The current surge of interest in postural orthostatic tachycardia syndrome commonly known as POTS requires good knowledge of the very complex physiology involved, but this is currently lacking. The often overlooked normal physiology of orthostasis is reviewed including the definition of normal postural orthostatic tachycardia. An illustrated functional anatomy that embeds orthostatic tachycardia within the learned and skilful motor functions in the human population is presented. The four physiological phases of orthostasis and the role of tachycardia are described in a laboratory‐controlled and progressive orthostatic stress in normal human volunteers. Standardized surrogate measures of autonomic control were used to quantify the trigger level for excessive tachycardia and the minimum autonomic control required to sustain viable arterial blood pressure during severe orthostatic stress in normal human volunteers. Tachycardia during orthostasis is part of a “democratic” contribution by four cardiovascular parameters of which the chronotropic function of the heart is just one of the parameters contributing toward cardiovascular compensation. It is adjusted during orthostasis in proportion to contributions from the other three parameters, namely inotropic function of the heart, windkessel vascular resistance and venous vascular capacitance. The physiological effects of the two stressors during orthostasis, gravity and isometric contraction of skeletal muscles are reviewed. A model of how the four cardiovascular parameters are regulated during orthostasis to achieve proportionate contributions is proposed emphasizing the necessity to quantify individual contributions from all these four parameters. Any one or more of these parameters may be compromised due to disease requiring disproportionate contribution of the prevailing magnitude of orthostatic tachycardia in an individual. It therefore requires neurophysiological assessment of the autonomic regulation of all the four cardiovascular parameters to assess the condition fully. We recommend here some current and novel neurophysiological methods that use modern medical technology to quantify laboratory standardized surrogate measures of some of these cardiovascular parameters including central parasympathetic regulation in postural orthostatic tachycardia syndrome. A four‐parameter model of cardiovascular regulation, two each in the cardiac zone C and vascular zone D to explain the normal physiology of postural orthostatic tachycardia in the human population. The International Consensus definition of an autonomic disorder known as Postural Orthostatic Tachycardia Syndrome (POTS) conversely describes a natural and physiological cardiovascular compensation in Phase 2 of severe orthostatic stress. The functional anatomy of orthostasis shows that it is part of a learned skilful motor function in the human population including the associated tachycardia. Although the disease POTS is a recognized dysautonomia, the whole phenomenon of postural orthostatic tachycardia has so far been turned into a popular disease due to lack of full knowledge of the complex but perfectly normal and natural physiology involved. The aim of this review is to restore the understanding of the natural and physiological basis of tachycardia during orthostasis (POT). This review will define the normal and natural POT in terms of a normal physiological phenomenon that can be reproduced in a normal human population in a physiology laboratory. The natural forces that exert the orthostatic stress that generates tachycardia in the human population are also presented. The functional arrangement of the neurons that generate tachycardia in POT in the human population  is presented for the first time in order to demonstrate the natural origin POT in humans. This review includes a four‐parameter model of cardiovascular compensation during orthostasis in humans and how they can be assessed in a clinical laboratory to investigate the disease POTS.1.21.2.1positura” meaning position and the adjective orthostatic originates from two Greek words; “orthos” meaning upright and “statos” meaning standing. Hermann Lebert who was a physician introduced the term tachycardia in medicine in 1867. Tachycardia comes from two words of different origins, an English word “tachy” which means swift and the Greek word “kardia” which means the heart. Tachycardia literally means “swift heart”. Orthostasis is a verb meaning standing upright without translational movements, indicating clearly that the position of the subject is not shifting relative to the ground on which he or she is standing. It is very important to carefully define the phrase “postural orthostatic tachycardia" so that we understand fully that it actually refers to a natural and normal response of the heart to various and often numerous challenges to the human body during orthostasis. These challenges will be discussed later in this review.The phrase “Postural Orthostatic Tachycardia” refers to the quickening of heartbeats in response to a change in the position of the body, usually from recumbent to an upright position. The adjective postural has the Latin origin “1.2.2The heartbeat can start to quicken early during the thought of changing body position, even before the body begins to move Figure . It is aThe heart rate is expected to stabilize and remain within a known normal range that is higher than it was in supine position for as long as the person maintains an upright stance without translational movement. This is known as Postural Orthostatic Tachycardia and the complex but normal physiological processes involved in achieving this is the subject of this review. A person overwhelmed by the orthostatic challenge and develops neurological symptoms like poor balance or lack of spatial awareness, or cardiac symptoms like weakness or palpitations, is described as having poor or sometimes total lack of orthostatic tolerance. The extreme of orthostatic intolerance is postural syncope.1.2.3Diagnostic orthostatic challenge can be achieved by asking the patient to rise up to an erect posture starting from a supine position Kahn, . There i1.31.3.1Ablation plus nonspecific near‐neuron stimulation techniques showed that there were distinctive tachycardia and bradycardia zones in the brainstem and were called tachycardia or bradycardia centers in those days  and it completes its exit out of the spinal cord at the level of thoracic segment number five (T5) in human  is a distinct area of the brain that regulates several functions of the autonomic nervous system. For example, the RVLM is a discrete area in the brainstem that regulates several autonomic functions and it is situated in a CARS site labelled as number 1 just for identification purposes only in this review. More of these regulatory sites and their identification numbers are shown in Figure Takeaway pointsFunctional organization of neurons in the caudal part of the medulla that was previously described as the bradycardia center is fully reviewed elsewhere  of the brain that uses blood oxygen level dependent (BOLD) signal intensity  of −15 mmHg, equivalent to a drop in central venous pressure (CVP) from 7 mmHg to 5 mmHg , an analogue of glucose. The concentrations of this tracer when imaged in the body will indicate tissue metabolic activity and corresponds to the regional glucose uptake at that moment. Other radioligands like 15O in the form of water (H215O) is used to indicate changes in regional blood flow in organs or tissues in the body. Three‐dimensional images of the tracer concentration within the body are constructed from gamma rays scanners by computer analysis. This gamma rays image is superimposed onto three‐dimensional images of the organ or the whole body acquired by other methods of scanning like x‐ray computed tomography (CT), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), and ultrasound.Positron‐emission tomography (PET) is a nuclear functional imaging technique that is used to track metabolic processes in the body, usually in real‐time. The system detects pairs of gamma rays emitted indirectly by positron emitting radioligands like 215O PET scanning while performing isometric contraction of skeletal muscles using their right hand and the heart rate (HR) was monitored during scanning  was monitored during scanning  was monitored during scanning  increase to 300% of the initial resting value and the heart rate increased by 19% in order to successfully defend the resting supine MAP, which did not change significantly during the external negative lower body pressure challenge. The reduced central venous pressure suggests that a reduction of the venous blood volume returned to the heart is the main cardiovascular stress in this example. The best way to have ascertained this would be to measure the cardiac output during this study, but it was not done. However, reduced venous return could have been achieved by mechanical manipulation of the venous vascular capacitance using negative pressure to suck, distend and enlarge the veins due to the much higher compliance of venous walls compared to arterial walls. Venous wall has about thirty times more compliance than arterial wall Gelman, . Increas1.4.3Gravity creates vascular hydrostatic pressure, which is proportional to the density of blood and the vertical height of the column of