We propose an ultra-low-cost at-home blood pressure monitor that leverages a plastic clip with a spring-loaded mechanism to enable a smartphone with a flash LED and camera to measure blood pressure. Our system, called BPClip, is based on the scientific premise of measuring oscillometry at the fingertip to measure blood pressure. To enable a smartphone to measure the pressure applied to the digital artery, a moveable pinhole projection moves closer to the camera as the user presses down on the clip with increased force. As a user presses on the device with increased force, the spring-loaded mechanism compresses. The size of the pinhole thus encodes the pressure applied to the finger. In conjunction, the brightness fluctuation of the pinhole projection correlates to the arterial pulse amplitude. By capturing the size and brightness of the pinhole projection with the built-in camera, the smartphone can measure a user’s blood pressure with only a low-cost, plastic clip and an app. Unlike prior approaches, this system does not require a blood pressure cuff measurement for a user-specific calibration compared to pulse transit time and pulse wave analysis based blood pressure monitoring solutions. Our solution also does not require specialized smartphone models with custom sensors. Our early feasibility finding demonstrates that in a validation study with N = 29 participants with systolic blood pressures ranging from 88 to 157 mmHg, the BPClip system can achieve a mean absolute error of 8.72 and 5.49 for systolic and diastolic blood pressure, respectively. In an estimated cost projection study, we demonstrate that in small-batch manufacturing of 1000 units, the material cost is an estimated $0.80, suggesting that at full-scale production, our proposed BPClip concept can be produced at very low cost compared to existing cuff-based monitors for at-home blood pressure management. Hypertension remains the leading preventable cause of premature death and disability worldwide, killing almost eight million people every year, and is projected to increase by 60% to affect 1.6 billion adults worldwide by 20255. Hypertension, beyond elevating risks of cardiovascular diseases including stroke, heart disease, chronic kidney disease, and end-stage kidney disease, has also been demonstrated to accelerate cognitive decline for middle-aged and older adults, with growing evidence that hypertension is associated with a higher risk of all-cause Mild Cognitive Impairment (MCI) and Non-Amnestic MCI. It is thought that hypertension may cause cognitive impairment through cerebrovascular diseases, such as atherosclerosis of cerebral blood vessels, and damage to the blood–brain barrier.Hypertension, defined as systolic blood pressure (SBP) of 7. These communities often face barriers to accessing healthcare services, which can lead to a lack of preventative care and increased risk for chronic diseases like hypertension9. For example, older adults living in rural communities may face challenges in accessing hypertension screening due to limited transportation options and distance from healthcare facilities. Pregnant women, particularly those from low-income backgrounds, may also struggle to access screening for preeclampsia, a potentially life-threatening hypertensive complication of pregnancy10. Refugees who may have limited access to healthcare services in their host country may also benefit from a low-cost BP monitor for at-home monitoring11. Making BP monitoring more accessible and affordable to enable measurements outside of the traditional clinics can also facilitate community-based hypertension management approaches proven to be effective for vulnerable populations14.The key areas where low-cost BP monitors can make a significant impact are low-income and/or disadvantaged communitiesBPClip, an ultra-low cost universal smartphone attachment that enables smartphones to measure blood pressure. The insight that enables our innovation is the use of computational imaging that combines a smartphone camera with a cheap plastic clip that employs a spring-loaded mechanism. This clip device, which has no electronic components, is compatible with any smartphone featuring a low-resolution (2 MegaPixels) camera and a light source, attributes found in virtually every modern smartphone, even the least expensive models. The basic functioning principle of the clip is called oscillometry. Oscillometry is a measurement of the arterial pulse amplitude as a function of applied pressure. Oscillometry is the basis of automated electronic BP cuffs commonly in use today and the preferred technique of the American Heart Association (AHA) and American Medical Association (AMA)15. Our system, called BPClip, performs oscillometry at the fingertip to measure BP. To enable a smartphone to measure the pressure applied to the digital artery, a moveable pinhole projection moves closer to the camera as the user presses down on the clip with increased force. As a user presses on the device with increased force, the spring-loaded mechanism compresses. In this way, the size of the pinhole encodes the pressure applied to the finger. In conjunction, the brightness fluctuation of the pinhole projection correlates to the arterial pulse amplitude. By capturing the size and brightness of the pinhole projection with the built-in camera, the smartphone can simultaneously measure the pressure applied to the finger and the resulting pulse amplitude to calculate a user’s BP with nothing but a low-cost, plastic clip and a smartphone app.In an effort to increase accessibility to this vital measurement, we introduce 22 and/or pulse wave analysis (PWA)25 or deep learning methods that use PPG and demographics27 to estimate blood pressure. This is because these indirect measurements are highly dependent on individual variations of arterial stiffness, vascular structure, and arm length. In order to use these other cuffless solutions, users must still have access to blood pressure cuffs, either personally or through a clinic. Additionally, due to changes in arterial stiffness over time, per-user calibration based systems must be recalibrated over time. Due to this reliance on calibration, PTT/PWA-based calibrated cuffless blood pressure monitoring solution is only suitable in use-cases focused on convenience of frequent/continuous monitoring of blood pressure for those who already have access to existing blood pressure monitoring infrastructure. In comparison, per-user calibration is not required for oscillometric-based methods because the measurement is performed locally at the artery using applied mechanical pressure.Numerous cuffless-optical solutions have been proposed for app-based and wearable BP monitoring, but all have failed to reach commercial viability due to the need for onerous and frequent per-user calibration. Per-user calibration means that to use the device, a user would need to first measure their BP with a cuff-based device at least once, but typically multiple times at different BP levels. This per-user calibration is necessary for any solution that relies on pulse transit time (PTT)28 or sensorized devices designed as a smartphone case29 requiring computation, communication, or sensor components. In comparison, our low-cost mechanical solution is compatible with any smartphone featuring a flash light emitting diode (LED) and a camera.In an estimated cost projection study, we demonstrate that in small-batch manufacturing of 1000 units, the material cost is an estimated $0.80, suggesting that at full-scale production, our proposed BPClip concept can be produced at very low costs compared to existing cuff-based monitors for at-home blood pressure management. Prior approaches that investigated the use of smartphones for oscillometric measurement have required specific smartphone models with a pressure-sensitive screenThe goal of this study is to provide feasibility findings of the potential measurement capability of a low-cost blood pressure monitoring concept that does not require per-user calibration. The ultimate translational goal is to provide widespread, at-home access to blood pressure monitoring without reliance on existing clinical infrastructure. We envision that through the incorporation of ultra-low-cost monitoring capability of vitals such as blood pressure, public health programs and telehealth services can augment these low-cost services with not just virtual consultation, but an additional quantitative measurement that is enabled through a device that is at a cost suitable for large-scale distribution.31. As such, our system does not require per-user calibration. The oscillometric method calculates BP based on the change of blood volume oscillations per heartbeat as the external pressure changes around the artery. Therefore, to use the oscillometric method, a device needs to have three features: (1) the ability to apply pressure on the artery; (2) the ability to sense how much pressure is applied to the artery; (3) the ability to measure blood volume changes as the applied pressure changes. Typically, automated blood pressure monitors exert increasing external pressure on the artery while sensing the pressure and blood volume oscillation with a pressure sensor , the acrylic cover ($0.001), two O-rings ($0.04), the anti-slip pads ($0.03), the metal rod and tube ($0.15) and the resin 3D printed material ($0.55), totaling $0.80. Even at low production, our proposed system is substantially less expensive than any commercial blood pressure monitor. With the majority of the cost from 3D printed plastic, this cost will be substantially lowered at scale with injection molding and bulk component costs.32. BPClip’s measurement achieved a mean absolute error (MAE) of 8.7 ± 10.0, 8.4 ± 10.3, and 5.5 ± 7.0 mmHg and bias of 1.72, 0.79, and 0.3 mmHg for systolic, mean, and diastolic BP, respectively. Five subjects were excluded from analysis for the estimation accuracy analysis due to either poor perfusion which resulted in the inability of the system to acquire pulse data (N = 4), or an atypically large difference between SBP and DBP of greater than 80 mmHg (N = 1). In order to investigate if the result is biased based on skin tone, we further performed a subgroup analysis on the accuracy within different ethnic groups. For SBP, the MAE for Asian, Hispanic, and White groups are 7.7 ± 4.2, 8.6 ± 5.2, and 10.2 ± 6.9 respectively. For DBP, the MAE for Asian, Hispanic, and White groups are 4.5 ± 4.6, 9.5 ± 6.4, and 6.5 ± 2.9 respectively. After running a one-way ANOVA test on these three groups, we found the p-values to be 0.61 and 0.62 for SBP and DBP respectively, indicating there is no significant difference in MAE among the three ethnic groups.The accuracy of BPClip is validated on data collected from 24 users with SBP ranging from 80-156 mmHg and DBP ranging from 57–97 mmHg. Figure Because using BPClip requires the user’s active interaction, we analyzed how much time it takes for a user to complete one measurement. The time spent in each trial was calculated from metadata for each