Cardiovascular diseases (CVDs) are the leading cause of death globally. An effective strategy to mitigate the burden of CVDs has been to monitor patients’ biomedical variables during daily activities with wearable technology. Nowadays, technological advance has contributed to wearables technology by reducing the size of the devices, improving the accuracy of sensing biomedical variables to be devices with relatively low energy consumption that can manage security and privacy of the patient’s medical information, have adaptability to any data storage system, and have reasonable costs with regard to the traditional scheme where the patient must go to a hospital for an electrocardiogram, thus contributing a serious option in diagnosis and treatment of CVDs. In this work, we review commercial and noncommercial wearable devices used to monitor CVD biomedical variables. Our main findings revealed that commercial wearables usually include smart wristbands, patches, and smartwatches, and they generally monitor variables such as heart rate, blood oxygen saturation, and electrocardiogram data. Noncommercial wearables focus on monitoring electrocardiogram and photoplethysmography data, and they mostly include accelerometers and smartwatches for detecting atrial fibrillation and heart failure. However, using wearable devices without healthy personal habits will cause disappointing results in the patient’s health. According to the World Health Organization (WHO) , noncommCVDs are the leading cause of death globally, claiming 17.9 million lives each year. The study of Global Burden of Cardiovascular Diseases and Risk Factors found hypertension to be the most prevalent CVD (65.5%) in 2019, followed by ischemic heart disease (11.4%), peripheral vascular disease (6.5%), cerebrovascular disease or stroke (5.8%), arrhythmias , rheumatic heart disease (2.3%), heart failure (1.5%), coronary heart disease (1.1%), hypertensive heart disease or cardiopathy (1.08%), congenital heart disease (0.7%), and cardiomyopathies (0.53%) [CVDs affect organs such as the heart and blood vessels, which can cause strokes and coronary and rheumatic diseases. More than 80% of CVD-related deaths are due to coronary heart disease and stroke, and 33% of those deaths occur prematurely in people under the age of 70 . AdditioMinistries of health worldwide collaborate to reduce the alarming statistics of global CVD incidence and related deaths. In parallel, wearable technologies are gaining increasing presence in the healthcare sector, as new generations of wearables emerge, driven by the desire of consumers to monitor their own health. Moreover, as new features allow wearable technologies to assess real-time biometric data, their impact on CVD management has become undeniable. The main clinical benefits of using wearable technology to tackle CVD include refining stroke prevention strategies, personalizing atrial fibrillation management, and optimizing the patient–physician relationship. Wearables are changing not only the way clinicians conduct research, but also the future of cardiovascular preventive and therapeutic care .Currently, Android technology is used in 70% of smartphones worldwide, which has resulted in the rising importance of Android application programming . With thThe literature reports a substantial number of scientific contributions to CVD management and prevention, including technology development, patient behavior analysis, and monitoring technologies. Researchers such as Lobello et al. , PevnickWhen compared to other reviews reported in the literature, our work has four differences. First, we discuss both commercial and noncommercial wearable devices currently available for CVD monitoring. Second, we classify such devices depending on their key features. Then, we identify the most important biomedical variables and sensors used in CVD monitoring. Finally, we discuss the status of the reviewed wearable technologies with respect to FDA (Food and Drug Administration) regulations. The goal of this review is, then, to identify (1) commercial and noncommercial wearable devices currently available for CVD monitoring, (2) the characteristics of such devices, (3) the primary biomedical variables used for monitoring the five most prevalent CVDs , and (4) the FDA status of the reviewed wearable technologies.CVD symptoms vary across people and depend on each condition; however, they usually include irregular heartbeat, high blood pressure, coronary artery–valve damage, and stroke. According to the WHO, more than 17 million people worldwide die from CVDs each year, which is equivalent to half of the deaths that occur in the United States . Around CVD monitoring using wearable technology involves measuring a series of biomedical variables and patient behaviors, such as lifestyle and eating habits. In the following paragraphs, we briefly explain the biomedical variables involved in CVD monitoring. Subsequently, Physical Activity (PA). PA benefits the health of every one person, at any age, both men and women. However, the number of people who do not have PA is increasing, and this is mainly due to the sedentary lifestyles that are prevalent today. Most of the world’s population lives in industrialized environments with access to technology, which facilitates tasks that previously required greater physical effort. In addition to the above, the number of leisure offers that do not require moving is increasing; impacting the general health of the world population, reflected in the increasing number of people with health problems such as diabetes, CVD, or cancer [r cancer . Some ofr cancer .Sleep. It is a basic human need and is essential for good health, excellent quality of life, and performing well during the day. Several indicators can be used to describe sleep disturbance or sleep disorders. These indicators include, for instance, sleep latency, number and duration of nocturnal awakenings, total sleep time, and repetitive nights of sleep disruption for one week or one month. Both poor sleep quality and short sleep duration are directly associated with CVD incidence. Sleep deficiency can lead to increases in blood pressure and early endothelial dysfunction, which contributes to CVD. Commercial wearable devices, such as the Fitbit Charge Heart Rate and the Oura Ring, aim at monitoring sleep in patients with CVDs through both heart rate and blood pressure [pressure . The twopressure .Heart rate (HR). It refers to the number of times the heart beats in one minute. Pulse rates vary from person to person and depend on numerous exogenous and endogenous factors, such as age, heart size, gender, genetics, health status, biorhythms, and stress/tension, among others. Wearable devices for HR monitoring are most often used when a patient with CVD performs exercise routines recommended by a health specialist [ecialist . In the ecialist .Average heart rate (AHR). This variable is estimated by counting the number of heartbeats in a given period of time. It is also commonly used in commercial portable devices to assess body condition during physical activity. AHR can be estimated through an ECG using QRS detection algorithms [gorithms ,55, whergorithms . AHR is gorithms  and is cgorithms . Recentlgorithms .Pulse rate variability (PRV). It refers to the variations of time intervals between heart beats. Traditionally, PRV is measured as the series of instantaneous cycle intervals obtained from ECG to determine the activity of the autonomic nervous system on cardiac function. PRV is generally measured at rest (sitting or lying down). At rest, in a healthy adult, PRV ranges from 60 to 100 beats per minute. Conversely, during physical activity, PRV oscillates between 150 to 200 beats per minute. Finally, PRV is usually around 60 beats per minute during sleep. Predicting abrupt variations in PRV can help timely diagnosis of CVDs. In fact, some studies claim that PRV may be a more relevant biomarker of CVD than AHR [than AHR .Blood pressure (BP). This biomarker refers to the force that blood exerts against the walls of the arteries. BP can be described with two numbers; that is, x/y in units of millimeters of mercury (mm Hg), where “x” measures the pressure in the arteries when the heart beats and pumps blood through the body, known as systolic pressure. Conversely, “y” refers to the pressure on the artery walls when the heart rests between beats, also known as diastolic pressure. Hypertension is the primary condition associated with increased BP. Overtime, the force or pressure that blood exerts on the artery walls is high enough to cause health problems, such as CVDs. If not treated timely, hypertension can lead to medical conditions such as heart disease, stroke, kidney failure, and eye problems, to name but a few [ut a few . A potenut a few .Blood oxygen saturation (2SpO). It indicates the amount of oxygen in red blood cells circulating throughout the human body. SpO2 levels for most healthy adults lie in the range of 95% to 100%. A level below this range is indicative that the person needs urgent medical attention, because their organs, tissues, and cells are not receiving the necessary oxygen for their body to function properly [properly . Pulse oproperly .Blood glucose (BG). BG comes from the foods that we consume or is produced by the liver and is found in the bloodstream  and inside the cells (it is transformed into energy). High BG levels are a common indicator of diabetes mellitus, which can cause kidney, neuronal, eye, and cardiovascular diseases. The probability of suffering from these complications increases as the BG level increases and vice versa [ce versa ,66,67,68ce versa .Blood cholesterol level (BCL). Cholesterol helps the human body build new cells, insulate nerves, and produce hormones. Normally, the liver makes all the cholesterol that the body needs, but cholesterol also enters the body through animal source foods. Too much cholesterol in blood builds up on the artery walls, narrowing them and slowing or blocking blood flow to the heart muscle. Since blood carries oxygen to the heart, high cholesterol levels may lead to a heart attack, since not enough oxygen is delivered [elivered . There aelivered .Other biomedical variables. Variables such as oxidative stress, translational signals, alterations in intracellular calcium management, and mitochondria dysfunction have been proposed as biomarkers of CVDs [ of CVDs . HoweverOxidative stress in cardiac disease. This happens when compounds that are not useful for their optimal functioning  are produced in the human body. If these compounds reach excessive levels in the body, the functionality of their membranes breaks and the cells die, resulting in cardiac dysfunction. In a healthy individual with a proper diet and lifestyle, oxidative