blood inside the blood vessel. Since gravitational force during orthostasis is downwards toward the center of the earth, the hydrostatic pressure in all the venous vascular system below the horizontal level of the heart is in opposition to venous return to the heart. Venous hydrostatic pressure facilitates pooling of blood within the veins due to the high compliance of venous vascular walls as discussed before. In other words, gravity increases the total venous vascular capacitance shown in Figure Gravity increases the total venous vascular capacitance by creating hydrostatic pressure that distends the high compliance venous walls leading to pooling effectGravity‐induced increase in venous capacitance holds back more than 10% of the cardiac output in the supine position in humans. This is however more than doubled in the upright position, when gravity‐induced increase in venous capacitance holds back more than 20% of cardiac output even in an upright sitting positionTachycardia is part of the natural compensatory mechanism in response to reduced venous return and is used to defend the appropriate target arterial blood pressure required for the prevailing physiological stateTakeaway pointsThe process of orientation to an upright stance and the balance to maintain the upright stance against gravity during orthostasis involves contraction of skeletal muscles. These muscles are sometimes described as antigravity  and women aged 35–50 years (40 ± 5 years) volunteered in this study. All volunteers did not have any known cardiovascular or neurological disorders and were not taking any medications. Important beat‐to‐beat cardiovascular parameters including heart rate (HR) representing chronotropic function of the heart, systolic (SBP), diastolic (DBP), the mean arterial blood pressures (MAP), and forearm vascular resistance (FVR), all representing windkessel vascular functions  84.9 ± 3.2 mmHg; HR, 63.9 ± 3.2 beats/min; CVT, 10.8 ± 2.6 LVS units  at 60 degrees, followed by a combination of HUT and lower body suction (LBNP) to achieve pre‐syncope. We defined pre‐syncope as a fall in SBP to below 80 mmHg accompanied by symptoms. All volunteers reached this level of cardiovascular decompensation.There are four phases of orthostasis revealed during a study of cardiovascular control during the period leading to pre‐syncope in patients with posturally related syncopal attacks  and CSBPhase 1 of orthostasis has early and late parts. The early part of phase 1 consists of several events that provoke readjustments of cardiovascular regulations. These events can be illustrated much better in the orthostasis during active standing more than during passive tilt. We shall therefore use the sequence of events illustrated in Figure Cardiovascular arousal is indicated by the beginning of withdrawal of baroreflex central sympathetic restraint measured here as CSB. It starts at the same time with the command to execute orthostasis and precedes all other cardiovascular events during the orthostatic processThe start of the ramp increase in heart rate during early orthostasis coincides with the beginning of withdrawal of central chronotropic restraint measured here as CVT. The withdrawal of CVT and increase in heart rate precedes any body movement during the initiation of orthostasisChanges in heart rate in early orthostasis have three stages; a ramp tachycardia followed by rebound bradycardia followed by recovery to stable but increased heart rate compared with the supine baseline level. The increase is about 17% above baseline level, with an average increase of 12 beats/min and a range of 5 to 25 beats/min above baseline levelThe magnitudes of heart rate changes in early orthostasis have been standardized as a 30:15 ratio test and adopted for use in clinical examinations of autonomic functionsFull cardiovascular compensation in orthostasis is achieved within 3 min of assuming an upright stance. The consensus statement on the definition of orthostatic hypotension recommend assessment of postural hypotension at three minutes in upright or tilt positionTakeaway pointsThe late part of orthostasis Phase 1 starts at full cardiovascular compensation  recommend a sustained heart rate increment of more than 30 beats/min within 10 min of orthostasis, but without orthostatic hypotension as a basis of the diagnosis of the disorder  in this laboratory‐controlled orthostatic stress and it is 11 s before the beginning of bradycardia in the illustration below Figure . ReductiThe collapse of arterial blood pressure during the vasodepressor response in Phase 4 orthostasis triggers a reset of the central restraint of the chronotropic function of the heart . It means either of the two functions can fail independently or any one of them can be used independently to compensate for failures of any other cardiovascular functions in zones C and D Figure . This meIt is evident from the description of the physiology of orthostatic tachycardia using our model Figure  that sta1.51.5.1The phrase “Autonomic Failure" when used as a clinical term means the inability of the autonomic nervous system to execute co‐ordinated and standardized autonomic tasks that have been identified and validated for clinical examinations of the system. The autonomic tasks are set up in the form of special maneuvers recommended for clinical tests of autonomic function by an International Committee in a consensus statement of San Antonio Kahn, . DiagnosThis is a measure of the central parasympathetic restraint of the chronotropic function of the heart  in the nucleus ambiguus (NA) in the brainstem as discussed previously in Functional Anatomy. The magnitude of respiratory gating of CVT at the level of cVPN in NA can be quantified Figure  and used−1. It is a beat‐to‐beat baroreflex negative feedback control of arterial blood pressure. The least value of CSB is zero representing no negative feedback cardiovascular control at all. The normal range in our laboratory population is between 6 and 12 ms.mmHg−1. The 95% confidence interval in the population sample used in the progressive orthostatic stress study described here in this review is between 5 and 11 ms.mmHg−1 similar to our laboratory normal range. The method allows the detection of rapid changes in CSB within a continuous measurement, which represents real‐time engagements and disengagements of the baroreflex negative feedback cardiovascular control. Disengagement of negative feedback cardiovascular control indicates cardiovascular arousal in preparation for imminent changes in either blood pressure alone, or heart rate alone . It is a measure of the well‐known baroreflex restraint of sympathetic activity, mainly the vasomotor tone in the RVLM, and the baroreflex restraint is coming through the NTS Dampney, . The res(3h‐5) ms.mmHg−1, where h is the subject's height in meters, or can be expressed in terms of the natural number “e” where BRR = 6.35 × 10(eh‐5) ms.mmHg−1. The observed value from the ratio ΔR‐R/ΔSBP should be within 50% of the predicted value in the age group 15–79 years (Our laboratory standard). The ECG R‐R intervals, CSB and the arterial blood pressure are monitored and measured continuously  for a target duration of three minutes to reduce and keep the baroreflex negative feedback cardiovascular restraint to its lowest level Figure . Withdray Figure .Carotid massage using digital pressure applied on the carotid sinus in a resting supine position at the rate of the subject's own heartbeats for the duration of 15 s should cause an increase in the CVT Figure , usually1‐adrenergic vasoactive drugs in a resting supine position should cause a concurrent rise in both blood pressure and ECG R‐R intervals and the two should be statistically associated with a gradient of R‐R intervals rise per systolic blood pressure rise between 5 and 12 ms.mmHg−1  and a correlation coefficient greater than 0.9 (Our laboratory standard). The ECG R‐R intervals and the arterial blood pressure are monitored and measured continuously using the NeuroScope . All the arterial blood pressures; SBP, DBP and MAP, including the parasympathetic restraints; CSB and CVT and the heart rate are monitored and measured continuously during this test using the NeuroScope  for the duration of 3 min to reduce and keep the baroreflex negative feedback cardiovascular restraint and the central parasympathetic tone to their lowest levels Figure . WithdraWe use the isometric contraction of the skeletal muscles of the dominant hand described above to reduce and keep the baroreflex negative feedback cardiovascular restraint and the central parasympathetic tone to their lowest levels in this procedure. The continual increase in diastolic blood pressure (DBP) during the second and third minute of sustained handgrip represents the central sympathetic vasomotor drive of the windkessel vascular resistance (Zone D, Figure We use a positive intra‐thoracic pressure of 40 mmHg lasting 15 s during Valsalva's maneuver to suddenly reduce venous return to the heart (Zone D, Figure I am the inventor of the NeuroScope, but the machine is patented by the University of Glasgow in the United Kingdom. The University sold the sole right of exploitation of the patent to Medifit Instruments Limited, London, the United Kingdom. I have no financial connection with this company but sometimes give them scientific advice without pay.