participant. The minimum possible time for a user to complete a measurement is approximately 140 s for the measurement, given 7 s per level for 20 levels if the user completes each level without repeating.On average, it took 251 ± 127 s for the first trial and 212 ± 45 s for the second trial. Because the right index finger is used for BPClip, we also recorded if the participant was left-handed or not. Among the recruited participants, 6 were left-handed, but none reported difficulty using BPClip. A t-test suggested that the difference in time to complete one measurement trial is not significant between left-handed users (N = 8) and right-handed users (N = 21) .29 study participants were recruited from UC San Diego main campus and UC San Diego Medical Center (Details in Appendix BPClip is designed with SolidWorks CAD software and printed with a resin 3D printer (Anycubic Photon Mono X with Hard Tough Resin—Black). The clip dimensions are The base clip is a 3D-printed clip-shaped piece that is mounted to the smartphone. It also includes a 3D-printed screw and nut which can tighten to help fix the clip in position. To ensure a firm and non-slip interface, a silicone pad is used to increase the friction between the clip and the phone screen. The bottom piece is flush with the camera and flashlight LED.The pressing platform is also 3D-printed and wraps around the bottom piece. It comes in contact with the user’s finger and is displaced as the user applies force to it. The contact area is a circular protrusion with a diameter of 10 mm. To ensure an even surface for the finger contact area, clear acrylic pieces are placed over the openings of the illumination slot and pinhole. Two flanges are used to constrain the angle of the index finger. Two notches are used to help users align their index finger with the pinhole.Interfacing the base clip and pressing platform is a compression spring with a k-constant of 0.49 N/mm, placed in between the pressing platform and base clip. It renders the pressing platform the ability to move up and down, depending on the amount of force applied by the finger. The spring is pre-loaded with a force of 0.1 N. 6.7 mm more space is allowed for the spring to compress, rendering the potential range of force applied to the finger from 0.1 to 3.3 N. With an area of a circle of 10 mm diameter, the pressure would range from 9.5 to 315 mmHg. Because the prototype is constructed with 3D printing, surface finishes are not perfectly smooth compared to injection molded plastic parts. Two pairs of guiding rods and tubes, with lubricants applied, are added to the pressing platform and base clip respectively to allow for smooth uniform displacement.A light guide and an imaging path are designed to maximize the light transfer and minimize light leakage. The light guides direct the flash into the protrusion and into the finger. To maximize light transfer from the flash to the finger, chrome spray paint  is applied to the inner surface of the light guide. A pinhole projects the light from the finger onto the camera via the imaging path. At the end of the light guide and imaging path, two O-Rings were respectively padded in between the bottom piece and the phone to reduce the external light influence.We developed an Android smartphone application to be used with BPClip. The application has 3 main features. First, it infers the applied finger force from the size of the pinhole reflected on the image captured by the camera. The pinhole is projected to the camera sensor as a circle. For each frame, the area of the circles is calculated from the number of pixels with a value above 20 (the image is encoded with unsigned 8-bit integers). To account for different baseline values within the circle due to different amounts of blood circulation, a histogram equalization operation was applied to the raw image before area calculation. The diameter of the circle is then calculated from the area of the circle. The force is plotted in real-time in the force plot UI. To avoid unnecessary confusion for the user, the force signal was processed with a low pass filter to remove the PPG artifact before being plotted.Second, the application can extract the PPG signal from the pixel values within the circle. For each frame, the average value of the pixels within the circle that have a value between 20 and 254 is calculated to be the PPG signal. The PPG is plotted in real-time in the PPG plot UI.Third, the application has a UI that helps the user maintain the applied finger force at a specific level. This UI consists of a brightness adjustment feature and a feedback feature. Because the brightness depends on the amount of total blood circulation as well as the skin tone, the size of the circle projected onto the camera at each force level changes depending on the person. To adjust for this, a simple brightness adjustment is performed before each measurement. To perform an adjustment, at the beginning of a measurement round, the circle size when the user rests the finger on the clip with no force is recorded , as well as the circle size when the clip is completely pressed down. . By capturing the 0% and 100% circle sizes, the ensuing measurement can be performed in proportion. 20 force levels are then equally divided from 5 to 95%. During the trial, a green line representing the current target force level appears in the force plot. An additional red indicator line showing the current force applied helps guide the user to adjust the applied force to meet the target force. While the applied finger force does not yet match the target, the indicator line remains red. As soon as the force is in the range close to the target (± 2%), the indicator turns yellow. The user is then expected to hold their finger in position to maintain a constant applied force. If the force stays within the range, after 2 s the indicator turns green from yellow, where the data is collected for 5 s. If the force goes out of the range (± 2%) anytime when the indicator is yellow or green, the indicator changes back to red, and any data collected will be discarded. The data for the current force level then needs to be recollected.This section elaborates on the process of preprocessing raw data recorded on the smartphone. As thoroughly explained in the prototype hardware section, the camera images contain a pinhole projection. The diameter of the pinhole projection corresponds to the force exerted on the finger. The pixel intensity fluctuations of the pinhole projection correspond to blood flow through the palmar arch artery.For the data analysis, we only use data captured during the 5-s intervals at the specified force levels from the smartphone application. For the applied force, this smartphone application ensures ± 2% tolerance on each force level. At each of the 20 force levels, the 5 s of recording allows for approximately 3–7 complete pulses of blood flow, as measured by the pixel intensity of the pinhole projection. For each of these force levels, we applied a 0.5–10 Hz band pass filter and then averaged the peak-to-trough amplitude of all complete pulses using peak prominence. This results in one average peak prominence value for each of the 20 force levels. These 20 points make up the subsampled blood volume oscillogram used to calculate blood pressure.The participant did not have sufficient perfusion to create a PPG signal with significant enough prominence values for interpretation (N = 4).The participant had abnormal blood pressure with more than 80mmHg difference between the reference systolic and diastolic BP measurements (N = 1).This resulted in N = 24 participants for the data analysis and validation steps of the study.During the data preprocessing, we excluded participants for the following reasons:This section describes our process of using preprocessed data to predict blood pressure. The preprocessed data contains a 20 point oscillogram of force versus blood volume measurements, where blood volume is measured by PPG prominence. We exclude the lowest and highest force levels of the oscillogram, because when at the lowest force, the finger can sometimes leave the clip, and at the highest force, the spring is fully compressed and the applied finger force may exceed the spring load. From the remaining 18 oscillogram points, we normalize the points between 1 and 0.33 to estimate systolic and mean BP. The predicted systolic and mean BP will be the input features for the diastolic BP estimation. For estimating diastolic BP, we use a linear regression model, where the only input features are the predicted systolic and mean BP values. For all BP prediction validation results, we use a leave-two-subjects-out validation  with N = 24 participants. This leave-two-subjects-out validation involves training the BP prediction models on 22 subjects and then predicting the BP for the 2 unseen participants. This process is repeated 12 times so each participant is in the holdout set exactly once.The blood pressure estimation consists of an estimation of mean and systolic BP followed by a subsequent estimation of diastolic BP. For the mean and systolic BP estimation, we use the 18 oscillogram points as the input into a Least Absolute Shrinkage and Selection Operator (LASSO) RegressionA key finding in our work is that there is no need to perform a per-user or per-device calibration. This is enabled by the simple top-bottom brightness adjustment that is included at the beginning of a measurement. By asking the user to hold the clip at the furthest compression and then once again at the closest compression, our system adjusts for the total brightness as reflected by a person’s finger. Thus, no matter the skin tone (where darker would absorb more light) or with a dimmer flash , the brightness adjustment equalizes the proportional amplitude of the PPG accordingly.34, it is possible to introduce highly biased measurements simply due to spring variance. Although it is possible to reduce this tolerance issue through quality assurance testing and selecting springs that meet a more stringent tolerance, we anticipate that this may increase the end cost significantly due to low yield. We instead would envision that a manufacturing pipeline would include calibrating an assembled clip using a mechanical testing system to obtain the force to pinhole projection as a calibrated parameter. A QR-code sticker, much like that of a quality assurance sticker will be placed on the device. For the user, the app would instruct them to scan the QR code and the calibration would automatically be downloaded for the clip. This QR generation, at production, can foreseeably be fully automated.The consistency of the spring constant is important, however, and cannot be calibrated for by the end-user. With commercial springs typically with a tolerance of ± 10%As with all optical-based pulse sensing systems, skin tone needs to be considered. Darker skin tones can absorb more light, thus leading to less total light reflected. Although we did not perform a formal skin tone study, our approach is not significantly