Hypertensive emergencies (HE) represent high cardiovascular risk situations defined by a severe increase in blood pressure (BP) associated with acute, hypertension mediated organ damage (A-HMOD) to the heart, brain, retina, kidneys, and large arteries. Blood pressure values alone do not accurately predict the presence of HE; therefore, the search for A-HMOD should be the first step in the management of acute severe hypertension. A rapid therapeutic intervention is mandatory in order to limit and promote regression of end-organ damage, minimize the risk of complications, and improve patient outcomes. Drug therapy for HE, target BP, and the speed of BP decrease are all dictated by the type of A-HMOD, specific drug pharmacokinetics, adverse drug effects, and comorbidities. Therefore, a tailored approach is warranted. However, there is currently a lack of solid evidence for the appropriate treatment strategies for most HE. This article reviews current pharmacological strategies while providing a stepwise, evidence based approach for the management of HE. Hypertensive emergencies (HE) are defined by a rapid increase in blood pressure (BP) with a systolic value greater than 180 mmHg and/or a diastolic value greater than 120 mmHg, often associated with neurologic, cardiovascular, or renal injury. This organ involvement is currently known as acute hypertension mediated organ damage (A-HMOD) ,4,5. TheThe most frequent clinical presentations of HE are stroke , followed by pulmonary oedema (35%) and coronary syndromes (25%) , which hThe choice of a therapeutic strategy, including the class of antihypertensive drugs as well as the timeline for BP reduction, varies according to the type of A-HMOD, previous comorbidities, specific drug pharmacokinetics, or possible adverse reactions to a certain drug.Therefore, a tailored approach is warranted. However, there is currently a lack of solid evidence for the appropriate treatment strategies for most HE. This article reviews current pharmacological strategies while providing a stepwise, evidence based approach for the management of HE.A clutter of terms has been used to describe clinical situations associated with increased BP such as HE, hypertensive urgencies, hypertensive crises, or uncontrolled hypertension. The current terminology, however, has retained only the terms HE and uncontrolled hypertension, which can now describe the whole clinical spectrum of acutely elevated BP .Hypertensive emergencies are defined as situations where a severely elevated BP, usually a systolic value higher than 180 mmHg and/or a diastolic value higher than 120 mmHg, is associated with acute, life-threatening organ damage in any of the following key organs: brain, arteries, retina, kidney, and/or heart ,12,13,14The distinction between these two clinical entities is essential because of the major differences in management and treatment . BrieflyWhatever the cause or clinical presentation may be, two statements are to be remembered. First, there is a lack of evidence from randomized controlled trials to establish the best therapeutic approach or the optimal drug in specific situations. Secondly, BP reductions should be obtained gradually, in a controlled manner, without compromising organ perfusion .Acutely increased BP is a frequent reason patients visit emergency departments (ED). For instance, in a survey of data collected over three years in 1,290,804 adult patients at 114 acute care facilities, systolic BP values higher than 180 mmHg ware present in almost 14% of the cases . The perSeveral clinical studies have been carried out to identify the most common predisposing factors leading to HE. These studies indicate that the most relevant factors responsible for the rapid elevation of BP are low adherence to antihypertensive drug therapy, discontinuation of BP-lowering drugs, abuse of illicit substances and recreational drugs, and poor control of common risk factors  ,25. In aThe importance of an appropriate therapeutic strategy is underlined by the increased in-hospital and out-of-hospital mortality of patients presenting with HE. Recent studies have reported a 12-month mortality rate ranging from 12% to 38.9% . MoreoveThe initial assessment should incorporate anamnestic information and physical examination as well as paraclinical evaluation, including imaging tests. A prompt and fast evaluation is critical to limit morbidity and mortality in hypertensive emergencies.A rigorous medical history should identify details regarding duration and severity of preexisting hypertension and whether HMOD has been previously identified. Antihypertensive medication, history of BP control, and intake of over-the-counter drugs or illicit drugs are important aspects of the medical history.Blood pressure should be monitored, both in supine and standing positions, as well as in both arms to assess the possibility of aortic dissection if it is found to be significantly different . PhysicaAll patients with suspected HE will be evaluated through usual investigations such as a basic metabolic panel, complete blood count, electrocardiogram, urinalysis, and chest X-ray. Further specific investigations should be based on symptoms and aligned with each associated condition’s differential diagnosis. For example, a patient presenting with altered mental status and BP > 220/120 mmHg will require brain imaging by computed tomography to assess for intracerebral hemorrhage or hypertensive encefalopathy. If neither is present, and there is no another explanation for the altered mental status, magnetic resonance imaging may be needed . Likewis2 and waist circumference values <94 cm in men and <80 cm in women); a healthy balanced diet with a high intake of vegetables, fruits, fish, and unsaturated fatty acids and a low intake of red meat and saturated fatty acids; constant physical activity (at least 30 min of moderate dynamic exercise on at least 5 to 7 days per week); and cessation of smoking [Preventing the occurrence of HE should be as important as the treatment itself. Therefore, implementing the main guideline recommended interventions for hypertension control is the key to such a prevention strategy. The main pillars of HTN control and preventions of the acute rise of BP are substantial lifestyle interventions and pharmacological management. The most important lifestyle changes that should be recommended are salt restriction (<5 g per day); reduction of alcohol consumption ; weight reduction  for close monitoring. The target is not to achieve a particular BP value, but to preserve organ perfusion and to prevent hypertensive target organ injury . ComorbiA general goal could be lowering BP in a controlled manner with a systolic BP reduction of no more than 25% within the first hour, followed by a gradual reduction to 160/100 mmHg within the next two to six hours, before cautiously reducing the BP to normal over the next 24 to 48 h [The most efficient drugs listed for HE treatment include nicardipine, labetalol, esmolol, and clevidipine. Nitroprusside was a pillar of treatment for many decades, but similar efficacy is shared by nicardipine and clevidipine, which are easier to titrate and present without risk of cyanide toxicity ,34,35,36Pharmacological therapies are available only in about 30% of the diseases identified, and many biological targets for numerous diseases are yet to be identified ; therefoIn an intensive care unit setting, nicardipine is a more effective antihypertensive agent than labetalol, with a better adverse effects profile, associated with less hypotension, bradycardia, and atrioventricular block, resulting in lower rates of drug discontinuation .A retrospective study involving 90 patients presenting with acute stroke and hypertension demonstrated that nicardipine is a viable alternative to labetalol, with similar tolerability and a trend towards less variability in BP response following nicardipine . MoreoveA study comparing cerebral hemodynamics in malignant hypertension demonstrated that both labetalol and nitroprusside reduce BP adequately, but labetalol reduced both systemic and cerebral vascular resistance, whereas sodium nitroprusside reduced the systemic vascular resistance rather than cerebral vascular resistance with a larger rate of reduction in the middle cerebral artery, which suggests a preferential blood flow to the low resistance systemic vascular bed rather than the cerebral vascular bed .Another study randomized 226 patients with acute hypertension to intravenous nicardipine or intravenous labetalol, which showed that patients treated with intravenous nicardipine are more likely to reach the specified BP goals within 30 min than those treated with intravenous labetalol .Current available data do not provide enough evidence suggesting that one specific intravenous (IV) antihypertensive agent is superior to another, with the possible exception of neurological HE, in which treatment recommendations are more evidence based with dihydropyridine agents such as nicardipine, clevidipine, and α/β blocker—labetalol as the most efficient agents .After achieving the target BP, switching to oral therapy is advised. Some clinical situations require different management strategies, as discussed below See .Generally, when a moderate rise in systemic BP occurs, the mechanism of cerebral autoregulation intervenes, resulting in the vasoconstriction of cerebral arterioles in order to preserve a constant blood flow rate to the brain . In the Thus, a controlled and gradual decrease in BP is the cornerstone of hypertensive encephalopathy treatment. The initial management should be aimed at lowering the mean arterial BP by 20 to 25% in the first hours . A furthIf not properly treated, hypertensive encephalopathy and posterior reversible encephalopathy syndrome can evolve to cerebral hemorrhage, coma, and death. An appropriate and optimal treatment can lead to full recovery , which hManaging hypertension in acute ischemic stroke can be cumbersome because increased BP can be beneficial as a compensatory physiological regulation to inadequate localized cerebral perfusion pressure while increasing cerebral hemorrhagic risk . ReducinPatients with suspected ischemic stroke who are eligible for thrombolysis must benefit from a rapid BP reduction to less than 185/100 mmHg and further maintenance for at least 24 h to reduce the risk of intracranial hemorrhage . HoweverManagement of