Delayed ischemic neurologic deficit (DNID) is a problem after cerebral aneurysm clipping. Intraoperative hypotension seems to be indicated as a risk factor, but it remains a controversial issue with varying low-blood pressure levels accepted.  A retrospective, hospital-based, case-control study was performed with patients who received general anesthesia for cerebral aneurysm clipping. 42 medical record charts were randomly selected and matched 1 : 2 (1 case with DNID : 2 controls without DNID) based on the type of general anesthetic techniques and severity of subarachnoid hemorrhage. The optimal cutoff points of hemodynamic response were calculated by the area under the curve. 2) and has poor diagnostic value for predicting DNID.  Data suggested that the optimal cutoff points for lowest blood pressure for prevention of DNID should be systolic blood pressure (SBP) of 95 mmHg , diastolic blood pressure (DBP) of 50 mmHg , and mean arterial pressure (MAP) of 61.7 mmHg . Furthermore, the optimal cutoff point mean difference baseline blood pressure was recommended as Δ SBP of 36 mmHg , Δ DBP of 27 mmHg , and Δ MAP of 32 mmHg . No significant difference between DNID and non-DNID groups was found for end-tidal carbon dioxide (ETCO To prevent DNID, we recommend that optimal blood pressure should not be lower than 95 for SBP, 50 for DBP, and 61.7 mmHg for MAP. Additionally, we suggest that Δ SBP, Δ DBP, and Δ MAP should be less than 36, 27, and 32 mmHg, respectively. Cerebral vasospasm (CVS) is a common problem following subarachnoid hemorrhage. Nearly sixty percent of aneurysmal subarachnoid hemorrhage patients will develop CVS . FurtherThis study was, therefore, conducted to investigate the association between intraoperative hemodynamic parameters and DNID in subarachnoid hemorrhage patients who underwent cerebral aneurysm clipping. The optimal target range of hemodynamic parameters was analyzed to prevent DNID. These results may guide the physician to control and adjust parameters towards achieving excellent neurological outcomes.2) measurement and recorded every fifteen minutes. The lowest point of blood pressure and ETCO2 was calculated from the average of three measurements including the lowest value and before and after the lowest value. The study was reviewed and approved by the Khon Kaen University Ethics Committee for Human Research (HE621246).This study used a hospital-based retrospective case-control design. Participants were patients selected from those who had received general anesthesia for cerebral aneurysm clipping at Srinagarind Hospital, Khon Kaen University, Thailand, between January 2013 and November 2018. A sample size of 42 subjects was chosen using simple random sampling with 1  : 2 matching (1 case with DNID : 2 controls without DNID) based on the type of general anesthetic techniques used  and severity of subarachnoid hemorrhage (SAH) following the World Federation of Neurological Societies (WFNS) and Fisher grading scales (FS). This sample size was deemed appropriate considering 95% confidence intervals, 2% error, and meaningful of the area under the curve of 0.76, calculated from the pilot study. Thus, medical record charts were required for 14 patients with DNID and 28 patients without DNID. Complete medical record charts of patients who underwent cerebral aneurysm clipping were enrolled; however, inadequate record charts that did not clearly indicate the severity of SAH and had insufficient hemodynamic response recording were excluded. Regarding blood pressure measurement, the oscillometric device was used for monitoring and it recorded every five minutes; however, capnogram in the anesthesia machine was used for end-tidal carbon dioxide  curves using STATA .Fisher's Exact Probability test was used to compare baseline characteristics between patients with and without DNID, including differences in gender, underlying disease, the severity of SAH, and general anesthetic techniques. The Mann–Whitney p < 0.05). Before the procedure, the DNID group had significantly higher mean blood pressure (p < 0.05), whereas the mean ETCO2 was lower in patients without DNID. During the procedure, the mean low-blood pressure points and ETCO2 were higher in the DNID group (p > 0.05). The mean difference between the lowest blood pressure point during operation and baseline blood pressure point and ETCO2 showed a significantly wider range of blood pressure in the DNID group (p < 0.05), whereas a narrower range of ETCO2 was observed in the DNID group (p > 0.05) (Patient demographics are presented in  > 0.05) .2 is recommended as 27 mmHg  with AUC of 0.6 (Recommendations for the optimized cutoff point for prevention of DNID are systolic blood pressure (SBP) of 95 mmHg , diastolic blood pressure (DBP) of 50 mmHg , and mean arterial pressure (MAP) of 61.7 mmHg . These ROC curves of SBP, DBP, and MAP allowed the area under the curve (AUC) of 0.6, 0.7, and 0.6, respectively. In addition, the lowest point of ETCOC of 0.6 .2 were calculated with the initial operation point and the lowest point during operation. The mean different ROC curves showed that the optimal cutoff points were SBP of 36 mmHg (sensitivity of 85.7%: specificity of 60.7%), DBP of 27 mmHg , and MAP of 32 mmHg . The mean different AUC of SBP, DBP, and MAP was 0.7, 0.8, and 0.9, respectively. The optimal cutoff point of the mean difference of ETCO2 was 3 mmHg  with AUC of 0.4 (The mean differences in blood pressure and ETCOC of 0.4 .p > 0.99)  . These rp < 0.05), similar to previous studies. For example, Claassen et al. [p < 0.05 and 87.9 ± 14.0 vs 68.9 ± 10.9; p < 0.05, respectively) that may be relative risk factors for DNID.Regarding the hemodynamic response, the relationship between the initial high blood pressure on admission and DNID was unclear. In our study, the initial mean of MAP in the DNID group was higher than that in the non-DNID group . For a cutoff point of blood pressure, including SBP, DBP, and MAP, we suggest that blood pressure should be not lower than 95, 50, and 61.7 mmHg, respectively. The lowest point of SBP of 95 mmHg in our study was similar to a previous study that showed SBP lower than 90 mmHg associated with DNID [Higher initial blood pressure in the DNID group seemed related to the mean of the lowest point of blood pressure and the cutoff point of the lowest blood pressure during operation. The mean of the lowest point of blood pressure in the DNID group seemed higher than that in the non-DNID group . The ROC curves of mean difference blood pressure provided better AUC (0.7–0.9) than the lowest point of blood pressure (0.6–0.7) and improved the prediction of development of DNID. We suggest the optimal cutoff points of blood pressure below the initial baseline as Δ SBP of 36 mmHg, Δ DBP of 27 mmHg, and Δ MAP of 32 mmHg. In a previous study, Hoff et al. [The mean difference between initial blood pressure and the lowest point of blood pressure during the operation showed better diagnostic value for predicting the effect of initial blood pressure. All of the mean differences in blood pressure were significantly higher statistically in DNID . Our ETCO2 result was similar to Akkermans et al. [2 and the development of DNID with an adjusted risk ratio of 0.95  for ETCO2 less than 30 mmHg. However, the lowest point of ETCO2 in our study is observed at 27 mmHg that yields a sensitivity of 78.6% and specificity of 35.7%. Additionally, the cutoff point of decreasing ETCO2 from an initial baseline of 3 mmHg provided a poor diagnostic value with a small AUC of 0.4. Thus, ETCO2 may not be a major factor in inducing DNID development.Regarding ETCOs et al.  that shoRegarding the strength of this study, we analyzed the diagnostic value of the optimal blood pressure that allows confident decision making in clinical practice to prevent DNID. Furthermore, the study was conducted with a matched case-controlled design that yielded to reduce confounding factors and balance baseline data. Unfortunately, the limitation of the study was found that some factors including body weight and intraoperative blood loss were significantly higher in the DNID group, though data were insufficient to show that these factors induced DNID. Moreover, the other limitation is its retrospective nature that yields a lack of investigating data including transcranial Doppler, computed tomographic angiogram, and follow-up angiography; therefore, further research is needed to be done in all aspects.2 is not a major risk factor associated with DNID.For preventing the development of DNID, we recommend that the optimal points of blood pressure  should not be lower than 95, 50, and 61.7 mmHg, respectively. Additionally, we suggest the mean difference of blood pressure should be less than 36 mmHg for Δ SBP, 27 mmHg for Δ DBP, and 32 mmHg for Δ MAP. However, we found that ETCO


