Continuous monitoring of arterial blood pressure (BP) outside of a clinical setting is crucial for preventing and diagnosing hypertension related diseases. However, current continuous BP monitoring instruments suffer from either bulky systems or poor user-device interfacial performance, hampering their applications in continuous BP monitoring. Here, we report a thin, soft, miniaturized system (TSMS) that combines a conformal piezoelectric sensor array, an active pressure adaptation unit, a signal processing module, and an advanced machine learning method, to allow real wearable, continuous wireless monitoring of ambulatory artery BP. By optimizing the materials selection, control/sampling strategy, and system integration, the TSMS exhibits improved interfacial performance while maintaining Grade A level measurement accuracy. Initial trials on 87 volunteers and clinical tracking of two hypertension individuals prove the capability of the TSMS as a reliable BP measurement product, and its feasibility and practical usability in precise BP control and personalized diagnosis schemes development. Continuous monitoring of arterial blood pressure is limited by bulky connecting systems and poor interfacial contact. Here, Li et al. report a wearable thin, soft, miniaturized system that integrates sensing, active pressure adaptation, and signal processing for improved performance and accuracy. Blood pressure (BP) as an important biomarker provides remarkable insights into many hemodynamic parameters, such as stroke volume, heart rate, and cardiac output, which are closely relate to CVDs5. Monitoring of BP routinely can effectively reduce the attacking risk of CVD related diseases, such as sleep apnea, stroke, and coronary heart disease, since hypertension is a vital risk index during the development of CVD related diseases9. At present, clinics mainly rely on the cuff-based sphygmomanometers to measure the static BP, in which only isolated casual systolic BP (SBP), diastolic BP (DBP) are recorded, and mean BP (MAP) can be calculated according to SBP and DBP. It is challenging to achieve continuous dynamic measurement of BP with current cuff-based sphygmomanometers due to the working mechanism of the cuff inflation13. In comparison, continuous BP monitoring not only provides an efficient monitoring method for patients with long-term or pre-diagnostic hypertension, but also makes a better prediction for CVDs related attacks in hypertensive individuals17.Cardiovascular diseases (CVDs), one of the leading causes of death worldwide, take an estimated of 18 million people’s lives annually20, which raises patients suffering and infection risk, and also too invasive for routine inspection and daily monitoring. In recent years, the rapid development of wearable electronics has made it possible to continuous monitor of some physiological indexes with wearable devices23. Therefore, continuous non-invasive BP monitoring with wearable devices has drawn great research attention. Several non-invasive methods, including optical based method 26, acoustic 28, bioimpedance9 and pressure sensor based tonometry31, have been developed for this purpose. Among them, PPG is one of the most commonly used methods, however, which also suffers from signal aliasing from venous arteries and insufficient penetration depth . In addition, the complicated data processing system and the stringent setups for optical information processing further limit the development of PPG systems into real wearable device for continuous and long-term BP monitoring34. Ultrasound wall-tracking and bioimpedance have been considered as the promising candidates for continuous BP monitoring due to their high penetration depth and robust sensing capability in hemodynamic parameters35. However, to realize wearable/portable continuous monitoring of BP not only needs the devices that are designed in wearable manner, but also puts high demand on signal sampling and post processing for the BP calibration. Although wearable ultrasound transducers27 and electrodes8 have been developed for continuous BP measurement, high precise sampling equipment and bulky interface block their further application in continuous ambulatory BP monitoring. Tonometry that facilitates a pressure sensor to detect the artery deformation generated by blood propagation has been also considered for BP measurement due to its simple structure and low requirement on signal processing. While high sensitivity pressure sensors, including piezoresistive based37and capacitive based ones39, all face the interfacial instability issue, and thus repeated calibration is required for BP evaluation.In clinic, the gold standard for continuous BP measurement is implanting an invasive fiber-based pressure sensor into the center of artery40. The active pressure adaptation unit is based on a build-in micro airbag together with a micro pump, which provides a powerful backpressure and close-looped feedback for the piezoelectric sensor array to effectively detect the arterial deformation generated by blood propagation. The measured blood pulse waveforms, and the time difference between their arrival at the two sensing units are preprocessed along with multiple extracted features and local pulse wave velocity (PWV) as input to a blood pressure estimation model. Compared to other cuffless BP monitoring devices , that is capable for continuously monitoring of BP in real wearable format, with whose accuracy is comparable to the professional medical equipment. The TSMS composes three subsystems, including a sensing module to detect the blood pulse wave, an active pressure adaptation module to provide powerful back pressure for improved interfacial properties, and a data processing module to in-situ extract pulse transit time interval and transmit the measured data to a graphical user interface (GUI). The entire system only weighs 50 g, as thin as 4 mm, that is encapsulated in silicone as a wristband to provide friendly wearable interface for users. Highly chemical/physical stability of the piezoelectric material PZT 5H enables the sensor array with excellent uniformity and robustness while maintaining superior sensitivity due to its high piezoelectric coupling coefficient41.Figure Piezo response is generated due to the potential difference across the sandwiched electrodes when suffering from mechanical deformation caused by blood propagation Fig. , and theThe active pressure adaptation system associates with backpressure generator, which composes of a micro pump (19 mm × 21 mm × 3.6 mm), a pair of soft silicone  based micro airbag array Fig. , and a sThe TSMS encapsulated by silicone in a wristband format provides an easy and efficient way for users to wear, where the sensor array can detect the mechanical pulse caused by blood propagation. While the use of PZT 5H as sensors is based on its excellent electrical, physical and chemical stabilities  to avoid discomfortable feelings while maintaining satisfactory signal quality , whe, whe2), , whe, whs in Eq.  and tooks in Eq. . The mea44. PWV has been widely used46 to improve the measurement accuracy of BP. However, global PWV reflects the elastic properties of arteries over a long segment, which might mask the initial variations in biomechanical properties in a small segment48. Moreover, incorrect estimation of blood travel distance would cause accuracy issue. In comparison, local PWV calculating pulse wave velocity in a short distance along arteries provides important diagnostic information of biomechanical properties for local artery walls49. However, the high propagation speed, normally ranging from 2 m/s to 20 m/s52, as well as the short propagation distance between two adjacent sensing units bring an issue of short time difference (Δt) between two sensors’ responses, and therefore requiring a high sampling rate53 (>1500 data points/s) to reduce the error in Δt calculation, which arises a big challenge for wearable wireless transmission. To solve this problem, we develop a strategy associated with a resampling and transmission method to resample and wirelessly transmit the measured blood propagation waveform while maintaining the high sampling rate of the ADC . Besides, creating a wide range of blood pressure fluctuations can help to improve the model prediction performance for high blood pressure subjects. Hence, four subjects were asked to perform sustained hand grip and cold pressor  equipped with CNAP monitor, which has been proved providing clinically acceptable accuracy BP Fig. . During  BP Fig. . To furt BP Fig. .Fig. 4Pe68. To study how the age and BMI affect BP and further validate the TSMS as a reliable continuous BP monitoring system, we selected 17 volunteers, with comprehensive age and BMI, to perform a pilot study to monitor their daily BP with TSMS and take BP measured with a commercial sphygmomanometer, the gold standard for noninvasive BP measurement, as a reference. The volunteers were grouped into 4 teams based on their age and 3 teams based on their BMIs, respectively. The BP in four age groups, teenager (<20), youth (20–35), middle-aged (35–50) and elderly (>50), is presented in Fig. Hypertension is a highly prevalent condition with numerous health risks that could be caused by various factors. Among those pathogenic factors, biological aging and body mass index (BMI) have been reported showing positive association with BPTo further explore the significance of continuous BP monitoring by the TSMS, we tracked the continuous BP data of the borderline hypertension individual and hypertension individual for a week  or cumbersome recalibration processes (ultrasound based and tonometry based), both of which have greatly hampered their uses in totally wearable/portable formats. Moreover, the unreliable interfacial contact between the device and artery will introduce extra noise signals to pulse wave, such as sliding noise caused by loose contact and occasional error, which will greatly reduce signal quality, and thus leading to poor measurement accuracy.By integrating a sensor array, an active pressure adaptation system, and a signal