stress can be minimized; not completely, but it can be controlled [ntrolled .Cell signaling in the cardiovascular system. The cellular elements of the heart and the vascular wall have a series of particular receptors and a complex intracellular mechanism that controls the appropriate responses to extracellular stimuli, that, in some cases, alters the functions of the cells in the heart and the vascular wall, causing pathological situations such as cardiovascular disorders [isorders .Abnormalities in intracellular calcium handling. The human body needs calcium (Ca), which is a mineral used to build and maintain its bones optimally in addition to performing other functions. Ca is the most abundant mineral in the body, and most is stored in the bones and teeth, which gives them structure and rigidity. Ca regulates various functions in the human body, including heartbeat, muscle contraction, and neuronal synapses. The weakening of cardiac contraction and the propensity for arrhythmias are related to an imbalance of calcium in cardiomyocytes (mainly in older adults) [ adults) .Mitochondrial dysfunction. This dysfunction is caused by a defect in energy production within the cells of an organism. Energy is produced within organelles contained in cells called mitochondria. All living beings need energy for their metabolism to work; for example, to grow, move, and think, among others. This dysfunction participates in the pathology of different diseases, such as neurodegenerative and cardiovascular [vascular .This paper is a review of sensor technologies from the IoT perspective to determine whether it is possible to monitor specific diseases, namely CVDs, using wearable devices and provide remote healthcare to older adults. The review follows the guidelines of the PRISMA  statemenInclusion and exclusion criteria. We initially obtained 24,900 search results from all the databases; yet, to refine the search, we deleted 632 results of works published before 2010, leaving 24,268 potential sources. Below, we describe the inclusion and exclusion criteria followed in this review.Inclusion criteria: The review comprises research works related to (1) wearable technologies for CVD monitoring, (2) wearable devices for CVD monitoring, (3) commercial and noncommercial wearable devices for CVD monitoring, and (4) FDA-approved medical devices published from 2010 to 2021.Exclusion criteria: We discarded (1) sources not written in English, (2) non-peer-reviewed sources, (3) letters and reports, (4) conference and symposium proceedings, (5) and non-primary studies.Information Sources. We grouped the keywords in our research questions into two categories or knowledge areas—healthcare and computing technology—to determine the databases for the review. In terms of healthcare, the search was conducted on AHA Journals, Annual Reviews, BioMed Central, Clinical Trials, JMIR, Medline Plus, and PubMed. Conversely, computing technology databases included the digital libraries of Hindawi, IEEE Xplore, Inderscience, IOP science, JACC, MDPI, Nature, Science Direct, Springer Link, and Wiley Online Library.Search Strategy. The search strategy used in this review was to combine keywords with Boolean connectors to limit the search results. The search keywords were considered from the key concepts that are part of the research questions that led to answering them. Intermediate searches were ordered to find the search terms to use in subsequent queries:Main CVDs worldwide.Biomedical variables of diagnosed CVDs.Wearable devices used to measure these biomedical variables.Sensor-based wearable devices available in the market.Commercial and noncommercial wearable devices for CVD monitoring.FDA-approved commercial wearable devices.Progressively, the results obtained from each query listed above contained new terms that were relevant to this study.Selection process. Initially, we identified 24,268 relevant papers based on their title and abstract. Then, three subject matter experts (SMEs) screened each work and organized the data into seven categories: device brand, device model, device type, targeted CVD, device functionality, used sensors, and FDA status. Following the SME analysis, we discarded 23,904 publications. Then, we thoroughly reviewed the 364 works left for further analysis in terms of their research goals and questions. Finally, only 42 of these studies were considered to comply with all the inclusion criteria. The selected 42 studies were downloaded in full text from their corresponding databases: Science Direct (20), NIH (3), Wiley Online Library (3), arXiv (2), AHA Journals (2), IOP science (2), JMIR (2), Springer Link (2), Annual Reviews (1), BioMed Central (1), IEEE Xplore (1), JACC (1), MDPI (1), and Nature (1).Data collection and analysis. We used structured tables to organize the information collected during the review of the 42 primary studies. Three SMEs oversaw the analysis to extract relevant information on current commercial and noncommercial wearable devices used for monitoring physiological variables in patients with CVDs. Information of interest included targeted CVD, wearable device brand, model, and type, key device features, device operating mechanism, used sensor(s), and FDA status.Our initial search for relevant papers yielded 24,900 results. This review analyzes both commercial and noncommercial wearable devices for CVD monitoring. Commercial wearable devices comprise both presale devices and those available in the market by the time of writing this paper. Conversely, prototype devices and research devices were classified as noncommercial. In total, we found 31 commercial and 32 noncommercial wearable devices for CVD monitoring.A substantial number of companies around the world market portable devices that conveniently help CVD patients monitor biomedical variables in their day-to-day life. However, not all of these devices have been approved by regulatory bodies. The US Food and Drug Administration (FDA) regulates the sale of medical devices and provides consumers with assurance that, once such devices are commercialized, they are safe and effective in their intended use. In other words, the FDA is responsible for protecting public health by ensuring that commercial medical devices meet a series of requirements. Most of the wearable devices commercially available for CVD monitoring are smartwatches and wristbands (35% of occurrence), whereas the least common devices include finger rings, vests, and devices attached to clothing (3% each). On the other hand, only 16% of the reviewed works use patches for monitoring CVD biomedical variables, even though the heart is the most affected organ in CVDs. Such results reveal a growing interest in sensor-based technologies, which can be conveniently and easily implemented in wearables such as wristbands and smartwatches. In fact, consumers usually prefer these devices to patches, since they can be comfortably worn and rarely interfere with day-to-day activities. With regard to device FDA status, we considered five categories: approved, partially approved, cleared, unapproved, and unknown. Both approved and partially approved status mean that the benefits of the wearable device outweigh its known risks for intended use. On the other hand, a cleared FDA status implies that the device manufacturer can demonstrate that their product is substantially equivalent to another legally marketed device. An unapproved status conveys that the FDA does not authorize the use of the device. Finally, an unknown status implies that we could not find information regarding the FDA status of a device. In this sense, it is worth mentioning that many commercial devices do not disclose public information on their FDA status. According to our findings, 58% of the reviewed commercial devices do have some FDA approval, whereas the remaining 42% are commercially available but lack FDA registration or approval. On the other hand, we were unable to find further FDA information on 19% of the reviewed commercial wearables. One of the main objectives of our review was to determine which biomedical variables are commonly monitored by wearable technologies for CVD care. In this sense, we found that wearable devices can usually read more than one type of biomedical variable. Such results were documented, and a summary of them is listed in 2, and ECG. Rapid scientific progress and modern technology have made it possible for companies to fabricate increasingly compact monitoring solutions that can be easily built in wearable items. In parallel, wearable technologies have turned into a relatively affordable consumer trend that allows for convenient self-health monitoring during day-to-day activities. However, a major challenge of commercial wearable devices remains to improve the monitoring performance and unobtrusive quality of such devices, regardless of their design and aesthetic characteristics.As shown in Research year of publication.Type of CVD that can be monitored.Type of wearable device .Brief description of the research contribution.Sensors or technology used for CVD monitoring.Device real-time monitoring capabilities.Our review of noncommercial wearable devices for CVD monitoring comprises both prototype devices and those devices developed solely for research purposes. Generally, prototype devices are primarily designed to assess their viability for monitoring the health status of patients with CVD. Our findings regarding noncommercial wearable technologies for CVD monitoring are organized in When compared to commercial wearable devices, noncommercial wearable technologies are generally developed for arrhythmia and heart failure monitoring. Wrist-worn devices such as smartwatches and smart wristbands are the most common wearable technologies in these cases (53% in arrhythmia monitoring and 59% in heart-failure monitoring). Conversely, less common technologies include patches, rings, t-shirts, and vests for arrhythmia monitoring, and vests, patches, and electrodes for heart-failure monitoring. Wrist-worn devices are usually preferred to other wearable alternatives due to a relatively high comfort–monitoring accuracy ratio. Monitoring patients with CVD in real time allows healthcare professionals and patients themselves to receive continuous, live health status updates during daily activities. Finally, This review provides insightful information on wearable health monitoring solutions for patients with CVDs. First, our findings reveal that commercial wearable technologies generally focus on measuring HR (20%), SpO2 (16%), and ECG (12%) as biomedical variables. Measurements are usually obtained via sensors or compact technologies easily integrated in the wearables. Additionally, the most commercial wearables for CVD monitoring include smart wristbands (19%), smartwatches (16%), and wrist sensors (6%). As for noncommercial wearables, most of them are wristbands. In addition, noncommercial wearables generally rely on accelerometers, PPG, and ECG (72%) for CVD monitoring.Second, in both commercial and noncommercial wearables, wrist-worn devices are preferred over other items and clothing , since they are comfortable and unobtrusive to patients. Nevertheless, ongoing research is exploring how to implement health monitoring technology into daily wear garments in a way that is just as convenient, affordable, and comfortable to consumers as wearing wrist-worn devices. However, these garments, of a shirt or dress type, for instance, must have certain characteristics to be as convenient, safe, and effective as wrist-worn devices. Some of these features are data reading accuracy, real-time wireless monitoring, water resistance, data security, and portability. Overall, we found that commercial CVD monitoring garments are significantly less common (21%) than their noncommercial counterparts (41%).Wearable technologies for CVD monitoring significantly help drive down the costs of in-hospital treatments. In terms of continuous and outpatient monitoring, smart wearables improve diagnosis precision, thus providing patients with convenient solutions for self-care through the ongoing monitoring of biomedical variables during daily routines. CVD monitoring techniques greatly vary, and their usability depends mostly on the type of condition to be prevented or managed and the type of monitoring. For instance, ECG and PPG are generally implemented for continuous and ambulatory monitoring in fitness bands and smartwatches. ECG is a test widely recommended in the follow-up of some heart diseases. It involves the recording of heart electrical activity through the surface of the patient’s body. Then, based on the difference in electrical potential between two distant points of the body, ECG can measure a series of biomedical variables to detect heart diseases such as heart failure and arrhythmias. However, ECG technology is not recommended for monitoring the risk of heart attack. In this case, conventional electrocardiography with electrodes remains the best option.PPG is another technique for monitoring CVD biomedical variables. It involves injecting photons into human body tissue and analyzing the reflected light. PPG has proved to yield better results when performed at the wrist level via bands or smartwatches, which are unobtrusive devices that patients can conveniently carry with them during day-to-day activities. As its main setback, PPG has little robustness and reliability during physical activity or when the patient is in motion.In addition to ECG and PPG, other techniques are used to monitor important heartbeat information, such as ballistocardiography (BCG) and phonocardiography (PCG). BCG is a technique used to measure ballistic forces generated by the heart. The technique produces a graphical representation of repetitive movements of the human body that arise as blood is suddenly ejected into the great vessels with each heartbeat. BCG is usually integrated into smart wearables using highly sensitive accelerometers connected to the patient’s body surface, usually the torso. In turn, PCG technology can be used to record heart sounds. Unfortunately, since both BCG and PCG are sensitive to ambient noise, it is unlikely that we will find them integrated into current wearable devices.The skin covers most of the human body, so it serves as an optimal mode for noninvasive wearable devices for medical care. Skin-based wearable devices can be used for physiological and psychological monitoring for the treatment of different diseases, for example, CVDs. In addition, it can also be used for the diagnosis of different diseases through the qualitative and quantitative analysis of skin secretions, such as sweat. In the case of epidermal wearable devices, they imply the direct union to the skin, such as a tattoo, generally known as electronic skin (e-skin). E-skin is made with flexible electronic components, such as conductive links , allowing each patient to be managed as a separate database of medical information, which is relevant to the medical staff caring for them. When an e-skin is inserted into the patient’s skin, it can record information about the patient’s biomedical variables through its small electrodes and simultaneously send such data to smartphones or other connected devices. In addition, e-skin can receive energy from the electrophysiological processes of the human body, making it possible to work without batteries. E-skin adapts to any shape and even works if bent, twisted, or stretched, since it has properties similar to those of light fabrics; that is, e-skin adapts to the flexibility of the human body, which is an advantage over conventional wearable devices. This noninvasive medical technology could allow healthcare experts to monitor and diagnose arrhythmia problems, heart activities of premature babies, sleep disorders, and brain activity, among other diseases.On the other hand, it is estimated that more than one billion people around the world have hypertension or elevated BP. Of that 1 billion, two-thirds are in developing countries that also lack adequate sanitary facilities. Daily monitoring of BP is vital for these patients since hypertension is often asymptomatic. Due to the lack of monitoring, hypertension is one of the main causes of premature death around the world. The precise measurement of the PA requires trained medical personnel; therefore the development of the e-skin adds to the challenge of meeting the objective of WHO to reduce hypertension by 25% by 2025. As healthcare technology becomes smaller and smarter, wearable devices such as e-skin could minimize ways in which they interfere with a patient’s daily life.Currently, e-skin continues to be improved through research and development work. Moreover, the trend in its development indicates that it could be more reliable and accurate and less invasive than traditional methods. Therefore, e-skin will strengthen confidence in consumers who are considering using it for self-care in health.As wearable trends progressively grow and improve, they begin to shape healthcare, along with current technological developments in hardware and software. Additionally, trends in the Internet of Things (IoT) and AI have become key allies in the development of mHealth wearables. AI techniques and neural networks are implemented into wearables  to overcome current technological barriers and improve the reliability of ambulatory monitoring systems and the accuracy of ECG and PPG signals. Overall, both AI and neural networks increase the performance of wearable devices and the accuracy of measurements of CVD biomedical variables. Hence, as the reliability and accessibility of wearable devices increases simultaneously, their acceptance also increases among consumers. Wearables are becoming increasingly convenient solutions for continuous ambulatory monitoring of CVD during day-to-day activities.The different sensors that make up mHealth wearables collect daily routine data that interact with technological platforms. In this sense, the IoT is a promising alternative for managing data provided by wearable devices. The IoT paradigm can generate medical information and critical event alerts that can be shared with health specialists and used to interact with social networks. A major challenge in the IoT paradigm, however, remains to find the best practices for handling confidential patient information. In this sense, multiple data privacy service providers are already working on it.Finally, CVD monitoring technologies can also be integrated in smartphones through device cameras or accelerometers. The main issue in this case is that not all smartphones have the same level of precision in terms of recording biomedical variables. Since this is a device function provided at the design level of the mobile device, it certainly goes hand in hand with the cost of the device.This review of commercial and noncommercial wearables for CVD monitoring has four main limitations. First, we did not take into account clinical scenarios or comparative studies assessing the quality of life of patients using wearables for CVD monitoring. Although remote healthcare technology is a current trend, certain usability factors remain to be further studied and improved before wearable technologies become widely accepted. Second, this review does not analyze the mobile applications associated with the reviewed wearable devices. Third, we did not review studies on consumer acceptance of wearables for CVD monitoring. Finally, FDA status information was not available for many of the reviewed devices. Unfortunately, CVD monitoring wearables lacking FDA approval may not have the opportunity to achieve high-quality remote healthcare.This review found that wearable devices for remote CVD monitoring rely on sensors/biosensors to obtain accurate measurements of relevant biomedical variables. As measured by these wearable devices, the most critical biomarkers of CVD include heart rate, oxygen saturation, and ECG. Consequently, only wearable devices with suitable sensors that are coordinated by computer applications can provide medical data relevant to CVD monitoring. The use of a given type of wearable over another type greatly depends on the condition to be monitored; however, overall, the wearables most frequently cited in the literature include wristbands (19%), smartwatches (16%), and patches. It remains uncertain whether wearable devices with built-in biosensors can be used for timely detection of lethal diseases, such as malignant neoplasms (various types of cancer). Once this question is resolved, it would be important to analyze the developmental stage of such devices for their broad use as a final product.In addition, this review analyzes the medical-grade precision and reliability of the cited wearables by listing their FDA status. In this sense, we found that 13% of the cited devices were FDA-approved, 3% were partially approved, 42% were FDA-cleared, 23% were unapproved, and 19% had an unknown FDA status.The scope of this research is limited to wearable biomedical devices that allow for CVD monitoring via the measurement and assessment of biomedical variables. Our main findings can be summarized as follows: 35% of the cited commercial devices are either smart wristbands or smartwatches, and 58% hold some FDA status . FDA-approved wearables monitor either AF, heart rate, or both. The most common biomedical variables for CVD monitoring are HR (20%), SpO2 (16%), and ECG (12%). Finally, most noncommercial wearable devices for CVD monitoring are smart wristbands, smartwatches, and patches.