affected by skin tone, except for signal strength, which can be addressed through digital amplification by adjusting the sensor sensitivity. Unlike calculating oxygen saturation  using a pulse oximeter . If the PI was A key contribution of our work is that the design of this ultra-low cost blood pressure monitoring attachment is suitable for almost all smartphones on the market. Although the studies presented in this paper were conducted using the Google Pixel 4 smartphone, BPClip relies only on the smartphone camera and flashlight, making our approach suitable for most phones. BPClip can be adapted to other smartphone models with minimal changes, as most phone models would only require adjustments in the distance between the flashlight and the camera. Our current design already takes that into account and uses a bend in the light guide to bring the flashlight to the finger from various distances. We surveyed the distances of flashlights to the closest camera lens from 50 smartphones out of 10 brands, across various pricing ranges Appendix . Our finCompared to a fully automated cuff, a limitation of our system is that users must have a reasonable level of finger dexterity to use BPClip, as they need to hold their index finger steadily while exerting various amounts of force. Therefore, although we have found that our middle-aged participants had no trouble using the device, for some older adults with weakened grip and/or hand tremors, it can be difficult to use BPClip. A future design could consider using a higher stiffness spring to allow for the same range of force application with less compression, resulting in easier force application overall. With smaller displacements we suspect that it will also be easier to perform a continuous force application with less motion artifact, which will be considerably faster to perform than the current 20 level measurement. Moreover, future designs that leverage the front-facing camera/screen could allow users to operate the device with their thumb, which is typically stronger and more dexterous for most people, making the device easier to use compared to controlling actuation with the index finger. This design would require modification to the pinhole design, such as including a low-cost lens, to focus the image to improve imaging resolution to offset smaller displacements of the spring.Finally, our system performs blood pressure measurements at the digital artery at the finger. Although we demonstrate in our feasibility study that the measurement made at the finger correlates well with that measured at the brachial artery using an automated cuff, there are a number of factors that may affect this end measurement. We suspect that finger callus and other conditions that affect the finger will lead to changes to the finger skin surface mechanics which will distort the force applied by the device to the finger artery. This will likely lead to inaccuracies. Therefore, it is important for future studies to incorporate varying finger conditions, such as callused fingers, vasoconstricted fingers, deformities, and size variations, in order to fully characterize how these differences affect the measurement. This will help determine whether additional calibrations or models are needed to address such variation and maintain accuracy across people.Health monitoring should be available to everyone, no matter their country of origin, their skin tone, their gender, and most of all, their income. In this paper, we propose a solution to democratize blood pressure (BP) monitoring by converting billions of smartphone cameras, even the cheapest ones, into BP monitors with an ultra-low-cost plastic clip that can be produced at-scale for mere cents. Our current prototype’s material costs less than $1 USD to manufacture at low quantities, but at scale, we expect that a blood pressure monitor will reach an even lower cost.Supplementary Information 1.Supplementary Information 2.Supplementary Information 3.Supplementary Information 4.Supplementary Video 1.Supplementary Video 2.Supplementary Legends.


Several outcome-based prospective investigations have provided solid data which support the prognostic value of 24 h ambulatory blood pressure over and beyond cardiovascular traditional risk factors. Average 24 h, daytime, and nighttime blood pressures are the principal components of the ambulatory blood pressure profile that have improved cardiovascular risk stratification beyond traditional risk factors. Furthermore, several additional ambulatory blood pressure measures have been investigated. The correct interpretation in clinical practice of ambulatory blood pressure monitoring needs a standardization of methods. Several algorithms for its clinical use have been proposed. Implementation of the results of ambulatory blood pressure monitoring in the management of individual subjects with the aim of improving risk stratification is challenging. We suggest that clinicians should focus attention on ambulatory blood pressure components which have been proven to act as the main independent predictors of outcome . Since diagnosis and clinical management of hypertension are based on blood pressure (BP) measurements taken in the physician’s office, most of the diagnostic and treatment recommendations issued by major hypertension guidelines are based on office BP ,2. NonetThe independent association between ambulatory BP, hypertensive target organ damage, and the risk of cardiovascular events in hypertensive patients (either treated or untreated) is now well established ,11,12,13ABPM enables clinicians to obtain a precise estimation of a patient’s BP profile by measuring BP during daytime and nighttime periods . Solid eSome landmark studies have addressed the independent prognostic value of average ambulatory BP. In the Ohasama study, ambulatory BP predicted the risk of cardiovascular mortality after adjustment for several potential confounders, including office BP . An analNumerous clinical studies and guidelines have defined white coat hypertension (WCH), also referred to as ‘isolated office hypertension’, as a phenotype characterized by hypertension detected by the doctor in his/her office in individuals with normal BP at home or during normal daily activities ,27,28,29The Lancet, we subdivided hypertensive patients with WCH into two groups with pretty low (<130/80 mmHg) or intermediate (between 130/80 and 131/86 mmHg in women or 136/87 mmHg in men) daytime ambulatory BP. The difference in the risk of major cardiovascular events between clinically normotensive subjects and the hypertensive group with WCH defined restrictively was not statistically significant. Conversely, the differences between the normotensive group and the WCH group defined less restrictively were significant. In other words, these results suggest that a daytime ambulatory BP < 130/80 mmHg identifies hypertensive patients with WCH who are really at low cardiovascular risk. This analysis has been more recently replicated in a huger sample of 3174 patients with 376 major cardiovascular events over a mean follow-up period of 7 years. The analysis confirmed that the clinically normotensive group and the group of patients with WCH defined more restrictively (daytime BP < 130/80 mmHg) were comparable in terms of their risk of major cardiovascular disease. Conversely, the differences between the clinically normotensive group and the WCH group defined less restrictively achieved significance. Notably, these data have been confirmed in independent prospective studies [In a study published in  studies  which in studies .An international collaborative clinical study collected individual patient data from 4406 patients from four prospective cohort studies conducted in Italy, the United States, and Japan who were followed for a median of five years . In a fuConsequently, hypertension guidelines suggest that subjects with WCH should be extensively investigated for concomitant risk factors and target organ damage in order to inform therapeutic decisions . So far,Over the years, several studies have addressed a new clinical phenotype with normal BP  in the doctor’s office and increased BP levels during usual daily activities outside the doctor’s office. Pickering defined this condition as ‘masked hypertension’ (MH). Clearly, the term MH underscores the concept that hypertension might not be diagnosed in these individuals on the basis of office BP measurements. Various factors are known to increase BP during usual daily life  and these factors could thus raise BP out of the doctor’s office.Several studies have shown that hypertensive organ damage is comparable between patients with MH and those with elevated BP during normal daily activities, despite the remarkable differences in office BP. From a prognostic standpoint, patients with MH showed a 1.5- to 3-fold higher risk of major cardiovascular disease than subjects with normotension, and their outcomes did not differ significantly from those of patients with elevated office and out-of-office BP ,34,35. Sn = 6) and (b) studies which investigated the prognostic impact of MH detected by self-measured BP (n = 2) [p = 0.001) or 24 h ABPM  [In a meta-analysis, we evaluated the prognostic impact of MH defined by either ambulatory or self-measured BP . We exam (n = 2) . The risOverall, these data strongly suggest that MH should be considered an insidious and prognostically adverse condition that can be reliably diagnosed by self-measured BP and ambulatory BP. Antihypertensive treatment is advised in these subjects, although the associated outcome benefits are still undetermined. So far, there are no randomized outcome-based studies specifically designed to assess the prognostic impact of hypertensive treatment in subjects with MH.Although average ambulatory BP  has been extensively investigated as a prognostic determinant in hypertension, other measures exist for describing different aspects of ambulatory readings. They include changes from day to night in BP, morning surges, pulse pressure (PP), and estimates of BP variability ,43,44,45It is now well established that there is a physiological decline in BP from the daytime to the nighttime window, with BP values tending to peak during the awake period and then falling to a nadir during the night ,47. In tThe “dipper/non-dipper” classification was first introduced by O’Brien in 1988 on the basis of clinical observations of a more frequent history of stroke among subjects with absent or blunted BP decline from day to night .Subjects with a day–night BP difference below a given value are usually referred to as ‘non-dippers’, and the remaining subjects are usually referred to as ‘dippers’. To date, the suggested values for this distinction range from 10% to 10/5 mmHg up to 0%  . FurtherAfter evidence of an association between “non-dipping” patterns and target organ damage  and left ventricular hypertrophy (LVH), may influence the degree of BP fall from day to night. Consequently, the prognostic impact of the day–night BP fall could be influenced by CKD and LVH. In a