sampling and processing module into a thin and soft wristband, we have demonstrated a powerful universal strategy that can provide real-time and reliable monitoring of continuous BP patterns. Excellent measurement robustness and accuracy, with 0.11 ± 3.68 mmHg for DBP and −0.05 ± 4.61 mmHg for SBP, was achieved by the TSMS. All these capabilities rely critically on three main advances over previously reported works: (i) a flexible, self-powered piezoelectric sensor array that generates a reliable piezo response in response to blood propagation; (ii) an active pressure adaptation system associating with backpressure adjusting and a multiple pumping control strategy to guarantee good contact between the sensor array and the skin; (iii) a machine learning based data model with a wireless communication strategy for local PWV transmission and continuous BP estimation. Benchtop studies, structural design, theoretical simulation, and initial trials on a total number of 87 volunteers have demonstrated the feasibility and practical utility of the TSMS in continuous BP monitoring. Furthermore, dynamic BP tracking of a hypertension individual and a borderline hypertension individual reveals the BP changes during a day and a week. We envision that the TSMS could play a crucial role in realizing precise BP control for hypertension individuals and cardiovascular disease prevention through continuous BP monitoring and the development of personalized diagnosis and treatment schemes. To realize long-term accuracy monitoring of continuous BP pattern, comprehensive pre-train process to the data model is needed with a balanced distribution on BP range and other factors that contribute to BP fluctuations. This study, instead, focused on limited size of human participants actual scenes. We believe further expanding the number of human participants and improving BP distribution will improve the BP estimation accuracy.2 (5 nm/50 nm) on the PI side by E-Beam. The electrode traces together with the PDMS substrate (200 μm in thickness) were exposed to UV-induced ozone for 5 min before heating in the oven at 80 °C for 10 min to enable the formation of covalent bonding between SiO2 and PDMS. Removing water-soluble tape and welding PZT to the electrodes with silver paste at 100 °C for 10 min enable the robust connection. Finally, injection of PDMS with a syringe, following by degas and curing at 80 °C for 1 h facilitated the removal of interfacial gaps and encapsulation of the sensor array.The fabrication process  in a 3D printed mold, with the inner diameter of 2.8 mm, outer diameter of 4.7 mm and 4.2 mm in thickness, following by degassing, curing at 80 °C for 10 min and punching hole (0.5 mm in diameter) sequentially  with the assistance of a 3D printed mold  participated in the experiments. The participants were required to stay in a sitting posture, with the cuff around the left upper arm and the sensor on the fingers, and the other arm wore our pulse sensor on the wristband Fig. . To syncTo make the device wearable and easy to use, a thin flexible printed circuit board (FPCB) was designed. Two photolithographically patterned copper conductor layers (17.5 μm thick) on polyimide substrate are used to connect the circuit, with an overall FPCB thickness of only 139 μm. The electronic components are soldered to the FPCB using solder paste and heat gun to fabricate the control unit. This circuit can collect the voltage data generated by the sensor in a relative high speed (like 4000 samples per second) and transmits the results to the phone via Bluetooth Low-Energy (BLE) wirelessly. At the same time, it can control the air pump to produce proper pressure on the sensor. To achieve these functions, a micro-controller unit (MCU) with integrated Bluetooth functionality , a 24-bit high speed analog-to-digital converter , a low dropout regulator , a multiple-output regulator , air pump driver chip , 2.4 GHz impedance matched balun , 2.4 GHz mini antenna  and passive components such as resistors, capacitors and inductors are integrated into this circuit. The LDO and multiple-output regulator is used to convert the 3.7 V output voltage from the Li-ion battery to 3.3 V and ±1.5 V to power the ADC and MCU. The ADC can collect the small signal generated by the sensor in a relative high speed. After that, MCU can access those data by Serial Peripheral Interface (SPI) and sent them to the phone via Bluetooth after a simple processing  with a constant sampling frequency at 1000 Hz. The dynamic loading was applied with a universal testing system , which allows precise control on loading force and loading speed. The photographs of morphology changing of the micro airbag were taken by a high-speed camera  with a recording frame rate at 300 fps. Thermal images were taken by fixed infrared thermal camera (FLIR A325sc).All procedures during the olfaction system testing from human participants are approved by Human and Artefacts Ethics Sub-Committee, City University of Hong Kong Research Committee with the reference number of HU-STA-00000393. The informed consent of all participants was obtained prior inclusion in this study.Further information on research design is available in the Supplementary InformationPeer Review fileDescription of additional supplementary filesSupplementary Movie 1Supplementary Movie 2Reporting Summary


Congenital Diaphragmatic Hernia (CDH) is a complex disease including a diaphragmatic defect, lung hypoplasia, and pulmonary hypertension. Despite its increasing use in neonates, the literature on the use of vasopressin in neonates is limited. The aim of this work is to analyze the changes in clinical and hemodynamic variables in a cohort of CDH infants treated with vasopressin.Among CDH infants managed at the Neonatal Intensive Care Unit (NICU) of our hospital from May 2014 to January 2019, all infants who were treated with vasopressin, because of systemic hypotension and pulmonary hypertension, were enrolled in this retrospective study. The primary outcome was the change in oxygenation index (OI) after the start of the infusion of vasopressin. The secondary outcomes were the changes in cerebral and splanchnic fractional tissue oxygen extraction (FTOEc and FTOEs) at near-infrared spectroscopy, to understand the balance between oxygen supply and tissue oxygen consumption after the start of vasopressin infusion. We also reported as secondary outcomes the changes in ratio of arterial oxygen partial pressure (PaO2) to fraction of inspired oxygen (FiO2), heart rate, mean arterial pressure, serum pH, and serum sodium.p = 0.003). A global significant improvement in FTOEc and FTOEs was detected  as a significant reduction in heart rate (p = 0.019). A global significant improvement in PaO2/FiO2 ratio was observed (p < 0.001) and also at all time points: at 6 h since infusion (p = 0.015), 12 h (p = 0.009), and 24 h (p = 0.006), respectively. A significant reduction in sodium levels was observed as expected side effect (p = 0.012). No significant changes were observed in the remaining outcomes.We included 27 patients with isolated CDH who received vasopressin administration. OI dramatically dropped when vasopressin infusion started, with a significant reduction according to ANOVA for repeated measures (Our data suggest that starting early vasopressin infusion in CDH infants with pulmonary hypertension could improve oxygenation index and near-infrared spectroscopy after 12 and 24 h of infusion. These pilot data represent a background for planning future larger randomized trials to evaluate the efficacy and safety of vasopressin for the CDH population. Despite improvements in prenatal and postnatal care and survival to discharge  in neonates is limited –5. Acker2.2.1.Among CDH infants managed at the Neonatal Intensive Care Unit (NICU) of “Bambino Gesù” Children's Hospital  from May 2014 to January 2019, all infants who were treated with vasopressin because of systemic hypotension and pulmonary hypertension were enrolled into this retrospective study. We excluded preterm infants born before 34 weeks of gestational age and those with major congenital malformations associated.During the study period, CDH patients were managed according to defined protocols (CDH EURO Consortium Consensus) . Our locIn the case of persistent pulmonary hypertension, we added an intravenous phosphodiesterase type 5 inhibitor (sildenafil) after about 24 h since the start of vasopressin.After surgical repair, if there was no or an insufficient response to iNO, intravenous prostacyclin or medication involving the endothelin pathway has been considered .Data of patients were obtained from electronic medical records.First, we recorded their demographic and clinical characteristics .In order to verify the hemodynamic instability of these infants, we recorded the use of vasopressin (hours of life at the start of infusion and maximum dose that was used), hemoglobin level at the start of vasopressin infusion, use of milrinone (hours of life at the start of infusion and maximum dose that was used), use of inhaled nitric oxide (iNO), use of further drugs for pulmonary hypertension , use of vasoactive drugs  and maximum vasoactive inotropic score, use of hydrocortisone, initial ventilation strategy used , use of ECMO, hours between birth and surgical repair.Therefore, we recorded changes in Clinical and Hemodynamic Variables before vasopressin infusion  and after 6 h , 12 h , and 24 h from the start of infusion .The primary outcome was the change in oxygenation index (OI) after the start of vasopressin infusion.2c and rSO2s, respectively) in all infants, in order to understand the balance between oxygen supply and tissue oxygen demand. Cerebral and splanchnic fractional tissue oxygen extraction (FTOE) was calculated using the following formula [FTOE = (SaO2 – rSO2)/SaO2 ], and changes after the start of vasopressin infusion were also evaluated  equipped with two independent emittent-sensor pairs was used for simultaneous measurement of regional cerebral and splanchnic tissue oxygen saturation  to the fraction of inspired oxygen (FiO2), heart