hypertension in patients following successful mechanical thrombectomy is still an area of study, current literature suggesting better outcomes when systolic BP is less than 160 mmHg, or even 140 mmHg . For patients not eligible for thrombolysis or thrombectomy, maintaining higher BP is advised, even as high as 220/120 mmHg to maintain cerebral perfusion with potentially reversible ischemia. In the first 24 h, a reduction of less than 15% can be considered safe and reasonable to pursue . Over thBlood pressure and coagulopathy management for intracranial hemorrhage and acute ischemic stroke are different; therefore, treatment should be started after the diagnosis is confirmed. Results from different large randomized controlled trials have been unable to formulate specific BP targets for patients suffering from spontaneous intracranial hemorrhage ,55.The INTERACT-2 trial, which enrolled patients within 6 h of symptom onset, demonstrated that reducing the systolic BP to less than 140 mmHg, rather than reducing it to only less than 180 mmHg, had slightly better functional outcomes . The ATABased on the available data, current guidelines have concluded that in patients presenting with hyperacute intracerebral hematoma (symptoms less than 6 h), lowering BP to less than 140 mmHg (but not lower than 110 mmHg) is advisable as it can lead to a reduction in hematoma expansion. Nonetheless, the magnitude of BP reduction should not be larger than 90 mmHg . There is currently a lack of evidence from randomized controlled trials to suggest an ideal drug for hypertension in the context of acute intracranial hemorrhage. Treatment should be started with an intravenous, rapid acting, easily titratable drug, such as clevidipine, labetalol, nicardipine, or urapidil . For insMyocardial infarction or unstable angina require an immediate recognition by performing an electrocardiogram and laboratory studies including measuring cardiac enzyme levels, oriented by a detailed medical history. A retrospective data analysis of 236 patients presenting with HE highlighted that patients with elevated cardiac troponin I levels had a nearly three-times higher risk of major cardiovascular or cerebrovascular events at two years follow-up versus patients with normal cardiac troponin I levels .Treatment of acute, ongoing, myocardial ischemia associated with severe BP elevations should be aimed at decreasing LV (left ventricle) preload and afterload while maintaining a low heart rate to provide adequate diastolic filling time and decrease myocardial oxygen demand. These can be achieved with the administration of intravenous nitroglycerin up-titrated for controlling the angina while rapidly lowering the systolic BP to less than 140 mmHg associated with intravenous β-blockers, usually esmolol or labetalol , which lThe selective α1 blocker urapidil is a good alternative for the management of hypertension in patients with acute coronary syndromes. In patients with ST elevation, myocardial infarction and percutaneous revascularization, urapidil improved coronary flow, myocardial perfusion, and LV function, were beneficial effects that were associated with an increased production of nitric oxide .Patients with acute coronary syndromes commonly receive anti-platelet medication, which increases the risk for cerebral hemorrhage in the presence of elevated BP, thus adequate control of BP values is a mandatory step . NonetheAcute heart failure and acute pulmonary edema are observed in up to 23% of ED visits for acute severe hypertension . These pThe BP should be lowered by about 20 to 25% within minutes to 1 h, then gradually to 160/100 mmHg within the next 2 to 6 h, and finally returned cautiously to normal over the next 24 to 48 h .A study randomized 104 patients with acute heart failure and hypertension to receive intravenous clevidipine versus standard-of-care intravenous antihypertensive drugs (87% intravenous nitroglycerin or nicardipine). The study showed that the target BP level was reached in 71% of patients treated with clevidipine versus 37% treated with the latter two. Clevidipine was also more effective at improving dyspnea at 45 min .Urapidil is a good alternative to nitroglycerine in patients with acute heart failure. The NITURA study showed a more pronounced decrease in BP and an improved respiratory and metabolic outcome in patients with acute pulmonary edema receiving urapidil versus nitroglycerine .Another prospective study comparing the efficacy of nicardipine and nitroprusside in HE presenting with acute pulmonary edema demonstrated that there were no time-dependent differences between the two groups, suggesting that nicardipine has similar therapeutic efficacy to sodium nitroprusside, at the same time being easier to administer .The annual incidence of all acute aortic syndromes, which include aortic dissection, is low in the general population, ranging from 4 to 6 cases per 100,000 persons/year, while in people older than 65 years, it increases to about 30 cases per 100,000 persons/year . MoreoveMedical therapy consists of controlling chest pain and administering the “anti-impulse therapy” represented by the rapid lowering of systolic BP to 100 to 120 mmHg with a concomitant reduction of heart rate to lower than 60 beats per minute ,69. ThisMalignant hypertension (M-HTN) is one the most severe forms of hypertension. As a HE, it can develop in patients with a known history of primary hypertension, but in most cases, up to 60%, it occurs de novo with no differences in signs, symptoms, or long-term survival . The fivThrombotic microangiopathy (TMA) results from hypertensive endothelial injury, which triggers platelets activation, trombi formation, microvessels obliteration, and disseminated intravascular coagulation .The HE involving TMA is similar to thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome. It is important to differentiate this disease from the former two, because antihypertensive treatment will usually improve TMA and associated renal failure, but thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome might require a specific treatment, such as plasma exchange and immune suppression in thrombotic thrombocytopenic purpura  or eculiThe first-line pharmacological treatment is with labetalol and nicardipine; alternatively, nitroprusside and urapidil can be used as a safe and effective treatment . The corPre-eclampsia can complicate 5 to 7% of pregnancies , with a Management requires a rapid initial lowering of systolic BP in the range of 140 to 150 mmHg and diastolic BP in the range of 90 to 100 mmHg . MedicalIn a recent meta-analysis, it was demonstrated that oral nifedipine can be considered as a first-line antihypertensive agent for reducing the risk of persistent high BP in pregnancy compared to intravenous hydralazine or labetalol, with no differences in the incidences of adverse effects, maternal or fetal outcomes, or maternal hypotension. For the same purpose, IV hydralazine was more effective than IV ketanserin in controlling BP during pregnancy, with no difference in the risk of maternal hypotension or maternal or fetal outcomes .Another systematic review reported that oral nifepidine has the highest therapeutic success in controlling the BP in pregnancy comparted to IV labetalol or IV hydralazine, while demonstrating no significant difference in the risk of adverse effects between these drugs . When the opportunity of switching to oral treatment arises, first choice drugs are methyldopa and long-acting nifedipine. Angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, direct renin-inhibitors, and sodium nitroprusside are contraindicated because of their teratogenic effects, and diuretics should be avoided because they reduce the placental blood flow .An undetected PPGL can have a variety of clinical presentations, including acute heart failure, acute coronary syndrome, aortic dissection, stroke, or eclampsia as first manifestation of the disease. Both plasma and urine tests of free normetanephrine and metanephrine are used for the screening of pheocromocytoma . These pα 1 blocking agents, either fentolamine or doxazosin, usually followed by a β blocker, is the first choice for achieving control of BP. The order should be as stated above, to avoid enhanced α1-mediated vasoconstriction. Labetalol is the only β blocker, which also has an α1 blocking effect when administered intravenously, that can be used without prior α1 blockade for the treatment of hypertensive emergencies. Rapidly acting diuretics should be discouraged, as patients suffering from PPGL have relative hypovolemia . In preoperative patients suffering from chronic hypertension, a thorough evaluation is mandatory to identify possible risk factors for HE. Adrenergic stimulation, postoperative pain, anxiety, and fluctuating intravascular volume can build up towards a perioperative HE. If it is not optimally treated, it can lead to increased bleeding risk and new HMOD . If BP tAs for the treatment agents, the utility of intravenous clevidipine, nitroglycerin, esmolol, or nicardipine is recognized ,86. ClevHypertensive retinopathy is a common finding at fundoscopy and is an important predictor of systemic morbidity and mortality due to HMOD . It has Flame-shaped hemorrhages and cotton wool spots, which suggest grade III retinopathy, and papillooedema, which suggests grade IV retinopathy, are a sign of microvascular dysfunction and impaired cerebral autoregulation and can be the only signs of an ongoing HE. These advanced forms of hypertensive retinopathy are associated with worse cerebral, renal, and cardiovascular outcome compared with hypertensive patients and no retinopathy . FundoscHypertensive emergencies, while a relatively rare reason for ED presentation, remains a major challenge for the practitioner due to its wide range of clinical patterns, diverse potential A-HMOD, and ability to negatively impact cardiovascular and cerebrovascular outcome. In this educational review, we summarized the current evidence-based knowledge and recommendations for the treatment of HE providing a A-HMOD-centered approach to allow the rapid recognition and proper treatment of these emergencies. The therapeutic strategy, including the magnitude and time course of BP decrease as well as the choice of antihypertensive drugs, should be individualized to the specific type of HE with the scope of limiting organ damage and improving prognosis.