recent analysis of the PIUMA study, the day–night BP fall remained a predictor of cardiovascular risk in the absence of data regarding CKD or LVH. However, somewhat unexpectedly, after adjustment for CKD (estimated glomerular filtration rate <60 mL/min or proteinuria) and LVH, the day–night BP fall was no longer significant for risk stratification in these patients . These dMore recently, some studies have analyzed the association between early morning BP surges and outcomes in hypertension. It is well known that myocardial infarction, stroke, and sudden cardiac death tend to cluster in the early morning, especially during the 4–6 h after awakening .These observations support the hypothesis of a pathophysiological relationship between hemodynamic aberrations in the early morning  and vascDifferent estimates of the morning surge in BP have been proposed ,66, inclThe early morning BP surge has been linked with vascular disease , LVH 6868, brainAmbulatory BP variability is traditionally assessed from the standard deviation (SD) of BP measurements over 24 h . However, other indices of BP variability have been proposed , includiAmbulatory BP variability has been extensively investigated in hypertension as a significant determinant of prognosis ,26,76,77A recent consensus document of the European Society of Hypertension synthetizes current evidence, clinical implications, and unmet needs in the setting of BP variability .Pulse pressure (PP) is a well-recognized marker of arterial stiffness. A fundamental mechanism underlying the rise in PP with aging is the stiffening of large arteries. An increased PP is thus a marker of stiff arterial walls, with several adverse implications of potential prognostic value . We founp < 0.01) [A link between PP and major cardiovascular events has been reported in several studies, and the link was independent of systolic BP and diastolic BP ,90. Ambu < 0.01) . Similar < 0.01) .p < 0.0001). In a multivariable analysis, 24 h ambulatory PP was an independent predictor of total cardiovascular events. For each 10 mmHg increase in 24 h PP, the risk of total cardiovascular events increased by 73% after controlling for the influence of other risk markers, including age, diabetes, serum creatinine, HDL cholesterol, LDL cholesterol, total white blood cell count, and left ventricular hypertrophy. Notably, office-recorded PP did not achieve significance when used in the same model [In a study conducted in postmenopausal hypertensive women , we founme model .Overall, these data strongly suggest that 24 h PP is a strong predictor of major cardiovascular disease events in hypertensive patients.To further characterize the clinical impact of PP, we also analyzed the different prognostic impact of 24 h mean BP and PP on stroke and coronary artery disease . We analThese findings strongly suggest that ambulatory mean BP and PP exert a different predictive effect on cardiac and cerebrovascular outcomes . While PThe available evidence supporting the prognostic value of ABPM is remarkable and soundly based on the outcome of prospective clinical studies . ABPM shThe European Society of Hypertension (ESH) guidelines remark the concept that ABPM and self-measured home BP are valuable alternative to traditional office BP measurements as it may enable the diagnosis of WCH and MH, which would not be possible using office BP alone. ABPM has advantages over home BP in terms of enabling multiple nighttime BP readings, its possible use in real-life settings , and more extensive evidence from the literature supporting it . Self-meAverage 24 h, daytime, and nighttime BP remain the main components of the ambulatory BP profile proven to be prognostically significant . Other a-Average ambulatory BP;-Pulse pressure;-Dipping status;-Variability.Several algorithms for the clinical use of ABPM have been proposed. However, in our opinion, the interpretation of ABPM should be simplified in individual patients to optimize their management. We should probably focus on those components of ABPM which more clearly improved risk stratification in long-term outcome studies:A-D-P-V: Average ambulatory BP; Dipping pattern; Pulse pressure; Variability in ambulatory BP) to correctly refine cardiovascular risk stratification and adapt treatment strategies (We suggest the use of the mnemonic ‘Ambulatory Does Prediction Valid’ (rategies . In subj


Although it is generally known that the type A behavior pattern (TABP) is associated with high blood pressure, recent studies have not consistently supported this association. Therefore, it is important to determine which factors moderate and mediate this relationship. The purpose of this study was to verify the moderated mediation effect of age and relaxation in the relationship between TABP and high blood pressure among middle-aged adults in South Korea. This study utilized data from the Korea Health and Genome Study (KHGS) supported by the Korea National Institute of Health. The participants in the present study were 10,022 Korean adults aged 40 to 69. To identify the conditional indirect effect of TABP on blood pressure through relaxation, with a consideration of age, a moderated mediation model using SPSS PROCESS macro 3.10 was applied. As is generally known, TABP was associated with high blood pressure, but its relevance was reversed through relaxation. Moreover, this relationship was moderated by age, which is known to be the most powerful predictor of high blood pressure. The lower age group with TABP exhibited a higher relaxation, whereas the higher age group with TABP demonstrated a lower relaxation. The findings demonstrate the need for relaxation education, stress management, or counseling to help individuals recognize their behavior patterns and strengthen the willingness and motivation for relaxation, especially among elderly people with TABP, in order to manage their blood pressure effectively. High blood pressure is major risk factor of cerebrovascular disorders and cardiovascular disease among middle-aged adults in South Korea , as wellTABP is typically characterized by individuals who exhibit excessive ambition, aggression, competitiveness, work-related drive, impatience, a need for control, a focus on quantity over quality, and a vulnerability to stress. It includes specific behaviors such as muscle tension, alertness, rapid and empathic vocal styles, and an accelerated pace of activities. Emotional responses associated with TABP encompass irritation, hostility, and an increased potential for anger . The oriAs such, TABP is a type of personality and behavior pattern that is vulnerable to psychosocial stress. It can be considered that people with TABP are continuously exposed to stress, regardless of the type or intensity of stressful event itself. Since it is well known that psychologically stressful factors can influence the pathogenesis of various physical diseases , it can Such inconsistency could result from a failure to consider mediating factors that may operate within the relationship between TABP and blood pressure. Since mediating factors are modifiable and can function as intervention strategies, understanding how these factors operate in the relationship between TABP and blood pressure becomes critical, as management is just as important as the early detection of hypertension. It is also necessary to consider moderating factors alongside mediating factors in order to fully comprehend the mechanisms that explain why certain individuals with a short-tempered disposition develop high blood pressure while others do not. This endeavor allows us to view TABP as a variable that is not easily changed, potentially possessing even more helpful characteristics for certain individuals. Therefore, this point allow to assume that the effects TABP on blood pressure may differ among individuals exhibiting TABP.In this study, relaxation is considered as one of the key factors that mediate the relationship between TABP and blood pressure. Given that individuals with TABP generally exhibit a hard-driving lifestyle, characterized by elevated levels of aggression, easily aroused anger, a sense of time urgency, and a drive for competitive achievement, they are more likely experience a higher level of physical and psychological tension and stress in their daily life . For thiFurthermore, most hypertension studies have reported that the effects of physical and behavioral factors, such as weight loss, diet, and exercise, on blood pressure vary across different age groups . These fH1: TABP is positively associated with blood pressure.H2: The relationship between TABP and blood pressure is mediated by relaxation (indirect relationship).H3: The indirect relationship between TABP and blood pressure through relaxation is moderated by age .This study utilized data from the Korea Health and Genome Study (KHGS), an ongoing population-based study of Korean adults aged 40–69, supported by the Korea National Institute of Health. The purpose of the KHGS is to investigate the frequencies and incidences of illnesses and their relationships with risk factors such as lifestyles, physical conditions, alcohol and food intake, smoking, psychological states, and personality traits. Trained interviewers and technicians conducted examinations through questionnaires, blood pressure measurements, anthropometries, and blood samplings. The data of 10,022 individuals from the 2008 samples were utilized in the present study.The trained interviewers administrated all questionnaires, and technicians conducted blood pressure measurements. TABP was assessed using 10 items on a 4-point Likert scale ranging from 1  to 4 . Example items include “People told me that I am easily upset” and “I can’t stand being late for an appointment or being slow to do something”. Relaxation was assessed with 3 items using response alternatives. An example item is “I try to relax by spending leisure time after work or on weekends”. The internal consistency reliabilities (Cronbach’s α) were 0.75 for TABP and 0.70 for relaxation.Blood pressure (BP) was measured following the guidelines of the International Society of Hypertension of the World Health Organization (WHO-ISH), using a mercury sphygmomanometer operated by a trained technician. Caffeine intake and smoking were restricted for thirty minutes before the measurements. BP readings were taken three times on either arm with thirty-second intervals. The mean score of the three measurements from both arms was used in this study. Age was calculated based on the date of birth.The methodology of Gutiérrez-Cobo and colleagues  was adopThe comprehensive findings, as presented in The mediation, moderation, and moderated mediation analyses conducted for systolic and diastolic blood pressure are outlined in Moreover, the analysis revealed that TABP also functions as a positive predictor of relaxation, with a coefficient of 0.313 . Conversely, relaxation was identified as a negative predictor of both systolic and diastolic blood pressure. The coefficient for systolic blood pressure was −6.719 , while for diastolic