rate, mean arterial pressure, serum pH, and serum sodium. PaO2 assessments were from radial artery punctures.Standard clinical echocardiography was performed before and within 24 h after vasopressin infusion to assess mean pulmonary arterial pressure and to compare it with systemic systolic pressure, defining it as <2/3 systemic systolic pressure (mild PH), ≥2/3 systemic systolic pressure (moderate PH), or systemic-to-suprasystemic pressure (severe PH) . The dir2.2.This preliminary study reported only a retrospective analysis of data available through the Institutional Database. Personal data were restricted to essential information and were treated in order to guarantee the respect of the privacy of the involved patients, as specifically stated by Italian Law D.Lgs n.196 of 2003 about personal data protection. Therefore, the study did not require preliminary evaluation by the local Ethical Committee.p-value <0.05 was considered significant. Statistical analysis was performed using software programs Microsoft Excel (2016 for Windows) and MedCalc (version 12.7 for Windows).Data are presented as numbers and percentages for categorical variables, comparing them with the Fisher test. Continuous variables are expressed as mean ± standard deviation (SD) if they were normally distributed or as median and interquartile range if normality could not be accepted, according to the D'Agostino-Pearson test. Global changes in clinical and hemodynamic variables after vasopressin infusion were compared with analysis of variance (ANOVA) for repeated measures with a Huynh-Feldt correction (when epsilon is greater than 0.75) or Greenhouse-Geisser correction (preferred when epsilon <0.75). Conversely, pairwise comparisons between different time points were analyzed with a Bonferroni post-hoc test. A 3.In this retrospective study, we evaluated the medical records of 70 CDH infants born during the study period. After excluding two patients born before 34 weeks GA and 20 patients with major congenital malformations, we initially considered for inclusion in this study 48 patients with isolated CDH. Among these, 21 patients in whom vasopressin infusion was not administered were also excluded: of these 21, fifteen survived (71.4%), four required patch repair (19.0%), four required other inotropes and ECMO (19.0%), and two received iNO (9.5%).Therefore, we analyzed data from 27 patients with isolated CDH who were managed with vasopressin administration .We reported the demographic and clinical characteristics of included infants in Only in 2 infants (7.4%) we observed a left ventricular dysfunction at echocardiographic evaluation. However, 22 infants (81.5%) received milrinone, starting at a median of 9 h (IQR 3-29). Twenty-six infants (96.3%) needed dopamine, four infants (14.8%) dobutamine, six infants (22.2%) epinephrine, and nine infants (33.3%) norepinephrine. Twelve infants (44.4%) were managed using inhaled nitric oxide (iNO): of them, all infants who died previously received iNO treatment. All infants also received hydrocortisone to maintain adequate blood pressure, sparing inotropes.We treated all 27 infants with vasopressin, starting infusion at a median of 12 h (IQR 7-30). The mean level of hemoglobin at the start of vasopressin infusion was 15.9 ± 2.1 g/L. Vasopressin was administered for about 72 h in most patients.p = 0.003) both in infants receiving milrinone and vasopressin and in infants receiving vasopressin only. Pairwise comparisons between OI values at T0 and OI values at T1, T2, and T3 showed that there were significant differences found after 12 h and 24 h of infusion , but not after the first six hours of infusion (p = 0.132).The oxygenation index (OI) dramatically dropped when vasopressin infusion started, as shown in p = 0.009 and p = 0.004, respectively) as a significant reduction in heart rate (p = 0.019).A global significant improvement in FTOEc and FTOEs was detected (p < 0.001) and also at all time points: at T1 (p = 0.015), T2 (p = 0.009), and T3 (p = 0.006), respectively.A global significant improvement in PaO2/FiO2 ratio was observed (p = 0.012). No significant changes were observed in the remaining outcomes  with fluid restriction: of them, 16/18 (88.9%) also received a careful supplementation of serum sodium during vasopressin administration.p = 0.004)  . None ofIntravenous sildenafil was added in 15 patients (55.6%) after about 24 h since the start of vasopressin infusion because of clinical signs of persistent pulmonary hypertension.After surgical repair, if there was no or an insufficient response to iNO, or if there was a left ventricular dysfunction contraindicating the use of iNO, 11 patients (40.7%) still had clinical signs of persistent pulmonary hypertension and were managed with other drugs .4.To our knowledge, this is the largest cohort study of vasopressin use in the setting of pulmonary hypertension including only infants with CDH to date. Newborns are not small children or adults, with special concerns regarding drug therapy and significant changes in the pharmacokinetics and pharmacodynamics of many drugs . Given tHemodynamic instability, which is common in CDH newborns, especially during the transition in the first hours of life, necessitates early identification, interpretation of the etiology, and efficient therapy to maximize perfusion and mitigate the symptoms of severe PH . BecauseIndeed, almost every infant born with CDH will have some degree of PH, with a prevalence that decreases substantially in the first weeks of life, and the majority showing a resolved PH by discharge . ExaminiIn our cohort, 29.6% of infants with PH died. This result is in line with observed survival rates for CDH neonates with PH (20%–45%) during the first year .The most widely used medication in neonatal PH management is inhaled nitric oxide (iNO) . iNO canMost CDH patients (92.5%) who required ECMO received iNO prior to or not on the same day as ECMO, among a large international cohort: the treatment with iNO was associated with a 15% higher absolute mortality rate . We confIn our cohort, vasopressin was started early and not only after patients met the criteria for initiation of ECMO, as in Acker's report . We starWe also observed a global significant improvement in cerebral and splanchnic oxygenation, which should be maintained as stable as possible, considering the modifications in cerebral and splanchnic hemodynamics on near-infrared spectroscopy these children undergo . Before Hyponatremia (serum Na < 134 mmol/L) is an expected side effect of vasopressin, which we reported in 66.7% of our infants. These findings are in line with the case series of infants treated with vasopressin described by Budniok et al. (64% of infants): they reported severe hyponatremia (less than 125 mmol/L) in 7 episodes (33%) (We have several data in favor of the biological plausibility of our findings. Sugawara et al. showed in a rat model of a pulmonary hypertensive crisis that vasopressin, but not phenylephrine or norepinephrine, resulted in better hemodynamic and vascular recovery. Indeed, vasopressin contracted femoral but not pulmonary arteries, whereas phenylephrine contracted both arterial beds. Hence, improvements with vasopressin might be associated with decreased pulmonary vascular resistance and selective systemic vasoconstriction . The vasThe effects of vasopressin are twofold: on the one hand, pulmonary vasodilatation; on the other, systemic vasoconstriction, and this can be useful to guarantee hemodynamic stability in infants with CDH and avoid global derangement. Goals for hemodynamic management include heart rate and blood pressure within the normal range for gestational age, arterial pH > 7.2, urine output >1 ml/kg/h, lactate concentration <3 mmol/L, and adequate end-organ perfusion .Our data support the use of vasopressin in infants with CDH, as previously reported in a case series by Acker et al. who described how vasopressin therapy increased mean arterial pressure and decreased pulmonary/systemic pressure ratio, heart rate, and the fraction of inspired oxygen .Our findings are limited by the small sample size of included infants, the lack of urine output data, and the need for standardized echocardiographic data collected prospectively at different time points due to the retrospective design of the study. Moreover, we don’t have a placebo control group or a comparable time-matched cohort, and therefore we don't have enough data to assess if the amelioration obtained with vasopressin was summatory to that obtained with other drugs or not. A prospective study is needed to fully evaluate the dynamic interplay of the cardiovascular system in these patients.Interestingly, a recent preprint reported a retrospective evaluation of term infants with persistent pulmonary hypertension under a standardized protocol, which included the use of vasopressin. Santelices et al. included 48 neonates with different disorders: of them, 39 neonates had CDH. They confirmed our findings also by echocardiographic within 6 h prior to the start of vasopressin and between 3 and 24 h from the start of the drug: furthermore, all patients were receiving iNO at 20 ppm. However, their results concern all patients and not only those with CDH .Conversely, we confirmed in a homogenous cohort of CDH infants the positive impact of vasopressin infusion in improving hemodynamic status and oxygenation. These pilot data represent a background for planning future larger studies to evaluate the efficacy and safety of vasopressin for the CDH population.5.Our data suggest that the vasopressin infusion in CDH infants can be useful in reducing pulmonary hypertension since we found a significant reduction in oxygenation index after 12 and 24 h of infusion, with a similar trend in both infants receiving milrinone and vasopressin and in those receiving only vasopressin. Furthermore, we also describe a significant improvement in cerebral and splanchnic oxygenation at near-infrared spectroscopy. However, further randomized studies are needed to confirm our uncontrolled retrospective findings in a multicenter cohort.


