcome, as it could be safer, less uncomfortable, and quick and easy to apply. We aimed to evaluate whether a non-invasive, finger plethysmographic device, the ccNexFin monitor, can replace invasively measured blood pressure in the radial artery, and whether cardiac output measurements from this device can be used interchangeably with measurements from the mini-invasive LiDCO monitor currently in use at our institution.Simultaneous invasive measurements were compared to ccNexFin in 23 healthy women during elective caesarean section under spinal anesthesia. We used Bland Altman statistics to assess agreement, and polar plot methodology to judge trending abilities with pre-defined limits.Mean arterial and systolic pressures showed biases (invasive – ccNexFin) of − 4.3 and 12.2 mmHg, with limits of agreement of − 15.9 – 7.4 and − 11.1 – 35.6, respectively. The ccNexFin trending abilities were within the suggested limits for mean pressure but insufficient for systolic pressure compared to invasive measurements. Cardiac output had a small bias of 0.2 L/min, but wide limits of agreement of − 2.6 – 3.0. The ccNexFin trending abilities compared to the invasive estimated values (LiDCO) were unsatisfactory.We consider the ccNexFin monitor to have sufficient accuracy in measuring mean arterial pressure. The limits of agreement for systolic measurements were wider, and the trending ability compared to invasive measurements was outside the recommended limit. The ccNexFin is not reliable for cardiac output measurements or trend in pregnant women for caesarean delivery under spinal anesthesia.ClinicalTrials.gov under number NCT01861132.Registered May 23, 2013, at  In a normal pregnancy, large alterations occur in the circulatory physiology. Blood volume, stroke volume, heart rate, and cardiac output (CO) increase, where blood pressure (BP) and peripheral resistance decrease . During Anesthetists are trained to observe and interpret heartbeat-to-heartbeat variables and often need to see trends and changes over time. In our department, the current standard tool for continuous cardiovascular monitoring is the LiDCOplus monitor . LiDCO offers continuous data on BP, peripheral resistance, and CO, among other variables. However, the monitor requires intra-arterial access and is reserved for delivery in high-risk pregnancies.It would be of great advantage for research and clinical monitoring of pregnant women if detailed and reliable continuous measurements could be obtained using non-invasive technologies. Advanced monitoring could be established more quickly and easily, and with less risk. For example, the ccNexFin monitor  is non-invasive and easy to apply. There is, however, currently insufficient evidence that non-invasive monitors are reliable for pregnant women.The objectives of the present study were to assess the agreement and trending abilities for systolic and mean arterial BP between ccNexFin and invasive BP measures, assess the agreement and trending abilities for CO between the ccNexFin and LiDCO monitors, and determine if ccNexFin can replace invasive measurements of BP and CO during CS under spinal anesthesia in healthy, pregnant women. The expected outcome was that the non-invasive measurements and trending abilities of BP are reliable compared to invasive measurements, but we expected CO to be less reliable.The study was approved by the Regional Committee for Medical and Health Research Ethics, Southern Norway (REC ID: 2012/1155 approved 01/02/2013). All participants provided written informed consent. The study followed the Declaration of Helsinki and was conducted according to Good Clinical Practice.Healthy, non-smoking, normotensive women with singleton pregnancies scheduled for elective caesarean delivery under spinal anesthesia were asked to participate in this study. Participants were recruited in collaboration with “The Placenta Project” (REC ID: 2011/2419) and, for this subset of the study population, a common information leaflet was developed. The information was released during the recruitment period and included detailed information about the anticipated pain during arterial cannulation and the extra time needed when establishing both invasive and non-invasive monitoring. As part of the study protocol for “The Placenta Project”, all participants received an intra-arterial line used for blood sampling at delivery. The protocol for The Placenta Project and description of the entire recruitment period was published previously [The LiDCOplus monitor  is in routine clinical use and has documented accuracy and trending abilities , and is The ccNexfin monitor  is based on the principle of the unloaded vascular wall , the Phy, Inc., Utah, USA) was placed in the radial artery after skin infiltration with lidocaine (5–10 mg). The cannula was connected to a Siemens Dräger Infinity Gamma XL hemodynamic monitor  via a Codan X-trans pressure transducer  and the signal calibrated according to standard departmental procedures. Peripheral IV catheters were placed on both arms.In this prospective observational study, a 20G BD arterial cannula (Becton Dickinson Infusion Therapy Systemsinv), invasive systolic arterial pressure (SAPinv), and invasive mean arterial pressure (MAPinv) were recorded at a rate of one sample per heartbeat. The COLiDCO estimated by PulseCO was also recorded. A single point calibration of CO was performed. The ccNexFin monitor was applied to one of the three middle fingers on the same arm as the intra-arterial cannula and corresponding variables  recorded.Intra-arterial BP data was passed through to the LiDCOplus monitor. Invasive heart rate  and fentanyl (20 μg) using a 27G pencil point needle. Co-loading with intravenous 0.9% NaCl (1000 mL) was started. The parturients were then placed in the supine position with a left lateral tilt using a wedge under the right hip. Immediately after injection of the drugs, an intravenous bolus of phenylephrine (25–50 μg) was given, followed by an infusion starting at 0.25 μg/kg/min and titrated according to invasive BP, aiming for a stable SAPTo acquire synchronous sampling from both monitors, measurements were sampled in real time by the same computer. Samples were acquired through the RS232 port of the LiDCO monitor and the analog output from the ccNexFin monitor using a data acquisition card and software from National Instruments. This setup was evaluated for electrical safety and approved by the appointed committee at Oslo University Hospital.Time-stamped data for inter-beat interval (IBI), SAP, MAP, and CO from both monitoring devices was recorded to a single dataset per subject, one sample per heartbeat, using software developed in-house using National Instruments LabVIEW®. Events were marked in real time and saved to