blood pressure, it was −2.400 . These results affirm the concept that higher levels of relaxation correspond to lower systolic and diastolic blood pressure. Subsequent mediation analysis unveiled a significant indirect effect of TABP on systolic and diastolic blood pressure, mediated through relaxation. The coefficient for the indirect effect on systolic blood pressure was −0.878 , and for diastolic blood pressure, it was −0.313 . These findings reinforce the second hypothesis, suggesting that individuals with a high TABP are more inclined to engage in relaxation, resulting in lower levels of both systolic and diastolic blood pressure.Furthermore, the results of the moderation analysis revealed a significant interaction between TABP and relaxation. Moreover, the moderation effect of age was taken into consideration. To estimate the conditional effect of TABP on relaxation, the pick-a-point approach  was emplThese results provide support for the third hypothesis proposed in this study, which suggests that the relationship between TABP and relaxation is influenced by age. After identifying the mediation and moderation effects, a moderated mediation analysis was conducted. The results reveal a significant conditional indirect effect on both systolic and diastolic blood pressure levels. For systolic blood pressure, the coefficient was 0.024 , and for diastolic blood pressure, it was 0.009 . These findings suggest that while TABP indirectly contributes to increased levels of systolic and diastolic blood pressure, the presence of relaxation as a mediating factor becomes particularly beneficial in reducing blood pressure in individuals with TABP, especially within the younger middle-aged adulthood range (40–50 years old). This underscores the importance of relaxation in mitigating the adverse effects of TABP on blood pressure, especially during the middle-aged adult years. By incorporating relaxation practices, individuals in this age group (40–50 years old) may experience a more significant reduction in systolic and diastolic blood pressure levels, thus promoting better cardiovascular health.By addressing the inconsistent research outcomes regarding the relationship between TABP (type A behavior pattern) and blood pressure, this study aimed to further explore the potential roles of age and relaxation as moderating and mediating variables in this association. Age, acknowledged as one of the foremost influential factors in predicting high blood pressure , is beliConsistent with previous findings, this study reinforces the idea that TABP is correlated with elevated blood pressure levels . IndividIndividuals with TABP are more susceptible to experiencing excessive stress, consequently heightening their need for relaxation. Interestingly, the outcomes of this study unveiled a positive association between TABP and relaxation, whereas relaxation was found to exhibit a negative correlation with blood pressure. Moreover, relaxation emerged as a significant mediator in the relationship between TABP and blood pressure. These findings potentially shed light on the inconsistent results observed in previous studies exploring the link between TABP and hypertension. It appears that certain modifiable factors, such as relaxation, hold the potential to influence the connection between TABP and blood pressure. In addition to relaxation, lifestyle adjustments, stress and depression management, and interventions addressing socioeconomic status (SES) have been acknowledged as effective psychosocial measures for reducing hypertension . For indThe results of this study provide support for the hypothesis concerning the moderating role of age. Specifically, the findings indicated a significantly stronger conditional indirect association between TABP, relaxation, and blood pressure among individuals aged 43, compared to those aged 51 and 64. This suggests that relatively younger middle-aged individuals with TABP are more prone to adopting relaxation practices than older individuals with TABP, ultimately resulting in blood pressure reduction. The moderated mediation model illuminated the critical significance of incorporating relaxation practices, particularly for individuals with TABP under the age of 60. Within this age group, a significant indirect relationship between TABP, relaxation, and blood pressure was established, underscoring the key role of relaxation in reducing blood pressure levels for these individuals. Conversely, no significant indirect relationship was observed between TABP and blood pressure among individuals aged 60 and above. These findings emphasize the varying impact of age on the relationship between TABP, relaxation, and blood pressure, suggesting that younger individuals with TABP may derive more substantial benefit from actively embracing relaxation practices to lower their blood pressure. On the other hand, among individuals aged 60 and above, additional factors or mechanisms may come into play, potentially influencing the connection between TABP and blood pressure.The outcome of this study illuminates the underlying factors contributing to the divergent outcomes observed in prior research works concerning the link between TABP and blood pressure. It becomes apparent that the inclusion of diverse moderators and mediators, including age and psychological–behavioral variables, is pivotal in comprehending this intricate association. By incorporating these elements, researchers can attain a more holistic comprehension of how TABP impacts blood pressure and discern effective intervention approaches.Mediating variables, like relaxation in this study, can serve as valuable intervention targets. The findings imply that advocating relaxation practices as a non-pharmacological means to reduce blood pressure could be especially advantageous for individuals under the age of 60 who have been diagnosed with hypertension and exhibit TABP traits. Offering education on comprehending one’s personality and behavioral type, coupled with highlighting the significance of relaxation, can empower individuals with essential knowledge and tools to proactively regulate their blood pressure levels.By customizing interventions according to the distinct characteristics and requirements of individuals, healthcare professionals can enhance the efficacy of their strategies. Acknowledging age as a moderating variable, interventions can be precisely tailored to concentrate on and cater to the necessities of individuals within the younger age group (<60 years old) who are diagnosed with hypertension and manifest TABP traits.The findings of this study hold significant practical implications for the formulation of clinical intervention and prevention programs aimed at individuals in their 40s and 50s exhibiting TABP. Considering the shielding role of relaxation in blood-pressure management, forthcoming initiatives should prioritize the integration of relaxation practices alongside established protective factors like a wholesome diet and consistent exercise.Incorporating stress management initiatives into these interventions can yield considerable benefits. Approaches such as mindfulness-based stress reduction (MBSR) ,30, acceMoreover, it is essential to acknowledge that relaxation training need not be exclusively delivered through professional programs. Encouraging individuals with TABP to consciously embrace relaxation in their daily routines can also yield a positive influence in warding off the onset of hypertension. Engaging in leisure pursuits, carving out dedicated moments of respite, or practicing uncomplicated relaxation practices can collectively contribute to stress reduction and effective blood-pressure management for individuals with TABP.To summarize, the practical implications derived from this study advocate that the forthcoming clinical intervention and prevention initiatives should concentrate on integrating relaxation practices for individuals in their 40s and 50s who exhibit TABP. These programs can encompass stress management methodologies such as MBSR, ACT, and autogenic training. Additionally, promoting relaxation in everyday life through leisurely pursuits and regular intervals of relaxation can further fortify safeguards against hypertension development in individuals with TABP.This study possesses several limitations that warrant acknowledgment. First, the use of cross-sectional data imposes constraints on the capacity to establish causal inferences concerning the relationship between relaxation and blood pressure. The findings derived from this study are founded on statistical assumptions and estimations, underscoring the necessity for further investigations employing longitudinal or panel data. Longitudinal studies would furnish more robust evidence regarding the causal interplay between relaxation and blood pressure, while also delving into how these dynamics may evolve across varying age groups over time.Secondly, despite benefiting from a substantial sample size, this study specifically concentrated on middle-aged individuals in their 40s to 60s. Consequently, the generalizability of the findings to other age brackets might be curtailed. Subsequent research should endeavor to encompass a broader spectrum of age groups, encompassing individuals over 70 years of age, considering the increasing life expectancy trends. Analyzing the interrelation between TABP, relaxation, and blood pressure in older populations can yield valuable insights into potential age-linked distinctions within this association. Thirdly, it is crucial to acknowledge that this study relied on self-report measures. The self-reported responses in this study might exhibit exaggeration, respondents could feel reluctant to divulge private details, and various biases could impact the outcomes, including social desirability bias.Additionally, it should be noted that this study does not account for potential confounding variables that could influence the relationship between TABP, relaxation, and blood pressure. Factors such as family history, lifestyle habits, medication use, comorbidities, socioeconomic status, and other diseases such as diabetes may impact the findings. Future research should aim to control for these confounders to attain a more accurate understanding of the relationship under investigation. Finally, it is essential to acknowledge the limitations of this study, primarily stemming from its reliance on secondary data. While this research endeavors to incorporate the current and pertinent data available, the 2008 data utilized in this study could inadvertently introduce findings that do not align with the latest developments in the field.In conclusion, while this study has contributed to our understanding of the mediating role of relaxation in the relationship between TABP and blood pressure, it is vital to recognize the inherent limitations in the study design. Future research should employ longitudinal data, encompass a broader age spectrum, and account for potential confounding variables to enhance the validity and generalizability of the findings.