Arterial hypertension is a worldwide public health problem. While it is currently diagnosed and monitored non-invasively using the oscillometric method, having the ability to measure blood pressure (BP) using a smartphone application could provide more widespread access to hypertension screening and monitoring. In this observational study in intensive care unit patients, we compared blood pressure values obtained using a new optical smartphone application  with arterial BP values obtained using a radial artery catheter (reference method) in order to help validate the technology.We simultaneously measured three BP values every hour for five consecutive hours on two consecutive days using both the smartphone and arterial methods. Bland–Altman and error grid analyses were used for agreement analysis between both approaches. The performance of the smartphone application was investigated using the Association for the Advancement of Medical Instrumentation (AAMI) and the International Organization for Standardization (ISO) definitions, which require the bias ± SD between two technologies to be below 5 ± 8 mmHg.Among the 30 recruited patients, 22 patients had adequate OptiBP™ values and were thus analyzed. In the other 8 patients, no BP could be measured due to inadequate signals. The Bland–Altman analysis revealed a mean of the differences ± SD between both methods of 0.9 ± 7 mmHg for mean arterial pressure (MAP), 0.2 ± 14 mmHg for systolic arterial pressure (SAP), and 1.1 ± 6 mmHg for diastolic arterial pressure (DAP). Error grid analysis demonstrated that the proportions of measurement pairs in risk zones A to E were 88.8% (no risk), 10% (low risk), 1% (moderate risk), 0% (significant risk), and 0% (dangerous risk) for MAP and 88.4%, 8.6%, 3%, 0%, 0%, respectively, for SAP.This method comparison study revealed good agreement between BP values obtained using the OptiBP™ and those done invasively. The OptiBP™ fulfills the AAMI/ISO universal standards for MAP and DAP (but not SAP). Error grid showed that the most measurements (≥ 97%) were in risk zones A and B.ClinicalTrials.gov registration: NCT04728477 Arterial hypertension is a leading predicting factor of poor health outcome worldwide, in both developed and developing countries –3. In 20The technological capabilities of our “smartphones” have evolved dramatically in recent years, which has led to the emergence of multiple health applications that can be used in the diagnosis, prevention, and management of several diseases , 9. NeweA new optical smartphone application for BP measurement (OptiBP™) has recently been developed by Biospectal  and tested against upper arm cuff oscillometry –19, but th, 2020 under the reference NCT04728477 .The Erasme Ethics Committee approved the study on February 2, 2021 under the reference A2020/665. The study took place between February 3 and April 1, 2021. We had written informed consent from each patient or their next of kin if a patient was unable to do it.This prospective study was registered on ClinicalTrials.gov on January 28We included all adult patients having invasive arterial BP monitoring using a radial artery catheter for at least 48 h. Exclusion criteria were patients with an inter-arm BP difference > 10 mmHg in systolic arterial pressure (SAP) measures using a brachial cuff, patient with dementia, psychological disorders, drug or alcohol abuse unless receiving mechanically ventilation, patient with atrial fibrillation and patient with finger lesions that would alter the correct capture of signals by the mobile phone.OptiBP™ is the name of the smartphone application used in the current study and it is an acronym of "optical blood pressure" . This software was deployed on a Samsung Galaxy S7 smartphone . Previous validation studies have been completed that describe how this technology estimates BP from pulse wave analysis of pulse oximetry signals . An algoThe Dräger Infinity Delta XL  was used to monitor patients during their ICU stay. The invasive arterial BP signal  was obtained using a radial artery catheter.Patients were managed according to standard practice throughout the study period. Before starting the study, the pressure transducer was zeroed or leveled and the dynamic response of the system was checked. When the patient was calm and not agitated, three BP values were simultaneously recorded every hour over a five-hour period using the two methods. This process was repeated the following day . The duration of each measurement was 30 s with one-minute break in between. The first three measurements were used as calibration with the following nine measurements used for analysis. At least one OptiBP™ value needed to be usable  at each time point in order for a patient to be included in the final analysis. The smartphone technology was used on the opposite arm to that of the radial artery catheter.No sample size was calculated for this study. However, the European Society of Hypertension  recommenPatient characteristics are presented as mean ± standard deviation (SD) or absolute number and percentage (%). SAP, diastolic arterial pressure (DAP), and mean arterial pressure (MAP) values obtained with the OptiBP™ were compared with invasive arterial measurements with Bland–Altman analysis by calculating the bias (BP of the test method minus BP of the reference method) together with SD, and 95% limits of agreement (mean of the difference ± 1.96 × SD) accounting for repeated measurements. We assessed the performance of the OptiBP™ with the ISO standards, which require the bias between the test and the reference method to be less ≤ 5.0 mmHg ± 8.0 mmHg .Error grid analysis recently proposed by Saugel et al.  was doneAll statistics were performed using Excel and MedCalc® Statistical Software version 19.6.4 , and the error grid analysis was done using Matlab .TM was able to capture at least one reliable BP value per measurement time point in 22 patients (73%) which were used for statistical analysis (8 patients (27% of the study collective) had inadequate OptiBPTM signals). Patient characteristics are shown in Table Thirty patients were enrolled in the study. Among them, the OptiBPThe bias ± SD, 95% limits of agreement between both methods were 0.9 mmHg  for MAP, 0.2 mmHg  for SAP, and 1.1 mmHg  for DAP , 10% (low risk), 1% (moderate risk), 0% (significant risk), and 0% (dangerous risk) for MAP and 88.4%, 8.6%, 3%, 0%, 0%, respectively, for SAP Fig. .Fig. 5ErOur results indicate that there is relatively strong agreement between BP values collected using the OptiBP™ technology and those collected with an arterial catheter for patients in the ICU. When looking specifically at which comparisons met AAMI standards, MAP and DAP values were both successful while SAP did not meet criteria. Additionally, 99% of measurement comparisons were in either risk zone A (no risk) or B (low risk) for MAP and 97% were in the risk zones A or B for SAP.There have been three previous studies investigating the OptiBP™ technology. The first study reported that the OptiBP™ measurements were accurate and precise compared to traditional double auscultatory oscillometric BP measurements in 50 patients measured in a hypertension department . The meaThe AAMI standards for non-invasive BP measurement state that, when comparing a new BP method with a reference method, a mean of the differences of less than 5 mmHg with a SD of ± 8 mmHg is clinically acceptable . It is iMoving beyond AAIM criteria and the Bland–Altman analysis, we wanted to assess the clinical relevance of the findings in order to better facilitate potential future application. We decided that an error grid analysis with various clinical risk zones to indicate the likelihood of potential harm if the OptiBP™ values were used. At least 97% of every SAP and MAP value was located in the "no risk" or "low risk” zones, while ≤ 3% of measurements lay in the moderate risk zone (which is slightly higher than in our previous study but this is understandable as the population in the present study was more severely ill).One notable strength of our current study is that multiple measurements at multiple times points were taken over a two-day study period in a population with expected variability in their blood pressure. However, the study also has weaknesses. Firstly, the initial calibration of the application requires a BP measurement with the reference method immediately before taking the measurements to be evaluated. As a result, all immediately subsequent BP values will most likely be quite similar to the recently recorded calibration measurement and any error in the method being tested would not be apparent. Secondly, the number of patients included in the study remains relatively small (30 patients) and the application provided measurements that could be analyzed in 73% of the included patients. It means that in 8 patients (27% of the study collective), no BP values could be measured. Reasons for inadequate signals are under investigation and may be multifactorial, such as artifacts related to poor positioning of smartphone on patient’s finger, inadequate signal due to bed / patient / smartphone movements, insufficient features recognition leading to signal non-processing by algorithm or morphological anomalies on finger of patient. However, this situation was anticipated given that the population tested was receiving intensive care, which likely effects peripheral vasculature. While not directly tested, judging the performance of OptiBP™ using results from ICU patients is not ideal as this population is often in poor general health, occasionally in the prone position, and potentially receiving vasoactive medications. This clinical setting is not what the algorithm was designed, trained or intended for, but our results still provide valuable information on the performance of the application because it is compared to an invasive gold standard in a population with higher BP variability than expected in the outpatient population. Thirdly, the portability (the ability of the application to be used on multiple smartphone models and operating systems) of the application needs to be addressed. Finally, among the patients included in this study, 64 had a hypertension during the study period, which means that 37% of patients did not have the condition for which this technology was developed. Moreover, as the sample size is relatively small, no subgroup analyses could be made (hypertension vs no hypertension or diabetes mellitus vs no diabetes mellitus).In conclusion, in ICU patients, we observed a good agreement between BP values obtained using the OptiBP™ and BP values obtained using the radial artery catheter. OptiBP™ values fulfilled the exigency of the AAMI/ISO for MAP and DAP and error grid analysis revealed that the most measurement pairs for MAP (≥ 97%) were in risk zones A (no risk) and B (low risk). However, these promising results should be taken with caution as in 8 patients, no BP values could be measured and calibration was still necessary for the remaining 22. This smartphone application will therefore need some technical improvements moving forward before any clinical integration.