Abrupt bradycardia and hemodynamic instability during spinal anesthesia for cesarean section are not uncommon and are considered as one of the primary causes of intraoperative nausea and vomiting (IONV). We hypothesized that prophylactic use of hyoscine butyl-bromide (HBB) could improve hemodynamics and reduce IONV in parturients undergoing cesarean section.−1). Secondary endpoints included changes in mean arterial blood pressure (MAP), the incidence of Intraoperative and Postoperative nausea or vomiting (IONV & PONV), the fetal heart rate and, Apgar score.A randomized, double-blind placebo-controlled trial was carried out in a tertiary university hospital, patients scheduled for elective cesarean section were equally randomized to receive either IV HBB 20 mg in 1 ml (Hyoscine group) or the same volume of 0.9% saline (Control group), one minute after spinal anesthesia. The primary endpoint was the incidence of intraoperative bradycardia (HR < 50 beats min−1) in the Hyoscine group  compared with placebo. MAP showed an insignificant difference between groups over time. HBB significantly decreased incidences of IONV and PONV (p = 0.002 & 0.004) respectively.Of the 160 subjects randomized, 80 received HBB and 80 received placebo. There was a significant reduction in the incidence of the primary endpoint of intraoperative bradycardia (HR < 50 beats minIn parturients undergoing cesarean section under spinal anesthesia, pretreatment with intravenous HBB was a safe measure for both the mother and the baby to reduce the risk of severe intraoperative bradycardia, but not hypotension. Furthermore, it was associated with less incidence of both IONV and PONV.https://clinicaltrials.gov/ct2/show/NCT04069078 In developing countries, anesthetic complications, particularly abrupt bradycardia progressing to sinus arrest, account for about 14% of maternal deaths amongst those undergoing Cesarean section (CS) .Furthermore, the unopposed vagal activity and maternal hypotension that occurs with sympathetic block associated with spinal anesthesia are one of the primary causes of intraoperative nausea and vomiting (IONV) , 4.Unlike atropine, Hyoscine butyl-bromide (HBB) is an anticholinergic with a quaternary ammonium structure making it unable to cross the blood–brain barrier and has lower placental transfer, so it could be more favorable for use with pregnancy , 6. FurtWe hypothesized that prophylactic use of HBB could prevent post spinal bradycardia with better hemodynamics and less incidence of IONV in parturients undergoing spinal anesthesia for CS.www.clinicaltrials.gov (NCT04069078) and first posted on August 28, 2019. The study was carried out in Assiut University Hospital, Egypt, between October 2019 and February 2020. This study was approved by the medical ethics committee of Assiut university with approval number [17300311]. All patients provided written informed consent. All methods were carried out in accordance with the Declaration of Helsinki 2013.The current study was a prospective single-center randomized, double-blind placebo-controlled trial registered at −2, Contraindication or refusal to undergo regional anesthesia, Baseline bradycardia (HR < 60 beats min−1), or any cardiovascular disease including arrhythmias, Patients on β-adrenergic blockers or any drugs that may alter the normal response to the study drug, Associated medical problem with pregnancy .All patients 18–40 years of age, American Society of Anesthesiologists (ASA) classification class I and II and scheduled for elective or semi-elective surgery (category 3 and 4 Cesarean section) under spinal anesthesia for a Single baby pregnancy of more than 32 weeks were included in this study. Exclusion criteria were Patient’s height < 150 or > 180 cm, Body mass index (BMI) > 35 kg mhttps://www.randomizer.org/) to generate codes placed within sealed, opaque, sequentially numbered envelopes by a research assistant who was not involved in patient care or assessment. This assistant also prepared the study solutions in identical syringes that were labeled ''study drug'' according to the assigned group as follow:Patients were allocated in 1: 1 ratio into the two study groups using a web-based randomizer , Blood pressure (BP) recording  and review of patients’ coagulation profile.Fasting for 8 h before the operation was acceptable. They were also premedicated with oral sodium citrate  one hour before the operation as anti-aspiration prophylaxis.In the operating room in all patients, large-bore intravenous access (18 gauge) was inserted in the left dorsum of the hand, and they were preloaded with 15 mL/kg of Ringer's solution intravenously. The 1st 500 ml was transfused by a pressure bag.All patients were connected to standard routine monitoring , with the peak heart rate in the hyoscine group at 3 min after injection then came to baseline within 20 min.Serial changes in heart rate are shown in Fig. P = 0.17].Changes in MAP over time are shown in Fig. P = 0.002) and,  respectively. .Despite using ephedrine which was found in a meta-analysis of vasopressor drugs used in CS  to be asp = 0.0248). They found the incidence of bradycardia to be 17% between controls but, they defined bradycardia as HR < 60 beats min−1 [To our knowledge, few studies investigated bradycardia as a target primary outcome and examined pharmacological interventions to decrease its incidence. Our results are parallel with a previous report by Chamchad D and others, who stated that prophylactic glycopyrrolate administered before spinal anesthesia prevents bradycardia during Cesarean section (ts min−1 .p = 0.50). Unlike our study, kee and co-authors calculated the sample size for cardiac output as a primary outcome [In contrast to our results, Tarkkila and Kaukinen, found insignificant effect of prophylactic glycopyrrolateon the incidence of bradycardia in an observational cohort of 1,881 patients. However, their study was without randomization or blinding and did not specify the number of patients who received glycopyrrolate or doses given . Also, K outcome .The incidence of bradycardia in parturients undergoing spinal anesthesia varied between studies to be as low as 4.2% & 10% in some studies , 15 and Atropine is perhaps the most commonly used anticholinergic drug. However, Hyoscine butyl bromide is a semisynthetic derivative of hyoscine hydrobromide (scopolamine), which has a quaternary ammonium structure that results in lower transfer through the blood–brain barrier causing less incidence of confusion and other central side effects , 6. our While the vagal blockade of glycopyrrolate persists for two to three hours , our stuOur results showed that HBB reduced the incidence of intraoperative nausea and vomiting significantly. These results were significant in our study because we used ephedrine, which carries a higher incidence of nausea and vomiting than the other vasopressor agents .The exact etiology of intraoperative nausea during spinal anesthesia is unknown. However, it is suggested that the unopposed vagal activity that occurs with sympathetic block during spinal anesthesia is the cause. Supporting this theory is the observation that atropine was more effective in relieving nausea during spinal anesthesia than was the elevation of the blood pressure with vasopressors .Intrathecal opioids are associated with a 30%–70% incidence of postoperative nausea and vomiting , 20. In Despite being a quaternary ammonium compound, HBB can target the chemoreceptor trigger zone due to the absence of a well-developed blood–brain barrier in the medulla oblongata. This central effect potentiates the antiemetic effects that it produces through local action on the smooth muscles of the gastrointestinal tract .Regarding neonatal outcome and in accordance with many studies –26, our This study is not without limitations; first, we used ephedrine as a vasopressor which appears to be the most likely agent to affect fetal and maternal outcomes adversely, but norepinephrine and phenylephrine are not available in limited-resource areas, in addition to carrying the risk of drug errors in wards outside of Critical Care Units . So thatpretreatment with intravenous HBB 20 mg in parturients undergoing CS under spinal anesthesia is a safe measure for both the mother and the baby to prevent the risk of severe intraoperative bradycardia with no noticeable effect on maternal hypotension. Moreover, it was associated with less incidence of both intraoperative and postoperative nausea and vomiting. Future studies are required to confirm our results, especially the effect on nausea and vomiting as a significant complication of hypotension and intrathecal morphine and as a measure of the quality of recovery after cesarean section.


We present our experience with retroperitoneoscopic pyeloplasty with simultaneous pyelolithotomy using a flexible cystoscope in patients with ureteropelvic junction obstruction(UPJO) complicated with kidney stones.The records of 37 patients who underwent retroperitoneoscopic pyeloplasty with simultaneous pyelolithotomy using a flexible cystoscope to manage UPJO complicated with kidney stones from July 2015 to December 2020 were retrospectively reviewed. All patients underwent one-stage retroperitoneoscopic pyeloplasty combined with flexible cystoscopic pyelolithotomy. The operative time, blood volume, stone clearance rate, length of hospital stay, complications and follow-up events were recorded.The operation went smoothly in all 37 patients. The mean operative time was 148.4 ± 24.2 min. The mean intraoperative blood loss volume was 54.3 ± 20.5 ml. The mean hospitalization time was 10.6 ± 3.7 days. The stone clearance rate was 81.08%. The mean follow-up period was 23.5 months (range 12–53 months). Hydronephrosis was significantly decreased in 33 of the 37 cases. The success rate of the operation was 89.19%. Stones recurred in 9 patients during follow-up, for a recurrence rate of 24.32%.Retroperitoneoscopic pyeloplasty with simultaneous pyelolithotomy using a flexible cystoscope in patients with UPJO complicated with kidney stones is safe, effective and worthy of promotion. Ureteropelvic junction obstruction is a common anatomic lesion in urology. Its congenital incidence is approximately 0.1% , 3. UPJOFrom July 2015 to December 2020, a retroperitoneoscopic method combined with the use of a flexible cystoscope was used for pyelolithotomy in 37 cases in our hospital, and it achieved favourable efficacy. The present study aimed to introduce our experience with combined retroperitoneoscopy and flexible cystoscopic pyelolithotomy for patients with UPJO complicated with kidney stones.The study was approved by the ethics committee of our hospital. Written informed consent was obtained from all patients. All patients underwent intravenous pyelography (IVP) and CT examinations routinely. If IVP imaging was not clear, retrograde pyelography was performed. Inclusion criteria were a diagnosis of UPJO complicated with kidney stones and treatment with retroperitoneoscopic pyeloplasty with simultaneous pyelolithotomy using a flexible cystoscope. Patients who were complicated with a nonfunctional kidney were excluded from our analysis. From July 2015 to May 2020, 37 patients with symptomatic ureteropelvic obstruction and kidney stones underwent retroperitoneoscopic pyeloplasty with concomitant pyelolithotomy. The age range of the participants was 27–67 years, and the mean age was 43.8 ± 11.1 years. The clinical manifestations included back pain in 29 patients, gross haematuria in 11 patients, and recurrent pyelonephritis in 10 patients. Mild hydronephrosis, moderate hydronephrosis and severe hydronephrosis were diagnosed in 3 cases, 25 cases and 9 cases, respectively. Seven patients had a single kidney stone, and 30 patients had multiple kidney stones, with a maximum diameter of 23 mm. Eight patients received other treatments prior to admission, such as high-pressure balloon catheter dilation or ureteral stent placement. Enhanced urinary computed tomography was performed preoperatively for all patients, and retrograde renal pyelography was employed for 9 patients to clarify the diagnosis. Other clinical data were shown in Two sets of endoscopic monitoring equipment were placed at the head of the patient. After general anaesthesia was induced, an indwelling catheter was placed. Then, the patient was placed in the flank position, depending upon the side to be operated on.The primary port, a 12 mm incision, was made 1 cm below the 12th rib margin of the posterior axillary line. Balloon dilation through this port was done to create the retroperitoneal space. Once balloon dilation was completed, the