Choosing the appropriate management approach for the preterm infant with low blood pressure during the transition period generally involved intervening when the blood pressure drifted below a certain threshold. It is now clear that this approach is too simplistic and does not address the underlying physiology. In this chapter, we explore the many monitoring tools available for evaluation of the hypotensive preterm and assess the evidence base supporting or refuting their use. The key challenge relates to incorporating these outputs with the clinical status of the patient and choosing the appropriate management strategy. For far too long, the management of babies with low blood pressure has been overly standardised; typically, if the mean blood pressure fell below a certain threshold, a series of interventions were executed, the goal of which was to improve the mean blood pressure value, often irrespective of the clinical condition of the infant ,2. EvideThis complexity has driven the development of technologies and strategies aiming to manage this common clinical scenario more precisely. In this review, we will explore the many monitoring tools available for evaluation of the hypotensive preterm. We will assess the current evidence base supporting their use in the preterm population. Whilst these devices may provide very valuable information, the onus of decision making still rests on the bedside clinician. The key challenges relate to making ‘sense’ of the information provided by objective bedside monitoring tools, whether they be continuous or intermittent, and incorporating these findings with the clinical status of the patient at any particular time. Thus, appreciating the shortcomings of clinical evaluation is important, but its inclusion remains critical.Bedside clinical assessment typically includes an evaluation of the newborn’s colour, capillary refill time, urine output, and overall activity level. Not only are these prone to significant variability but, independently, their relationship with cardiovascular instability in preterm infants is also ill-defined. Colour has been shown to be very subjective and prone to significant interrater variability. O’Donnell and colleagues highlighted the marked discrepancy between skin colour and oxygen saturation when neonatologists reviewed video recordings from the delivery suite . Attemptp < 0.0001). A lactate value of ≥6.9 mmol/L has a sensitivity of 77% and specificity of 78% to predict mortality [Bedside measures of lactate and acid–base status are helpful but, again, need to be interpreted carefully secondary to the normal physiological changes that occur in the first days of a preterm infant’s life. Extremely preterm infants experience a normal self-limiting, non-anion gap metabolic acidosis with a peak typically on day four of life. High lactate values at three hours of life have been associated with adverse short-term outcomes in extremely preterm infants . Similarortality . Sequentortality ,24.Preterm infants have a characteristic pattern of urinary output in the first week of life  characteObjective measures readily available at the bedside include heart rate and blood pressure values. Less commonly considered is the pulsatility index. Measures often performed in paediatric and adult intensive care such as central venous pressure measurements are not practical in the care of very preterm infants. Where it has been performed, normal values for CVP in preterm infants have a wide range (2.8–13.9 mmHg), and most infants who have cardiovascular instability during the first days are typically not volume-depleted, thus limiting their clinical utility. Heart rate varies with gestational and postnatal age and can be influenced by many factors, such as stress, temperature, pain, and medication administration. As such, absolute heart rate values may poorly reflect systemic perfusion. Despite its shortfalls, valuable information may also be obtained by interrogation of its evolution over time, and it is an important parameter to always consider.The primary driver of intervention remains the mean blood pressure (BP) value, measured either invasively or noninvasively. Noninvasive BP measurements can be challenging . The Haeassociated with severe intracranial haemorrhage, ischemic cerebral lesions, or death within 48 h in a cohort of 33 infants of less than 31 weeks’ gestation [Numerous BP reference ranges exist, a comparison of which reveals notable differences. Ranges are often based on gestational age, birth weight, and postnatal age criteria ,32,33,34estation . No seveestation . It is aestation ,38.The different components of the BP measurement may give us greater insight into the underlying circulatory status. The systolic component largely reflects left ventricular contractility. Low systolic pressures, therefore, may be caused by a decreased preload, an increase in left ventricular afterload, or a reduction in myocardial contractility. Diastolic blood pressure reflects the resting vascular tone and the intravascular blood volume and is important in determining coronary blood flow. Causes of diastolic hypotension include reduced preload and/or decreased systemic vascular resistance. Thus, considering these individual components may provide better insight into the underlying physiology.Whilst awareness of the limitations of BP monitoring is essential, it remains an important biomarker of circulatory status. One should be cognisant of the natural increase in BP in the first days and that BP does not equate directly with flow. It should be incorporated into decision-making algorithms but rarely be the sole criterion to initiate therapy. Perhaps it is best to think of blood pressure values in terms of evaluation pressures and trigger pressures. Unlike assessing a child with neonatal encephalopathy and deciding on instituting therapeutic hypothermia, no such validated scoring system or assessment tool is available to guide interventions in preterm infants at risk of cardiovascular instability, a condition much more readily encountered in the neonatal unit. What is clear is that there is significant value in including clinical, biochemical, and objective bedside data prior to deciding on management approaches. Perhaps one of the greatest additions to this assessment over the last 10 years has been the incorporation of echocardiography to enhance decision making.Echocardiography use in the neonatal intensive care unit (NICU) has grown exponentially over the last decade as evidenced by an increase in publications relating to its use, the growth of numerous targeted neonatal echocardiography (TNE) programmes across the world , and theOver the last 10 years, guidance on neonatal haemodynamic assessment with TNE has evolved but is primarily by consensus and experience . While rThe exact role of echocardiography in the evaluation of the hypotensive preterm infant has yet to be delineated. Measurements such as volume status and right and left ventricular output may not be as useful in this population. There is no agreed objective measure of volume status in the preterm infant. TNE measurements commonly used for this aim include inferior vena cava diameter. Markers of the inferior vena cava diameter are often of limited use in this population given their inaccuracy with positive pressure ventilation. Left ventricular end-diastolic diameter is influenced by variations in preload and afterload. Measures of cardiac output are prone to shunt-related effects, and determining normative ranges is problematic. More advanced tissue doppler imaging may overcome some of these challenges. While TNE may provide valuable information regarding cardiac dysfunction or other abnormalities, in the setting of transitional hypotension with normal clinical parameters, a normal TNE assessment should provide reassurance that non-intervention is appropriate, thus avoiding potentially harmful medications.Thus, several questions remain to be answered. Should all preterm infants of less than 28 weeks’ gestation have an early echo performed to identify potential cardiovascular compromise? This would be very resource-heavy and would result in a significant number of infants having an echocardiogram performed who ultimately do not require the handling involved in performing an echocardiogram. Should only those infants deemed to be at risk of cardiovascular compromise have an echocardiogram performed? They may be difficult to identify but may include those not in receipt of antenatal corticosteroids or delayed cord clamping, those mechanically ventilated, and perhaps the more extreme preterm infants such as those born below a certain gestational age, e.g., below 25 weeks. Should only those infants who demonstrate potential cardiovascular compromise have an echocardiogram performed, such as those with a borderline mean blood pressure so-called ‘evaluating blood pressure’? These questions remain to be answered. Ultimately, the information provided by echocardiography may help to better understand the underlying problem but may not be sufficient to accurately identify low-flow states in such a complex transitional circulation. Other technologies are required to augment our assessment of end-organ blood flow. These are outlined in 2), renal, and peripheral muscle oximetry as measured by NIRS to improve outcomes relating to cardiovascular dysfunction, PDA, and necrotising enterocolitis (NEC). While the technology is safe and has been adopted into routine clinical practice in many centres, the evidence to support resultant improvement in outcomes is lacking. The evaluation of ArSO2 as an assessment tool for necrotising enterocolitis (NEC) is ongoing, but, as NEC aetiology is considered multifactorial and not solely rooted in low-blood-flow states, its discussion is outside the scope of this review. Furthermore, no work has been conducted to simultaneously assess splanchnic blood flow and ArSO2 [Indirect, continuous, objective, and noninvasive monitoring of end-organ perfusion is possible using near-infrared spectroscopy (NIRS). Commercially available neonatal NIRS sensors have been developed with the primary focus of cerebral monitoring, and several centres have highlighted the potential short- and long-term benefits of cerebral NIRS monitoring ,53,54,55nd ArSO2 . Hypotennd ArSO2 . This nond ArSO2 .2. Nevertheless, a few studies have demonstrated that CrSO2 values are not significantly different between preterm infants with and without mild to moderate hypotension [2 was no different in those treated with dopamine compared to placebo, indicating that simply improving mean arterial pressure may not mitigate the adverse outcome. Transfer function gain, a derived parameter from the CrSO2 signal, may be a better marker of impaired autoregulation in hypotensive infants than the absolute values [Studies that have evaluated cerebral and peripheral NIRS concurrently note differences in readings presumably because of adaptive cerebral blood flow due to cerebral autoregulation (CAR). However, in the context of hypotension, very premature infants are at greater risk of cerebral injury given their immature CAR pathways. It is presumed that in such circumstances, failure