Demographic variables significantly impact medication adherence. HRQOL was found to be deteriorating with a significant impact on mental health compared to physical health. Conclusions: Patients on maintenance dialysis for kidney failure have a significant burden of physical and mental symptoms, depression, and low HRQOL. Given the substantial and well-known declines in physical and psychological well-being among kidney failure patients receiving hemodialysis, the findings of this research imply that these areas related to health should receive special attention in the growing and expanding population of kidney failure patients.Background: Kidney failure is a global health problem with a worldwide mean prevalence rate of 13.4%. Kidney failure remains symptomless during most of the early stages until symptoms appear in the advanced stages. Kidney failure is associated with a decrease in health-related quality of life (HRQOL), deterioration in physical and mental health, and an increased risk of cardiovascular morbidity and mortality. This study aimed to evaluate the factors associated with decreased HRQOL and other factors affecting the overall health of patients. Another objective was to measure how medication adherence and depression could affect the overall HRQOL in patients with kidney failure. Methodology: The study used a prospective follow-up mix methodology approach with six-month follow-ups of patients. The participants included in the study population were those with chronic kidney disease grade 4 and kidney failure. Pre-validated and translated questionnaires  and assessment tools were used to collect data. Results: This study recruited 314 patients after an initial assessment based on inclusion criteria. The mean age of the study population was 54.64 ± 15.33 years. There was a 47.6% male and a 52.4% female population. Hypertension and diabetes mellitus remained the most predominant comorbid condition, affecting 64.2% and 74.6% of the population, respectively. The study suggested a significant ( Chronic kidney failure is a public health problem worldwide and can lead to conditions such as kidney failure and cardiovascular problems . In diffConsidering the high incidence of kidney failure and the challenges posed by the patients undergoing dialysis, rehabilitating one’s life is crucial. Patients suffer from different emotional and physical challenges during kidney failure . SurvivaHRQOL has been significantly affected among patients with advanced chronic kidney disease and kidney failure. The fact that patients with CKD of various racial and ethnic backgrounds have varying HRQOL scores confirms the need to individualise the notion of HRQOL to evaluate critical aspects of life in patients and incorporate these domains into an all-encompassing plan of care. The urgency of HRQOL measurement and the need to advance our multidimensional tools with technology and a more patient-centered view of HRQOL is highlighted by these recent findings ,9.In dialysis patient populations, low HRQOL scores measured utilizing the Medical Outcomes Study Short Form-36 (SF-36) were associated with hospitalization and death in studies ,11,12,13The Dialysis Outcomes and Practice Patterns Study (DOPPS) found a strong link between depressive symptoms and mortality and hospitalization rates . On the Therefore, it is crucial to assess all such parameters while dealing with a patient’s critical condition with kidney failure. This study was carried out to emphasize the use of tools to measure the HRQOL of patients and treatment outcomes ,24,25,26Previous studies have found that drug adherence rates range from 33.0 to 87.7%. Seng et al. investigated medication adherence in kidney failure. A pooled medication adherence rate of 67.4%  61.4–73.3%) was found in a meta-analysis of 54,652 patients. Between prospective and retrospective studies, the prevalence of adherence to medication among patients with dialysis kidney failure was similar  vs.  ,29,30. AIn Pakistan, kidney failure is the most common cause of morbidity and mortality . AccordiThere is a significant upsurge in the prevalence of kidney failure worldwide, particularly in low- to middle-income countries . It is eThis multicenter prospective cohort follow-up study was carried out in Rawalpindi and Islamabad districts. The study was conducted from April 2019 to February 2020. The patients were recruited from the Nephrology Unit of 3 major tertiary care hospitals, i.e., Federal Government Polyclinic Hospital, Islamabad, Pakistan Institute of Medical Sciences, Islamabad, and District Headquarter Hospital Rawalpindi, Pakistan.2 diagnosed by a physician as a patient having CKD grade 4 and kidney failure grade 5 were enrolled in the study. All patients diagnosed with kidney failure were graded based on their history and investigation conducted in the hospital’s medical unit. According to hospital guidelines, CKD-EPI was used to estimate the eGFR; however, to reduce factors such as weight and body mass index, Cockcroft–Gault formulae were used to determine the eGFR level of the participants. The final diagnosis to determine the grades of kidney failure was made using multiple creatinine assessments. As per the guidelines provided by the study centers, they used Cockcroft–Gault formulae to give better risk stratification in cardiovascular events [A total of 400 patients were recruited for the study. After initial screening, 314 participants met the eligibility criteria for the study. All patients aged >18 years with an eGFR value of <30 mL/min/1.73 mr events .Participants attended a baseline clinic after being referred by their physicians. All patients were informed about the purpose of the study and written consent was obtained during the patient recruitment phase. We excluded patients diagnosed with malignancy, hospitalized patients, and patients who did not have complete laboratory investigations available at the time of recruitment. We also excluded patients with cognitive disabilities or any other mental illness who could not correctly respond to our questionnaire or other limitations that hindered their participation in this study.The following tools were used to achieve the study’s goal.It was designed by the study’s principal investigators to assess the relevant socio-demographic variables, e.g., age, gender, education status, duration of kidney failure treatment, and comorbidity condition.During the baseline visit, the serum potassium, calcium and phosphorus, hemoglobin, and urea levels was collected from medical records. The same laboratory investigation was also assessed after the completion of the follow-up visit at six months’ duration.The study included different Urdu pre-validated and translated questionnaires to achieve the study’s objectives. All these questionnaires have been validated for use among the Pakistani population. Therefore, no further validation test was measured during the study ,21,22,23The Urdu version of the KDQOL-SF-36 is reliable and validated for assessing HRQOL in kidney disease patients on dialysis in Pakistan [The Hamilton Depression Rating Scale was used in patients who speak Urdu. The HAM-D-U is an effective tool used for determining the magnitude of depression. Internal accuracy , test–retest reliability, and inter-rater reliability were reasonably good for the Urdu version of the HAM-D (HAM-D-U) . A HAM-DNo depression at all: <8Mild (subthreshold): 8–13Moderate (mild): 14–18Severe (moderate): 19–22Very severe (severe): >23HAM-D-U scores are interpreted as follows:The Morisky Levine Green adherence questionnaire (MLGS) was used to evaluate medication adherence. It is a four-item questionnaire with high reliability and validity that has proven to be particularly useful in chronic conditions such as hypertension, kidney disease, and other cardiovascular diseases. It assesses deliberate and accidental adherence using criteria such as forgetfulness, carelessness, and stopping the drug while feeling better and worse. Each question in the survey was answered with a 0 or 1 response. The total score of the four elements represents the degree of prescription adherence. Medication adherence is indicated by a score of 4, while a score of less than 4 indicates non-adherence. The questionnaire was translated into Urdu using the standard forward–backwards process, yielding a Cronbach alpha of 0.570, within the appropriate range (0.45–0.9) ,39.The tools were administered in the following manner:All questionnaires were administered to patients using a self-reporting approach. In order to validate the responses of the patients, researchers conducted random interviews with the patients during their dialysis procedure. The details schematic flow of patient enrollment, data collection and questionnaire administration are displayed The Bio-Ethics Committee (BEC) of Quaid-i-Azam University Islamabad permitted this prospective observational study in Tertiary Care Hospitals (BEC-FBS-QAU2017-13). The study was also approved by the Ethical Review Board of Shaheed Zulfikar Ali Bhutto Medical University (1-1/2015/ERB/SZABMU). Informed written consent was taken from all the participants included in this study. The study was conducted per the Declaration of Helsinki and reported according to “The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)” guidelines.® IBM version 20, Armonk, NY, USA) program. The KDQOL SFTM1.3 scoring program v.2.0  was used to compute and calculate PCS and MCS. Continuous variables were expressed in terms of means and standard deviations, whereas categorical variables were expressed in frequencies and percentages. To summarize sample characteristics, descriptive statistics were used.Primary data were entered into Microsoft Excel 2010, and anonymous patient coding was used to generate secondary data. The data were analysed using the Statistical Package for Social Sciences  and 95% confidence intervals (CIs). The study variable includes dependent variables  and independent variables .Moreover, normality tests were assessed with the Shapiro–Wilk test. Data had normal distribution; therefore, continuous data’s mean and standard deviation have been presented. Categorical variables were presented as numbers and percentages. The Mann–Whitney U test was used to compare the depression and HRQOL domains. A n = 125) were CKD grade 4, 9.2% (n = 29) with grade 5 not on hemodialysis yet, and 50.9% (n = 160) were at kidney failure grade 5 on hemodialysis.During the study recruitment period, 400 patients were enrolled at the treatment sites. Eighty-six patients did not meet the eligibility criteria and were excluded. In total, 314 patients participated in the study and completed KDQOL, HAM-D-U, and MLGS. The demographic characteristics of the study participants are shown in The comorbidity conditions among the study populations are depicted in p-Value < 0.05). Contrary to this, the physical composite score was greatly affected by parameters such as hematological serum iron and renal function concentration in the blood, as shown in There were abnormalities in laboratory parameters, and their impact was also analysed in the overall HRQOL of patients. Statistical analysis suggested that