Plasma free hemoglobin (FHB) and creatinine clearance (CCr) were assayed to indicate the renal function. Both 0.03 MPa suction (≥4-unit load) and >5 units transfusion changed the levels of FHB and CCr significantly when measured 24 h post-operation compared to pre-operation. Under 0.02 MPa suction (≥4-unit load), the alteration of FHB and CCr returned to normal after 24 h. Under 3 units transfusion, the levels of FHB and CCr at 6 and 12 h post-operation changed significantly compared to pre-operation , and this alteration could be restored to normal at 72 h post-operation. After an exhaustive investigation, less than 4 units transfusion and less than 0.03 MPa suction pressure are recommended for intraoperative salvage autotransfusion.Although some investigations have been performed to determine the effects of transfusion load and suction pressure on renal function during intraoperative salvage autotransfusion, the precise threshold is still undetermined. A total of 625 patients undergoing surgery with the Continuous AutoTransfusion System (CATS Besides financial burden, allogenic transfusion remains a challenge considering the risk of developing transfusion-transmitted virus and bacterial infections, acute lung injury and circulatory overload, hemolytic and allergic reactions, variant Creutzfeldt-Jakob disease, and even death –4. ThuIntraoperative salvage autotransfusion is reported to affect post-operative renal function ,8. In thThis investigation was designed to comprehensively evaluate the effect of transfusion volume and suction pressure on renal function, which will help to set up a unified standard of intraoperative salvage autotransfusion.®plus, Fresenius Kabi, Germany) were screened from January 2016 to December 2018. Inclusion criteria were: over 18 years of age; willing to participate and sign an informed consent; and underwent orthopedic surgery, cardiovascular surgery, organ transplant surgery, brain surgery, emergency surgery, and other surgeries. Exclusion criteria were: surgical patients with comorbidities such as hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and chronic renal disease; surgical field blood contaminated with digestive, bile, urine, and amniotic fluid; surgical field blood at risk of contamination in open trauma; blood conservation beyond 6 h; patients with infectious diseases; patients with malignant tumors and those who died during or within 72 h after surgery; patients with kidney injury before operation. After evaluation, a total of 625 eligible patients were enrolled in the final investigation.This investigation was performed in Quanzhou First Hospital of Fujian Province, and the protocols were approved by the Ethical Committee of Quanzhou First Hospital. Study design and procedures are shown in Figure S1. A total of 936 typical cases that underwent surgery using the Continuous AutoTransfusion System  mixed with 30,000 IU of sodium heparin. A double-lumen suction catheter specific for blood collection was utilized to salvage the bloodshed from the surgical field. Salvaged blood was suctioned with different vacuum pressures according to the study design , and further collected into the reservoir of the CATSplus. High-quality wash performed with the CATSplus was processed to minimize the residual FHB (<100 mg/dL), and the separated erythrocytes were further collected and transfused into the patients. Residual heparin levels were guaranteed to be less than or equal to 0.1 IU/mL in all post-treatments to minimize the clinical risk for intra- or post-operative hemorrhage.The CATSAge, gender, body mass index (BMI), and smoking habit were obtained and recorded. Hematological variables, such as blood urea nitrogen (BUN), blood creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), plasma FHB, and creatinine clearance (CCr), were measured.GraphPad Prism v7.0 software  was used to analyze the data. Numerical variables are reported as means±SD. Categorical data are reported as percentage (%) and were compared between groups by Pearson chi-squared and Fisher's Exact tests. Because the data of FHB and CCr were not in a normal distribution , the Mann Whitney test was used to test the statistical significance of FHB and CCr. A significance level of P<0.05 was used in all tests.Preoperative data  of participants involved in this investigation are reported in Postoperative renal function change was indicated by the alteration of plasma FHB and CCr. A significant difference in FHB and CCr 24 h post-operation compared with pre-operation in the case of 0.03 MPa suction and ≥4 units transfusion and 0.02 MPa and >5 units transfusion (P<0.05 or P<0.01)  was founTo decipher the relative long-term effect of transfusion volume and suction pressure on the risk of developing renal function damage, a time-course detection and analysis were performed. Under the situation of 0.02 MPa suction (>5 units transfusion), the levels of FHB and CCr altered significantly compared with the pre-operation condition at 6, 12, 24, and 72 h, as expected , while such changes were restored to normal at 72 h post-operation at 0.03 MPa suction . Only atIn this investigation, both FHB and CCr were utilized to indicate renal function. Intraoperative salvage hemolysis can release FHB, which can precipitate in the renal tubules with resultant tubular dysfunction –15. In plus system has some advantages, such as higher oxygen-carrying capacity and lower volume requirement for transfusion. The efficiency of erythrocyte collection during cell salvage can be attributed to suction pressure. Previous investigations suggest that minimal suction pressures and a suction tip with a relatively large diameter should be adopted to aspirate blood from a surgical field to minimize blood-air interfaces and maximize the efficiency of erythrocyte recovery (plus system to process; in this research, less than four units transfusion was determined for minimal renal function damage (Intraoperative salvage autotransfusion performed by the CATSrecovery ,20. The recovery ,21,22. In damage ,24.The introduction and development of minimally invasive surgery will limit the utilization of intraoperative salvage autotransfusion due less blood loss and transfusion requirements –27. ConIt must be mentioned that prolonged large-volume autotransfusion may cause coagulopathy due to the dilution of clotting factors with transfusions. Thus, together with appropriate transfusion load and suction pressure, regular coagulation function or close patient monitoring is required ,33. The Our investigation has both scientific and practical implications for the utilization of intraoperative salvage autotransfusion, which will help clinicians prescribe the appropriate amount of autotransfusion volume and suction pressure.Although a more precise design and multi-center investigation are needed, this study showed that less than four units transfusion and less than 0.03 MPa suction pressure may be recommended for intraoperative salvage autotransfusion.