of autoregulatory capacity would be reflected by falling CrSOotension ,59. Pichotension . The abootension . We prevotension . Howevere values . Ultimate values . The tere values ,66. The r = 0.71, p < 0.001). Interestingly, infants developing intraventricular haemorrhage and/or necrotising enterocolitis showed initial lower CO followed by a more pronounced increase, suggesting ischemia-reperfusion injury as a pathophysiological mechanism. Furthermore, the lowest registered CO was lower in infants with adverse outcomes, while the lowest mean BP did not differ significantly between the groups. Hence, NICOM seems to provide a more sensitive marker of haemodynamic imbalance in transitioning preterm infants compared to the traditional monitoring of BP. However, the study was conducted on a small population with few adverse outcomes, and a formal analysis of the predictive value of CO in the case of hypotension was not performed. Despite these encouraging reports, concerns remain regarding NICOM accuracy in particular conditions commonly encountered in sick preterm infants during the transition, such as invasive and noninvasive ventilation [Cardiac output (CO) is a key physiological parameter to assess the haemodynamic status of transitioning infants, being one of the major determinants of arterial BP in combination with systemic vascular resistance. A complex interplay exists between these forces to determine systemic blood flow and end-organ perfusion. Low- and high-CO states have been associated with increased morbidity and mortality and adverse neurodevelopmental and respiratory outcomes ,68. As ttilation ,79,82, ttilation ,83, and tilation . Hence, An alternate method of assessment of end-organ blood flow is to measure brain activity with EEG or aEEG. A normal EEG in the setting of low blood pressure or cardiac output may suggest that cerebral autoregulation is intact. However, this is something not routinely utilised in preterm infants in this setting, and EEG assessment is also very much gestation-dependent. However, a few groups have explored the relationship between measures of brain activity and cardiac output/blood pressure. Weindling et al., in an observational study of 35 very low birth weight infants, found that cerebral activity was abnormal when the mean blood pressure was less than 23 mmHg, but the overall number with abnormal EEG was low . In a siAn enormous amount of continuous physiological data are generated daily for an individual NICU patient. This extraordinarily rich data source is currently underappreciated and, in many centres, underutilised. Often, the data are captured in the patient electronic health records hourly, which significantly limits its potential usefulness. Real-time continuous monitoring of heart rate, blood pressure, the pulsatility index, oxygen saturation, carbon dioxide, cerebral and somatic oxygenation, and EEG and, ultimately, developing decision support tools are very appealing and would allow a more personalised approach to care. Understanding the complexity of cardiovascular physiology in the first days of life and trying to decipher the interplay between many of these parameters is key. Neonatal care has seen some recent advances in the diagnosis and management of certain conditions utilising real-time data acquisition. Heart rate variability has proved useful in detecting infants at risk of sepsis . SeizureEfforts have been made to develop real-time haemodynamic monitoring systems but remain a long way off from incorporating them routinely into clinical care. With advances in biomedical engineering, the capability to collect, filter, store, and analyse huge quantities of physiological data is now feasible. Relating these to clinical outcomes, utilising artificial intelligence, and developing decision support tools are the next key steps. Some centres have developed such ‘monitoring towers’ to allow the capture of these data . Others The evaluation of cardiovascular compromise at the bedside remains a key challenge in neonatology. The goal is to identify infants at the earliest stage possible stage to initiate therapies to avoid unnecessary morbidity and, importantly, to prevent the unnecessary use of potentially deleterious interventions. In the early stages of cardiovascular compromise, clinical evaluation may be falsely reassuring, thus introducing the necessity to re-evaluate the infant frequently. Echocardiography can provide important objective measures of cardiovascular status and currently remains the most important objective monitoring tool currently available. Continuous bedside tools such as cerebral NIRS may be important. NICOM is very appealing but has many limitations at present. The development of multimodal monitoring platforms with incorporated decision support tools has the potential to transform the diagnosis and management of cardiovascular compromise. The next decade should see a paradigm shift in the evaluation of preterm cardiovascular instability.


Although chronic kidney disease (CKD) can be detected by relatively simple blood and urine tests, it remains underdiagnosed even in patients at high risk for the disease. Deep learning-based approaches are now being developed to detect CKD based on electrocardiogram (ECG) data. Communications Medicine article on deep learning-based detection of chronic kidney disease using ECGs. The author interprets the study’s findings in light of its limitations and outlines key considerations in the clinical implementation of such an approach.Kooman outlines the findings of a  According to eGFR, CKD is subdivided into five different stages, with stage 5 indicating kidney failure. CKD is estimated to be the 12th leading cause of death worldwide. The global prevalence is estimated to exceed 800 million cases1. Changes in lifestyle factors and early treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers can delay progression of CKD as well as cardiovascular disease2. Nevertheless, many patients with CKD remain undetected, even those with risk factors such as hypertension2.Chronic kidney disease is a long-term condition involving abnormalities of kidney structure or function that can impact patients’ health. The diagnosis requires either an estimated glomerular filtration rate (eGFR)—a measure of kidney function—below 60 ml/min/1.73 mCommunications Medicine, Holmstrom et al. describe a potential screening approach using a convolutional neural network-based deep learning model to detect CKD from ECG waveforms3. Deep learning is a type of machine learning-based artificial intelligence inspired by the human brain, whereby multiple layers of algorithms called convolutional neural networks learn from unstructured data to perform classification or prediction tasks.In an article now published in 4, are exciting advances which, if further validated and implemented in the clinic, have the potential to improve detection of patients with CKD using data routinely acquired for other purposes. Here, the findings and clinical implications of the study by Holmstrom et al. are discussed, along with similar studies.The model developed by Holmstrom et al., and similar recently developed approachesThe primary cohort studied by Holmstrom et al. consisted of 111,370 patients and included 247,655 ECGs, of which 100,233 were randomly allocated to the training set and 11,137 to the test set. The model achieved an accuracy of 0.767 in the primary cohort and 0.709 in an external validation cohort. Accuracy was higher with more advanced stages of CKD and in younger patients. This might be explained by the fact that on one hand, ECG alterations are more likely to be prevalent in patients with more advanced CKD, whereas in younger patients, ECG abnormalities due to causes other than CKD are less prevalent.The definition of CKD was based on ICD-9/10 codes, identifying 7816 patients with a diagnosis of CKD in the primary cohort who had an ECG taken within a 1-year window of a CKD diagnosis. Aside from this relatively long time window, which is of potential relevance because renal function may significantly change over this time period, an important limitation of the study is that data on eGFR were available in only 49% of patients at any point in time. Thus, in 51% of cases, diagnosis only appeared to be dependent on the ICD-9 definition and no connection with the level of kidney function impairment could be made. Moreover, it cannot be excluded that in the population without an ICD-9 diagnosis of CKD, renal impairment might still be prevalent given the fact that CKD is underdiagnosed in the general population. The cohort might also not be representative of the general population, given the relatively high prevalence of end stage kidney failure (2.6%) and because the indication to perform an ECG by itself will introduce selection bias, as the prevalence of CKD is higher in patients with cardiovascular disease. Still, despite these limitations, the fact that model performance was similar in the population in which data on eGFR or albuminuria were present, the consistency of the model performance in different subgroups and comparable performance in the external validation cohort provides confidence that the reported data are sufficiently robust.5. In a population-based cohort, reduced eGFR and albuminuria were associated with an increase in the cardiac biomarkers troponin T and I indicating cardiac damage6. In the same cohort, changes in these cardiac biomarkers were associated with ECG alterations suggestive of cardiac damage7. In more advanced stages of CKD, ECG abnormalities were also related to cardiovascular mortality8. The ability of deep learning models to detect CKD based on ECG changes is therefore likely explained by the high prevalence of these subclinical abnormalities, which result in subtle changes that can remain undetected on routine ECG interpretation. In the study by Holmstrom et al., ECG changes identified to be associated with CKD were primarily observed in the QRS complex and PR interval.Subclinical cardiac abnormalities, such as myocardial fibrosis and left ventricular hypertrophy, are frequently present in patients with kidney dysfunction, even if it is mild9, and can be predictive of other electrolyte imbalances10. While detailed data on electrolytes were not available in the study of Holmstrom et al., the accuracy of the model was similar in patients with and without hyperkalemia in the subgroup where potassium levels were available, which suggest that variations in potassium levels did not have a major influence on the detection of CKD by the model.An important possible confounder in the interpretation of ECG changes in patients with CKD are abnormalities in serum potassium. Deep learning models based on ECG interpretation have been validated for the detection of hyperkalemia4. In that study, the model was trained to detect an eGFR level of <45 ml/min/1.73 m2 (i.e. stage 3B or higher). Accuracy of the model was higher in the study of Kwon et al., which might be due to the fact that data on eGFR were available for all patients or that only patients with a more pronounced decline in renal function were included, with demographic features also included in the model. This