Intradialytic hypotension (IDH) is a severe complication of hemodialysis (HD) with a significant impact on morbidity and mortality. In this study, we used a wearable device for the continuous monitoring of hemodynamic vitals to detect hemodynamic changes during HD and attempted to identify IDH. End-stage kidney disease patients were continuously monitored 15 min before starting the session and until 15 min after completion of the session, measuring heart rate (HR), noninvasive cuffless systolic and diastolic blood pressure (SBP and DBP), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR). Data were analyzed retrospectively and included comparing BP measured by the wearable devices (recorded continuously every 5 s) and the cuff-based devices. A total of 98 dialysis sessions were included in the final analysis, and IDH was identified in 22 sessions (22.5%). Both SBP and DBP were highly correlated (r > 0.62, p < 0.001 for all) between the wearable device and the cuff-based measurements. Based on the continuous monitoring, patients with IDH had earlier and more profound reductions in SBP and DBP during the HD treatment. In addition, nearly all of the advanced vitals differed between groups. Further studies should be conducted in order to fully understand the potential of noninvasive advanced continuous monitoring in the prediction and prevention of IDH events.

Background Respiratory rate (RR) is used for the diagnosis and management of medical conditions and can predict clinical changes. Heavy workload, understaffing, and errors related to poor recording make it underutilized. Wearable devices may facilitate its use. Methods RR measurements using a wearable photoplethysmography-based monitor were compared with medical grade devices in complementary clinical scenarios: Study one included a comparison to a capnograph in 35 healthy volunteers; Study two included a comparison to a ventilator monitor in 18 ventilated patients; and Study three included a comparison to capnograph in 92 COVID-19 patients with active pulmonary disease. Pearson’s correlations and Bland-Altman analysis were used to assess the accuracy and agreement between the measurement techniques, including stratification for Body Mass Index (BMI) and skin tone. Statistical significance was set at p ≤ 0.05. Results High correlation was found in all studies (r = 0.991, 0.884, and 0.888, respectively, p < 0.001 for all). 95% LOA of ±2.3, 1.7-(−1.6), and ±3.9 with a bias of < 0.1 breaths per minute was found in Bland-Altman analysis in studies 1,2, and 3, respectively. In all, high accordance was found in all sub-groups. Conclusions RR measurements using the wearable monitor were highly-correlated with medical-grade devices in various clinical settings. Trial registration ClinicalTrials.gov , https://clinicaltrials.gov/ct2/show/NCT03603860 .

Introduction: Body temperature is essential for diagnosing, managing, and following multiple medical conditions. There are several methods and devices to measure body temperature, but most do not allow continuous and prolonged measurement of body temperature. Noninvasive skin temperature sensor combined with a heat flux sensor, also known as the “double sensor” technique, is becoming a valuable and simple method for frequently monitoring body temperature.Methods: Body temperature measurements using the “double sensor” method in a wearable monitoring device were compared with oral and core body temperature measurements using medical grade thermometers, analyzing data from two prospective clinical trials of different clinical scenarios. One study included 45 hospitalized COVID-19 patients in which oral measurements were taken using a hand-held device, and the second included 18 post-cardiac surgery patients in which rectal measurements were taken using a rectal probe.Results: In study 1, Bland-Altman analysis showed a bias of −0.04°C [0.34–(−0.43)°C, 95% LOA] with a correlation of 99.4% (p < 0.001). In study 2, Bland-Altman analysis showed a bias of 0.0°C [0.27–(−0.28)°C, 95% LOA], and the correlation was 99.3% (p < 0.001). In both studies, stratifying patients based on BMI and skin tone showed high accordance in all sub-groups.Discussion: The wearable monitor showed high correlation with oral and core body temperature measurements in different clinical scenarios.