However, HFNC was more efficient than COT in elevating PO2 in patients with severe bronchial asthma complicated with respiratory failure, while no statistically significant difference in PCO2 reduction was found between the two groups. Heart rate (HR) and respiratory rate (RR) between the two groups on admission (0 h) and at 2, 8, 24, and 48 h after admission were compared. Both indicators significantly decreased with time. No significant differences in HR and RR were found between the groups at 0, 2, and 8 h after admission. However, these indicators were significantly lower in the HFNC group compared with the COT group at 24 and 48 h after admission. HFNC could significantly elevate PO2 and reduce HR and RR. Thus, it is a promising option for patients with severe bronchial asthma complicated with respiratory failure.Severe bronchial asthma complicated with respiratory failure, a common critical illness in respiratory medicine, may be life-threatening. High-flow nasal cannula (HFNC) is a novel oxygen therapy technique developed in recent years. HFNC was applied in this study for treating adult patients with severe bronchial asthma complicated with respiratory failure. Its efficacy was analyzed comparatively to conventional oxygen therapy (COT). HFNC and COT were randomly performed based on conventional treatment. The HFNC group was similar to COT-treated patients in terms of response rate, with no significant difference in efficacy between the two groups. In patients with bronchial asthma, effectively increased PO Bronchial asthma is a chronic inflammatory disease of the airways characterized by cough, paroxysmal wheezing, and chest tightness. Approximately 300 million individuals are affected by asthma worldwide . In ChinHFNC is a novel oxygen therapy developed in recent years, in which oxygen at a certain concentration mixed with high-flow gas is directly delivered to patients through a nonsealed nasal cannula , 7. ThisThis study was performed in the Affiliated Hospital of Inner Mongolia University for Nationalities . It included adult patients with acute severe bronchial asthma complicated with respiratory failure admitted to the above hospital between June 2017 and January 2019. It was a single-center, open-label, randomized controlled trial designed to analyze the efficacy and safety of HFNC versus COT in improving oxygenation. The present study was approved by the Ethics Committee of the Affiliated Hospital of Inner Mongolia University for Nationalities, and patients who agreed to participate were required to sign the informed consent form.From June 2017 to January 2019, adult patients with a primary diagnosis of acute severe bronchial asthma complicated with respiratory failure, admitted to the emergency, pulmonary medicine, and intensive care medicine departments of the hospital, were enrolled in this study.A total of 3862 patients aged 18–75 years initially diagnosed with bronchial asthma were enrolled. Diagnosis of adult severe bronchial asthma with respiratory failure was performed independently by two attending physicians based on the following inclusion criteria. In case of discrepant diagnosis, the patient was excluded.2 < 60 mmHg, with or without PCO2 ≥ 45 mmHg, under room air according to blood gas analysis on admission.Inclusion criteria were as follows: (1) acute severe bronchial asthma confirmed according to the Global Initiative for Asthma (GINA) diagnostic criteria; (2) PO2 or current dialysis]; (10) contraindications for positive–airway pressure devices; (11) pneumonia.Exclusion criteria were as follows: (1) immediate requirement of tracheal intubation; (2) myocardial infarction ; (3) altered consciousness; (4) hemodynamic involvement (noninvasive blood pressure < 90/60 mmHg); (5) pregnancy in women; (6) respiratory rate (RR) > 45 breaths/min; (7) blood pH < 7.30; (8) untreated pneumothorax; (9) end-stage renal disease  = 57%; a 40% reduction) in the control group (confidence level [1−α] = 95% and power level[1−β] = 80%).Based on the controlled trial design for two intervention groups, with a binominal primary endpoint , the samus study , 21 and t-test, and those with skewed distribution by the rank-sum test. Percentages were compared by the χ2 test. Two-sided P < 0.05 was considered statistically significant. The SPSS software  was used for data analysis.Measurement data are P > 0.05)  .P = 0.87), with no significant difference in efficacy between the two groups  after the treatment, while PCO2 was reduced . However, the between-group comparison showed that the HFNC group was more efficient compared with the COT group in elevating PO2 in patients with severe bronchial asthma complicated with respiratory failure. No statistically significant difference in the effect on PCO2 was found between the two groups (P > 0.05)  .P > 0.05). However, both indicators were significantly lower in the HFNC group compared with the COT group at 24 and 48 h after admission (∗P < 0.05) (HR and RR in both groups on admission (0 h) and at 2, 8, 24, and 48 h after admission were assessed. The results suggested that these indicators in both groups significantly decreased with time. No significant differences in HR and RR were observed between the two groups at 0, 2, and 8 h after admission ( < 0.05) .P > 0.05)  .P=0.01), but no significant differences in hospital stay, further treatments, and overall efficacy were noted between the two groups [The present study showed that HFNC had the same clinical efficacy as COT in patients with severe bronchial asthma complicated with respiratory failure, with no significant differences in tracheal intubation rate and hospital stay between the two groups. Although adult patients with bronchial asthma are rarely studied, the current observations were basically consistent with previous reports on children with moderate-to-severe asthma treated with HFNC , 22. Bal2 in patients with severe bronchial asthma complicated with respiratory failure. Although related studies on HFNC in treating adult patients with asthma are rare, these findings corroborated previous studies evaluating type I respiratory failure [2 in patients with type I respiratory failure and mild type 2 respiratory failure [We also demonstrated that, compared with COT, HFNC effectively elevated PO failure , 24. Man failure –11, 25.  