a file using the same software.Due to subject movement following spinal anesthesia, placement of a hip wedge, and adjustment of the arterial pressure transducer and the ccNexFin heart reference system, we considered data from the first 2 min after spinal anesthesia as unreliable. The arterial line was used for blood sampling just prior to delivery, causing a pause in our registration, and following delivery there was again more subject movement causing unreliable data. It is also the experience of our group that the LiDCO needs recalibration after delivery . We inclDue to differences in processing time between the two monitors, the LiDCO samples were ahead of the ccNexFin samples, by approximately two heartbeats on average, though they were sampled synchronously from the outputs of the monitors. For each session, this difference was adjusted by calculating the lag using a cross-covariance analysis of the IBI time-series, which are assumed to be equal between monitors, and then shifting the ccNexFin recording ahead by the calculated lag in order to align the recordings for comparison at equivalent beats. This was performed in Matlab R2014b .Artefacts were reduced using a previously published method for detecting and removing outliers in continuous BP and CO recordings . Data poMethods were compared using Matlab and Stata v15 . We used the method first described by Bland and Altman to investigate the agreement of the ccNexFin monitor with invasive BP and LiDCO CO measurements , 14. EarPolar plots were used to assess trending abilities for both BP and CO . As suggOf 63 subjects approached to participate in the study, 45 agreed to participate. Of these women, 7 went into labor prior to the CS, and study personnel were not available at the time of the CS for 12. Another two women were excluded due to technical problems with the recording equipment, and in one woman we did not succeed in placing an intra-arterial line. This left us with 23 participants eligible for BP analysis. Two additional women were excluded from the analysis of CO due to unsuccessful calibration of the LiDCO monitor  time from spinal anesthesia to blood sampling was 16.1 (5.5) minutes, with values ranging from 5.6 and 31.7 min. We had some missing data, mostly due to delivery sooner than 12 min after spinal anesthesia, or misalignment of the ccNexFin heart reference system. For the BP analysis, 209 of a theoretical maximum of 230 data points remained (90.9%). For the 21 participants included in the CO analysis, 187 of 210 possible data points remained (89.0%).The Bland Altman plots and Polar plots are shown in Fig. Even though the anesthetist aims to keep the patient as stable as possible during caesarean delivery, rapid and major fluctuations in BP and CO are common. Both spinal anesthesia and injections of oxytocin result in sudden drops in the peripheral resistance, with decreases in BP and concomitant increases in CO , 17. StaThe definition of a gold standard for BP is debatable. Although auscultatory BP, measured on the upper arm, may still be considered the gold standard, it is too slow and impractical for use in the setting of caesarean delivery. For most patients, intermittent oscillometric measurements are sufficient, but in more challenging cases, continuous measurements are needed. These measurements are usually obtained invasively. For invasive measurements, the gold standard may be the BP in the ascending aorta, but this measurement is not obtainable. The radial artery is the preferred site, as it is conveniently located, easy to cannulate, and the incidence of complications is low . Still, Oscillometric non-invasive BP measured in the upper arm underestimates high BP and overestimates low BP, whereas mean pressures are similar compared to intra-arterial measurements in the radial artery . In 1990In 1951, Wood et al. simultaneously measured the BP in radial and brachial arteries in 17 healthy subjects and found that the SAP in the radial artery was 6 mmHg higher, and MAP and DAP slightly lower (2 and 1 mmHg), than in the brachial artery. For hypertensive subjects, the difference in systolic pressure was increased . Pauca eThe ccNexFin measures BP in a finger. The waveform is transformed to approximate invasive brachial BP  using a An analysis by Klöhr et al. reviewing definitions of hypotension after spinal anesthesia for caesarean delivery found that, in research, relative limits seem to be more popular than absolute thresholds . This anAuscultatory, oscillometric, invasive, and finger plethysmographic techniques use different principles to measure or estimate BP. In addition, measurements are made at different anatomic sites. It is important to be aware of the measurement techniques used in scientific studies, their definitions of safe limits for BP, and to consider the characteristics of these methods compared to the ones being used in clinical practice.From this perspective, the inaccuracy of ccNexFin compared to invasive arterial pressure has a minor impact, and we recommend finger plethysmographic measurement for clinical use and in research.The degree to which two monitors agree in their ability to track changes is also crucial. For the Polar plot method we applied, Critchley et al. suggest using a limit of ±5° for angular bias and radial limits of no more than ±30° for good trending abilities . Only thRegarding CO, we did not find sufficient agreement between the monitors. Even though the bias was small, the limits of agreement were wide, more than ±40% of the mean CO. Both the angular bias and radial limits of agreement were far outside recommended limits, suggesting that ccNexFin cannot reliably track changes in CO. This is consistent with the results in a study comparing this technology to echocardiographic estimates of CO . Based oIn this study, we presented the accuracy (bias) and precision (variability) of agreement between two methods. We calculated limits of agreement and assessed the use of ccNexfin against invasive measurements for BP and the LiDCO monitor for CO. As described by Hapfelmaier et al. , the preA total of 21 patients were analyzed and a larger sample could have increased the precision and generalizability. However, it is important to take into consideration the large number of repeated measurements per patient and that the analyses included all of these data points to assess trending abilities.We consider the ccNexFin monitor to have sufficient accuracy in measuring MAP. The limits of agreement for systolic measurements were wider, and the trending ability compared to invasive measurements was outside the recommended limit. The ccNexFin is not reliable for CO measurements or trending ability in pregnant women undergoing caesarean delivery under spinal anesthesia.