hematological and serum iron studies were laboratory parameters that significantly affected the mental composite score  was used to determine the study population’s pre-study and post-study analysis of depression levels.It was observed that throughout treatment, there was no educational or counselling support provided to any of the patients. Analysis of the depression data was given by 314 patients in the pre-assessment questionnaire and 244 in the post-assessment questionnaire. A total of 45 patients refused to fill out the post-study HAM-D-U.The frequency distribution of the depression assessment at baseline found that there was a significantly high depression level in both kidney failure populations . There wp-value > 0.05).Upon the follow-up visit, it was observed that there was a significant increase in depression levels among the study population. Respondents indicated a higher level of depression in both the study populations compared to their previous state. However, further analysis with the Pearson Chi-square test found no significant difference between the baseline and post-study depression levels (n = 122) of the 314 participants scored 4 and had high adherence, while the majority  belonged to a non-adherent population with a score of less than 4. In addition, the findings revealed no statistically significant relationship between adherence and gender, age, marital status, education level, smoking status or the number of medications (p > 0.05).Around 38.8% (p = 0.68). However, the overall mental health composite measured by the MCS at baseline was significantly lower for the grade 4 population than the grade 5 population, i.e., 36.66 ± 6.57 and 48.66 ± 5.44, respectively .A total of 314 patients completed the KDQOL-SF-36 questionnaire during a baseline visit. As shown in p-value < 0.05). The other major KDQOL-SF-36 domains that impacted both populations were Physical Functioning, Role Limitations-Physical, and Emotional well-being, as well as energy and fatigue evident from For the KDQOL-SF-36 domain, the Mental Health Composite was the factor that affected the study population the most, which showed a statistically significant level in both the study groups (p < 0.05). In the KDQOL-SF-36 scales, there was significant deterioration in Physical function, Emotional well-being, and Energy level in patients with grade 5 .In the follow-up visit, 244 patients agreed to respond to the questionnaires. In the post-study, 35 patients with grade 4 and 10 patients with grade 5 did not respond. In the post-analysis, a marked deterioration was seen in KDQOL-SF-36 domains and scale parameters among patients with advanced kidney failure. Grade 4 patients scored significantly lower than grade 5 in the Problem’s list/Symptom, Burden of Kidney Disease, and Mental Health composite domains  scores, although the mental HRQOL of all individuals decreased significantly during the follow-up period. Studies have shown that baseline eGFR levels influence physical deterioration in HRQOL . HoweverIt was also observed that the physical and mental health composite tends to deteriorate in patients with kidney failure. Previous studies reported that patients with moderate-to-progressing kidney disease had a lower PCS than MCS . A previA study by Ajeebi and his colleagues showed that patients with advanced kidney failure could likely be unaware of the effects of chronic renal replacement therapy on their physical and mental health . FollowiHowever, in the case of patients with kidney failure, complaints of sleep problems, muscle cramps, dry mouth, and lightheadedness are the most frequent. Although these discrepancies did not reach statistical significance after several comparisons, the biologi-cal plausibility of such differences warrants further investigation. In light of the results, it is evident that patients with kidney failure have lower scores on the SF-36 physical func-tion subscale. However, there were no variations in PCS scores due to this observation. As per the study referred to, this provides preliminary information on the subdomains of HRQOL that may differ between these two populations . In a stNumerous studies have shown that dialysis has a detrimental effect on depression and that patients who experience severe depression are more likely to die. According to 15 large-scale investigations, there is an important link between depression and mortality among dialysis patients. Several longitudinal studies that evaluated the recurrent measurement of depression found that patients receiving dialysis therapy had significantly greater mortality risks when depressive symptoms were present. According to studies, early dialysis therapy initiation is associated with depression ,46,47.The general demographic features of our sample of grade 4 kidney failure were close to those of the United States population of grade 4 chronic kidney disease. On the contrary, the study’s kidney failure cohort had a higher proportion of men than the total population of kidney failure patients. The result supported the study mentioned above, as it was discovered that the depression rate was observed to worsen with time; a linear increase was identified from the start of the study until the second administration of the questionnaire 6 months later. Possible causes for this finding are likely to be lifelong dialysis therapy with at least 3 dialysis operations per week, patients taking too many medications at once, the economic strain on patients and their families, and changed familial and social ties. In a group of chronic HD patients, depression symptoms increased linearly and a link was discovered between poor sleep quality, unemployment, pruritus, hypoalbuminemia, diabetes, and depressive symptoms .The findings of the current study and the prior research provided evidence that patients suffering from kidney failure are likely to develop mental health issues that the prolonged effects of illness could cause.Chronic renal diseases are frequent in the population but often remain challenging to demonstrate clinically, as their symptoms are crude . It is tIn addition, the treatment of hemodialysis patients includes all possible measures to reduce the impact of symptoms encountered in kidney failure . These sMoreover, mental health depends on individual, genetic, and hormonal factors, but also relational, community, and societal factors. Patients of kidney failure of all ages suffer from certain mental disorders more frequently, with more comorbidities. It also impacts their physical health and family and social balance. Specificities exist at the clinical level, as well as concerning the use of psychotropic drugs, their side effects, and adherence to care. The primary care physician’s role is essential for preventing and detecting mental disorders in kidney failure patients for their psychological support, guidance, and follow-up ,55.The current study has some limitations. The study only has a 6-month follow-up period; the findings should be interpreted cautiously. Although the variables have been adjusted for changes in physical activity, the possibility of residual confounders cannot be ruled out as one of the typical limitations of all cohort studies. For example, the health consciousness of an individual eating healthier also makes other more beneficial lifestyle changes that the questionnaire could not completely capture. A multicenter investigation with a large sample size and an extended follow-up period is required to corroborate the findings of the current study. Furthermore, future research in this domain needs to consider the comparison of mentioned health-related domains in a much more comprehensive sample of patients with kidney failure, including those with severe comorbid illnesses. In this study, which investigated several variables associated with low HRQOL in patients with kidney failure, depression significantly predicted a lower HRQOL. Therefore, our study emphasizes the potential need for randomized controlled trials in future research to determine the temporal relationship between low HRQOL and depression in kidney failure patients and to further assess the impact of early identification of depression and appropriate treatment of depression on the health outcomes of these patients. Despite these drawbacks, our study’s strength is that we performed thorough analyses to look at factors associated with HRQOL in patients with kidney failure, including medication adherence, depression, and modifiable and nonmodifiable clinical features.The patients on maintenance dialysis for kidney failure have significant burdens of physical and mental symptoms, depression, and low HRQOL. Given the substantial and well-known declines in physical and psychological well-being among patients with kidney failure receiving hemodialysis, findings drawn in this research imply that these health-related areas should receive special attention in the vast and expanding population of patients with kidney failure.


P < 0.001). Moreover, the ESM-1 and Gal-3 levels exhibited a positive linear correlation  in the acute STEMI patients. In conclusion, the ESM-1 and Gal-3 levels were found to be significantly elevated and correlated in the STEMI patients. Thus, combining these two biomarkers of endothelial dysfunction and inflammation might be useful for the diagnosis and assessment of STEMI.The biomarkers galectin-3  and endothelial cell-specific molecule 1 (ESM-1) reflect endothelial function and inflammation. As a consequence, they play an important role in both the diagnosis and characterization of ST-segment elevation myocardial infarction (STEMI). However, no prior study has explored the association between ESM-1 and Gal-3 in STEMI patients. This study is aimed at determining the ESM-1 and Gal-3 levels in the serum of STEMI patients and then exploring the correlation between the levels of these two biomarkers and their clinical significance in STEMI patients. The participants were divided into two groups: the ST group comprised 35 hospitalized STEMI patients while the control group comprised 24 people with normal coronary arteries. In all the patients, venous blood was taken from the middle of the antecubital fossa. The serum ESM-1 and Gal-3 concentrations were determined using an enzyme-linked immunosorbent assay. The results revealed that the ESM-1 and Gal-3 levels in the STEMI patients were 1.6 and 2.8 times higher, respectively, when compared with the controls ( ST-segment elevation myocardial infarction (STEMI) is a type of coronary heart disease (CHD) that can be either moderate or severe. It is characterized by a rapid onset, rapid course, and poor prognosis , 2. As aThe pathogenesis of STEMI and the associated myocardial damage are mostly related to the rupture of the atherosclerotic plaque and the vascular obstruction caused by secondary thrombosis . Cardiacβ-galactoside-binding lectin, is a new biomarker thought to reflect both fibrogenesis and inflammation. Moreover, it is known to be associated with myocardial injury in cases of myocardial infarction. After Gal-3 knock-out in mice, the infarct regions have been found to robustly express Gal-3, leading to it being regarded as a