failure .2 levels was found between the two groups, corroborating previous reports assessing hypercapnic patients [2, HFNC increases tidal volume, reduces respiratory rate, and decreases CO2 [2 is increased after HFNC therapy [2 reduction in asthmatic patients may be explained by findings reported by Braunlich et al. in COPD patients [2 reduction by HFNC therapy does not correlate with mean airway pressure increase, but with elevated leakage and airflow. This indicates airway washout and the reduction of functional dead space as important mechanisms of HFNC therapy. Although we used a relatively high flow rate, leakage-inducing techniques were not applied to the patients, which may explain the relatively low efficiency in CO2 reduction in this study.In the present study, no difference in PCOpatients , 27. Stuases CO2 , 29. Oth therapy . These dpatients . The latBased on conventional treatments, such as intravenous and nebulized inhaled glucocorticoids, patients with severe bronchial asthma complicated with respiratory failure must undergo oxygen therapy to maintain oxygenation. HFNC, as a novel oxygen therapy method, provides high-flow gas at the rate of 8–80 L/min through the air–oxygen mixing device, and the oxygen concentration of these gases can be set to 21%–100% according to the patient's needs, thus theoretically meeting the needs for improved oxygenation . In addiSimilar to previous findings about acute dyspnea , HFNC coOther studies suggested that inhalation of heated and humidified gases is particularly more important in patients with bronchial asthma compared with those suffering from other respiratory diseases . InhalinMoreover, HFNC can meet the requirements of a high flow rate for inhaled gases in patients with respiratory failure, thereby reducing the work of breathing and significantly lessening both HR and RR. In adults with severe bronchial asthma complicated with respiratory failure, the maximum inspiratory flow rate can be 30–60 L/min according to the asthma grading standard . HFNC ca2 levels was found between the two groups, likely because leakage-inducing techniques were not applied to the patients, which should be considered in the future studies.The limitations of this study should be mentioned. First, there was no follow-up evaluation, which could help assess the recurrence rate of asthma, the number of days of acute attack in a year, the 90-day mortality rate, and the time to discharge. This could better illustrate the therapeutic value of the high-flow oxygen inhalation technology. In addition, the sample size was relatively small, and no multicenter, large-scale prospective randomized controlled trials have provided evidence on the clinical guidance for efficiently treating patients with severe bronchial asthma complicated with respiratory failure. Thus, multicenter clinical studies should be conducted in the future to address these shortcomings. Finally, in the present study, no difference in PCO2 and reduce HR and RR. Thus, HFNC is a promising option for such patients.The current study showed that HFNC is generally consistent with COT in terms of overall clinical response rate in patients with severe bronchial asthma and respiratory failure but could significantly elevate PO


Background and objectivesAsthma is a common chronic inflammatory disorder of the lung that can be exacerbated by environmental triggers during sandstorms. This study aimed to evaluate the usefulness of C-C chemokine ligand 5 (CCL5) chemokine and interleukin 5 (IL-5) cytokine and determine the total eosinophil count in blood and sputum for use as biomarkers in Saudi patients with chronic asthma who visited emergency departments during sandstorms.MethodsThe study included 42 Saudi patients with chronic asthma and 20 healthy controls. Plasma levels of CCL5, IL-5, and total immunoglobulin E (IgE) were measured using a specific enzyme-linked immunosorbent assay (ELISA). Total eosinophils in peripheral blood were counted using a hematology analyzer ; in sputum, eosinophils stained with Giemsa were examined under a microscope, counted, and expressed as a percentage of the total cells.ResultsTotal IgE levels were significantly higher in patients with asthma  as compared to normal controls (139 IU/ml). There was no significant difference in the levels of CCL5 in patients with asthma (625 pg/ml) as compared to normal controls . No correlation was found between total IgE and CCL5 levels. IL-5 was not detected in patients with asthma or in controls. Moreover, the total counts of eosinophils in the blood did not increase in patients with asthma as compared to controls while eosinophils in sputum samples were increased in the former (mean =3.128%).ConclusionPlasma levels of CCL5 and IL-5 or eosinophil counts in the peripheral blood may not be useful diagnostic biomarkers to evaluate airway inflammation and monitor asthma severity. Conversely, the sputum eosinophil count may represent a useful diagnostic marker for assessing the magnitude of asthma exacerbation during sandstorms. Asthma is a common chronic inflammatory disorder of the lung characterized by bronchial hyperresponsiveness with clinical symptoms, including wheezing, coughing, mucus production, migration of inflammatory immune cells into airways, and shortness of breath . AccordiMajor sandstorms are common in the Middle East . During Atopic asthma is classified as a type-1 hypersensitivity, where immunoglobulin E (IgE) has a crucial function in the allergic reaction . EosinopRegulated upon activation, normal T-cell expressed and secreted (RANTES), a chemokine also known as C-C chemokine ligand 5 (CCL5), is a member of the CC chemokine family with a molecular weight of 7.5 kDa that plays an important role in the inflammatory process . CCL5 isInterleukin 5 (IL-5) is a Th2 cytokine with a molecular weight of approximately 52 kDa that has also been shown to play an important role in the pathogenicity of asthma. IL-5 interacts with its receptor (IL-5Ra) expressed on eosinophils, maintaining airway inflammation and resulting in worsened asthma symptoms. Targeting IL-5 or its receptor has been shown to be a promising therapeutic approach for severe asthma . Based oIn this study, the plasma levels of the chemokine CCL5 and cytokine IL-5 and total IgE and eosinophil counts in the peripheral blood and sputum were investigated in patients with asthma and normal controls during sandstorms to assess their possible use as biomarkers to evaluate disease exacerbation in patients exposed to sandstorms.SubjectsForty-two people with allergic asthma (mean age 37.06 years) and 20 normal controls (mean age 31.08 years) were enrolled in this study. The characteristics of the subjects with asthma are shown in Table MethodsBlood Collection and IsolationPeripheral blood was collected from healthy donors and patients. Following collection, the blood was transferred immediately to tubes containing the anticoagulant ethylenediaminetetraacetic acid (EDTA). The blood was centrifuged at 1800 rpm for 5 min at room temperature. After centrifugation, the plasma aspirated and divided into aliquots in small plastic tubes.Eosinophil Counts in Peripheral Blood and Sputum3. The sputum samples were processed as follows. Briefly, all study subjects were requested to cough sputum into plastic containers. The sputum samples were examined macroscopically to ensure that they were free of salivary contaminants. Satisfactory sputum samples were treated with dithiothreitol (1% Dithiothreitol (DTT)) in phosphate-buffered saline for 20 min to homogenize and disrupt the disulfide bonds in the mucous and disperse the cells. The suspension was centrifuged, and the cell pellet was resuspended, transferred, and distributed thinly and evenly over a microscope slide. Giemsa staining was performed, and the number of eosinophils was assessed under a microscope. The eosinophil count is expressed as a percentage (%). A sputum eosinophil count ≥2% of total leukocytes in a sputum sample was considered abnormal based on the Saudi Initiative for Asthma guidelines (2019) [After collection in EDTA tubes, a hematology analyzer  was used to determine the complete blood counts (CBCs) and differential counts of white blood cells (WBCs), including