Understanding the effects of high oxidation reduction potential (ORP) levels on sperm parameters will help to identify patients with unexplained and male factor infertility who may have seminal oxidative stress and determine if ORP testing is needed. This study aimed to evaluate the association between seminal ORP and conventional sperm parameters.6sperm/mL was used. Sperm parameters were compared between infertile men with normal sORP  and high sORP values .A total of 58 patients who provided a semen sample for simultaneous evaluation of sperm parameters and ORP between January and September 2019 were enrolled in this retrospective study. To identify normal and high ORP levels, a static ORP (sORP) cut-off value of 1.36mV/106sperm/mL had significantly lower total sperm count (TSC) (p <0.001), sperm concentration (p <0.001) and total motile sperm count (TMSC) (p <0.001). In addition, progressive motility (p=0.04) and fast forward progressive motility (p <0.001) were significantly lower in the study group. A negative correlation was found between sORP and TSC , sperm concentration , TMSC  and progressive motility . Non-progressive motility positively correlated with sORP .Men with sORP values >1.36mV/106sperm/mL. Presence of oligozoospermia, reduced progressive motilty or low TMSC in sperm analysis should raise the suspicion of oxidative stress and warrants seminal ROS testing.This study has shown that TSC, sperm concentration, progressive motility and TMSC are associated with seminal oxidative stress, indicated by a sORP cut-off of 1.36mV/10 Reactive oxygen species (ROS) are generated as by-products during normal metabolic events and play a crucial role in various cellular processes. The imbalance between ROS and antioxidant capacity due to excess production of ROS leads to oxidative stress . OxidatiROS are normally present in human semen at low levels. The presence of leukocytes and immature, morphologically abnormal spermatozoa are the main causes of ROS in semen. Besides, exogenous stimuli including infections, environmental factors, and tobacco use can contribute to seminal ROS . Normal Oxidative damage to sperm is a significant contributing factor in 30-80% of male factor infertility cases . FurtherGiven the high incidence of seminal oxidative stress-related infertility, ROS screening during diagnostic evaluation of the male partner seems a reasonable approach. However, analysis of semen ROS status is not a standard procedure during fertility work-up, due to high cost and lack of a recognized, standardized measurement method . A new tThis study aimed to evaluate the association of normal and elevated ORP levels with conventional sperm parameters in patients with unexplained and male factor infertility. A further aim was to investigate the correlations between seminal ORP and sperm parameters. We hypothesized that by establishing the effects of high ORP levels on sperm parameters, it would be possible to identify patients likely to have seminal oxidative stress, based on routine semen analysis and determine if further ORP testing is needed.This was a retrospective cohort study conducted at Kocaeli University Faculty of Medicine Assisted Reproductive Technologies (ART) Clinic, Kocaeli, Turkey. The Institutional Review Board of Kocaeli University Faculty of Medicine approved the study .The study population included men attending the ART clinic for infertility evaluation between January and September 2019. Men providing a semen sample for simultaneous evaluation of sperm parameters and ORP were included. All patients underwent andrological evaluation including medical history, physical examination and sperm analysis and their partners were assessed for female infertility factors including tubal occlusion, and evidence of uterine pathologies and/or ovulatory disorders. Men with a diagnosis of a sexually transmitted disease, a history of chemotherapy or radiotherapy or a loss of sample during collection were excluded from the study. Men using antioxidant supplementation for any reason were also excluded.6per mL and one normozoospermic patient with a varicocele evident during a Valsalva maneuver were considered as having male factor infertility. The remaining 18 normozoospermic patients had unexplained infertility .Between January 2019 and September 2019, a total of 58 men were eligible for the study. Of these, 23 were normozoospermic and 35 had altered semen characteristics according to the World Health Organization (WHO) 2010 criteria . Four no6sperm/mL, as established by Agarwal et al. was used  and high sORP values (study group).To identify normal and high ORP levels, a static ORP (sORP) cut-off value of 1.36 mV/10was used . Men wit6sperm/mL) and the percentage of A+B motility divided by 100% . The norming of sORP values to sperm concentration was performed and normed sORP values were expressed in mV/10All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) version 21.0 . Kolmogorov-Smirnov tests were used for the assessment of the normality of data distribution. Continuous variables with normal distribution were expressed as mean±standard deviation (SD) and continuous variables with non-parametric distribution were expressed as median and interquartile range (IQR). The comparison of numerical variables was performed using Student t-test for continuous variables with normal distribution and Mann-Whitney U test for continuous variables without normal