Supplementary Table from An Exercise-Induced Metabolic Shield in Distant Organs Blocks Cancer Progression and Metastatic Dissemination

Background: Currently-used tools for early recognition of clinical deterioration have high sensitivity, but with low specificity and are based on infrequent measurements. We aimed to develop a pre-symptomatic and real-time detection and warning tool for potential patients' deterioration based on multi-parameter real-time warning score (MPRT-WS). Methods: A total of more than 2 million measurements were collected, pooled, and analyzed from 521 participants, of which 361 were patients in general wards defined at high-risk for deterioration and 160 were healthy participants allocation as controls. The risk score stratification was based on cutoffs of multiple physiological parameters predefined by a panel of specialists, and included heart rate, blood oxygen saturation (SpO2), respiratory rate, cuffless systolic and diastolic blood pressure (SBP and DBP), body temperature, stroke volume (SV), cardiac output, and systemic vascular resistance (SVR), recorded every 5 min for a period of up to 72 h. The data was used to define the various risk levels of a real-time detection and warning tool, comparing it with the clinically-used National Early Warning Score (NEWS). Results: When comparing risk levels among patients using both tools, 92.6%, 6.1%, and 1.3% of the readings were defined as "Low", "Medium", and "High" risk with NEWS, and 92.9%, 6.4%, and 0.7%, respectively, with MPRT-WS (p = 0.863 between tools). Among the 39 patients that deteriorated, 30 patients received 'High' or 'Urgent' using the MPRT-WS (42.7 ± 49.1 h before they deteriorated), and only 6 received 'High' score using the NEWS. The main abnormal vitals for the MPRT-WS were SpO2, SBP, and SV for the "Urgent" risk level, DBP, SVR, and SBP for the "High" risk level, and DBP, SpO2, and SVR for the "Medium" risk level. Conclusion: As the new detection and warning tool is based on highly-frequent monitoring capabilities, it provides medical teams with timely alerts of pre-symptomatic and real-time deterioration.

Background Recent technological developments enable big data-driven insights on diurnal changes. This study aimed to describe the trajectory of multiple and advanced parameters using a medical-grade wearable remote patient monitor. Methods Parameters were monitored for 24 h in 256 ambulatory participants who kept living their normal life. Parameters included heart rate, blood pressure, stroke volume, cardiac index, systemic vascular resistance, blood oxygen saturation, and respiratory rate. Diurnal variations were evaluated, and analyses were stratified based on sex, age, and body mass index. Results All parameters showed diurnal changes ( p < 0.001). Females demonstrated higher heart rate and cardiac index with lower systemic vascular resistance. Obese participants had a higher blood pressure, and lower stroke volume and cardiac index. Systemic vascular resistance was higher among the elderly. Diurnal changes corresponded with awake–sleep hours and differed between sex, age, and body mass index groups. Conclusion Wearable monitoring platforms could decipher hemodynamic changes in subgroups of individuals, and might help with efforts to provide personalized medicine, pre-symptomatic diagnosis and prevention, and drug development.

Sexual dimorphisms are responsible for profound metabolic differences in health and behavior. Whether males and females react differently to environmental cues, such as solar ultraviolet (UV) exposure, is unknown. Here we show that solar exposure induces food-seeking behavior, food intake, and food-seeking behavior and food intake in men, but not in women, through epidemiological evidence of approximately 3,000 individuals throughout the year. In mice, UVB exposure leads to increased food-seeking behavior, food intake and weight gain, with a sexual dimorphism towards males. In both mice and human males, increased appetite is correlated with elevated levels of circulating ghrelin. Specifically, UVB irradiation leads to p53 transcriptional activation of ghrelin in skin adipocytes, while a conditional p53-knockout in mice abolishes UVB-induced ghrelin expression and food-seeking behavior. In females, estrogen interferes with the p53–chromatin interaction on the ghrelin promoter, thus blocking ghrelin and food-seeking behavior in response to UVB exposure. These results identify the skin as a major mediator of energy homeostasis and may lead to therapeutic opportunities for sex-based treatments of endocrine-related diseases.