molecule directly related to early myocardial inflammation following myocardial infarction [Endothelial cell-specific molecule 1 (ESM-1), as a molecule capable of contributing to the progress of pathological atherosclerosis and endothelial dysfunction , has beefarction . In casefarction . Furtherfarction , 13. Thufarction . Moreovefarction . Such evPrior studies have demonstrated the additive value of combining biomarkers, including those for myocardial necrosis, myocardial stress, and vascular inflammation, in terms of the prediction and diagnosis of STEMI . HoweverThis study was conducted in the inpatient clinic of the Department of Cardiology, Xuzhou Central Hospital, China. Approval to conduct the study was granted by the Ethics Committee of Xuzhou Central Hospital. In addition, all the research procedures complied with the requirements set out by the Ethics Committee of Xuzhou Central Hospital and the 1964 Declaration of Helsinki and its subsequent amendments or similar ethical standards. The study involved 35 patients who were initially admitted to the hospital with acute STEMI between January 2018 and December 2019. In total, the patient population comprised 22 males and 13 females with a mean age of 57.25 ± 10.58 years (range: 30–75 years). The control group comprised 24 subjects with normal coronary arteries as diagnosed using coronary angiography or coronary computed tomography angiography.The inclusion criteria for the study were elevated TnI levels within 12 hours of onset and at least one of the following: chest pain lasting for more than 30 min; an electrocardiogram (ECG) showing ST-segment elevation of two or more thoracic leads or limb leads of ≥0.2 mV or ≥0.1 mV, respectively, and potentially, a left bundle branch block; an ECG showing an abnormal Q wave; loss of myocardial activity or abnormal ventricular wall movement; and/or intravascular thrombosis according to coronary angiography or autopsy .The exclusion criteria for the study were heart function graded III–IV according to the New York Heart Association (NYHA) standards, as complicated by acute or chronic infection or immune system disease ; a history of PCI for the treatment of CHD; and/or a history of cerebrovascular or peripheral vascular disease.The participants' name, gender, age, body mass index (BMI), risk factors for cardiovascular disease , and levels of creatinine, aspartate aminotransferase, alanine aminotransferase, TnI, and left ventricular ejection fraction (EF) were recorded in both groups.In all the participants, 5 mL of venous blood was collected via venipuncture at the center of the elbow immediately after the onset of STEMI and admission to the hospital. Following coagulation for 1 h and centrifugation for 15 min at 3000 r/min at 4°C, the serum was then separated from the blood, transferred to an Eppendorf tube, and stored in a -80°C refrigerator before testing. The ESM-1 and Gal-3 concentrations were determined using the ELISA according to the manufacturer's instructions. More specifically, the ESM-1 ELISA kit was purchased from Shanghai Enzyme-linked Biotechnology Co., Ltd. , whereas the Gal-3 ELISA kit was purchased from Bender MedSystems .n/%), while the measured data were presented as the mean ± standard deviation (SD). If the data for the two groups fitted a normal distribution, an independent samples t-test was used for the difference analyses. By contrast, if the data did not fit a normal distribution, the Mann–Whitney rank sum test was used. The Pearson product-difference and Spearman correlation analyses were used for the correlation analysis, with the former being suitable for those variables that conformed to a bivariate normal distribution. Statistical significance was set as a P value of less than 0.05.All the data analyses in this study were performed using Statistical Package for the Social Sciences (SPSS) version 23.0 software . The chi-square test or Fisher's exact probability method was used to analyze the differences between the groups. The count was expressed as the number of cases/percentage (P > 0.05). However, the levels of low-density lipoprotein cholesterol, aspartate aminotransferase, alanine transaminase, and TnI were significantly higher in the patients with acute STEMI than in the control group (P < 0.05), while the EF value in the acute STEMI patients was significantly lower than in the controls (P < 0.05)  . ElevateP < 0.001)  . Moreover = 0.758, P < 0.001), suggesting that when patients have increased levels of Gal-3, they may also have increased levels of ESM-1 in their blood.A bivariate Spearman correlation analysis was performed to explore the association between the ESM-1 and Gal-3 levels in the acute STEMI patients. The results revealed there to be a positive linear relationship between the ESM-1 and Gal-3 levels (The present study compared the serum ESM-1 and Gal-3 levels of venous blood drawn from the center of the elbow between 35 patients with STEMI and 24 controls with normal coronary arteries and then examined the correlation between the concentration changes. It was determined that both the serum ESM-1 and Gal-3 levels were increased in the patients with STEMI. In addition, there was a positive correlation between the ESM-1 and Gal-3 levels.ESM-1 is recognized as an important marker of vascular endothelial cells , while aThere are a few reports in the literature concerning the release kinetics of ESM-1 in STEMI patients, with such studies indicating the ESM-1 levels in patients with acute myocardial infarction to be significantly higher than those in the controls, which is consistent with the present results . Qiu et The inflammatory reaction represents an important process that occurs during pathogenesis and may also be present at the onset of acute myocardial infarction. When experiencing myocardial ischemia, both the local and systemic immune systems are activated and so release different cells and biomarkers able to be detected in the peripheral blood . Gal-3 iGiven the existence of contrasting findings, the secretion kinetics of Gal-3 at the onset of acute myocardial infarction remain uncertain. Animal experimental data have shown that 30 minutes after acute myocardial infarction, the level of Gal-3 messenger RNA begins to increase, whereas a significant increase in the plasma Gal-3 concentration does not occur until 24 hours later . As for The importance of ESM-1 and Gal-3 in terms of the diagnosis and prediction of CHD and STEMI has been proven in several studies. ESM-1 is thought to be a biomarker of endothelial dysfunction, whereas Gal-3 is considered to be a biomarker of atherosclerotic plaque progression and instability . VariousWhile this study has been able to present some prospective findings concerning the correlation between ESM-1 and Gal-3 in STEMI patients, it must be acknowledged that it had several limitations. The first limitation concerns the blood sampling procedure. Intracoronary blood sampling with a high aspiration catheter rather than peripheral blood sampling may be more conducive to ensuring the accuracy of the detected ESM-1 and GAL-3 levels. Second, this pilot study had a small sample size, meaning that it was underpowered. The sample size does not meet the criteria for drawing conclusions regarding a causal relationship, which represents an important limitation of this investigation. Conducting studies with larger sample sizes will improve the persuasiveness of the present results. Moreover, although this study was performed in accordance with safety regulations concerning STEMI patients, there were several related limitations, including certain safety and ethical issues. Therefore, further animal and cell experiments are necessary to further elucidate the role of the ESM-1 and Gal-3 cell signaling pathways in a STEMI model.In conclusion, the ESM-1 and Gal-3 levels were found to be increased in the serum of patients with STEMI. Additionally, the elevated serum ESM-1 level was positively correlated with the elevated serum Gal-3 level, indicating there to be an inherent interaction between these two biomarkers during the acute stage of STEMI. The present study is the first to clarify the significant association between the ESM-1 and Gal-3 levels in STEMI patients. Timely and appropriate treatment based on the changes that occur in the levels of these two biomarkers should serve to reduce the mortality rate in patients with STEMI.


Background: Non-pharmacological management of hypertension includes weight loss, alcohol and sodium restriction, regular exercise, and relaxation. In people with overweight hypertension, systolic blood pressure (SBP) and diastolic blood pressure (DBP) can be decreased via exercise and weight loss together. Breathing exercises are one method of relaxing.Objectives: The aim of this scoping review is to map the information that is currently available about the advantages of breathing exercises in decreasing blood pressure in hypertension patients.Methods: This scoping review adheres to Arksey and O’Malley’s framework, which entails identifying review questions, seeking pertinent evidence, choosing pertinent studies, mapping data, and discussing, concluding, and reporting the findings. The PRISMA flowchart is used to show how the evidence search process works.Results: As a result, 339 articles in total were retrieved from the three databases. 20 papers total were included in this review after screening. In 14 of the 20 investigations, participants with stage 1 and stage 2 essential hypertension, two with pre-hypertension, and four with Isolated Systolic Hypertension (ISH) were studied. The respondents’ ages ranged from 18 to 75. The systolic blood pressure declined by 4–54.22 mmHg, while the diastolic blood pressure dropped by 3–17 mmHg.Conclusion: Slow breathing can be used as an alternate, non-pharmacological therapy for hypertension individuals to reduce blood pressure.Systematic Review Registration: (https://osf.io/ta9u6/). High blood pressure, often known as hypertension, is a serious medical condition that increases the risk of heart disease, stroke, kidney failure, and other disorders. In the past 30 years, the number of adults aged 30–79 years with hypertension has risen from 650 million to 1.28 billion, with approximately half of these people unaware of their condition. According to WHO data from 2018, around 26.4 percent of the world’s population has hypertension, with a male-to-female ratio of 26.6 percent and 26.1 percent, and approximately 60 percent of those with hypertension live in developing countries, including Indonesia. In 2018, the National Institute of Basic Health Research (Riskesdas) reported an increase in the prevalence of hypertension in Indonesia’s 260 million population, which was 34.1 percent in 2018 compared to 27.8 percent in 2013 . HypertePharmacological management of hypertension are often used to lower morbidity and mortality among adults with hypertension and prehypertension, by achieving and maintaining arterial blood pressure at or less than 140/90 mmHg. Keeping blood pressure under control can lower the chance of developing cardiovascular disease . EvidencBreathing exercise is a useful non-pharmacological