distribution. Depending on data distribution, Pearson or Spearman's Rho correlation coefficients were used to test the association between numerical variables. A p-value <0.05 was considered statistically significant.6sperm/mL whereas the study group had a median sORP of 6.71 (2.35-21.17) mV/106sperm/mL.During the study period, 58 men presented who were eligible for the study. Of these, 23 (39%) had normal sORP values and constituted the control group and 35 (61%) had high sORP values and made up the study group. Baseline characteristics and comparison of sperm parameters between the control and study groups are presented in 6sperm/mL whereas male factor infertility patients had a median sORP value of 5.52 (1.42-19.32) mV/106sperm/mL. Male factor infertility patients had significantly higher seminal sORP values compared to unexplained infertility patients (p <0.001).When patients were grouped according to etiology of infertility; four of 18 (22%) patients with unexplained infertility had elevated seminal sORP and 31 out of 40 (77.5%) patients with male factor infertility had elevated sORP values. Median sORP value of unexplained infertility patients was 0.38 (0.28-1.07) mV/106sperm/mL whereas men with altered semen parameters had a median sORP value of 6.50 (1.84-21.17) mV/106sperm/mL (p <0.001).When patients were grouped according to WHO semen analysis reference values, normozoospermic patients had significantly lower sORP values compared to non-normozoospermic ones. Normozoospermic men had a median sORP value of 0.420 (0.340-1.480) mV/106sperm/mL had significantly lower total sperm count (TSC) (p <0.001), sperm concentration (p <0.001) and TMSC (p <0.001). In addition, progressive motility and fast forward progressive motility were significantly reduced in the study group .Men with sORP values >1.36mV/10Semen volume (p=0.399), total motility (p=0.302), non-progressive motility (p=0.081), immotility (p=0.163) and round cell numbers (p=0.689) did not differ significantly between the study and control groups. The mean total motility was above the WHO lower reference limit (40%) in both the control and study groups.Correlations between sperm parameters and sORP are presented in ORP, measured by the MiOXSYS system, is a direct measure of oxidative stress in semen and evaluates the balance between all oxidants and all available antioxidants in the sample . In thisOxidative stress has been shown to play a direct role in the etiology of male infertility . SeveralRecently, a new entity, male oxidative stress infertility (MOSI), has been proposed to define infertile men with seminal oxidative stress and the authors suggested ORP as the clinical biomarker of MOSI . AlthougCorrelation analysis of ORP levels with TSC showed a strong negative correlation. Sperm concentration also negatively correlated with sORP. Our findings confirm previous results , 8, 13. A prospective cohort study evaluating the effects of oxidative stress on sperm plasma membrane integrity found that hydrogen peroxide caused a dose-dependent decrease in sperm motility . AgarwalThe relationship between oxidative stress and sperm motility can be explained by the pathological processes which occur in spermatozoa in the presence of ROS. Excessive levels of ROS initiate a process leading to lipid peroxidation. As the sperm plasma membrane is rich in lipid components, it is a potential target for oxidative stress . It has Our analysis showed that men with higher sORP had lower TMSC. In addition, there was a strong negative correlation between sORP and TMSC. The 5th Edition of the WHO manual classifies the quality of semen based on three sperm parameters: number; motility; and morphology . AbnormaSpermatozoa are protected from oxidative stress by several antioxidants. Once oxidative stress is diagnosed as the underlying cause of male infertility, there are available options for treatment. Apart from the identification of possible causes of oxidative stress, lifestyle modifications and avoiding environmental exposure, oral antioxidants are an effective treatment option with low cost and relatively minor side effects . VariousOur research has some limitations. The first is the retrospective design of the study. The second is we did not evaluate the correlation between sperm morphology and sORP due to high interobserver variability in the assessment of morphology and low predictive value of morphology for pregnancy success . ImportaSemen analysis is the initial step in andrological evaluation. However, seminal ROS measurement is not carried out routinely as part of male infertility workup. Given that elevated ROS levels have been demonstrated in patients with male factor infertility and also unexplained infertility, seminal ROS evaluation may need to be adopted more widely during male fertility assessment.It is essential to diagnose oxidative stress-related infertility since there are effective treatment options leading to improved pregnancy rates. As it is not feasible to perform seminal ROS analysis in every patient, identification of sperm parameters associated with elevated ROS levels will be of benefit. Our analysis has shown that total sperm count, sperm concentration, progressive motility, and TMSC are related to seminal ROS. The presence of oligozoospermia, reduced progressive motility or low TMSC in a sperm analysis should raise the suspicion of elevated ROS and warrants seminal ROS testing.