study did not, however, evaluate the detection of earlier stage CKD, such as stage 3A disease that is less severe but nevertheless still associated with increased cardiovascular mortality.In support of the present study, another study by Kwon et al. also assessed the prediction of CKD by ECG analysis using a deep learning model based on convolutional neural networks11. As in CKD, left ventricular hypertrophy and myocardial fibrosis are also common in patients with diabetes and might induce comparable ECG changes. As detailed data on (pre)diabetic status and blood pressure control were missing in the study by Holmstrom et al., the question remains to which extent the model in the study is specific for CKD. As the relation between ECG changes and CKD is likely mediated by subclinical cardiac injury, it may also miss patients with CKD without cardiac damage. However, although this needs to be addressed in future studies, the model may indicate those patients with CKD who are at higher risk for adverse cardiovascular outcomes. Interestingly, in a study where a deep learning model was applied to predict hypo- or hyperkalemia from ECGs, the risk of mortality was higher in those patients where the model indicated abnormalities in serum potassium as compared to laboratory values12. This is also relevant for patients with CKD, given the increased prevalence of hyperkalemia and the associated mortality risk in these patients.Machine learning models based on ECG analysis have also been used in the detection of various types of heart failure, as well as other chronic diseases such as diabetes mellitus4, analysis of single lead (I)-ECG resulted in a comparable model performance as compared to the 12-lead ECG. Twelve-lead ECG provide a far more complete of the heart’s electrical activity compared to a single-lead ECG, but is not available in a wearable format. Their comparable performance in this study is of relevance since some newer generation smartwatches are able to perform single lead (I) ECG measurements13, which suggests it might one day be possible to detect CKD with a smartwatch in the general population.Both in the study of Holmstrom et al. as in the study by Kwon et al.14. Artificial intelligence models that process more granular data from different sources, including ECGs, might be useful as prescreening tools15. These could be followed by more detailed measurements of health status, including blood pressure, and measurements of glucose, renal function and albuminuria.At present, given the relatively low sensitivity and specificity, detection of CKD by ECG features alone might not be suitable for widespread implementation as a screening method. However, predictive power may be improved by addition of data from other sources. Recently, it was shown that a machine learning model based on physiological measurements from wearable devices was able to predict to some extent laboratory parameters including blood urea nitrogen16.The remaining question is how, with further validation, the models developed by Holmstrom et al. and Kwon et al. could find their way into future clinical practice. A relatively straightforward way would be to incorporate the model into automated analysis of 12-lead ECG, indicating the need for further analysis in a patient identified at risk of CKD. As ECGs are generally performed for a specific reason, patients have already entered the healthcare system and adding another analysis step might not be too difficult, providing patients have provided consent for this. A different scenario is the one described above, in which data from wearable devices, which may include single lead ECG measurements, are used to identify persons at risk in a general population. In this case, the number of false positive cases is likely high and may be associated with health anxiety and a larger demand on the healthcare system. Moreover, there may be concerns with digital and societal equity as smart wearables may have substantial costs and therefore not be accessible for all socioeconomic groups. For smartwatch-based detection of atrial fibrillation, various ethical and data privacy concerns have also been raised, such as underrepresentation of minority groups in the training data and storage of medical data by commercial partiesCommunications Medicine may be a welcome aid by prompting the subsequent use of conventional screening tools. However, even with successful validation, applying these tools on a population basis using wearable sensors would introduce additional ethical, societal, and regulatory challenges that would need to be carefully considered.In conclusion, the application of deep learning to detect CKD based on ECG data, as proposed by Holmstrom et al., is an interesting application of a widely used technology will need to be followed by additional validation studies, which should consider integration of different data types. These studies should be performed both in high-risk patients as well as in population-based cohorts, and in patients of different sexes or genders, ethnicities and from different geographical locations. As CKD, even in high-risk populations such as patients with hypertension, remains underdiagnosed, new methods such as the one described in


Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a new subtype listed by the 2016 World Health Organization (WHO) classification, which occurred in end-stage renal disease (ESRD) patients. This study will present the imaging characteristics of the four cases diagnosed with ACD-RCC. Ultrasound is expected to help detect abnormalities early in the follow-up of patients on regular dialysis, allowing patients to receive early treatment.We searched the pathology database of our hospital for all inpatients diagnosed with ACD-RCC between January 2016 and May 2022. Pathology, ultrasound, and radiology readings are performed by experienced physicians with the title of attending physician or higher. Four cases were included in this study, all of whom were male, aged from 17 to 59. Two cases suffered from ACD-RCC in both kidneys, and kidney nephrectomies were performed. One case underwent renal transplantation, whose creatinine was back to normal, and the rest were on hemodialysis. On the pathological images, heteromorphic cells and oxalate crystals can be seen. Both ultrasound and enhanced CT showed an enhancement of the solid component of the occupancy. We followed up with outpatient and telephone visits.In clinical work, ACD-RCC should be considered when the mass appears in the background of multiple cysts in the kidney in patients with ESRD. A timely diagnosis will help with treatment and prognosis. Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a new subtype in the light of the 2016 World Health Organization (WHO) classification, which occurred in end-stage renal disease (ESRD) patients . The maiAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). The need for informed consent was waived.All inpatients diagnosed with ACD-RCC from January 2016 to May 2022 were searched in the pathology database of our hospital. Experienced physicians with the title of attending physician or higher performed ultrasound, radiology, and pathology imaging reading. A total of four cases  were included, all of whom had a history of CKD. Two cases received nephrectomies due to bilateral ACD-RCC, while the remaining two underwent unilateral nephrectomies. One of the cases underwent a kidney transplant and his creatine levels returned to normal, while the rest were on hemodialysis.Case 1 is a 58-year-old man diagnosed with chronic kidney disease (CKD) 20 years ago, in regular hemodialysis for more than 15 years, and renal hypertension for more than 20 years, who was admitted to the hospital in 2017 for a right renal occupancy. The contrast-enhanced ultrasonography (CEUS) of the kidney (sulfur hexafluoride microspheres) demonstrated that the parenchyma of both kidneys was echogenically enhanced, with indistinct corticomedullary demarcation. A cystic-solid mixed echogenic nodule of approximately 1.8 × 1.5 cm in size with clear borders and regular morphology was detected in the middle part of the right kidney, which was deeply enhanced in the cortical phase and low enhanced in the medulla phase. Multiple cysts were detected in both kidneys, with well-defined borders and regular morphology, and dotted echogenicity was seen in part of the capsule wall. Acquired cystic lesions and possible tumor lesions in the right kidney were considered in the enhanced CT. The ultrasound and enhanced CT images are shown in Case 2, a 39-year-old man with a history of CKD for more than 10 years and a history of hemodialysis for more than 7 years, was admitted to the hospital in 2016 for a physical exam that revealed an occupied right kidney. CT examination suggested that “a lobulated mass protruded from the lower lateral part of the right kidney with calcified spots inside and partially enhanced under the background of chronic nephritis, where the kidney cancer cannot be excluded.” The ultrasound examination showed a hypoechoic mass sized 4.1 × 2.5 × 3.1 cm, where there was sparse blood flow, surrounded by ring-like echogenic with dot echogenic focus inside under the background of multiple cysts . Post-operative pathology and immunohistochemistry showed that it accorded to ACD-RCC. He presented to the local hospital again in 2018 for right side back pain. CT demonstrated multiple cysts in the right kidney and the possibility of right kidney hemorrhage. He then underwent a nephrectomy on his right kidney. Post-operative pathology and immunohistochemistry of the right kidney demonstrated that there was calcium oxalate crystal deposition, and expressed CK7, RCC, CD10, PAX2, and CAIX immunohistochemical markers, which accorded with ACD-RCC , with a number having cystic components . BerkenbGenerally, ACD-RCC is considered to be indolent and has a favorable prognosis, whose standard treatment is partial or total nephrectomy . The NCCThere were some limitations in our study. Firstly, the number of cases is small. In the future, we will enlarge the sample size to acquire more generalizable ultrasound features to provide some reference for the early diagnosis of ACD-RCC. Secondly, some imaging examinations were absent, and only one case did CEUS. More cases are needed to summarize its imaging features.ACD-RCC occurs frequently in ESRD patients with ACD who generally have a lengthy history of dialysis. For these patients, a regular ultrasound or CT examination of the kidney system is necessary. In spite of its indolent behavior, a timely diagnosis will result in a favorable prognosis for the patient.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Biomedical Ethics Review Meeting of West China Hospital of Sichuan University. Written informed consent was obtained from the patients/participants for the publication of this case report.YY performed the case series and wrote the manuscript. Besides, HC is the Equal & First author in this manuscript. HC and YL supported the data collection and manuscript revision. JZ supervised the writing and revision of the manuscript. All authors contributed to the article and approved the submitted version.