interventions in controlling hypertension . It is hi) To summarize the research that has been done so far on the intervention method of breathing exercises for patients with hypertension.ii) To visualize the reported outcomes (Blood pressure and heart rate) for hypertension patients who had breathing exercise interventioniii) To determine the breathing exercise intervention’s gaps and restrictions for patients with hypertension.Although there are available reviews on breathing exercise, however there is none specifically addressed the outcome of breathing exercise on hypertensive patients. This review would provide an overview on the effect of breathing exercise particularly on patients with hypertension. In this scoping review, we aim to map out the evidence from available studies and relevant literature regarding breathing exercises to support the management of hypertensive patients. The specific objectives of this scoping review are:This scoping review was conducted according to the PRISMA Extension for Scoping Reviews , thus emThe inclusion criteria for the search will be empirical and theoretical studies related to breathing exercises for hypertensive patients aged 18 and above without any other uncontrolled cardiovascular or other diseases, with or without antihypertensive medications. For those on treatment, they should be stable on anti-hypertensive treatment for a minimum of 2 months prior to the study and no change in medications during participation in the trial, published in English, in the period from August 2010 to November 2022. Studies including multiple modalities of complementary and alternative medicine (CAM) techniques and research where breathing exercises are combined with other modalities will be excluded.In brief, relevant studies were retrieved from electronic databases . A list of references from reviews discovered through electronic searches was checked to ensure that pertinent papers were included in the scoping review. We also looked for several sources of gray literature, such as the websites of local, national, and worldwide organizations and related scientific or medical organizations, to ensure that all pertinent material is considered.To build a search strategy, given the research questions mentioned above, literature searches from articles were guided by PCC: Population (hypertensive patients), Concept (breathing exercise), and Content . Search terms are generated by the research team member from keywords, subject headings and synonyms such as “breathing exercise”, “hypertension”, “heart rate”, and “quality of life”, to get an overview of all potential resources from the databases. The list of keywords is shown in Screened articles that passed the initial selection process and were deemed suitable because they met the inclusion criteria—After the title and reading of the abstract were subjected to full-text analysis. From each study taken. First author’s name; Year of publication; Title; Population characteristics; Study design; The number of samples; Age and gender; and outcome. Two reviewers extracted the data, and disagreements were resolved by convention.Results from the data extraction table was collated and summarised according to our review objectives. Even though it is nota compulsory in a scoping review, we also included quality appraisal to strengthen our finding. Assessment of literature quality was conducted using PEDro quality scale, which is an 11-item scale assessing internal and external validity of clinical trials. The PEDro scale scores can range from 0 to 10, with a higher score indicating better methodological quality. Responses to items 2 to 11 are summed to create a total score, and item 1 relates to external validity Results , while others were published in China (n = 3), India (n = 3), Malaysia (n = 1), Brazil (n = 2), Italy (n = 1), Taiwan (n = 1), Poland (n = 1), and United States of America (n = 1). The 19 selected articles were randomized controlled trial (RCTs), while 1 article was considered prospective observational. A total of 940 respondents involved in this research. All studies aim to find out whether breathing exercises can be beneficial for lowering blood pressure in hypertensive patients. 14 of the 20 studies were conducted on respondents with stage 1 and 2 essential hypertension, two studies were conducted on respondents with pre-hypertension, and four studies were conducted on respondents with isolated systolic hypertension (ISH). The age range of the respondents was 18–75 years   Hering  Oneda e, HRV He Wang et, and thr2O , 30 min daily (4 studies), and 60 min daily (2 studies). Six studies were performed two times per day, the rest did the exercises once a day. There are 2 studies that have done breathing exercises 60 times a day with a frequency of 6 breaths per minute. The minimum duration was 3 min for 1 session, which is done 5 times a day so the total training time was 15 min per day. The effect of breathing exercises was seen in the duration of 12 weeks (2 studies), 8 weeks (12 studies), 6 months, 5 weeks, 4 weeks, and 5 days each in 1 study. There were 2 studies that looked at the direct effect of breathing exercises.The effects of breathing exercise on cardiovascular condition, autonomic nerve activity, blood inflammatory biomarkers, and lung health were studied in this study. Only three research reported no change in blood pressure after receiving breathing training treatment, despite the fact that 17 studies reported a decrease in blood pressure, both systolic and diastolic. The systolic blood pressure declined by 4–54.22 mmHg, while the diastolic blood pressure dropped by 3–17 mmHg.The autonomic nervous activity was determined in 5 of the 20 papers. MNSA was the subject of three studies, but only one of the recommended revisions. Sympathetic nerve activity reduces as people breathe slowly. Muscle sympathetic activity decreases during the fifth and 10th minutes of BIM use. At the time, the breathing frequency was already around ten breaths per minute, implying that sympathetic activity is linked to breathing frequency .In contrast to the Oneda study, p 0.05), and it continued to diminish after 3 months of training (p 0.05). TNF-α decrease levels did not change significantly between participants with and without comorbidities . Other biomarkers such as IL-6, IL-1ra, galectin-3, and CRP, on the other hand, did not demonstrate any significant alterations during the study period.According to a study, TNF alpha, IL 6, IL 1 receptor agonist, and C reactive protein levels are lower. TNF-α decreased significantly throughout the 3-month training period: the difference was significant after 1 month of DGB exercise training  and inspiratory capacity (IC). The SLB has a higher tidal volume due to the lower breathing rate. Meanwhile, one study found that after being given Device-guided slow breathing, there was no change in plasma catecholamines .An imbalance of the autonomic nervous system in the form of increased sympathetic activity and decreased parasympathetic activity has a major role in the etiology of hypertension . AnotherAccording to research, slow breathing lowers sympathetic tone and raises parasympathetic tone. This could be partially mediated by alterations in intrathoracic pressure , stimulaSlow breathing is defined as a respiratory rate of fewer than 10 breaths per minute with prolonged, rhythmic, slow, and deep expiratory periods. Slow and deep breathing can have a relaxing effect, through changes in the body’s biochemistry, such as increasing endorphins (substances that cause relaxation), lowering adrenaline, and lowering blood acidity , increasReduced SBP and enhanced psychological well-being are linked to elevated HRV . In hypeAdditionally, there may be a close connection between the respiratory center, where voluntary control is present, and the autonomic nervous system, as evidenced by the fluctuating activity of the muscle sympathetic nerve and baroreceptor sensitivity during the respiratory cycle . TherefoBy stimulating stretch receptors in the aortic arch and carotid sinuses, the baroreflex is activated, which is one of the main mechanisms relating to the favorable cardiovascular effects of deep breathing . By actiWe found many actionable research needs as a result of our study. First, because hypertension is linked to stress and anxiety, more research is needed to determine the effects of breathing exercises in lowering stress and anxiety, which can lead to reduced blood pressure. Second, only one journal in this review measured plasma catecholamines, whereas an increase in blood pressure or hypertension is frequently accompanied by metabolic changes such as impaired glucose tolerance, hyperinsulinemia, hyperlipidemia, obesity, humeral changes such as increased renin activity, plasma, catecholamines, and aldosterone, and hemodynamic changes such as left ventricular hypertrophy and impaired diastolic function, as well as humeral changes such as increased renin activity, More research is needed to establish the impact of breathing exercises on metabolic parameters in the body.Because the time spent conducting breathing exercises varied widely in this analysis, more research is needed to discover the minimal duration and intensity required to produce advantages for hypertension patients in decreasing blood pressure and many cardiovascular parameters. Finally, a study on how long breathing exercises can help hypertension patients should be conducted.It is noteworthy that the included studies demonstrate a homogenous breathing exercise technique, which enables us to draw more conclusive findings. We also conducted quality appraisals on all included studies to improve the trustworthiness of our review. However, even though we did not limit the geographical region in our article search, the retrieved studies mainly originated from Asia countries. This might limit the generalization of the finding from this review.Slow deep breathing can be a non-pharmacological alternative therapy for people with hypertension in addition to lifestyle modification. Slow deep breathing is easy for people of all ages and does not have to be expensive. This research gathered 20 studies on the benefits of breathing exercises in hypertension patients. Breathing exercise lowers blood pressure and pulse during and after exercise, as well as MSNA, but it has no effect on plasma catecholamines. In one trial, inflammatory biomarkers  decreased, but CRP remained unchanged. Enhanced chest and abdominal expansion, as well as increased inspiratory muscular strength, were also obtained. One There were no significant changes in plasma catecholamines, according to the study. There are still some questions to be answered about the frequency and intensity of breathing exercises that are useful for hypertension patients and how long the effects last.This review mapped the outcomes of breathing exercises, one of the non-pharmacological approaches to managing hypertension. Almost all included studies demonstrate that this affordable approach leads to positive effects. This finding can be the basis of the breathing exercises implemented by healthcare providers for patients with hypertension.