House dust mite (HDM) is the most common sensitising allergen in asthma. Ethnic minority groups (EMGs) in the UK are more likely to live in deprived conditionings with a greater exposure to HDM and other aero‐allergens.To compare the ethnicity‐based patterns of sensitisation to aero‐allergens and the impact of ethnicity on clinical outcomes in patients with difficult‐to‐treat asthma (DTA).Data of patients with DTA were extracted from the registry of the Birmingham Regional Severe Asthma Service (BRSAS), which have a catchment population of 7.3million from Central England. Patients from White and EMG backgrounds were compared in terms of the prevalence of atopy, total serum immunoglobulin E (IgE), specific serum IgE (ssIgE) and asthma related clinical outcomes. Logistic regression analysis was conducted to explore ethnicity‐based risk factors for HDM sensitisation.p < 0.0001. Positive HDM sensitisation was more prevalent in the EMG than in the White group . The median HDM ssIgE level was higher in the EMG than in the White group . The odds ratio for positive sensitisation to HDM conveyed by the EMG status was 2.61 , p < 0.0001. Compared to the White group, the EMG had higher median total serum IgE , higher blood eosinophil count  versus 0.23 , p < 0.000001), were marginally more atopic  and were less likely to being on maintenance oral corticosteroids .A total of 1272 patients  with a median age of 51 years (range 16–97) were included in the analysis. Patients from EMG were more likely (64%) to reside in the worst scale of index of multiple deprivation (IMD) than the White patients (25.5%), In this DTA cohort, positive HDM sensitisation was greater amongst the EMG than the White patients. The EMG status was a significant risk factor for HDM sensitisation. High income countries (HICs) including the UK, USA and Australia have immigrant population from the Indian subcontinent, Africa and elsewhere. There is evidence that clinical outcomes are poorer in ethnic minority groups (EMGs) in asthma, food allergy and anaphylaxis.Most evidence regarding aetio‐pathogenesis and therapeutics in allergic conditions comes from research conducted in the Caucasian White populations in HICs. House dust mite (HDM) is the most common allergen implicated globally in allergic airways disease, and environment plays a key role in sensitisation.A clear understanding of ethnicity‐based disparities in allergen sensitisation in asthma might be relevant to primary and secondary prevention strategies and shaping better healthcare policies to address inequity and inequalities of care. There is some evidence that grass pollen and birch pollen immunotherapy prevent progression to asthma in patients with hay fever, although similar evidence is lacking in the context of HDM related allergic rhinitis.The Birmingham Regional Severe Asthma Service (BRSAS) is one of the largest severe asthma centres in the UK, serving a population of 7.3 million from central England . BRSAS catchment area is geographically wide, ethnically varied and include Birmingham which is the second largest city in the UK with a great ethnicity mix in the population  and high deprivation index making delivery of an equitable and standardised management for severe asthma challenging,The main aim of this study was to investigate ethnicity‐based disparities in atopic status, sensitisation patterns to common aeroallergens and determine the risk factors for HDM sensitisation employing the BRSAS Registry in patients with difficult‐to‐treat asthma (DTA). Secondary aims were to compare physiological variables and clinical outcomes.22.1This was a cross‐sectional study of patients with DTA presenting to our service in which allergic sensitisation and other outcomes were compared between the White and EMG patients.2.2The Birmingham Regional Severe Asthma Service (BRSAS) Dendrite Clinical Systems registry collected data on all patients referred to our centre with DTA, and for this study we included data from patients whose first assessment in our service was between January 2010 – December 2021. Patients provided written consent to be included in the registry and the study is approved by the University Hospitals Birmingham NHS Teaching Trust as a service improvement project (CARMS‐19251). The sources of referrals to BRSAS were mainly from secondary care (93%) and minority from primary care (7%).2.2.1The registry recorded data on demographics, clinical characteristics, type 2 inflammation (T2) biomarkers and phenotyping, treatment, and ethnic origin . The parameters tested in this study represented baseline cross‐sectional clinical data obtained at the first patient review in the service.1), forced vital capacity (FVC), FEV1/FVC ratio, and the lower limit of normal (LLN) for FEV1, which identifies the lower 5th percentile of healthy non‐smokers.Specific serum IgE (ssIgE) to aeroallergens was measured on the ImmunoCAP 250 platform . Atopy was defined as having a positive ssIgE result to at least one allergen (positive ssIgE ≥0.35 KUA/L). Asthma control was measured using the asthma control questionnaire (ACQ‐7)https://imd‐by‐postcode.opendatacommunities.org/imd/2019).Index of Multiple Deprivation as quintile (IMD‐quintile) was calculated from patients post code  to improve the power of the study.2.4https://www.medcalc.org; 2022).Comparisons between White and EMG were conducted using parametric and non‐parametric tests as deemed appropriate. Sensitisation to HDM and other aeroallergens were compared both as dichotomous and continuous variables, using chi‐squared tests , Kruskal Wallis tests (non‐parametric continuous data) and one way analysis of variance (ANOVA) . Normal distribution of data was assessed by D’Agostino‐Pearson test. Multivariate logistic regression was conducted to investigate the effect of ethnicity, IMD‐quintile, age, gender, and blood eosinophils on HDM sensitisation (defined as ssIgE ≥0.35 KUA/L). Goodness of fit was examined using the Hosmer‐Lemeshow test. Lung function, biomarkers, asthma control and exacerbations were compared as continuous or binary variables as appropriate. Statistical analysis was conducted using MedCalc® Statistical Software version 20.114 ] than the EMG , with 67.6% of the EMG had FEV1 < LLN compared to 56.2% of the White group, p = 0.0083. EMG also had lower FVC and lower total lung capacity (TLC) than the White group, but had similar residual volume and coefficient diffusion of carbon monoxide (KCO).The clinical characteristics of this study population at the time of the first assessment at our service are provided in Table 9 vs. 0.23, p < 0.000001). The highest ever blood eosinophil count was also significantly higher in the EMG than in the White group . However, we observed no significant difference in fraction exhaled nitric oxide (FeNO) level between the two groups. Allergic rhinitis was more prevalent in the EMG than the White group . Otherwise, we observed no significant difference in the prevalence of nasal polyps, atopic dermatitis, non‐steroid anti‐inflammatory drug (NSAID) intolerance, or occupational factors between the groups.The median blood eosinophil count was significantly higher in the EMG than the White group  health scale was lower in EMG than the White groups . The binary HDM ssIgE trait (positive HDM ssIgE ≥0.35 KUA/L) demonstrated significantly higher sensitisation amongst the EMG (65.7%) than in the White group (44.5%), p < 0.0001. The median ssIgE to aspergillus fumigatus was higher in the EMG than the White group , however, despite a marginal increase in the binary positive aspergillus ssIgE in the EMG (24.2%), than the White group (20.9%), it did not reach statistical significance (p = 0.3). Similarly, the median mixed grass ssIgE was higher in the EMG than in the White group , but positive mixed grass ssIgE binary was not different between the EMG (45.3%) and the White group (41.5%), p = 0.3. Conversely, there was statistically non‐significant trend towards higher cat ssIgE positive binary in the White group (34%) than EMG (28.7%), p = 0.14, but the median cat ssIgE level was not different between the two groups. The positive dog ssIgE binary was also higher in the White 24.2% than in the EMG 20.9%, p = 0.05, but the median ssIgE level was not statistically different between the two groups. Exposure to pets at home was significantly higher in the White group (52.7%) than EMG group (24.8%), p < 0.0001. The proportion of polysensitised patients  was marginally higher in the EMG than in the White group [114/232 (49.14%) versus 383/898 (42.7%)], which did not reach statistical significance p = 0.08.Results of atopic trait analyses comparing EMG and White groups are provided in Table 3.3In addition to the significantly higher proportion of patients in the EMG group who met the positive HDM ssIgE criteria of ≥0.35 KUA/L, as compared to the White group Figure , the sevp < 0.0001]. This model correctly identified 64.25% of cases. The ORs for IMD‐quintiles, age, gender and blood eosinophil count were 0.89, 0.96, 0.54, and 1.0, respectively  and HDM negative 488 (50.6%). The odds ratio (OR) for EMG as a predictor for HDM sensitisation was 2.61 [(95% CI 1.8 to 3.75); 41 and more frequent attendance to emergency department for acute exacerbations amongst the EMG, in keeping with recently published dataThis is the first British study to show that ethnic minority status enhances risk for HDM sensitisation in DTA. Furthermore, our data showed greater prevalence of HDM sensitisation, higher levels of specific serum IgE to HDM with a greater proportion of EMG patients showing more severe sensitisation. Our data also showed a significantly higher total serum IgE level and peripheral blood eosinophil count, lower FEVEthnicity‐based disparities in immune‐mediated disorders including asthma have been reported in HICs including the USA, Australia and the UK.Serum total IgE and peripheral blood eosinophil count are important biomarkers in allergy and asthma. The clinical significance and reasons underpinning higher levels in EMGs remain uncertain and are beyond the scope of this study. It is plausible that higher levels of T2 biomarkers including blood eosinophils, specific IgE to HDM and total