Background and Objectives: This study aimed to assess the level of selected biochemical parameters in venous blood and their potential effects on the development of pressure ulcers in patients treated in intensive care settings. Materials and Methods: Fifty patients hospitalised in an intensive care unit (ICU) were enrolled for the study. The methods used included controlled observation, literature review and medical record analysis. The observation protocol applied in the study consisted of two parts comprising the basic information, sociodemographic data, results of laboratory tests  as well as the Braden Scale for Predicting Pressure Ulcer Risk. Results: The subjects presented moderate to high risk of pressure ulcers, reflected by the mean score of 8.18 ± 1.3 points, with minimum and maximum scores of 6 and 12 points, respectively. Normal albumin level was identified in only five subjects (10.0%) while 45 subjects (90.0%) were found with results below the norm. A statistical relationship was observed between such variables as albumin concentration (p < 0.01) and total protein level (p = 0.007). The findings show a strong correlation between the score in the Braden Scale and the level of albumins (R = 0.55). Conclusions: In our study, lower concentrations of albumins and total proteins correspond to a greater risk of pressure ulcers. Patients hospitalised at intensive care units (ICU) are particularly at risk of adverse health-related consequences and systemic complications . A serioThere is a direct relationship between nutritional status and the development of pressure ulcers. Prevention of tissue damage caused by simple pressure and a lack of movement involves systematic, multistage activities performed mainly by nursing personnel. Simple procedures designed to relieve the pressure, to change the position of the body and to keep the skin clean in practice are carried out on a daily basis. The process of maintaining adequate nutritional status through personalised selection of dietary energy supply as well as by the administration of enteral/parenteral feeding is a much more advanced model, requiring the cooperation of specialists in various disciplines . Basic laboratory tests to assess nutritional status include serum levels of albumin, prealbumin, transferrin, absolute lymphocyte count (ALC), C-reactive protein (CRP) and the retinol binding protein (RBP). Current research indicates that opinions regarding their usefulness vary. The main controversy relates to the numerous factors disturbing the interpretation process, such as the coexisting inflammatory process . AccordiMonitoring and optimised nutritional management based on changes in body composition and biochemical parameters are among the many factors reducing the risk of pressure ulcers. By introducing reliable assessment of nutritional status  as well as analysis of data from prophylactic treatments, it is possible to effectively prevent pressure ulcers in patients in the ICU ,6. ReseaThe present study was designed to assess selected biochemical parameters of venous blood and their potential effects reflected by the development of pressure ulcers in patients treated in an intensive care setting. The study was conducted over a period of three months from September 2018 to January 2019. The study protocol was approved by the ethics committees of the involved institutions (Bioethics Commission at the University of Rzeszow: Decision no. 2018/01/07f on 7 January 2018) and performed according to the Declaration of Helsinki.n = 5), being feverish (n = 12) during the observation period or finding incomplete history in the remaining 3 patients. Additionally, the subjects were divided according to the risk of developing a pressure ulcer . Mean hospitalisation time was 10.86 days, with a 70% occupancy rate  scale, those with a score of 10 or less on the GCS (Glasgow Coma Score), those with circulatory failure without congestive features, those with cancer and those 18 years of age or older. The set of criteria excluded those whose stay in the ICU exceeded 48 h, patients treated in other clinics, those with circulatory failure, those with kidney failure, those with sepsis and those below 18 years of age. Finally, fifty subjects qualified for the study were recruited among patients receiving treatment at the ICU of an intentionally selected hospital within the Podkarpackie Region. The study group comprised 18 women (36.0%) and 32 men (64.0%). The subjects ranged in age from 19 to 96 years, with the mean age amounting to 58.6 years ± 21.22 years. The patient observation protocol developed for the needs of the study consisted of two parts. Part I comprised information related to sociodemographic data, health status and medical history, as well as GCS assessment of the level of consciousness, and assessment based on the Braden Scale for Predicting Pressure Ulcer Risk. The Braden Scale is a validated tool enabling assessment of pressure ulcer risk in ICU patients; it consists of six subscales assessing mobility, sensory perception, skin moisture, activity, friction and shear as well as nutritional status. Possible scores in the subscales range from 1 to 3 or 1 to 4; hence, the total score on the Braden Scale is in the range of 6–23; the lower results correspond to greater risk of pressure ulcers. Based on the total score, the risk is classified as very high (<9), high (10–12), moderate (13–14), low 15–18) or minimal (19–23). The authors applied a cut-off point of <9 to identify patients significantly at risk of pressure ulcers ,8. or minimPart II of the protocol contained information related to laboratory tests: albumin and total protein levels in blood serum, CRP (C-reactive protein), PCT , HGB (haemoglobin), WBC (white blood cells). Nutritional status was assessed based on albumin level <3.5 g/dL) shown in the patient’s record, qualifying for nutritional therapy. The patients were assessed for pressure ulcer risk with the Braden Scale  g/dL sho. A totalp-value below 0.05 was considered to be statistically significant. The statistical power of our study was 0.88, which is over the lowest recommended power of 0.88.Statistical analysis was performed using Statistica 13.1 software . In terms of descriptive analyses, categorical variables were described as numbers and percentages. Data were reported as mean with a 95% confidence interval (CI) for quantitative measures, and as percentages for all categorical variables. Distribution normality was assessed using the Shapiro–Wilk test. The discrepancies in albumin levels in the four groups were assessed by the one-way ANOVA test, and the relationships between the laboratory test results and the Braden Scale were assessed according to the Spearman’s rank correlation test. A Most subjects were hospitalised in the ICU due to conditions resulting from extensive neurosurgical procedures within the skull (42%), injuries of multiple organs (22%), conditions following sudden cardiac arrest (SCA) (14%), as well as inefficiency of organs, including respiratory failure due to pneumonia (24%). The comorbidities occurring in the study group, according to the medical records, included: diabetes (36%), hypotension (28.0%), hypertension (46%), atherosclerosis (58%), alcohol dependence (18%) and other conditions  and multiple-organ failure) (28%). Detailed information is shown in The value of acute-phase protein (CRP reference range of 0.0–5.0 mg/L) at the time of the patients’ admission to ICU on average amounted to 129.56 mg/L ± 100.18 mg/L. Quality assessment of CRP showed normal values in four subjects (8.0%) and rates significantly above the normal range in 46 patients (92.0%). The value of procalcitonin (PCT reference range of 0.00–0.50 ng/mL) in the relevant group of patients on average amounted to 5.26 ng/mL ± 14.3 ng/mL and ranged from 0.04 ng/mL to 84.63 ng/mL. As for the quality of PCT, normal results were identified in 23 subjects (46.0%) while 27 subjects (54.0%) were found with values outside the normal range. The mean value of haemoglobin (HGB reference range of 13–17.5 L g/dL) in the study group amounted to 10.75 g/dL ± 2.07 g/dL. The test results showed normal haemoglobin levels in eight subjects (16.0%) while the results of 42 subjects (84.0%) showed abnormal values, ranging from 7.10 g/dL to 12.6 g/dL; these were patients with injuries. The mean level of white blood cells (WBC reference range of 4–11 103/with the µL) amounted to 11.64 103/µL ± 4.52 103/µL g/dL. p = 0.004). p = 0.413) The lowest level of albumins in the blood occurred in the patients who had the highest CRP. Based on the albumin levels upon the patients’ admission, normal nutritional status was identified in five subjects (10.0%), mild malnutrition was found in nine subjects (18.0%), while 19 subjects (38.0%) and 18 subjects (36.0%) presented moderate and severe malnutrition, respectively. The values of albumin concentrations and CRP in the three groups did not differ significantly (p = 0.039). Statistically significant differences were identified between the scores of Group II (injuries of multiple organs) and the results for patients in Group III (condition due to SCA) p = 0.038. The highest scores on the Braden Scale were found in Group II (81.84), and the lowest in Group III (78.86)  . p < 0.001) and total protein level (p = 0.007) versus pressure ulcer risk. Detailed listing of the specific factors is shown in The value of total protein amounted to 5.09 g/dL ± 0.98 g/dL. The findings show a relationship between the level of selected biochemical parameters and pressure ulcer risk. Statistically significant differences were found between such variables as albumin concentration  corresponded to higher albumin and total protein values. The correlation of the Braden score to albumin level was strong (R = 0.55) and to total protein level was moderate (R = 0.38) . Malnutrition among hospitalised patients is still a common problem. It is estimated that 35–55% of patients admitted to hospitals are malnourished and approximately 20% of these require immediate nutritional therapy ,10. MoniThe performed tests showed normal albumin levels in 10% of patients, with simultaneous body weight loss. It is important to note that patients with the lowest albumin values also had the highest reported CRP values. This may suggest mobilisation of this protein type during the production of acute-phase proteins. Serum albumin is considered to be a hallmark of both inflammation and cachexia, or possibly malnutrition. However, because dietary restrictions do not always lead to serum albumin reduction, it has been suggested that the significance of inflammation outweighs the effects of malnutrition when measuring serum albumin levels .Serra et al. assessed albumin levels in critically ill patients hospitalised in ICUs. They established that reduced concentrations correlated with incidence of presser ulcers. Protein supplementation and albumin level maintained at 2.8 g/dL or more favourably affected the process of pressure wound healing . SimilarOpinions regarding the nutrition of critically ill ICU patients were presented by Fontes et al., who emphasised the difficulties related to the diagnosis of protein–energy malnutrition (marasmus). The authors carried out a study involving 185 critically ill patients in order to determine which method of assessing nutritional status is more effective. For this purpose, the researchers applied anthropometric and laboratory methods as well as a Subjective Global Assessment (SGA) scale. Based on the laboratory tests, protein–energy malnutrition was diagnosed in 100 (54%) patients, including 23 (12.4%) with severe malnutrition. The findings showed that malnourished patients were significantly more often readmitted to the ICU, and the mortality rate was 8.12 times higher compared to the patients with normal nutritional status. A comparison of the different methods for their consistency in diagnosing malnourishment showed their varied usefulness [A study focusing on pressure ulcer risk assessment was also conducted by Terekeci et al., who investigated a group of 142 patients in ICUs. The researchers showed that the factors contributing to the incidence of pressure ulcers include age, low score on the Norton scale, duration of hospitalisation, low arterial blood pressure and hypoalbuminemia .A study by Jaul et al. focusing on the development of pressure ulcers in patients with comorbidities showed that chronic conditions and other coexisting complicating factors associated with immobility, ischaemia and malnutrition contribute to the incidence of pressure ulcers, not only in hospital but also in the home setting and in care facilities . The curCramer et al., in their research related to methods of predicting the incidence of pressure ulcers at ICUs, applied electronic health records (EHR) to define patients’ profiles. The process took into account such data as Braden score, results of specific laboratory tests, diagnostic codes and the patients’ overall condition. The authors showed that initial EHR assessment could be an effective tool used in the screening of patients admitted to ICUs, allowing the identification of patients particularly at risk of pressure ulcers .In their study focusing on the optimisation of nutritional care in the case of pressure injuries in hospitalised patients, Citty et al. report that more than one in two patients are affected by malnutrition, which contributes to the suppression of immune processes in the body, leading to the deterioration of the overall condition and promoting the development of pressure ulcers. Measures focusing on the prevention of pressure ulcers are necessary and multidimensional. The authors particularly emphasise the benefits of adequate nutritional care and report improved progress in pressure ulcer healing in patients subjected to such measures .Intensive care is intended to create optimal chances for survival in critically ill patients who are in a potentially reversible, life-threatening condition. Management of critically ill patients requires highly specialised therapeutic and treatment procedures, including nutritional care. Traditionally, nutritional intervention in the case of critically ill patients involves the provision of nutrients in order to alleviate the effects of catabolic processes and to sustain fat-free body mass. Today, however, nutritional care is intended to reduce cell damage due to oxidative stress, and to beneficially modulate the immune response ,27. PrevOur study is obviously not free from some limitations. The presented results involve a small group of critically ill patients with additional burden of chronic disease, which may be reflected in the obtained study results and subsequent conclusions. Due to the fact that a complete blood cell count was not feasible, the study did not report total leukocyte count (TLC) values, which are the basic indicator in nutritional status assessment. Having considered the above, further studies would allow for a thorough analysis of the presented variables.The study demonstrates that concentrations of albumins and total proteins correspond to a greater risk of pressure ulcers. The method based on the screening of patients with the Braden Scale and the monitoring of specific biochemical parameters can effectively be used to predict pressure ulcer risk in patients hospitalised in ICUs.