The purpose of this study is to validate the transthoracic ultrasonographic measurement of superior and inferior vena cava variation in predicting fluid responsiveness of mechanically ventilated patients after surgery.The volume status of patients after major abdominal surgery constantly varies owing to postoperative diverse issues comprising fluid loss or capillary leakage secondary to systemic inflammatory reaction syndrome, A total of 70 patients undergoing the scheduled major abdominal surgeries in the anesthesia ICU ward were included. The superior vena cava (SVC) collapsibility index (SVCCI), the inferior vena cava distensibility index (dIVC), SVC variation over the cardiac cycle (SVCV), and cardiac output (CO) were measured by transthoracic ultrasonography were recorded before and after fluid challenge test of 5 ml/kg crystalloid within 15 min. The responders were defined as a 15% or more increment in CO.P < 0.0001) and 0.727  and 0.751 , respectively. AUCdIVC and AUCSVCV were significantly lower when compared with AUCSVCCI (P < 0.05). The optimal cutoff values were 19% for SVCCI, 14% for dIVC, and 15% for SVCV. The gray zone for SVCCI was 20%-25% and included 15.7% of patients, while 7%-27% for dIVC including 62.9% of patients and 9%-21% for SVCV including 50% of patients.Thirty patients (42.9%) responded to fluid challenge, while the remnant forty patients (57.1%) did not. The areas under the ROC curve (AUC) of SVCCI, dIVC and SVCV were 0.885 (95% CI, 0.786–0.949; Superior vena cava-related parameters measured by transthoracic ultrasound are reliable indices to predict fluid responsiveness. The accuracy of SVCCI in mechanically ventilated patients after abdominal surgery is better than that of dIVC and SVCV.ChiCTR-INR-17013093. The initial registration date was 24/10/2017. Rational goal-directed fluid management is one of the crucial components of anaesthesiologists' daily tasks. The latest multicentral retrospective study demonstrated that inappropriate fluid administration is correlated with increase in postoperative complications . Thus, eTraditional static hemodynamic parameters, such as central venous pressure (CVP) and pulmonary capillary wedge pressure, have shown little value in guiding volume expansion . In addiAmong these echocardiographic variables, superior vena cava (SVC) collapsibility index (SVCCI), and SVC variation over the cardiac cycle (SVCV) have shown promising results in mechanically ventilated patients, but SVC measurements required transesophageal echocardiography (TEE) technique, which currently limited its routine clinical application –11. WithThe Institutional Ethics Committee of Nanjing Drum Tower Hospital approved this trial (No.2017–122-02) that was registered in the Chinese Clinical Trial Registry . All patients provided written informed consent. All methods were carried out in accordance with the relevant guidelines and regulations of Nanjing Drum Tower Hospital.From September to December 2020, the prospective observational study was conducted in the AICU of a tertiary teaching hospital. Mechanically ventilated patients who need further treatment in the AICU after major abdominal surgery, aged 25 to 75 years, conforming to the American Society of Anaesthesiologists physical status II to III were recruited in this study. Patients with spontaneous respiratory effort, cardiac arrhythmias, primary peripheral vascular disease, cardiopulmonary dysfunction, and intraabdominal hypertension, as well as those who may be jeopardized by fluid challenge test, were excluded.−1 at a respiratory rate of 12 breaths min−1, the inspiratory to the expiratory ratio of 1:2 and the positive end-expiratory pressure was set with 5 cmH2O before ultrasound assessment. Patients were sedated with continuous intravenous infusion of propofol at the rate of 1 mg kg−1 h−1, and dexmedetomidine 0.2 ug kg−1 h−1. During the study period, the sedative drugs, as well as ventilation settings, remained constant. All hemodynamic variables were collected, and ultrasound examination and measurements were performed before and after the fluid challenge, using 5 ml kg−1 of compound sodium chloride infused within 15 min. According to the changes in cardiac output (CO) increased ≥ 15% or not, patients were classified as responder group or non-responder group.On arrival at the AICU immediately after the operation, the patients were sedated and mechanically ventilated in a volume-controlled mode with the following parameters: tidal volume of 8 ml kgAll transthoracic ultrasound measurements were performed by a proficient investigator in echocardiography using EPIQ 7C machine  equipped with an S5-1 probe. All Doppler echocardiographic measurements were taken offline from videotape recordings. Another investigator performing measurement was blinded to the patients’ hemodynamic parameters.1, SVCmin1) was measured, and SVCCI was calculated as SVCCI = (SVCmax1-SVCmin1) / SVCmax1. According to the electrocardiogram anonymously recorded on the echocardiography images, the maximum (SVCmax2) and minimum (SVCmin2) diameter over the cardiac cycle were recorded, and SVCV was computed as follows: SVCV = (SVCmax2-SVCmin2) / SVCmax2 , the phased-array ultrasound probe was positioned in the right mid-axillary line at the level of the diaphragm with the probe marker towards cephalad. The maximum IVC diameter (IVCmax) on inspiration and the minimum IVC diameter (IVCmin) on expiration during a respiratory cycle were measured 2–4 cm distal the cavo-atrial junction under M-mode modality. The distensibility of IVC under mechanical ventilation was calculated using the equation: dIVC = (IVCmax-IVCmin)/IVCmin.–1)2 × VTI × HR. Each measurement was performed three times, and the average was used in the final analysis to reduce the statistical error.After achieving the velocity–time index (VTI) of left ventricular outflow tract (LVOT) blood flow with pulsed-wave Doppler in an apical five-chamber view and the diameter (D) of LVOT from the parasternal long-axis view at the level of aortic valve annulus in early systole, CO can be then evaluated using the formula CO = 3.14 ×  and dIVC (0.8), with a power of 0.8 and a two-tailed type I error of 0.05, assuming the fluid responsiveness incidence of 50% in postoperative patients. To allow for a possible 20% dropout rate, a sample size of 79 was used.P-value less than 0.05 was considered statistically significant.The Shapiro–Wilk test was performed to test the normal distribution of variables. Numerical data were expressed as mean (SD) or median (interquartile range) where appropriate. Hemodynamic and echocardiographic parameters at baseline between two groups were compared using an independent t-test or the Mann–Whitney U test. The effects of fluid loading on variables within groups were studied with a paired t-test or Wilcoxon test. The Pearson and Spearman correlation coefficient was used to assess the relationships of the percentage change in CO with vena cava-related parameters. Receiver operating characteristic (ROC) curve analysis was performed to determine the efficiency of vena cava-related parameters in predicting fluid responsiveness, and the areas under the ROC curve (AUC) with a 95% confidence interval (CI) were calculated. The optimal cut-off value was determined by the point of the maximum Youden index. A comparison of AUCs between two indicators was conducted following the methodology described by Delong and his colleagues . The graSeventy-nine patients were assessed for eligibility during the study period. A total of seventy patients were included in the final analysis, whereas nine patients were excluded because of poor SVC image quality. Of those, there were 30 responders (42.9%) according to the criterion of the fluid challenge test.P > 0.05).Baseline demographic characteristics of the patients are presented in Table P < 0.05) compared to non-responders at baseline. Baseline SVCCI significantly correlated with the change in CO (ΔCO) , while dIVC and SVCV had weak correlation with ΔCO .As shown in Table P < 0.05). In addition, there was an increase in heart rate (HR) in responders but a decrease in HR in nonresponders (P < 0.05). No statistical differences in the SVCCI, dIVC and SVCV were noted before and after fluid loading, respectively (P > 0.05).After the fluid challenge, significant increases in CVP, VTI, and CO in both groups were observed (P < 0.0001). The optimal cut-off value for SVCCI was 19%, with a sensitivity of 93.3% and a specificity of 75%  and 0.751 , which were significantly lower than the AUC for SVCCI (P < 0.05), respectively. Besides AUC, the gray zone of dIVC (7%-27%) and SVCV (9%-21%) includes 62.9% and 50% of patients, respectively . A dIVC > 14% discriminates responders from non-responders with a sensitivity of 62.5% and specificity of 80%, respectively. However, the gray zone of dIVC (7%-27%) includes more than half of the patients, suggesting that dIVC was not clinically useful in mechanically ventilated patients after abdominal surgery which may be inflicted by multiple factors including the intra-abdominal pressure, intrathoracic pressure, and pericardial pressure as well.The cyclic effect of positive pressure ventilation on the changes in vena cava diameter depends on the transmural pressure, which is determined by intravascular pressure (circulating volume and right heart function) and surrounding pressure  . IVC resCompared with IVC, SVC is located entirely in the thoracic cavity, so it is hardly affected by intra-abdominal pressure , 18. VieIn the existing studies, however, the SVC measurement was available in almost every ventilated patient by TEE . Ugalde Cardiac variation in the great veins was verified to be caused by venous return, driven by the systemic filling pressure rather than by pressure propagation from the aorta –25. TherAlthough our present study has highlights, several limitations have to be addressed. First, we did not monitor the intra-abdominal pressure directly. The population we investigated is patients after abdominal surgery whose abdominal pressure may be abnormal. The monitoring of bladder pressure in all patients is not a routine in our institution. Secondly, although the golden standard to evaluate the effect of CO is pulmonary artery catheterization, echocardiography has been validated to correlate well with this invasive method . ThirdlySuperior vena cava-related parameters measured by noninvasive transthoracic echocardiography have higher diagnostic effectiveness in predicting fluid responsiveness in mechanically ventilated patients after major abdominal surgery. Especially, the SVCCI is superior to the conventional variables of dIVC and SVCV in terms of the prediction reliability and the proportion of subjects in the gray zone. Therefore, the SVCCI assessment by the surface thoracic ultrasound should be advocated in mechanically ventilated patients undergoing major abdominal surgery.