second port, a 12 mm incision, was placed 1 cm below the 12th rib margin of the anterior axillary line. The third port, a 12 mm incision, was made at the midaxillary line approximately two finger breadths cephalad to the anterior superior iliac spine. The third port was used to hold the laparoscope. Antibiotics were administered during anaesthesia induction. The perirenal fascia was longitudinally opened. The inferior pole of the kidney was dissociated. The renal pelvis and upper ureter were exposed. A 15 mm incision was made in the pelvis. The flexible cystoscope was placed into the retroperitoneal space through a 12 mm trocar and then inserted into the pelvis to detect the stone with the aid of the assistant . The stoThe operation went smoothly in all 37 patients. The mean operative time was 148.4 ± 24.2 min . The mean intraoperative blood loss volume was 54.3 ± 20.5 ml . The mean hospitalization time was 10.6 ± 3.7 days (range 7–11). Six patients suffered from complications (Clavien I and IIIa). Three patients had postoperative fever, which was treated medically. Three patients suffered urine leakage from the double-J stent bending; the perirenal effusion was absorbed two weeks later after repositioning of the double-J stent. At two months, 7 patients had residual calculi, for a stone clearance rate of 81.08%. Consequently, these patients underwent further stone management, including ureteroscopy and shock wave lithotripsy. The mean follow-up period was 23.5 months (range 12–53 months). Frequent haematuria occurred in 8 patients before removal of ureteral stents, and 11 patients presented with mild back pain. Hydronephrosis was significantly decreased in 33 of the 37 patients, for a success rate of the UPJO operation of 89.19%. Stones recurred in 9 patients during follow-up, a recurrence rate of 24.32% .UPJO is a common anatomic lesion in urology. Its congenital incidence is approximately 0.1%. Up to 20% of UPJOs are complicated with kidney stones due to obstruction and hydronephrosis. In the past 20 years, with the development of laparoscopy, laparoscopic pyeloplasty has become the main treatment for UPJO. The laparoscopic technique is superior to open surgery due to its low trauma, favourable field of exposure and ease of suturing .In patients diagnosed with UPJO complicated with kidney stones, the stones tend to be located in the lower calyx of the kidney. The treatment of UPJO complicated with kidney stones with a laparoscopic method alone is frequently not desirable. When percutaneous lithotripsy has been performed to treat both UPJO and kidney stones, the postoperative follow-up indicated poor outcomes –6. A twoThe angle of the renal pelvis and lower calyx make it very difficult to deal with kidney stones. The treatment of UPJO combined with kidney stones using a laparoscopic or endoscopic method alone is difficult and unsatisfactory. In recent years, some scholars have reported that the combination of laparoscopic or robotic laparoscopic surgery and flexible cystoscopy in the treatment of UPJO complicated with kidney stones leads to excellent outcomes in terms of both the stone clearance rate and protecting renal function. Peng et al. introduced a flexible guiding tube as a simple modification of laparoscopic pyeloplasty combined with a flexible cystoscope for the treatment of UPJO complicated with renal calculi . An et aSince July 2015, we have used retroperitoneoscopic pyeloplasty combined with antegrade flexible cystoscopic pyelolithotomy in one stage to treat 37 cases of UPJO complicated with kidney stones, with a stone clearance rate of 81.08% and a UPJO operation success rate of 89.19%. The advantages of our procedure include the following: (1) When UPJO is complicated with kidney stones, most of the stones are located in the lower renal calyx, and the angle of the renal pelvis and lower calyx makes it very difficult to deal with kidney stones there. However, in anterograde flexible cystoscopic pyelolithotomy, the stone clearance rate is almost unaffected by the angle. (2) The body of the flexible cystoscope used for pyelolithotomy is thick and short, making it more manipulable through anterograde procedures than a flexible ureteroscope. However, for patients with a narrow calyceal neck, an antegrade flexible ureteroscope can be used to remove the stone. Of the 37 cases here, 6 needed the flexible ureteroscope due to a narrow calyx neck, while the remaining procedures were completed by flexible cystoscopic pyelolithotomy. (3) A 15 mm incision in the renal pelvis is a good size. A smaller incision causes difficulty removing stones, and larger incisions cause difficulties in filling the renal pelvis with perfusion fluid, leading to renal pelvis collapse and no room for the operation. During flexible cystoscopic pyelolithotomy, perfusion fluid in the renal pelvis is removed through a suction apparatus by an assistant to help keep the surgical field clear. (4) Patience and carefulness are indispensable for performing antegrade flexible cystoscopic pyelolithotomy due to changes in operating habits. Larger kidney stones can be broken into pieces with a holmium laser, followed by removal with a stone basket. (5) The retroperitoneal approach is as effective as the intraperitoneal approach, with little interference by abdominal organs and rapid postoperative recovery. Sometimes, operation through the intraperitoneal approach may cause abdominal infection and intestinal adhesion. (6) Two procedures, retroperitoneoscopic pyeloplasty and flexible cystoscopic pyelolithotomy, can complement each other to combine their advantages and avoid their disadvantages and clear stones to the greatest extent. (7) Retroperitoneoscopic pyeloplasty and flexible cystoscopic pyelolithotomy can be used to manage UPJO complicated with kidney stones in one stage, thus avoiding a second surgery and reducing medical costs.Retroperitoneoscopic pyeloplasty combined with antegrade flexible cystoscopic pyelolithotomy for UPJO complicated with kidney stones is advantageous in terms of minimal trauma, rapid recovery and a high stone clearance rate. Retroperitoneoscopic pyeloplasty and antegrade flexible cystoscopic pyelolithotomy can complement each other. This technology can avoid a second operation, reduce the medical costs to patients, and efficiently treat UPJO complicated with kidney stones. Of course, there are some limitations to our work. Due to the lack of a DVSS here, we were unable to compare the pros and cons of DVSS and retroperitoneoscopy in the management of UPJO complicated with kidney stones, which may be a more interesting question. Though it is the most sensitive indicator of renal function, we rarely do kidney scans for a variety of reasons, and this might affect the quality of our conclusions. We look forward to conducting a larger, prospective, multicentre, well-equipped clinical trial to further investigate the treatment of UPJO complicated with kidney stones.


Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. Its pathogenesis encompasses functional alterations involving elevated intraglomerular and systemic pressure, increased activity of the renin-angiotensin system (RAS) and oxidative stress, and the eventual development of renal fibrosis. The management of DN involves the optimization of blood pressure (BP) and blood glucose targets. However, treatment of these risk factors slows down but does not stop the progression of DN. Innovative pharmacologic therapies for dyslipidemia and type 2 diabetes mellitus (T2DM) could play a key role in bridging this gap and attenuating the residual risk of DN beyond traditional risk factor management. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 inhibitors (SGLT-2is), and inhibitors of mineralocorticoid receptor-mediated sodium reabsorption are recently introduced drug classes that have been shown to have positive effects on kidney function in individuals with T2DM. The aim of this review is to provide an update on the therapeutic options available in order to prevent or slow the onset and progression of DN in diabetic patients. Diabetic kidney disease (CKD), or diabetic nephropathy (DN), is a major complication that takes a significant toll on communities globally . In geneThe pathogenesis of DN encompasses a number of functional alterations involving increased intraglomerular pressure, stimulation of the renin-angiotensin system (RAS), oxidative stress, and fibrotic changes that are superimposed on an innate genetic predisposition . In addiTreatment strategies for the management of DN include (a) intensive blood glucose control; (b) attainment of blood pressure goals with the inclusion of angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE)-inhibitors in the pharmacologic regimen; (c) weight management with dietary caloric restriction and aerobic physical exercise; (d) dietary protein restriction; (e) smoking cessation; (f) lipid management with statin therapy as the preferred choice; and (g) avoidance of nephrotoxic drugs such as contrast agents, antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs) ,7. One oNovel pharmacologic approaches are on the horizon to slow the progress and evolution of DN and thereby protect the kidneys ,14. SGLTDN begins with glomerular hyperfiltration, which abates with the onset of early renal damage ,3,6,7. TSeveral factors contribute to the pathophysiology of DN. Hyperglycemia leads to the increased formation of advanced glycation end products and a proinflammatory state, which have been correlated with a progressive reduction in GFR ,3,6,7. TWe searched electronic databases (MEDLINE (1975–2022), EMBASE and SCOPUS (2000–2022)) and Web of Science Core Collection (1997-present) using combinations of the following keywords: diabetes, diabetic nephropathy, incretins, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sodium-glucose transporter-2 inhibitors, kidney disease, therapy, treatment. The methodology used in extracting the relevant studies and reviews is summarized in the flow chart .Blood pressure (BP) control by renin-angiotensin system (RAS) blockade reduces proteinuria and effectively slows down the evolution of diabetic and nondiabetic nephropathies through local and/or systemic actions . The optClinicalTrials.gov Identifier: NCT00949286) study  and kidney-specific outcomes  with respect to the untreated group; the dapagliflozin group also had a significantly reduced frequency of composite cardiorenal outcome  and kidney-specific outcomes  compared to the placebo group [p < 0.0125) but also in renal outcome in all UACR groups (p < 0.05) [In the DECLARE-TIMI trial of 58 subjects with CKD and T2DM receiving dapagliflozin compared to subjects with CKD but without diabetes, a reduction in cardiorenal outcomes  is cited [2 treated with canagliflozin 100 mg/day or for the untreated group; the safety committee terminated the study prematurely after an analysis demonstrated superiority. The primary outcome that including a doubling of serum creatinine level, composite of end-stage kidney pathology, or renal or CV death was decreased by 30%, and secondary outcomes showed positive benefits with the use of canagliflozin. These results in a high-risk population of diabetic with renal insufficiency subjects confirm the observations of secondary outcomes in CVOTs and prove the necessity to use SGLT2is in the management of T2DM, CKD, and CVD. In addition, some of the GLP-1RAs may offer modest kidney beneficium [2, and dapagliflozin would be helpful in chronic renal failure patients with an eGFR ≥ 25 mL/min/1.73 m2 at risk of CKD progression. Though canagliflozin decreased the risk of the evolution of chronic renal failure, cardiovascular death, and hospitalization for heart failure (HHF) only in diabetic subjects with albuminuria ≥ 300 mg/g, dapagliflozin is designed to decrease the risk of evolution of CKD and HHF regardless of albuminuria in all CKD subjects with or without T2DM, as well as decrease the risk of cardiovascular and HHF death in heart failure subjects with a low ejection fraction [In the ESC guidelines of 2019 , the stuneficium : a meta-neficium . Based ofraction .2 within three weeks of therapy and 4.0 mL/min/1.73 m2 within two weeks. This reduction persisted and remained constant throughout the year and was lower with SGLT-2is drugs than in the untreated control group [SGLT2is reduce in glomerular hyperfiltration, possibly due to an increase in preglomerular vasoconstriction and a reduction in postglomerular vascular resistance ; this eGol group ,62. A deol group .DPP-4is boost the levels of GLP-1 and GIP, which inhibit the release of glucagon, increasing insulin secretion, reducing