eosinophils. Blood eosinophilia was identified at a cutoff of 5% and/or >300 cells/mms (2019) .Cytokine Measurement by ELISAThe plasma obtained from the healthy controls and patients was used for measuring protein concentrations using specific ELISAs. Total IgE levels were measured using Quantikine ELISAs . Human RANTES or CCL5  and IL-5  levels were also measured using Quantikine ELISAs. The assays were conducted as described in the manufacturer’s instructions for each kit. The optical density (OD) of each well at 450 nm was determined using a microplate reader . KC Junior software (BioTek) was used to determine the final protein concentrations.StatisticsData are expressed as mean ± standard deviation (SD), and an independent nonparametric sample test (Mann-Whitney U test) was employed to evaluate statistical significance using GraphPad Prism 6 software . Pearson’s test was applied to evaluate correlations. P-values <0.05 indicate significance.Total IgE was significantly increased in patients with asthma as compared to normal controlsAtopic asthma is an allergic disease that is characterized by increased levels of IgE. To ensure that the samples received from the hospital were from patients with allergic asthma, plasma IgE levels were measured using an ELISA. Total IgE levels were significantly elevated in all patients with asthma (mean 433 IU/ml) P=0.0001) as compared to normal controls (139 IU/ml)  and normal controls (663 pg/ml) (P=0.57) Figure . FurtherIL-5 cytokine was not detected, and total eosinophil counts were not increased in blood but in the sputumIL-5 was not detected in the plasma of normal controls or patients with asthma. The eosinophil count in the peripheral blood of the patients was within the normal range (mean 2.55%) and was not significantly different when compared to that of the normal controls (mean 2.81%) Figure . HoweverThis study aimed to evaluate plasma CCL5 (chemokine) and IL-5 (cytokine) as well as eosinophils in peripheral blood and sputum and their possible role in patients with chronic asthma who visited emergency rooms during sandstorms.Unsurprisingly, a significant increase in total IgE was observed in patients with asthma (mean 433 IU/ml) as compared to normal controls (139 IU/ml). The normal levels of total IgE values show a wide range of distribution. Total IgE levels ≥100 IU/mL) have been used to determine atopic status 0 IU/mL h. This isIn addition, there was no significant increase in CCL5 levels in the plasma of patients with asthma (mean 641 pg/ml) relative to that in the healthy controls (588 pg/ml). Furthermore, no correlation was found between CCL5 and total IgE.This finding is similar to that of Erten et al., who found no difference in CCL5 levels in patients with asthma relative to normal controls . This fiTaken together, these results suggest that CCL5 may not be a useful marker of asthma severity during sandstorms, especially if the patients used ICS treatments during the storms. Furthermore, anti-CCL5 treatment would not be a useful therapeutic approach for this patient group.IL-5 plays a key role in eosinophil growth, differentiation, activation and effector function, and survival . It has In this study, IL-5 was not detected in the plasma of patients with asthma or normal controls. The lower detection limit for IL-5 in the ELISA is 25 pg/ml, and most studies have shown a range between 5 pg/ml and 20 pg/ml, which is below the detection limit in the current study; therefore, the cytokine would not be detected. Moreover, treating asthma patients with ICS has been shown to suppress the transcription of the gene encoding IL-5 . This fiIt has been proposed that blood eosinophil counts reflect the severity of asthma . In addiInterestingly, the total number of eosinophils in the sputum of patients with asthma patients was increased as compared to the normal range. Despite the importance of ICS in reducing sputum eosinophils and asthma exacerbations, the variability in response among patients with asthma must still be considered, as not all of these patients respond equally to ICS -30.Taken together, the observations suggest that the eosinophil count in sputum, but not in blood, maybe a marker for predicting the severity of disease during asthma exacerbations and whether patients require higher doses of ICS to manage their asthma severity.The limitations of the current study are that asthmatic patients with high plasma levels of total IgE were not examined for further evidence of allergic bronchopulmonary aspergillosis or parasitic infection. In addition, the analysis of CCL5 and IL-5 in the sputum was outside the scope of this work, and thus, consequent studies should investigate the probability that sputum cytokine expression is a good indicator of asthma activity.In conclusion, the plasma levels of CCL5 and IL-5, as well as the eosinophil count in peripheral blood, may not be useful diagnostic biomarkers to evaluate airway inflammation and monitor asthma severity during sandstorms, especially if the patients have used ICS. However, the eosinophil count in the sputum may represent a useful diagnostic marker for asthma exacerbation.


In this study, 200 patients with CKD were evaluated for renal prognosis. Survival analyses and logistic regression analyses were conducted, generating time-series pseudo-R2 values. The mean and percent change of the pseudo-R2 values from the 6th year to the 10th year  were calculated for determining the cut-off points for the medium-term renal prognosis. Multivariate Cox regression analysis revealed that the V/S ratio was significantly associated with renal outcomes and that the VFA category (VFA ≥ 100 cm2) had significant interactions with the V/S ratio regarding renal prognosis. The hazard ratio (HR) of the V/S ratio was higher in the sub-cohort of VFA < 100 cm2 than in the sub-cohort of VFA ≥ 100 cm2 (HR: 6.42 vs. 1.00). Regarding sex differences, a strong association was noted between the V/S ratio and renal prognosis in women but not in men (HR: 2.40 vs. 1.10). On the other hand, 6Y–10Y Mean of the pseudo-R2 values indicated differences in the cut-off points of the V/S ratio between men and women (V/S ratio: 0.75 vs. 0.5). Our findings indicate that it may be clinically meaningful to consider the differences in sex and the amount of VFA ≥100 cm2 for the V/S ratio in relation to renal outcomes in patients with CKD. The 6Y–10Y Mean of the pseudo-R2 values contributed to determining the cut-off points of the V/S ratio according to the sex difference.Whether the visceral-to-subcutaneous fat ratio (V/S ratio) is associated with renal prognosis in patients with chronic kidney disease (CKD) remains unclear. Furthermore, little is known about the effect of sex and the absolute amount of visceral fat accumulation such as visceral fat area (VFA) ≥100 cm Visceral fat accumulation is thought to be the most important central pathological condition in metabolic syndrome (MetS) , 2 and iFurthermore, obesity-related or adiposity-related glomerulopathy has been attracting attention. Increased production of proinflammatory adipokines is involved in the pathogenesis of CKD, causing oxidative stress, inflammation, endothelial dysfunction, hyperfiltration, activation of the sympathetic and renin–angiotensin