N-oxide (TMAO), created by gut microflora from dietary l-carnitine and choline, cleared by the kidney, has been implicated in the causation of cardiovascular diseases in patients with chronic kidney disease. However, whether it associates with hospitalization risk for these patients is unclear.Hospitalization is a significant outcome measurement for maintenance hemodialysis pantients. Trimethylamine-In this study, 69 patients undergoing outpatient dialysis were enrolled. Enzyme-linked immunosorbent assay was used to quantitate the baseline plasma TMAO levels in patients. The patients were divided into a high TMAO level group (TMAO ≥ 15 μmol/L) and a low TMAO level group (TMAO < 15 μmol/L). During the 1-year follow-up, 1-year dialysis-related data and all-cause hospitalization events were recorded.p = 0.0004). After adjustment age, sex, CK-MB and albumin, the results of multivariate Cox proportional hazard analysis showed that high TMAO level was an independent risk factor for hospitalization in maintenance hemodialysis patients.The incidence of hospitalization events was significantly higher in the high TMAO level group than in the low TMAO level group (91 per 100 patient-year vs. 32 per 100 patient-year). The Kaplain–Meier survaial analysis showed that the incidence of hospitalization events in the high TMAO level group was significantly higher than that in the low TMAO level group (log-rank TMAO is an independent risk factor for hospitalization events in patients receiving maintenance hemodialysis. It may be a new therapeutic target for improving the outcomes of these patients. Chronic kidney disease (CKD) is a global public health concern and is a particularly serious problem in developing countries . CompareN-oxide (TMAO), are intimately associated with the cardiovascular disease outcomes in patients with CKD [Recently, some studies have shown that protein-binding toxins synthesized by the gut microbiota, such as trimethylamine-with CKD . TMAO iswith CKD .The gut with CKD ,11. TMAOwith CKD ,13. As Twith CKD ,15. Howewith CKD ,17. TherHospitalization is a significant outcome measurement because it provides insight into the morbidity and the cost of treatment among dialysis patients . CurrentA total of 69 patients undergoing outpatient maintenance hemodialysis in the hemodialysis center of Fudan University Affiliated Huashan Hospital North Hospital were included in this study. We excluded the subjects who took broad-spectrum antibiotics within one week and with malignant tumor whose expecting life were less than one year. All patients were received three times hemodialysis a week. Each session is four hours. The patients were followed up from 1 June 2017 to 31 May 2018 for all-cause hospitalization events. The study protocol was approved by the Ethics Committees of Huashan Hospital .Demographic and dialysis-related data were collected: age, sex, body mass index, vascular access, dialysis vintage, blood pressure before and during dialysis, comorbidities, and the increase in body weight during dialysis .g at 4 °C for 15 min, and then the supernatant was collected. Enzyme-linked immunosorbent assay  was employed to measure plasma TMAO levels.Venous blood was collected from the 69 patients in fasting and resting status before mid-week dialysis following enrollment. The blood samples were centrifuged appropriately to obtain plasma samples, which were stored at −80 °C. Laboratory indexes were detected using the blood samples, including blood cell count, hemoglobin (Hb), albumin (Alb), prealbumin, creatine kinase isoenzyme (CK-MB), troponin I (TnT), N-Terminal pro-brain natriuretic peptide (NT-proBNP), β2 microglobulin, blood urea nitrogen (BUN), creatinine (Scr), high sensitivity C-reactive protein (hs-CRP), transferrin saturation (TSAT), intact parathyroid hormone (iPTH), blood calcium (Ca), and blood phosphorus (P), total cholesterol (CHO), low-density lipoprotein cholesterol (LDL), etc. A 5 mL volume was collected from the median cubital vein of the patients into an EDTA tube, centrifuged at 12,000 × All-cause hospitalizations were documented. Cardiovascular hospitalizations were defined as hospitalizations for myocardial infarction, ischemic heart disease, heart failure, arrhythmias, stroke and peripheral vascular event. The hospitalizations for fistular dysfuntion were documented. The events of autologous or graft internal fistular dysfunction included 1) the reduction of flow rate ; 2) thrombosis; 3) occlusion; 4) infection. The hospitalization rates defined as the number of admissions divided by 100 person years (PY) of follow-up.t-test or Mann–Whitney U test  was used to compare the differences in continuous variables, and the Chi-square test or Fisher’s exact test was used to compare categorical variables. The patients were divided into the high TMAO group (TMAO ≥ 15 μmol/L) and low TMAO group (TMAO < 15 μmol/L) according to the cutoff point. The cutoff point of serum TMAO was calculated by obtaining the highest Youden index. The cumulative incidence of hospitalization was described using the Kaplan–Meier method and were statistically tested with the log-rank test. Cox proportional hazard model was used to analysis the impact of