IgE might at least in part be contributing to disease severity. A limitation of this analysis is that the data was not corrected and normalised for ethnicity, as ethnicity‐specific reference ranges have not yet been established and are not routinely reported in the UK NHS laboratories and variables potentially driving total IgE and peripheral blood eosinophil count were not explored and factored into the analysis. Ethnicity‐based differences in blood eosinophils, neutrophils and total serum IgE have been reported in African‐American, Mexican American and Puerto Rican children with severe asthma.1 in the EMG was significantly lower than in the White group. The reason underpinning this observation is uncertain and is likely to be multifactorial. In part, this may be explained by previous studies reporting higher normalised FEV1 and FVC in the White people compared to South Asians and Black ethnicity.1 was also significantly lower in the EMG compared to White patients. This suggests greater disease severity in the EMG. The RASP biomarker study reported that patients from EMG are more likely not to follow medical advice required to optimise asthma therapy.The ‘actual’ FEVThe greater prevalence of HDM sensitisation in the EMG is an important finding. Early childhood HDM sensitisation was associated with the onset of asthma at the age of 11 years.Blood eosinophils and total serum IgE were significantly higher in the EMG than the White group. Causes of these observations are unclear at present. Our study did not factor in diurnal variations in blood eosinophils and variation in eosinophil counts over time, however the highest‐ever eosinophil counts were also higher in the EMG than the White group. Other potential causes of eosinophilia and high total IgE that were not factored in our study include travel history, helminth infection, tuberculosis history and birthplace. A recent British study involving a pooled analysis of total white cell counts and differential counts from healthy volunteers from 35 clinical trials showed no significant differences between White and Asian group, but the total white cell count and lymphocyte counts were significantly lower amongst Black volunteers in comparison to non‐Black volunteers.This study has limitations. The EMG sample size was relatively small but proportionate to the British population demographics, and was mainly represented by patients from the Indian subcontinent with less representation of other ethnic groups. Therefore, potential differences within the EMG in allergen sensitisation patterns were not studied. Conversely, one of our study cohort strength is its wide catchment area in central England with a diverse ethnic mix. In this study, we did not investigate other important determinants of healthcare disparities such as English language proficiency, and social and religious factors.In conclusion, our data showed that ethnic minority status enhances risk for HDM sensitisation independent of IMD in DTA and that there is a higher prevalence and severity of HDM sensitisation in the EMG alongside higher serum total IgE and blood eosinophils. Further studies are needed to investigate plausible mechanisms that enhance the risk of HDM sensitisation in EMG in order to pave the way for novel primary and secondary prevention strategies.Adel H. Mansur: Conceptualization (lead); data curation (lead); formal analysis (lead); investigation ; methodology ; writing – original draft (lead). Julie Marsh: Data curation ; project administration ; resources ; software . Ali Bahron: Data curation ; formal analysis ; resources ; software ; validation ; writing – review & editing . Maximillian Thomas: Data curation ; investigation ; writing – review & editing . Gareth Walters: Conceptualization ; investigation ; methodology ; writing – review & editing . John Busby: Data curation ; formal analysis ; writing – review & editing . Liam G. Heaney: Methodology ; visualization ; writing – review & editing . Mamidipudi Thirumala Krishna: Conceptualization ; data curation ; formal analysis ; methodology .This study is an investigator led and did not receive funds from pharmaceutical companies. AHM declares institutional and personal funds for talks, advisory boards and research grants from AZ, GSK, BI, Chiesi, Teva, Novartis, Sanofi outside the submitted work. LGH declares personal fees from Novartis, Hoffman la Roche/Genetech Inc, Sanofi, GSK, AZ, Teva, Theravance, Circassia, and grants from Medimmune, Novartis UK, Roche/Genentech Inc, GSK, Amgen, AZ, Aerocrine, Vitalograph, all outside the submitted work. MTK received research grants from NIHR, MRC CiC, FSA, GCRF and University of Birmingham outside of the work presented in this manuscript. MTK is participating in a Delphi Advisory panel for treatment pathway for sublingual immunotherapy in allergic rhinitis and asthma organised by ALK Abello. MTKs department received educational grants from ALK Abello, Thermo‐Fisher Scientific, MEDA and other pharmaceutical companies for annual PracticAllergy course over the years. JB has received research grants from AstraZeneca outside the presented work and has received personal fees for advisory board attendance from NuvoAir.Professor Adel H Mansur is the guarantor of the content of the manuscript, including the data analysis.


CYP27B1) produced by proximal tubular cells of the kidney catalyzes the synthesis of calcitriol, the most active form of vitamin D , which plays an integral role in calcium homeostasis. Because of their multiple roles, kidneys are considered life-sustaining organs. The articles on this topic provide a comprehensive understanding of kidney function in various endocrine abnormalities, discuss the intricate role of intrarenal and systemic endocrine factors on kidney function, and investigate strategies for early and specific diagnosis of renal complications.The principal function of the kidneys is to keep the blood clean and chemically balanced by filtering out waste products of metabolism and maintaining water, electrolyte, and acid-base balance. Kidneys help retain glucose, amino acids, vitamins, hormones, albumin, antibodies and other vital components in the blood while eliminating urea and creatinine. The kidneys’ ability to elicit selective filtration and tight regulation of the composition of urine is accomplished by the glomerulus and tubular region of the nephron, the functional unit of the kidney. The severity of impairment of renal function is characterized by decreased glomerular filtration rate (GFR) and albuminuria, which are markers for kidney excretory function and glomerular barrier dysfunction, respectively. Further, impairment of renal function is characterized by elevated serum creatinine (SCr), cystatin C or blood urea nitrogen (BUN). Several endocrine factors secreted by kidneys regulate various physiological functions. Kidneys synthesize renin to maintain arterial blood pressure, whereas excess renin secreted by the injured kidney contributes to hypertension. Erythropoietin secreted by the kidney stimulates the production of RBC by the bone marrow, and in conditions of reduced kidney function, insufficient erythropoietin results in anemia. Notably, decreased kidney function is often presented with anemia and is associated with a reduced quality of life and increased morbidity . 25-hydrKidney diseases are a modern-day epidemic, a direct cause of morbidity and mortality and a significant risk factor for cardiovascular disease (CVD) . Acute kSeveral factors can contribute to the pathogenesis of CKD. Hypertension, diabetic kidney disease (DKD), obesity, and aging are the most common causes, whereas factors such as HIV, exposure to toxins, and heavy metals contribute to the burden of CKD. In some areas of developing countries where CKD is endemic, precise causal factors remain to be established. These scenarios contribute to different factors that manifest in long-term glomerular and tubular damage and ultimately manifest in ESKD. In diabetes, elevated pituitary growth hormone (GH) circulatory levels are implicated in impaired renal function. Receptors for GH and its mediator IGF-1 are abundantly expressed in glomerular and tubular cells. GH can act directly on the kidneys or via circulating or paracrine-synthesized IGF-1. The GH/IGF-1 system regulates glomerular hemodynamics, tubular sodium and water, phosphate, calcium handling, and renal gluconeogenesis. The GH/IGF-1 system governs klotho synthesis, a coreceptor of the phosphaturic hormone fibroblast growth factor 23 (FGF-23) in the renal tubule. Although recombinant GH is widely used in treating short stature in children, including those with CKD, studies from experimental animals and acromegalic patients demonstrate that GH excess can have harmful effects on the kidney, including glomerular hyperfiltration, renal hypertrophy, and glomerulosclerosis . In addiZhang et al.). In comparison, hyperthyroidism is associated with increased GFR and renal plasma flow. In patients with CKD, low T3 levels are independent predictors for all-cause mortality in euthyroid patients with ESKD. TH-TH receptor (TH-TR) axis alterations are critically involved in the pathogenesis of DKD. Despite low T3 levels, patients of DKD are presented with reexpression of fetal isoform TRα1 in podocytes and are concomitant with maladaptive cell-cycle induction/arrest (Although the thyroid hormones (TH) contribute to the development of the kidney, both hypo- and hyperthyroidisms affect GFR, renal blood flow, tubular function, and electrolyte balance. Hypothyroidism is associated with a reversible increase in serum creatinine, reduced GFR and renal plasma flow. If hypothyroidism can be corrected with levothyroxine therapy, some individuals’ blood creatinine levels can return to normal  with CKD was investigated by Lau et al. Among men, no associations were observed between androgens, eGFR, and CKD. In women, a higher T/DHT (Testosterone/dihydrotestosterone) ratio was associated with higher CKD prevalence and that higher circulating levels of free DHT were associated with a lower incidence of CKD.Abnormalities in the synthesis of estrogen and progesterone are common in women with CKD . AbnormaLee et