OBJECTIVES:. Cardiac output (CO) measurements in the ICU are usually based on invasive techniques, which are technically complex and associated with clinical complications. This study aimed to compare CO measurements obtained from a noninvasive photoplethysmography-based device to a pulse contour cardiac output device in ICU patients. DESIGN:. Observational, prospective, comparative clinical trial. SETTING:. Single-center general ICU. PATIENTS:. Patients admitted to the general ICU monitored using a pulse contour cardiac output device as per the decision of the attending physician. INTERVENTIONS:. Parallel monitoring of CO using a photoplethysmography-based chest patch device and pulse contour cardiac output while the medical team was blinded to the values obtained by the noninvasive device. MEASUREMENTS AND MAIN RESULTS:. Seven patients (69 measurements) were included in the final analysis. Mean CO were 7.3 ± 2.0 L/m and 7.0 ± 1.5 L/m for thermodilution and photoplethysmography, respectively. Bland-Altman showed that the photoplethysmography has a bias of 0.3 L/m with –1.6 and 2.2 L/m 95% limit of agreement (LOA) and a bias of 2.4% with 95% LOA between –25.7% and 30.5% when calculating the percentage of difference from thermodilution. The values obtained by thermodilution and photoplethysmography were highly correlated (r = 0.906). CONCLUSIONS:. The tested chest patch device offers a high accuracy for CO compared to data obtained by the pulse contour cardiac output and the thermodilution method in ICU patients. Such devices could offer advanced monitoring capabilities in a variety of clinical settings, without the complications of invasive devices.

The relationship between changes in the various biochemical, performance, biomechanical, and perceptual markers throughout the recovery period from an aerobic-based protocol causing exercise-induced muscle damage remains unclear. Objective: To explore the relationship between changes in biochemical, performance, perceptual and biomechanical indices immediately post and up to 48 h following an aerobic-based muscle damaging exercise. Methods: Recreationally active men (n = 28; 35 ± 10 y; 75.9 ± 11.2 kg; 474 ± 204 min/week of endurance training) completed 60-min downhill run (DHR) on a treadmill at -10% incline and at 60% of maximal heart rate. Blood markers of muscle damage (creatine kinase (CK) and lactate dehydrogenase (LDH), inflammation (interleukin (IL)-6, TNF-a), perception of muscle soreness using 1-15 visual analog scale (VAS), maximal isometric voluntary contraction (MVC) of the knee extensors, counter-movement jump (CMJ), running biomechanics [stride-length and cadence] were recorded at baseline, immediately-post, 30 min, 120 min, 24 h, and 48 h post DHR protocol. Correlations between markers, as percentage change relative to baseline, were evaluated using Pearson’s r. Results: First, elevated levels of CK at 24 h (∆335%) and 48 h (∆175%) post the DHR protocol were statistically correlated (p < 0.05) with the following at 24 h and 48 h: increases in VAS (r = 0.44 and 0.45, respectively), decreases in stride-length (r = -0.57 to -0.43, respectively), and increases in cadence (r = 0.55 to 0.45, respectively). Second, elevated levels of IL-6 at 48 h post the DHR (∆16%) were statistically correlated with reductions (∆ -14 to -24%) in MVC at all-time points (r = -0.62 to -0.74). Third, lower levels of the proinflammatory cytokine TNF-a at 48H (∆25%) were statistically correlated with reductions in CMJ at 30 min to 48 h (∆ -11 to -6%; r = -0.45 to -0.57). Conclusion: Biochemical perturbations are moderately to strongly correlated with heightened perception of muscle soreness, alternation in running biomechanics, and reductions in force production and jump height. Accordingly, these subjective, biomechanical and performance outcomes can be carefully used to assess the severity of muscle damage when invasive biochemical measures are unavailable.

There are no clear guidelines for diuretic administration in heart failure (HF), and reliable markers are needed to tailor treatment. Continuous monitoring of multiple advanced physiological parameters during diuresis may allow better differentiation of patients into subgroups according to their responses. In this study, 29 HF patients were monitored during outpatient intravenous diuresis, using a noninvasive wearable multi-parameter monitor. Analysis of changes in these parameters during the course of diuresis aimed to recognize subgroups with different response patterns. Parameters did not change significantly, however, subgroup analysis of the last quartile of treatment showed significant differences in cardiac output, cardiac index, stroke volume, pulse rate, and systemic vascular resistance according to gender, and in systolic blood pressure according to habitus. Changes in the last quartile could be differentiated using k-means, a technique of unsupervised machine learning. Moreover, patients’ responses could be best clustered into four groups. Analysis of baseline parameters showed that two of the clusters differed by baseline parameters, body mass index, and diabetes status. To conclude, we show that physiological changes during diuresis in HF patients can be categorized into subgroups sharing similar response trends, making noninvasive monitoring a potential key to personalized treatment in HF.