gastric emptying, and decreasing blood glucose levels. They are suitable for subjects with advanced T2DM and kidney dysfunction . In addiClinicalTrials.gov Identifier: NCT01107886) study [ClinicalTrials.gov Identifier: NCT00790205) study on sitagliptin, significant reductions in sitagliptin-associated albuminuria were observed without no changes in eGFR [In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus Thrombolysis in Myocardial Infarction  study , saxagli6) study . In the  in eGFR .ClinicalTrials.gov Identifier: NCT01897532) showed cardiovascular safety of the drug with no significant differences in renal outcomes except for less progression of albuminuria than for the placebo [ClinicalTrials.gov Identifier: NCT01792518) trial followed patients with elevated urine albumin excretion  who were treated with linagliptin. This drug improved glycemic control without showing a statistically significant effect on albuminuria values [The Cardiovascular and Renal Microvascular Outcome Study with Linagliptin  and the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease  trials were two randomized controlled, phase three trials that investigated the beneficial effects of finerenone on the renal and cardiovascular systems in patients with type 2 diabetes mellitus (T2DM) and CKD. FIDELIO-DKD and FIGARO-DKD had a primary and secondary endpoint but were inverted  [The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease  ,11; the r trial) . In addir trial) .CKD patients have high concentrations of LDL-C, very low-density lipoprotein (VLDL), and lipoprotein (a), as well as low concentrations of Apo A-I . AccordiThe management of dyslipidemia in CKD patients remains challenging. Patients with less severe renal insufficiency appear to have a consistent benefit from lipid-lowering treatment with statins in both primary and secondary prevention ; howeverThe use of combination lipid-lowering therapies to attain lower LDL cholesterol targets is an effective therapeutic approach in reducing the cardiovascular risk in subjects with CKD. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a fundamental modulator of LDL receptors in the liver ,75. PCKKClinicalTrials.gov Identifier: NCT01764633) study investigated the potential benefit of treatment with PCSK9 inhibitors to decrease residual risk among subjects with ASCVD and CKD. The use of evolocumab was shown to be safe and effective overall eGFR ranges above 20 mL/min/1.73 m2; it is not known whether the benefits of evalocumab extend to patients at lower risk [ClinicalTrials.gov Identifier: NCT03399370) showed the safety and efficacy of inclisiran in subjects with dyslipidaemia [PCSK9 has pleiotropic functions in the body, including trafficking of the epithelial sodium channel . The Furwer risk . Data frpidaemia .The impact of traditional and emerging therapies on diabetic nephropathy is summarized in The consensus report advises a patient-focused approach to selecting the suitable drug treatments for hyperglycemia : For patNephropathy is considered a microvascular complication very frequently associated with diabetes; therefore, traditional therapies are not able to fully protect against the evolution of renal failure. Innovative treatments could be useful in preventing and treating diabetic nephropathy by modulating the underlying inflammatory process: A new field of research may be a challenge for SGLT-2 inhibitors or GLP-1 agonists and so forth. The main effects of traditional and innovative therapies on diabetic nephropathy are summarized in


Severe obstetric hemorrhage is a leading cause of severe maternal morbidity. A perinatal blood transfusion is the key factor in the treatment of severe obstetric hemorrhage. Our aim is to identify patients with a high risk of perinatal blood transfusions before Cesarean Section, which can promote the effectiveness of the treatment of severe obstetric hemorrhage, as well as improve obstetric preparations.This study retrospectively analyzed the data of 71 perinatal blood transfusion patients and 170 controls, who were both underwent Cesarean Section from July 2018 to September 2019. These data were included in the training set to build the risk prediction model of needing blood transfusion. Additionally, the data of 148 patients with the same protocol from October 2019 to May 2020 were included in the validation set for model validation. A multivariable logistic regression model was used. A risk prediction nomogram was formulated per the results of the multivariate analysis.The strongest risk factors for perinatal blood transfusions included preeclampsia , abnormal placentation , maternal age , predelivery hemoglobin  and predelivery fibrinogen . A risk prediction model of perinatal blood transfusions for cesarean sections was developed .The risk prediction model can identify the perinatal blood transfusions before Cesarean Section. With the nomogram, the model can be further quantified and visualized, and clinical decision-making can subsequently be further simplified and promoted.The online version contains supplementary material available at 10.1186/s12884-022-04696-x. Severe obstetric hemorrhage is the leading cause of maternal death and severe maternal morbidity worldwide, especially in developing countries . Severe The risk factors of severe PPH include uterine inertia, placental factors, soft obstetrical canal cracks, and coagulation disorders –7. UnderThis was a retrospective study that was performed in the Obstetrics Department of the Second Hospital of Shandong University, which is a Grade III general hospital in China in which the annual number of births exceeds 6,000 births every year. All the patient data that were extracted from the clinical electronic medical record system were deidentified, such that all private information was not included. All the procedures complied with the principles of the Declaration of Helsinki and were approved by the Ethics Committee of the Second Hospital of Shandong University. The requirement for informed consent was waived by the Ethics Committee because of the retrospective nature of the study.In our study, the components of blood transfusion include PRBCs, platelets, and FFP or cryoprecipitate. The blood transfusion was defined as at least 2 units PRBC and/or 200 ml plasma and/or 1 unit platelet and/or 4 units cryoprecipitate transfusion. Besides, the time to prepare blood transfusion was intraoperative or postoperative within 24 h.Data were obtained from patients who had undergone cesarean sections in the Obstetrics Department of the Second Hospital of Shandong University from July 2018 to May 2020. The participants were eligible for inclusion if they were hospitalized due to cesarean sections at gestational age ≥ 28 weeks, at age ≥ 18 years, and did not meet any of the exclusion criteria. We excluded the following patients: those patients who underwent vaginal births after cesarean procedures; those patients who had missing information on blood transfusions; and those patients with missing information in their medical records.After we applied the inclusion and exclusion criteria, 71 perinatal blood transfusion patients and 170 controls were recruited into the training set to build risk prediction model from July 2018 to September 2019. An additional file shows this in more detail [see Additional file thRevision, Clinical Modification (ICD-9) diagnosis codes.Clinical characteristics, which are based on prior known risk factors for PPH and clinical experiences in daily practice , 14–16, Data of the clinical characteristics were collected, and all the data were obtained from the electronic medical record system, which records the information of all hospitalized patients in the past 5 years in the Second Hospital of Shandong University, and these data can be verified by using hospital numbers.Predelivery hemoglobin, predelivery hematocrit, and predelivery platelet levels  were derived from routine blood results that were measured with the SYSMEX XN-9000 Automatic Blood and Body Fluid Analyzer , Liver function tests were performed with a Roche 702 Biochemical Analyzer , Hepatitis B virus antigens and antibodies were measured with an Abbott Architect i2000 automatic immunoassay analyzer .The continuous variables are presented as means and standard deviations or medians and range were compared by using Student's t tests or Wilcoxon signed rank tests. The categorical variables are expressed as absolute numbers with percentages, and Pearson’s chi-square tests or Fisher’s exact tests were used to compare the differences.A multivariable logistic regression model was used to develop a prediction model for perinatal blood transfusions with the training set. A univariate analysis was first used; subsequently, the variables that were significant at a α level of 0.10 were included in the multivariate logistic model. A bidirectional stepwise elimination approach was used to simplify the model on basis of the Akaike information criterion. The variance inflation factor was used to measure multicollinearity, and a value > 10 was the criterion for the assessment of the multicollinearity of the factors.A nomogram was formulated  by using the rms package. To use the nomogram, the position of each variable on the corresponding axis was identified, a vertical line was drawn to the points axis for the number of points, the points from all the variables were summed, and a vertical line from the total points axis was drawn to determine the transfusion probabilities at the lower line of the nomogram .The diagnostic value of the nomogram for the perinatal blood transfusions was expressed as the following values: sensitivity, specificity, critical value, and the area under the receiver operating characteristic curve (AUC). The bootstrap test  was applied to test the stability of the AUC. The comparisons of the AUCs were performed with the Z-score test.P value < 0.05 was accepted as significant. Additionally, the confidence intervals for the proportions are reported as 2-sided exact binomial 95% CIs.All the statistical analyses were performed by using the rms and Statistical Product and Service Solutions (SPSS) packages. In the univariate analysis, the variables that were significant at a α level of 0.10 were included in the multivariate logistic model. The other statistical tests were 2-sided, and a In the training set, 241 patients who underwent cesarean sections were included in this study: the average age was 31.61 ± 4.73 years, and the average gestational age was 272 days. When comparing the training set and the validation set, there were no significant differences in age, gestational age, the number of previous deliveries, the number of abortions, or the number of previous cesarean deliveries  .To verify the applicability and stability of the model, we used the Z-score test to compare the AUCs between the training set and the validation set. The results demonstrated that our model has good applicability and stability , it is suggested that sufficient preoperative preparations, adequate blood preparations, and a multidisciplinary cooperation is needed to initiate stabilization strategies, including circulatory support, as well as the maintenance of adequate tissue oxygenation, coagulation function, body temperature, and ionic equilibrium.This study had some limitations. First, this was a retrospective analysis conducted at a single hospital with regional limitations. A multicentre and randomized controlled trial may help better evaluate the blood transfusion risks in patients. Second, although our model demonstrated good discrimination during internal validation, several important next steps are necessary, including the external validation of the model via the use of another cohort of patients. Third, the model established in this study only provides a risk assessment of whether a blood transfusion is required; it does not provide further predictions of required blood transfusion volumes. In addition, this model did not include those patients who required blood transfusions for treatment but were not transfused due to personal factors, although the number of these patients was extremely limited. More in-depth studies should therefore be conducted in the future.This study established a risk prediction model for perinatal blood transfusions in this region, using a nomogram. With the nomogram, the model can be further quantified and visualized, and clinical decision-making can subsequently be further simplified and promoted.Additional file 1. It is the training set to build risk prediction model.Additional file 2. It is the validation set for the verification of the model.