al. demonstrated deficiency of serum 25-hydroxy vitamin D levels was significantly associated with only severe CKD stage (4&5) among the Korean cohort. Vitamin D receptor agonists, nutritional vitamin D, and calcimimetic agents to reduce parathyroid hormone are prescribed to treat CKD-MBD and to influence the survival rate in patients with ESKD. Notably, elevated serum PTH levels were significantly associated with an increased risk of peritonitis in the Chinese cohort undergoing continuous ambulatory peritoneal dialysis . Further, Kee et al. evaluated the influence of residual kidney function in patients undergoing prevalent hemodialysis on the detrimental effect of serum FGF-23 levels in CVD development.The complex interplay among parathyroid hormone (PTH), calcitriol, and FGF-23 help regulate the normal serum calcium (Ca) and phosphorous (P) levels. Kidneys play an instrumental role in maintaining serum Ca and P levels by regulating these three hormones. CKD-related mineral bone disorder (MBD) represents a complex disease with elevated PTH and FGF-23, reduced levels of calcitriol and klotho . This adLin et al. report that higher CVAI is associated with an increased risk of renal damage (as assessed in terms of eGFR and proteinuria) in patients with hypertension and abnormal glucose metabolism. Furthermore, CVAI strongly predicts renal damage incidence compared with the above mentioned indices. Therefore, a simple assessment of visceral adiposity by calculating CVAI may be helpful for the early identification of high-risk individuals and for adopting strict BP and glucose management, thereby reducing the risk of renal damage. Serum apolipoprotein B (ApoB) levels had the strongest correlation with CKD among all lipid variables, and accumulation of ApoB levels might precede the occurrence of CKD .Dyslipidemia and abnormal lipid metabolism contribute to kidney cell injury, increasing the risk of CKD in obese individuals . SeveralGraňák et al. revealed A/L(< 0.5) as a predictor of acute rejection in the early post-transplant period after kidney transplantation.Adiponectin (A) and leptin (L) are two hormonally active molecules secreted by adipose tissue and are critical mediators of cardiometabolic risk in obesity . In healCao et al. performed two independent cross-sectional studies to explore whether plasma levels of urea cycle-associated amino acids with risk of DKD. According to this study, plasma citrulline levels were significantly associated with the risk of DKD in type II diabetes in the Chinese population. The protein concentration of urinary extracellular vesicles (UEV) in diabetic individuals is higher than in healthy controls before and after adjusting the urinary creatinine (UCr) . The ratio of uEV-to-UCr may better indicate the progression of diabetic renal complications over the urine protein–Cr ratio or albumin-Cr ratio. Since albuminuria is associated with high glycemic variability in type II diabetic patients, avoiding fluctuations of blood glucose levels using flash monitoring methods could help better manage renal health among the diabetic population in the Indian cohort .Considering the magnitude of the global burden of kidney disease and the seriousness of morbidity and mortality of ESKD, we solicit biomarkers that help early diagnose the individuals at high risk of renal complications with endocrine abnormalities, in addition to intervention strategies. AP: Writing – original draft, Writing – review & editing. SK: Writing – review & editing. MS: Writing – review & editing.


Chronic kidney disease (CKD) is a prevalent and progressive condition affecting millions worldwide. It is a long-term condition characterized by gradual loss of kidney function over time. The management of CKD is complex and requires a multidisciplinary approach. This review aims to outline the current management guidelines for CKD. The study included a comprehensive search of various PubMed, Embase, and the Cochrane Library databases for articles published between 2010 and 2023. The search terms used were "chronic kidney disease," "management," and "guidelines." The inclusion criteria were articles that provided management guidelines for patients with CKD. A total of 23 articles were included in the review. Most articles were based on the Kidney Disease Improving Global Outcomes guidelines, the most widely recognized and used guidelines for managing CKD. The study found that the guidelines emphasize the importance of early detection and management of CKD and the need for an approach that involves multiple disciplines in its management. The guidelines recommend several interventions to slow the progression of CKD, including blood pressure control, glycemic control in diabetic patients, and reduce proteinuria. Other interventions include lifestyle modifications such as dietary changes, physical activity, and smoking cessation. The guidelines also recommend regular monitoring of kidney function and referral to a nephrologist for patients with advanced CKD or other complications. Overall, the current management guidelines for CKD emphasize the importance of early detection and a multidisciplinary approach to its management. The management of CKD is crucial to prevent the progression of the condition to end-stage renal disease (ESRD) and to reduce the risk of cardiovascular disease and other complications. Various management guidelines are available for CKD, which different organizations and expert panels develop.Chronic kidney disease (CKD) is a significant public health problem globally, affecting millions of people worldwide. Such a review can also help to identify gaps in the existing guidelines and areas where further research is needed to improve the management of CKD.A comprehensive review of the current management guidelines of CKD can provide valuable insights into the similarities and differences among these guidelines. It can help identify the best practices for managing CKD. Another study by Ong et al reviewed the guidelines from 14 organizations and found that the recommendations were generally consistent. Still, there were variations in the evidence supporting the recommendations.Several studies have comprehensively reviewed the current management guidelines for CKD – one study by Schena FP. (2011) analyzed the guidelines from 6 organizations and found considerable variability in the recommended management strategies for CKD.The objectives of treatment for chronic kidney disease (CKD) are to slow down the progression of the disease, manage complications and symptoms, prevent or delay the commencement of end-stage kidney disease, and improve the patient’s quality of life, which requires dialysis or kidney transplantation for survival. To achieve these objectives, treatment may involve a combination of lifestyle modifications, medications, and medical procedures, such as:High blood pressure is a common complication of CKD, and controlling it is essential in slowing the progression of the disease. Medications like angiotensin converting enzyme inhibitors and angiotensin receptor blockers are often prescribed to manage hypertension.If the patient has diabetes, tight control of blood sugar levels can help to prevent or delay the onset of renal damage.A diet low in salt, phosphorus, and protein may be recommended to reduce the kidney workload and manage symptoms.Medications may be prescribed to manage anemia, bone disease, and other CKD-related complications.In advanced stages of CKD, when the kidneys have lost most of their function, dialysis or kidney transplantation may be necessary to replace the kidney function and maintain the patient’s health.Millions of people are affected by CKD, a common and progressive condition. Successfully managing CKD is a complex process requiring a collaborative, multidisciplinary approach. Therefore, a review of current management guidelines for CKD was conducted to outline the best practices for CKD management.The review included a comprehensive search of various PubMed, Embase, and the Cochrane Library databases for articles published up until 2022. The search terms used were “chronic kidney disease,” “management,” and “guidelines.” The inclusion criteria were articles that provided management guidelines for CKD patients.Two reviewers independently screened all titles and abstracts for eligibility after the initial search. The same 2 reviewers reviewed full texts of potentially relevant publications. A third reviewer resolved any disagreements. The inclusion criteria were articles that provided management guidelines for CKD patients.Two reviewers collected data independently using a predefined data extraction form. The extracted data included the author’s name, year of publication, country of origin, CKD stage, interventions, and outcomes. A third reviewer resolved any disagreements.The review identified 23 articles that met the inclusion criteria. Most articles were based on the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, the most widely recognized and used guidelines for managing CKD. According to the study, the guidelines prioritize the timely detection and treatment of CKD and advocate for a collaborative approach involving multiple disciplines in its management.The guidelines recommend several interventions to slow the progression of CKD, including blood pressure control, glycemic control in diabetic patients, and reducing proteinuria. Other interventions include lifestyle modifications such as dietary changes, physical activity, and smoking cessation.The review identified some limitations of the current guidelines, such as the lack of consideration for specific patient populations, such as the elderly and those with comorbidities. Also, there is a need for more studies on the effectiveness of interventions and personalized management of CKD.In conclusion, the current management guidelines for CKD emphasize the importance of early detection and a multidisciplinary approach to its management. Nevertheless, more research needs to be done on personalized management and consideration for specific patient populations. The findings of this comprehensive review help healthcare professionals better understand the current management