Purpose: Compare recovery rates between active young (Y) and middle-aged (MA) males up to 48H post aerobically based, exercise-induced muscle damage (EIMD) protocol. A secondary aim was to explore the relationships between changes in indices associated with EIMD and recovery throughout this timeframe.Methods: Twenty-eight Y (n = 14, 26.1 ± 2.9y, 74.5 ± 9.3 kg) and MA (n = 14, 43.6 ± 4.1y, 77.3 ± 12.9 kg) physically active males, completed a 60-min downhill running (DHR) on a treadmill at −10% incline and at 65% of maximal heart rate (HR). Biochemical, biomechanical, psychological, force production and muscle integrity (using MRI diffusion tensor imaging) markers were measured at baseline, immediately-post, and up to 48H post DHR.Results: During the DHR, HR was lower (p < 0.05) in MA compared to Y, but running pace and distance covered were comparable between groups. No statistical or meaningful differences were observed between groups for any of the outcomes. Yet, Significant (p < 0.05) time-effects within each group were observed: markers of muscle damage, cadence and perception of pain increased, while TNF-a, isometric and dynamic force production and stride-length decreased. Creatine-kinase at 24H-post and 48H-post were correlated (p < 0.05, r range = −0.57 to 0.55) with pain perception, stride-length, and cadence at 24H-post and 48H-post. Significant (p < 0.05) correlations were observed between isometric force production at all time-points and IL-6 at 48H-post DHR (r range = −0.62 to (−0.74).Conclusion: Y and MA active male amateur athletes recover in a comparable manner following an EIMD downhill protocol. These results indicate that similar recovery strategies can be used by trainees from both age groups following an aerobic-based EIMD protocol.

Abstract Background Recent technological developments enable non-invasive monitoring of advanced hemodynamic parameters, allowing big data-driven insights on diurnal changes for the first time. This study aimed to describe the trends of multiple advanced cardiovascular parameters among ambulatory individuals using a medical grade wearable monitor. Methods Common and advanced cardio-respiratory parameters were monitored for 24 hours in ambulatory volunteers using a photoplethysmography-based wearable monitor. The multi vital ambulatory monitoring (MVAM) included stroke volume (SV), cardiac index (CI), systemic vascular resistance (SVR), blood oxygen saturation (SpO2), respiratory rate (RR), systolic (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), and heart rate (HR). Diurnal variations were evaluated among all participants, and analyses were stratified based on sex, age, and body-mass index (BMI). Results A total of 256 participants were included in the analysis. All measured parameters showed significant (p<0.001) diurnal changes. Nighttime values were lower excluding RR and SVR, reaching the nadir at 5 am, and then increasing to a maximum at 10 am, plateauing, and then gradually declining from 7 to 8 pm. CI demonstrated a reduction of 0.6 L/min/m2 (20%), while SVR demonstrated the opposite trend and was higher during the night increasing by up to 212 dynes/sec/cm5 (16%). Females demonstrated higher HR and CI with lower SVR during daytime and nighttime. Obese participants (BMI >30 kg/m2) had a higher SBP and DBP, and lower SV and CI. SVR was higher among the elderly. Conclusions Diurnal changes using MVAM corresponding with awake-sleep hours were noticed in the monitored parameters and differed between sex, age, and BMI groups. This suggests that wearable monitoring platforms could shed more light on hemodynamic changes in subgroups, and might help with future efforts to provide tailored personalized medicine and pre-symptomatic diagnosis and prevention. Funding Acknowledgement Type of funding sources: None.