Background: Systemic sclerosis is a chronic multisystem autoimmune disease, characterized by diffuse fibrosis and abnormalities of microcirculation and small arterioles in the skin, joints and visceral organs. Material and Methods: We searched for the relevant articles on systemic sclerosis and kidney involvement in systemic sclerosis in the NIH library of medicine, transplant, rheumatologic and nephrological journals. Results: Half of patients with systemic sclerosis have clinical evidence of kidney involvement. Scleroderma renal crisis represents the most specific and serious renal event associated with this condition. It is characterized by an abrupt onset of moderate to marked hypertension and kidney failure. Early and aggressive treatment is mandatory to prevent irreversible organ damage and death. The advent of ACE-inhibitors revolutionized the management of scleroderma renal crisis. However, the outcomes of this serious complication are still poor, and between 20 to 50% of patients progress to end stage renal disease. Conclusions: Scleroderma renal crisis still represents a serious and life-threatening event. Thus, further studies on its prevention and on new therapeutic strategies should be encouraged. Systemic sclerosis (SSc), also called scleroderma from its typical skin involvement, is a chronic multisystem autoimmune disease, characterized by diffuse fibrosis and abnormalities of microcirculation and small arterioles in the skin, joints and visceral organs, including the gastrointestinal tract, lungs, heart, and kidneys . SSc priThe etiology of SSc remains incompletely understood. Genetic studies have supported the opinion that SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated . Also noThe pathogenic mechanism that brings to the development of SSc in a genetically predisposed subject remains elusive. However, early morphologic endothelial cell injuries, which can be seen before the disease develops, suggest that SSc pathogenesis starts in the vasculature  12]. Th. Th12]. Activation of autoantibodies and cell-mediated autoimmunity, through the mediation of endothelin 1 (ET-1), may also lead to endothelial dysfunction and development of microvascular endothelial cells/small vessels fibroproliferative vasculopathy, with subsequently chronic ischemia of the affected tissues . ET-1 isIn this permissive genetic background, abnormalities of the innate and adaptive immune systems, coupled with increased expression of ET-1  and reduAlso platelets are activated in SSc and can release chemokines, cytokines and growth factors, including transforming growth factor-β1 (TGF-β1), which increases the production of collagen and extracellular matrix . In the Thus, the interplay between immune components, inflammatory processes and vascular changes generates a population of activated connective tissue-producing fibroblasts and myofibroblasts, eventually causing excessive accumulation of collagen and other matrix components in skin, joints, and visceral organs .Kidney disease in SSc is common, as demonstrated by autopsy studies, in which renal histological involvement was present in 60 to 80 percent of patients ,37. ScleBeyond SRC, some patients may show mild hypertension and normal renal function. These patients are initially asymptomatic or show only mild proteinuria, microscopic hematuria and occasional casts. Nephrotic syndrome is uncommon. Mild kidney dysfunction may be also common, as demonstrated by Iliopoulos et al., which examining 796 SSc patients from five different studies observed that 31.5% had a glomerular filtration rate (GFR) < 90 mL/min and 19.5% a GFR < 60 mL/min . PatientThere may be also positivity for anti-dsDNA antibodies or antineutrophil cytoplasmic antibodies (ANCA), which may indicate a possible evolution to another connective disease even in the absence of clinical changes ,44,45. ASRC may occur in about 10% of all patients with scleroderma , and it’SRC typically presents with an abrupt onset of moderate to marked hypertension and kidney failure without signs of glomerulonephritis . HyperteSeveral risk factors for SRC have been identified. These include the presence of a diffuse skin involvement, the presence or absence of some serum autoantibodies and the use of certain drugs, as glucocorticoids and cyclosporine (CYC). In a large retrospective study, the following variables were significantly associated with the risk of SRC: proteinuria, anemia, hypertension, chronic kidney disease, elevated erythrocyte sedimentation rate, thrombocytopenia, hypothyroidism, anti-Ro antibody and anti-RNA-Polymerase III antibody seropositivity. Three or more of these risk factors present at SSc diagnosis were sensitive (77%) and highly specific (97%) for future SRC . The mosIn around 15% of cases, SRC may present with normal blood pressure and is termed normotensive SRC . The iniAlthough the pathogenesis of SRC is not yet fully elucidated, it is likely that both endothelial dysfunction and vascular damage concur to produce a series of insults to the kidneys resulting in vasospasm and narrowing of renal arterioles. The frequent presence of anti-RNA-Polymerase III antibodies and the previous exposure to glucocorticoids makes it possible to speculate that exogenous stimuli may induce vasoconstriction of renal arterioles in predisposed patients with SSc. ET-1 may represent the trigger since its overexpression has been shown in glomeruli and arterioles of kidney biopsies of patients with SRC ,62. ET-1The histologic changes are seen characteristically in arcuate, interlobular and small arteries, and arterioles . The early changes consist in proliferation of intimal cells and accumulation of mucopolysaccharides and glycoproteins. This proliferation damages the internal elastic lamina allowing muscle-like cells to migrate into the intima. A fibrous thickening of adventitia also occurs. Gross narrowing of the blood vessels leads to ischemia which may be aggravated by vascular thrombosis, with consequent atrophy of the nourished tissues. Fibrinoid changes in the walls of arterioles and microinfarcts are also frequent ,67. GlomIn the frequent cases of thrombotic microangiopathy, there are mesangiolysis, thickening of capillary walls, intracapillary thrombosis and areas of fibrinoid necrosis. Juxtaglomerular apparatus is hypertrophic. Immunofluorescence studies are non-specific with occasional glomerular and vascular deposits of IgM, C3 and fibrin. Electron dense deposits are not seen. The tubules may show changes due to ischemic injury with tubular degeneration and necrosis in acute stages. When the damage becomes chronic, tubular atrophy and interstitial fibrosis develop and are proportional to vascular injury . Both poSSc may overlap with lupus nephritis , while tThe prognosis of scleroderma renal crisis largely depends on the rapid control of malignant hypertension and improvement of the ongoing renal ischemia. The advent of angiotensin-converting enzyme inhibitors (ACEIs) allows for the reversal of the unfavorable outcome of SRC. In a pivotal prospective study carried out in a cohort of 108 SRC patients, the 1 year survival rate was 76% in those treated with ACEIs and 15% in those who were not in treatment with ACEIs . DespiteSSc may present with a wide spectrum of manifestations. Thus, the treatment should be tailored to the type of organ involvement and to the disease subset .Often patients are treated with symptomatic therapy for the specific organ involvement, as proton pump inhibitors for gastrointestinal reflux or calcium channel blockers (CCBs) for Raynaud phenomenon. Immunosuppressive drugs, such as methotrexate, azathioprine, mycophenolate and cyclophosphamide (CYC), are used to manage interstitial lung disease, which remains the leading cause of mortality in SSc ,79,80. HIn SSc patients with chronic kidney disease, a careful check and treatment of arterial hypertension is recommended . TreatmeDespite this, ACEIs are still considered as the first choice in SRC treatment, but their use should be more closely monitored ,95. In cEven with treatment with ACEIs, about 20 to 50% of patients with SRC require dialysis ,73. BothMany patients do not recover kidney function and remain dialysis-dependent. However, a few patients may recover kidney function after a long period of dialysis. Thus, decisions regarding kidney transplantation should be taken after 1–2 years of dialysis . SclerodUp to half of patients with SSc have clinical evidence of kidney involvement, such as mild proteinuria, elevated serum creatinine concentration, or hypertension. Despite the identification of possible risk factors, as the use of glucocorticoids and the presence of autoantibodies directed against RNA polymerase III, SRC develops in about 10% percent of SSc patients, most commonly within 3 to 5 years of diagnosis, and in those with dcSSC. Early and aggressive treatment is mandatory to prevent irreversible organ damage and death. The mainstay of therapy in SRC is a prompt and effective blood pressure control using ACEIs. Despite the advent of ACEIs, about 20 to 50% of patients with SRC progress to ESRD and require dialysis. However, a significant proportion of patients on renal replacement therapy will recover renal function. Kidney transplantation should be considered after a period of 1 to 2 years on dialysis. Considering the poor outcomes that still characterize SRC, further studies on its prevention and on new therapeutic strategies should be encouraged.