guidelines for CKD and inform their practice. The epidemiology of CKD is complex and influenced by various factors, including age, gender, race/ethnicity, and comorbidities.Chronic renal disease is a global health problem affecting millions worldwide. In the United States, CKD affects around 15% of the adult population, with higher rates observed in older adults, African Americans, and Hispanics. In Asia, the prevalence of CKD is estimated to be around 10% to 15%, with a higher burden of disease in countries such as China and India.The prevalence of CKD varies across different populations and is influenced by various factors such as age, gender, race/ethnicity, and comorbidities. In Asian countries such as Japan and South Korea, the incidence of ESRD is higher among older adults.The incidence of CKD is also influenced by numerous factors such as age, gender, race/ethnicity, and comorbidities. In the United States, the incidence of ESRD due to CKD is highest among African Americans, followed by Hispanics, Native Americans, and Asians. Other risk factors, e.g., obesity and smoking, have also been associated with a high risk of CKD.CKD is a complex disease influenced by multiple risk factors, including diabetes, hypertension, obesity, smoking, and a family history of kidney disease. Hypertension and diabetes are the leading causes of CKD globally, accounting for around two-thirds of all cases. It is most often an insidious process compared to its more acute counterpart, Acute Kidney disease.Chronic Kidney disease can arise from cell injury that may cause damage to a kidney section that may or may not have been directly impacted by an insult or toxin. The glomerular capillaries may also be prone to injury because glomerular filtration depends on high intra and trans-glomerular pressure; hence any disease process that raises this pressure may affect them negatively. Glomerular hypertension and hyperfiltration are 2 common culprits implicated in the development of CKD.The kidneys have been observed to have a greater rate of blood flow than other well-perfused organs, and as such, they are more likely to be exposed to substances that may be toxic to them.,10 Damage to a glomeruli, e.g., from hypoxia, can spread to the tubulointerstitial compartment causing injury or remodeling of the tissue because decreased blood flow either before or at the glomerulus can cause decreased peritubular blood flow and ultimately damage the tubulointerstitium.The negatively charged molecules on the membrane of the glomerular filtration apparatus would generally act like a filter preventing the passage of anionic macromolecules, which would explain why some of those macromolecules in the urine would serve as an indication of glomerular dysfunction. Some biochemical pathways have been noted to contribute to the progression of CKD. Angiotensin II can induce TGF-β1, as well as other inflammatory mediators like connective tissue growth factor, leading to the compression and the consequent elaboration of the extracellular matrix; it can also induce oxidative stress, which can upregulate TGF-β1 leading to the propagation of a fibrosing response by inducing the formation of extracellular matrix.,11 Tissue proteases that would typically degrade matrix proteins are inhibited.Glomerulosclerosis and tubulointerstitial fibrosis are often implicated in CKD of any underlying cause.Some of the more popular causes of renal injury are based on immunologic reactions, tissue hypoxia, ischemia, exogenic agents, e.g., drugs, endogenous substances, e.g., glucose in excess, genetic defects, etc. An immune complex deposition is often associated with many Kidney diseases, and various disease conditions can occur depending on the location of the deposition, e.g., mesangial deposition as in Henoch Schonlein Purpura, Subendothelial deposition as in Membranoproliferative Glomerulonephritis Subepithelial deposits as in Membranous nephropathy, etc. When circulating inflammatory cells come in contact with these immunoglobulins, it forms a strong inflammatory reaction; these inflammatory cells can ultimately cause damage to the vascular walls and filtration barrier, causing even more recruitment of inflammatory cells and worsening kidney damage. Complement activation can also mediate tissue injury after immune complex deposition. Injury can also be non-immunologic glomerular, as in hemodynamic, metabolic, or toxic injury.CKD’s pathophysiology can be due to a glomerular, tubular, or vascular injury that has occurred over time. Glomerular impairment can be due to a hereditary condition, e.g., as seen in Alport syndrome; it can also be acquired from an injury, toxin, or prolonged stress. It is seen when the blood pressure is high enough to exceed the protective autoregulation of the kidney, causing glomerular filtration barrier injury. In chronic hypertension, arteriolar vasoconstriction and sclerosis can lead to glomerular and tubulointerstitial atrophy, while glomerular hypertension will cause glomerulosclerosis; all these processes ultimately damage the kidneys.Systemic and glomerular hypertension are other processes frequently implicated in CKD. Fibrosis is also associated with proinflammatory, profibrotic, and vasoconstrictive factors that worsen kidney disease.Tubulointerstitial impairment can also cause long-term renal impairment because their associated fibrosis results from inflammatory infiltrates that cause extracellular matrix accumulation.,11 This process has been associated with the worsening of fibrosis and renal failure. It is also related to the accumulation of extracellular matrix. Changes in the expression of this factor have been noted to correlate with the extent of tubulointerstitial damage.Hypoxia-inducible factor 1 is a factor that has been noted to stimulate the transition of epithelial cells into mesenchymal cells.Proteinuria is also associated with damage to the tubulointerstitium due to direct toxicity to the tubules themselves, changes in the epithelial metabolism of the tubules, increased cytokine and chemokine synthesis, and increased expression of adhesion molecules.,14Other associated factors include decreased perfusion of the kidneys as in shock, smoking, chronic non-steroidal anti-inflammatory drugs use, congenital disabilities that affect the kidney, like the presence of posterior urethral valves, and aging-related changes.CKD is a severe medical condition affecting millions worldwide. It is a common medical condition characterized by a progressive loss of renal function over time. The KDIGO defines CKD as abnormalities of kidney structure or function, present for more than 3 months, with health implications.Table  The key recommendations for managing CKD from KDIGO include the following:The latest guidelines for managing CKD are provided by the KDIGO organization. These guidelines were last updated in 2020.Accurate and timely diagnosis and staging of CKD using the Kidney Disease Outcome Quality Initiative (KDOQI) guidelines or KDIGO guidelines.Identifying and managing risk factors for CKD progression, including blood pressure control, glycemic control in diabetes, lipid management, smoking cessation, and weight management.Regularly monitor kidney function, proteinuria, blood pressure, and other risk factors for CKD progression.Use of renin-angiotensin-aldosterone system (RAAS) blockade in patients with albuminuria and hypertension unless contraindicated.Use non-steroidal anti-inflammatory drugs cautiously in CKD patients and avoid nephrotoxic agents whenever possible.Evaluation and management of CKD-associated complications, including anemia, mineral and bone disorders, cardiovascular disease, and infectious diseases.Education and counseling of patients with CKD to promote self-management and adherence to treatment.Referral to a nephrologist when appropriate, based on the patient’s CKD stage and progression risk.These guidelines provide a comprehensive approach to managing CKD and can be used to improve patient outcomes and quality of life. Table CKD is a progressive and irreversible condition that can lead to ESRD requiring dialysis or kidney transplantation. Over the years, various management guidelines have been developed to optimize care for patients with CKD and reduce the risk of complications.The current management guidelines for CKD recommend early detection and intervention to slow or halt the progression of the disease. This involves regular monitoring of kidney function, blood pressure control, and lifestyle modifications, such as a healthy diet, regular exercise, and smoking cessation. The guidelines also recommend using medications to manage complications such as anemia, bone disease, and cardiovascular disease.Additionally, the guidelines highlight the importance of a multidisciplinary approach to managing CKD. This involves collaboration between nephrologists, primary care physicians, dietitians, pharmacists, and other healthcare professionals to provide comprehensive and coordinated care. With proper management and timely intervention, it is attainable to slow or halt the progression of CKD and improve outcomes for patients with this condition.Conceptualization: Chukwuka Elendu, Rhoda C. Elendu, Joy M. Enyong, Chinazo J. Okenwa.Data curation: Ibukunoluwa V. Ishola, Kehinde A. Opashola, John O. Fatoye.Formal analysis: Ozigis O. Mutalib.Investigation: Chukwuka Elendu.Methodology: Joy M. Enyong, Chinazo J. Okenwa.Project administration: Emmanuel S. Meribole, Kehinde A. Opashola.Resources: Emmanuel O. Egbunu, Chinazo J. Okenwa, Ewezugachukwu D. Umeh, Ozigis O. Mutalib.Software: Emmanuel O. Egbunu.Supervision: Chukwuka Elendu, Rhoda C. Elendu.Validation: Joy M. Enyong, Chinazo J. Okenwa.Visualization: Chukwuka Elendu, Rhoda C. Elendu, Emmanuel O. Egbunu.Writing – original draft: Chukwuka Elendu, Rhoda C. Elendu, Joy M. Enyong, Ozigis O. Mutalib, Kehinde A. Opashola.Writing.–.review & editing: Jennifer O. Ibhiedu, Ibukunoluwa V. Ishola, Emmanuel S. Meribole, Sodiq O. Lawal, Geraldine C. Okafor, Ewezugachukwu D. Umeh, John O. Fatoye, Temitope I. Awotoye, Jewel I. Tobih-Ojeanelo, Habiba I. Ramon-Yusuf, Abiola Olanrewaju, Rechner N. Afuh, Joseph Adenikinju, Opeyemi Amosu, Abdulgafar Yusuf.