Introduction: Invasive monitoring is considered the gold standard of hemodynamic monitoring, yet it is associated with inherent risks. We compared advanced hemodynamic measurements taken using a noninvasive wearable photoplethysmography-based (PPG) monitor and an invasive Swan-Ganz catheter (SGC). Methods: Patients with a prior diagnosis of heart failure undergoing right heart catheterization as part of their clinical assessment were recruited. The noninvasive PPG monitor was applied and readings of cardiac output (CO) and stroke volume (SV) commenced in parallel to the invasive hemodynamic study. Bland-Altman plots and Pearson’s correlations were used to assess the accuracy and degree of agreement between techniques. Results: 90 patients (19-89yo, 53 males) were recruited and included in the final analysis. The mean values of the CO measured using the indirect Fick method, the PPG device, and the thermodilution (TD) method was 5.0±1.4 L/min, 4.9±1.3 L/min, and 4.9±1.6 L/min, respectively. Bland-Altman analysis showed that the PPG had a bias of 0.1 L/m (1.7 - -1.5 L/m 95% LOA) and the TD had a bias of 0.2 L/m (2.2 - -1.8 L/m 95% LOA). The mean SV with the indirect Fick method, the PPG device, and the TD method were 63.6±20.2 mL/beat, 62.0±17.0 mL/beat, and 61.3±20.8 mL/beat, respectively. Bland-Altman analysis showed that the PPG device had a bias of 1.6 mL/beat (23.2 - -20.0 mL/beat 95% LOA) and the TD had a bias of 2.3 mL/beat (28.3 - -23.7 mL/beat 95% LOA). Correlations between the indirect Fick method and the PPG device, and between the indirect Fick method and the TD method were 82.5% and 77.7% for CO, and 83.7% and 79.6% for SV, respectively. Conclusions: The PPG device provides CO and SV measurements that highly correlate with the gold standard invasive indirect Fick method, similarly to the invasive thermodilution method.

Background Clinical trial guidelines for assessing the safety of vaccines, are primarily based on self-reported questionnaires. Despite the tremendous technological advances in recent years, objective, continuous assessment of physiological measures post-vaccination is rarely performed. Methods We conducted a prospective observational study during the mass vaccination campaign in Israel. 160 participants >18 years who were not previously found to be COVID-19 positive and who received the BNT162b2 COVID-19 (Pfizer BioNTech) vaccine were equipped with an FDA-approved chest-patch sensor and a dedicated mobile application. The chest-patch sensor continuously monitored 13 different cardiovascular, and hemodynamic vitals: heart rate, blood oxygen saturation, respiratory rate, systolic and diastolic blood pressure, pulse pressure, mean arterial pressure, heart rate variability, stroke volume, cardiac output, cardiac index, systemic vascular resistance and skin temperature. The mobile application collected daily self-reported questionnaires on local and systemic reactions. Results We identify continuous and significant changes following vaccine administration in nearly all vitals. Markedly, these changes are observed even in presumably asymptomatic participants who did not report any local or systemic reaction. Changes in vitals are more apparent at night, in younger participants, and in participants following the second vaccine dose. Conclusion the considerably higher sensitivity of wearable sensors can revolutionize clinical trials by enabling earlier identification of abnormal reactions with fewer subjects.

Abstract Exercise prevents cancer incidence and recurrence, yet the underlying mechanism behind this relationship remains mostly unknown. Here we report that exercise induces the metabolic reprogramming of internal organs that increases nutrient demand and protects against metastatic colonization by limiting nutrient availability to the tumor, generating an exercise-induced metabolic shield. Proteomic and ex vivo metabolic capacity analyses of murine internal organs revealed that exercise induces catabolic processes, glucose uptake, mitochondrial activity, and GLUT expression. Proteomic analysis of routinely active human subject plasma demonstrated increased carbohydrate utilization following exercise. Epidemiologic data from a 20-year prospective study of a large human cohort of initially cancer-free participants revealed that exercise prior to cancer initiation had a modest impact on cancer incidence in low metastatic stages but significantly reduced the likelihood of highly metastatic cancer. In three models of melanoma in mice, exercise prior to cancer injection significantly protected against metastases in distant organs. The protective effects of exercise were dependent on mTOR activity, and inhibition of the mTOR pathway with rapamycin treatment ex vivo reversed the exercise-induced metabolic shield. Under limited glucose conditions, active stroma consumed significantly more glucose at the expense of the tumor. Collectively, these data suggest a clash between the metabolic plasticity of cancer and exercise-induced metabolic reprogramming of the stroma, raising an opportunity to block metastasis by challenging the metabolic needs of the tumor. Significance: Exercise protects against cancer progression and metastasis by inducing a high nutrient demand in internal organs, indicating that reducing nutrient availability to tumor cells represents a potential strategy to prevent metastasis. See related commentary by Zerhouni and Piskounova, p. 4124