baseline characteristics, laboratory indexes and TMAO on time to hospitalization. For arteriovenous fistula disfunction and cardiovascular event, Cox proportional hazard analysis was not perfomed because of the very small number of these events. A difference of p < 0.05 was considered to be statistically significant. The SPSS 21.0 statistical software  was used for data processing and analysis .Continuous variables were expressed as mean ± standard deviation or median (interquartile range), and categorical variables are expressed as number and percentage. Student’s n = 27, 39.1%), hypertensive nephropathy , polycystic kidney disease , diabetic nephropathy , obstructive nephropathy , and other causes . Baseline characteristics were well balanced between the groups. There were no statistical differences in the markers of myocardial injury, hs-CRP, hemoglobin, β2 microglobulin, prealbumin, albumin, predialysis Scr, predialysis BUN, calcium, phosphorus, and iPTH levels, iron metabolism, and lipids between the two groups  men and 33 (47.8%) women. The mean age was 61.28 ± 11.99 years, and the median dialysis vintages was 37 (26.5–81) months. The causes of ESRD included chronic glomerulonephritis , cardiovascular disease events , parathyroidectomy , pneumonia , urinary tract infection , lung cancer  and depression . The causes of hospitalization in the low TMAO group included the incidents of arteriovenous fistula disfunction events , cardiovascular disease events , pneumonia , urinary tract infection , parathyroidectomy , gastric ulcer , uterus cancer  and car accident .There were total 35 hospitalization events in both group during one year follow-up, 20 events for the high TMAO level group and fifteen events for the low TMAO level group. The total hospitalization rates (per 100 patient-years) were 91 in the high TMAO group and 32 in the low TMAO group. The causes of hospitalization in the high TMAO group included the incidents of arteriovenous fistula disfunction events (p = 0.0004) (p = 0.042). (p = 0.048). On multivariate Cox proportional hazard analysis included TMAO, CK-MB, albumin, high TMAO level was consistently retained as indepent risk factors for hospitalization  . Univari 0.042).  After adlization .via dysregulation of lipid handling and macrophage function as well as directly causing vascular inflammation and platelet activation leading to thrombosis. Elevated TMAO levels may lead to the occurrence and development of certain chronic diseases such as atherosclerosis, hypertension, and cardiac insufficiency. Tang et al. [Recent studies found that the enterogenous toxin TMAO is closely associated with the occurrence and development of cardiovascular events in patients with uremia . In receg et al.  further g et al.  study, tg et al. , and foug et al.  considerg et al. , pneumong et al. , tumor fg et al. , and othIn this study, we enrolled 69 patients undergoing outpatient hemodialysis and divided them into the high and low TMAO level groups. We conducted follow-up evaluations of hospitalization events in these patients over one year. The result showed that the maintenance hemodialysis patients with higher TMAO level had higher risk of hospitalization. The arteriovenous fistula dysfunction and cardiovascular disease were the top two causes of hospitalization for both of groups. For the short follow-up, the number of cardiovascular events was small and we did not observe the differences of cardiovascular events between two groups. However, we observed that the dialysis patients with high TMAO were more likely to suffer from vascular access dysfunction than those with low TMAO in one-year follow-up, although they had no differences in the complication of hypertension and diabetic mellitus, level of incidence of interdialytic hypotension, calcium, phosphorus and iPTH, and low-density lipoprotein. On one hand, it demonstrated TMAO might take part into the vascular access sclerosis or thrombosis. On the other hand, because TMAO is both an osmolyte and a protein stabilizer, it has multiple effects on the body and tends to cause various diseases in patients, which increases hospitalization events . Our stuThe multivariate Cox regression analysis showed that the TMAO level is an independent risk factor for hospitalization in patients undergoing hemodialysis. TMAO is a potential marker for the clinical assessment of outcomes in these patients. At present, some researchers believe that TMAO is a new therapeutic target for improving the outcomes of patients with uremia .This study has some limitations. First, the sample size is small. The second limitation is the short follow-up period, which translates to few cardiovascular events. The third limitation is the lack of dietary data of the patients. Whether the timing of blood sample collection and the type of food intake have any effects on the quantitation of TMAO levels remain unclear.In summary, our study has proven that TMAO level is an independent risk factor for all-cause hospitalization events in patients undergoing maintenance hemodialysis. Further studies are needed to determine whether decreasing TMAO levels will slow the progression of vascular disease and improve outcome in these patients.