High systolic blood pressure (SBP) is an important risk factor for the progression of heart failure (HF); however, the association between SBP and prognosis among patients with established HF was uncertain. This study aimed to investigate the association between SBP and long-term clinical outcomes in patients hospitalized for HF.This study prospectively enrolled adult patients hospitalized for HF in 52 hospitals from 20 provinces in China. SBPs were measured in a stable condition judged by clinicians during hospitalization before discharge according to the standard research protocol. The primary outcomes included 1-year all-cause death and HF readmission. The multivariable Cox proportional hazards regression models were fitted to examine the association between SBP and clinical outcomes. Restricted cubic splines were used to examine the non-linear associations.The 4,564 patients had a mean age of 65.3 ± 13.5 years and 37.9% were female. The average SBP was 123.2 ± 19.0 mmHg. One-year all-cause death and HF readmission were 16.9 and 32.7%, respectively. After adjustment, patients with SBP < 110 mmHg had a higher risk of all-cause death compared with those with SBP of 130–139 mmHg . Patients with SBP < 110 mmHg  and SBP ≥ 150 mmHg  had a higher risk of HF readmission, and the association between SBP and HF readmission followed a J-curve relationship with the nadir SBP around 130 mmHg. These associations were consistent regardless of age, sex, left ventricular ejection fraction, hypertension, coronary heart disease, and medications for HF.In patients hospitalized for HF, lower SBP in a stable phase during hospitalization portends an increased risk of 1-year death, and a J-curve association has been observed between SBP and 1-year HF readmission. These associations were consistent among clinically important subgroups. Heart failure (HF) is a major global public health problem, with a prevalence of 64.3 million cases worldwide . HF is tAmong patients hospitalized for HF, previous studies have shown that those with lower admission SBP were at a higher risk of clinical outcomes –12; whilAccordingly, this study aimed to investigate the association of SBP in a stable phase during hospitalization with 1-year clinical outcomes in the overall population and in clinically important subgroups based on a prospective multicenter cohort with a large number of patients hospitalized for HF, which could provide more evidence for future recommendations on BP management, and help physicians optimize BP management strategies to improve outcomes of patients with HF.The study design of the China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study) has been described previously in detail . In briewww.clinicaltrials.gov (NCT02878811).The Central Ethics Committee at the Fuwai Hospital and Local Internal Ethics Committees at Study Hospitals have approved the China PEACE 5p-HF Study. The study was registered at via central medical record abstraction. We used a standardized questionnaire for information collection particularly regarding demographic characteristics, socioeconomic characteristics, smoking status, and self-reported health status by face-to-face interview during index hospitalization by trained local clinicians. The local clinicians entered data into laptop computers which were equipped with a customized electronic data collection system allowing real-time off-line logic checks to verify the accuracy and completeness of the data. The trained clinicians measured LVEF during hospitalization based on the standard echocardiogram protocol. Low-density lipoprotein cholesterol, N-terminal pro-brain natriuretic peptide (NT-proBNP), and serum creatinine were according to the central laboratory tests—blood and urine sample tests taken within 48 h of admission by unified protocol or the last local laboratory tests before discharge if the central laboratory tests were unavailable (missing rate < 2.8%).Clinical status, comorbidities, and medications were obtained The measurement of SBP was conducted on the upper arm of each participant in a stable phase during hospitalization before discharge  using unified electronic BP monitor (Omron HEM-7111) by trained site investigators according to the standard research protocol. The mean SBP of two or three successive measurements was calculated (if the difference between the first and second measurement was >5 mmHg then taking the third measurement).2, and diabetes as HbA1c ≥ 6.5%. And we evaluated self-reported health status using the short version of Kansas City Cardiomyopathy Questionnaire (KCCQ) sum score at baseline, the scores of which ranged from 0 to 100 .Patients were classified by LVEF into heart failure with reduced ejection fraction , mid-range ejection fraction , and preserved ejection fraction . HF types included decompensated chronic HF (defined as patients having had HF for a period of time and then being admitted because of the chronic stable HF deterioration) and new-onset HF. Hypertension, coronary heart disease, atrial fibrillation, diabetes, reduced renal function, anemia, stroke, chronic obstructive pulmonary disease, and valvular heart disease were defined according to the medical record  or positive laboratory test results. We defined the diagnosis criteria of laboratory tests of anemia as hemoglobin <120 g/L in men or <110 g/L in women, reduced renal function as estimated glomerular filtration rate <60 ml/min/1.73 mThe primary outcomes of this study were 1-year all-cause death and HF readmission. We also included cardiovascular death and all-cause readmission as secondary outcomes. Cardiovascular death was defined as sudden death, death due to HF, stroke, acute myocardial infarction, or other cardiovascular causes, or presumed/unknown cardiovascular death. Information on the clinical outcomes was collected from follow-up interviews and the national death cause database. We also collected medical records of potential outcome events to do central adjudication by trained clinicians at the national coordinating center.n = 117) and those with SBP <90 mmHg (n = 98).Categorical variables were expressed as count and percentage and tested using the chi-square test; continuous variables were reported as mean ± SD or median (IQR) and tested by the one-way ANOVA or the Kruskal–Wallis test, as appropriate. For continuous variables, we performed tests for linear trend by entering the median value of each category of SBP as a continuous variable in the models; for categorical variables, a trend was tested with the Cochran–Armitage trend test . The proThe interactions between SBP groups and subgroup parameters were also included in the Cox models when assessing the association of SBP with all-cause death and HF readmission. Subgroup parameters included age (<65 or ≥65 years), sex , LVEF type , HF type (decompensated chronic HF or new-onset HF), NT-proBNP (< median or ≥median), hypertension (yes or no), diabetes (yes or no), atrial fibrillation (yes or no), coronary heart disease (yes or no), valvular heart disease (yes or no), reduced renal function (yes or no), prescriptions of ACEIs/ARBs (yes or no), β-blockers (yes or no), and aldosterone antagonists (yes or no).P < 0.05 was considered statistically significant.There were 79 (1.7%), 13 (0.3%), 5 (0.1%), and 4 (0.1%) patients without the value of NT-proBNP, low-density lipoprotein cholesterol, heart rate at discharge, and serum creatinine, respectively. Assuming that they were missing randomly, multiple imputations were utilized to account for missingness. SAS Version 9.4  and R programming language version 4.1.1  were used for all statistical analyses, and a two-sided n = 32), did not attend the follow-up visit (n = 9), or without SBP measurement (n = 302) were excluded; and 4,564 patients met the inclusion criteria for this study  deaths, 668 (14.6%) cardiovascular deaths, 1,886 (41.3%) all-cause readmissions, and 1,492 (32.7%) HF readmissions occurred. Of patients with SBP < 110 mmHg, 262 (23.4%) died compared with 93 (13.6%) of those with SBP of 130–139 mmHg. There were 411 (36.8%) patients with SBP < 110 mmHg having HF readmission and 136 (34.6%) patients with SBP ≥ 150 mmHg having HF readmission, compared with 191 (27.9%) of patients with SBP of 130–139 mmHg . The cumP < 0.001) for SBP < 110 mmHg (P = 0.001) and SBP ≥ 150 mmHg  were more likely to have readmission due to HF compared with those with SBP of 130–139 mmHg , and the nadir of risk occurred when the SBP was around 130 mmHg with the risk increasing below or above that cutoff . The interactions were not significant in other important subgroups, including age, sex, HF type, hypertension, diabetes, coronary heart disease, prescriptions of ACEIs/ARBs, β-blockers, and aldosterone antagonists  from the Ministry of Science and Technology of China, the CAMS Innovation Fund for Medical Science (2021-1-I2M-009), and the National Key Technology R&D Program (2015BAI12B02) from the Ministry of Science and Technology of China.JLi reported receiving research grants, through Fuwai Hospital, from the Chinese government and Chinese Academy of Medical Sciences for work to improve the management of hypertension and blood lipids and to improve patient outcomes of cardiovascular disease and COVID-19; receiving research agreements, through the National Center for Cardiovascular Diseases and Fuwai Hospital, from Amgen for a multicenter clinical trial assessing the efficacy and safety of omecamtiv mecarbil and for dyslipidemic patient registration; receiving a research agreement, through the Fuwai Hospital, from Sanofi for a multicenter clinical trial on the effects of sotagliflozin; receiving a research agreement, through the Fuwai Hospital, with the University of Oxford for a multicenter clinical trial of empagliflozin; receiving a research agreement, through the National Center for Cardiovascular Diseases, from AstraZeneca for clinical research methods training outside the submitted work; and receiving a research agreement, through the National Center for Cardiovascular Diseases, from Lilly for physician training outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.