Early detection of influenza may improve responses against outbreaks. This study was part of a clinical study assessing the efficacy of a novel influenza vaccine, aiming to discover distinct, highly predictive patterns of pre-symptomatic illness based on changes in advanced physiological parameters using a novel wearable sensor. Participants were frequently monitored 24 h before and for nine days after the influenza challenge. Viral load was measured daily, and self-reported symptoms were collected twice a day. The Random Forest classifier model was used to classify the participants based on changes in the measured parameters. A total of 116 participants with ~3,400,000 data points were included. Changes in parameters were detected at an early stage of the disease, before the development of symptomatic illness. Heart rate, blood pressure, cardiac output, and systemic vascular resistance showed the greatest changes in the third post-exposure day, correlating with viral load. Applying the classifier model identified participants as flu-positive or negative with an accuracy of 0.81 ± 0.05 two days before major symptoms appeared. Cardiac index and diastolic blood pressure were the leading predicting factors when using data from the first and second day. This study suggests that frequent remote monitoring of advanced physiological parameters may provide early pre-symptomatic detection of flu.

Background InBody-770 and SECA mBCA 515 are multifrequency bioelectrical impedance analysis (BIA) devices, which are commonly used in the clinic to assess fat-free mass (FFM) and body fat (BF). However, the accuracy between devices in clinical settings, across different body mass index (BMI) groups remains unclear. Methods Body composition for 226 participants (51% men, aged 18–80 years, BMI 18–56 kg/m²) was assessed by two commercial multifrequency BIA devices requiring standing position and using eight-contact electrodes, InBody 770 and SECA mBCA 515, and compared to results from dual-energy X-ray absorptiometry (DXA). Measurements were performed in a random order, after a 3 h fast and no prior exercise. Lin’s-concordance correlation and Bland–Altman analyses were used to compare between devices, and linear regression to assess accuracy in BF% across BMI groups. Results We found strong correlation between DXA results for study population BF% and those obtained by InBody ( ρ c = 0.922, 95% confidence interval (CI) 0.902, 0.938) and DXA and SECA ( ρ c = 0.940, CI 0.923, 0.935), with 95% limits of agreements between 2.6 and −8.9, and 7.1 and −7.6, respectively. BF% assessment by SECA was similar to DXA (−0.3%, p = 0.267), and underestimated by InBody (−3.1%, p < 0.0001). InBody deviations were largest among normal weight people and decreased with increasing BMI group, while SECA measurements remained unaffected. Conclusions Both BIA devices agreed well with BF% assessment obtained by DXA. Unlike SECA, InBody underestimated BF% in both genders and was influenced by BMI categories. Therefore, in clinical settings, individual assessment of BF% should be taken with caution.

Abstract Background Ambulatory blood pressure monitoring (ABPM) using cuff-based devices is used for diagnosis and treatment of hypertension. Technical limitations, low compliance and complex procedures limit their use. Purpose The aim of the present study was to test the accuracy of a new technique of 24H ABPM using a photoplethysmography (PPG)-based, wearable device (Wrist-monitor) as compared to the standard cuff-based ABPM device. Methods In this prospective observational study, 24H ABPM was performed in parallel for both devices on volunteers aged 18–65 years, while documenting their daily activities. Level of comfort and activity disturbance of both devices were recorded. Linear regression and Bland-Altman were used to evaluate the agreement between devices. Receiver Operating Characteristic (ROC) curve analysis was used to assess the capability of the Wrist-monitor to identify abnormal BP values. Results The study included 28 subjects (18 men) mean age 41.5±16.2 years. Bland-Altman analysis resulted in 24H bias of −1.1 mmHg for both diastolic blood pressure (DBP) and systolic blood pressure (SBP). Mean daytime bias was −1.9 mmHg for DBP and SBP, while nighttime bias was smaller (0.7 and 0.4 mmHg for DBP and SBP respectively). ROC curve analysis on all BP readings (n=2381) yielded a mean area under the curve (AUC) for 24H of 0.965 for both SBP and DBP. 24H ABPM with the Wrist-monitor caused significantly less inconvenience compared to the cuff-based device (p<0.001). Conclusions The cuff-less device provides comparable measurements to those obtained with the currently used cuff-based ABPM device, with significantly less inconvenience to the subject. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The ABPM devices were given for free by BioBeat LTD. Petach-Tikva, Israel. No other support was given.