To explore the association of delivery mode and the number of pregnancies with anorectal manometry data in patients with postpartum constipation.This retrospective study included women with postpartum constipation treated at the pelvic floor rehabilitation department of Huzhou Maternity & Child Health Care Hospital between January 2018 and December 2019.P > 0.05). The patients with a spontaneous delivery had a lower change in maximal contracting sphincter pressure compared with those with Cesarean section (14.3 (4.5–25.0) vs. 19.6 (13.4–40.0), P = 0.023). Only the delivery mode (Cesarean vs. spontaneous) independently affected the changes in contracting sphincter pressure ; age (P = 0.201), number of pregnancies (P = 0.190), and constipation duration (P = 0.161) were not associated.Among 127 patients included, 55 (43.3%) had one pregnancy, 72 (56.7%) had two pregnancies, 96 (75.6%) delivered spontaneously, 25 (16.7%) underwent Cesarean section, and six (4.7%) needed a Cesarean section despite spontaneous labor. The median duration of constipation was 12 months . There were no differences between the two groups for any manometry parameters (all The patients with a spontaneous delivery had a lower change in maximal contracting sphincter pressure compared with those with a Cesarean section, suggesting that patients with Cesarean may retain a better “push” function during defecation. Study Highlights:WHAT IS KNOWN.Changes in anal manometry are involved in constipation, and delivery affects the pelvic floor.2)WHAT IS NEW HERE.Patients with Cesarean section have higher changes in contracting sphincter pressure than vaginal delivery.The reported prevalence of postpartum constipation is 45.8% . PostparThe anal sphincter generates pressure that can be measured using manometric techniques  –5. NormaSince constipation might involve pelvic muscle floor dyssynergia  and sincStill, the exact impacts of the delivery mode and the numbers of pregnancies on anorectal manometry are mostly unknown. Such data are needed to be able to monitor the changes during PFMT. Therefore, this study aimed to explore the association of delivery mode and the number of pregnancies with anorectal manometry data in patients with postpartum constipation.This retrospective study included women with postpartum constipation treated at the pelvic floor rehabilitation department of Huzhou Maternity & Child Health Care Hospital between January 2018 and December 2019. This study was approved by the Ethics Committee of Huzhou Maternity & Child Health Care Hospital. As a retrospective study, the requirement for informed consent was waived.Constipation was diagnosed according to the Rome Criteria IV. The inclusion criteria were 1) with at least two of the following symptoms: (a) straining more than 25% of the defecations, (b) lumpy or hard stools of more than 25% of the defecations, (c) sensation of incomplete evacuation of more than 25% of the defecations, (d) sensation of anorectal obstruction/blockage more than 25% of the defecations, (e) manual maneuvers to facilitate more than 25% of the defecations, and (f) fewer than three spontaneous bowel movements per week, 2) hardly with loose stools if not using laxatives, 3) not meeting the irritable bowel syndrome diagnostic criteria, 4) underwent blood routine examination, blood examinations for thyroid functions, blood glucose, and blood calcium examinations to rule out relevant gastrointestinal diseases, and 5) no history of gastrointestinal diseases or relevant surgeries, and with no endocrine diseases. All patients did not use antibiotics, crude fiber, polysaccharides, probiotics, or other micro-ecological drugs. The exclusion criteria were (1) perianal diseases or relevant surgery history, (2) severe cardiovascular, cerebrovascular, or endocrine diseases, or (3) psychological diseases and could not cooperate with the examinations.Demographic data of the patients  were collected from the medical record system of the hospital. Data from the cough test, perception threshold, maximum volume, tolerance, and compliance were also collected.The institution has strict examination preparation that is routinely applied for anorectal manometry. (1) The patient has to be free of serious perianal diseases such as hemorrhoids and anal fissures recently. (2) The patient is instructed to defecate at least 4 h before the examination and to lie down quietly for 5 min before the examination. (3) The patient is fully informed of the whole examination process and problems that might be encountered so that patients have full mental preparation. (4) If a spasm occurs during the test, the test is interrupted and tried again after a rest of 1 h.The routine examinations for constipation include an evaluation using an 8-channel water-perfusion system (GAP 08 A) to measure the anorectal motility and anorectal pressure, including rectal dilatation threshold volume induced ), rest pressure and maximal pressure of the anal canal, and length of the high-pressure zone.n (%) and analyzed using Fisher’s exact test. The Shapiro-Wilk test was used for the normality test of the continuous data, showing that the data were not in normal distribution; therefore, the median (quartile) was used for description, and the Mann-Whitney U-test was used for comparison. The Spearman correlation test was used to assess the correlations between variables. A multivariable linear regression test was used to investigate the influencing factors of anorectal manometry data. Two-sided P-values < 0.05 were considered statistically significant.SPSS 26.0  was used for statistical analysis. Categorical data were described as Table P > 0.05). Table P = 0.023).Table P = 0.006); age (P = 0.201), number of pregnancies (P = 0.190), and constipation duration (P = 0.161) were not associated (Table Only the delivery mode (Cesarean vs. spontaneous) independently affected the changes in maximal contracting sphincter pressure (B = 10.32, 95%CI: 2.95–17.69, ed Table .This study aimed to analyze the anorectal manometry data of patients with postpartum constipation, to investigate the characteristics of the rectal pressure in patients with postpartum constipation, and to explore whether the mode of delivery, the number of pregnancies, and the postpartum time have an impact on postpartum constipation. The results suggest that the patients with a spontaneous delivery had a lower change in contracting sphincter pressure compared with those with Cesarean section, suggesting that patients with Cesarean retain a better “push” function during defecation. The results help provide a basis for better management of postpartum women and how to avoid post-delivery constipation in the future.Understanding the physiology of the anal sphincter and anorectal pressure is important to improve the management of patients with dysfunctional defecation. Indeed, the anal sphincter maintains the anal function of the normal human body and controls the contraction and relaxation of the anus, including the external anal sphincter and internal anal sphincter . The phyThe rectum is another important structure involved in defecation. In the quiet state, the rectum is generally empty and collapsed. At that time, the resting pressure is about 0.49 kPa, and there are about five peristaltic waves per minute. When the amount of feces entering the rectum at one time reaches 10 ml, and the speed is fast, it will trigger the rectal dilatation threshold volume induced: the vertical contraction of the external sphincter and the puborectal muscle suddenly increases the anal pressure, which only lasts for 1 to 2 s. Then, the tension of the internal sphincter decreases slightly, and the anal pressure decreases slightly. After a few seconds, it can return to normal , 20. WheTherefore, the present study examined the anorectal manometry parameters in women after delivery and the factors possibly influencing these parameters. The present study suggests that the number of pregnancies does not influence the anorectal manometry parameters. In addition, the only difference between patients with spontaneous delivery vs. Cesarean was a higher change in maximal contracting sphincter pressure than in patients with a cesarean. This higher value suggests that the patients with Cesarean retained a higher push strength and anorectal coordination during defecation , 22, as Available data suggest that PFMT can help improve the symptoms of dyssynergic defecation –14. In aThis study has limitations. The sample size was small because the patients were from a single center. No control group was included since the patients were all from a department for pelvic floor rehabilitation. The retrospective nature of the study limited the data to those available in the patient charts. Among others, whether the patient displayed dyssynergia or whether the test had to be interrupted and retried could not be determined. The present study was retrospective, and only the anorectal manometry data could be analyzed. Causal relationships could not be determined. The actual meaning of the changes in anorectal manometry after delivery and the differences in manometry between modes of delivery in relation to the development of postpartum constipation and how to intervene on these changes remain to be investigated. This study was preliminary, and the sample size will be increased in the future. A prospective study is currently under preparation to investigate the dynamic changes in anorectal manometry after delivery and the impact of PFMT on manometry.The results suggest that the patients with a spontaneous delivery had a lower change in maximal contracting sphincter pressure compared with those with Cesarean section. The clinical significance of this weaker defecation push strength and how it fits within PFMT remain to be determined.