systems in the kidneys, and insulin resistance –14. HistR2 values [R2 value during follow-up or show an increasing pattern in pseudo-R2 values over time are considered useful as medium-term and long-term prognostic factors [R2 values for the renal prognosis using several V/S ratio cut-off values in patients with CKD.Considering the aforementioned differences in the V/S ratio, research on renal prognosis evaluating sex differences and differences according to abdominal fat accumulation is desired. Furthermore, considering that cut-off values are needed to guide clinical decision-making , researc2 values , 21 is s factors . In the The patients’ human rights and methods for protecting their personal information were considered in detail. All the relevant and responsible staff adhered to the principles of the Helsinki Declaration (amended October 2013) and the Ethical Guidelines for Clinical Studies  in the execution of this study. This cohort study was approved by the Medical Ethics Committee of Tokyo Women’s Medical University (#4599). All participants gave their informed consent at the time of entry.We reviewed the data of 2012 outpatients with CKD who visited the Kidney Center at Tokyo Women’s Medical University Hospital in Japan between August 2006 and August 2007. Among these, 201 patients without nephrotic syndrome underwent abdominal computed tomography (CT). After excluding one patient with nephrotic syndrome, the remaining 200 were enrolled in the present study. CKD was diagnosed according to previously described criteria .During a regular outpatient clinic visit, anthropometric and physical examinations were conducted, including assessments of blood pressure components, body height, body weight, visceral fat area (VFA), and subcutaneous fat area (SFA). The VFA and SFA were measured on images obtained by a multidetector-row CT examination using a GE LightSpeed scanner . An index image was obtained before scanning, and the umbilicus to the L4–5 level was identified as previously described , 30. HorThe study’s endpoint was kidney disease progression, which was defined as a ≥30% decline in the eGFR from baseline (≥30% eGFR decline) or the development of end-stage renal disease (ESRD) requiring renal replace therapy .2) [R2 values (%/year) was calculated as follows: % pseudo-R2 change = pseudo-R2 slope/baseline pseudo-R2 ×100. The pseudo-R2 slope was calculated by the least-squares method. Renal prognostic factors were also evaluated in Cox regression analyses, and the Kaplan–Meier method was used for survival analyses. We followed standard methods to estimate the sample sizes for the multivariate logistic and Cox regression analyses; at least five outcomes were needed for each included independent variable [2, <100 cm2) and each variable of interest were considered by adding sex or VFA category and the corresponding interaction term to the multivariate Cox proportional hazards model. P-values <0.05 were considered statistically significant. All statistical analyses were performed using JMP Pro software, Windows v15.0.0 .Continuous variables are expressed as means and standard deviations (SDs) or as medians . Categorical variables are expressed as percentages, unless otherwise stated. Group differences were evaluated using the unpaired Student's t-test, Mann–Whitney U test, chi-square test, or Fisher’s exact test, as appropriate. Logistic regression analyses were used to assess the goodness of fit of renal prognostic models. The goodness of fit was assessed using McFadden’s pseudo-R-squared (pseudo-R2) , which ivariable . Interac2 and 129 patients with VFA ≥ 100 cm2. Patients with VFA ≥ 100 cm2 had a higher V/S ratio (0.97 ± 0.46 vs. 0.58 ± 0.41) and lower eGFR (53.4 ± 22.7 vs. 60.7 ± 21.3 mL/min/1.73 m2) than did patients with VFA < 100 cm2. Additionally, male patients had a higher V/S ratio (1.08 ± 0.45 vs. 0.54 ± 0.32) and lower eGFR (52.8 ± 22.5 vs. 59.7 ± 21.9 mL/min/1.73 m2) than did female patients. The median follow-up duration was 12.8 years (interquartile range: 5.9–12.9 years), during which 8 patients died, 47 were lost to follow up, and 84 reached the end-point .<100 cm2 than in the sub-cohort of patients with VFA ≥ 100 cm2 (HR: 6.42 vs. 1.00) (2 increase), with all other variables fixed, the VFA (10-cm2 increase) failed to demonstrate a statistical association with renal outcomes in patients with VFA <100 cm2  . Additio<100 cm2 . In cont<100 cm2 . Fig 1 s<100 cm2  and sex <100 cm2 .R2 values for the eGFR, which is an established potent risk factor for CKD progression . Interestingly, unlike the comparison between men and women, there was a difference in the time-series changes in pseudo-R2 values for the eGFR from the 6th year to the 10th year between patients with VFA <100 cm2 and patients with VFA ≥100 cm2. Specifically, the 6Y–10Y Mean for eGFR was clearly higher in patients with VFA <100 cm2 than in patients with VFA ≥100 cm2 (2 vs. VFA ≥100 cm2: 0.3301 vs. 0.1603). The pseudo-R2 values for the eGFR in patients with VFA <100 cm2 showed an almost flat (slightly increasing) pattern from the 6th year to the 10th year, with a 6Y–10Y Change of 1.1 (%/year)   , Fig 2E.(%/year) , Fig 2F,R2 values for the renal outcome in terms of different cut-off points for defining a high V/S ratio , and rose to its highest value (0.0522) at the end of the follow-up period  was obtained with a V/S ratio ≥0.5. When stratified by sex, the highest value of the 6Y–10Y Mean in men (0.2875) was obtained with a V/S ratio ≥0.75, and the highest value of the 6Y–10Y Mean in women (0.0959) was obtained with a V/S ratio ≥0.5. Importantly, the pseudo-R2 values for a V/S ratio ≥0.5 in men with VFA <100 cm2 showed an increasing pattern after 6 years, with a 6Y–10Y Change of 2.7 (%/year), and rose to its highest value (0.0645) at the end of the follow-up period  significantly interacted with the V/S ratio in terms of the renal prognosis; there was a strong association between the V/S ratio and renal prognosis in patients with VFA <100 cm2, but not in patients with VFA ≥100 cm2. Interestingly, in patients with VFA <100 cm2, the V/S ratio was a more useful renal predictive factor than the VFA itself, when the renal outcome was defined as a ≥30% eGFR decline or the development of ESRD. Third, although sex did not significantly interact with the V/S ratio in terms of the renal prognosis, when stratified by sex, there was a strong association between the V/S ratio and renal prognosis in women but not in men. Furthermore, men and women differed in the critical cut-off points for the V/S ratio in terms of the renal outcome . Fourth, on Kaplan–Meier analysis, even in men, the kidney survival rate of patients with a V/S ratio ≥0.75 and VFA <100 cm2, was significantly lower than that for patients with a V/S ratio <0.75 and VFA <100 cm2. Furthermore, we found that the 6Y-10Y Change for a V/S ratio ≥0.5 in terms of kidney disease progression showed an increasing pattern in men.The major findings of the present study are as follows. First, the V/S ratio as evaluated using CT was, for the first time, proved to be associated with CKD progression. Second, VFA category , consistent with the results of previous reports [2, and this state is more likely in men, the critical cut-off value of the V/S ratio for renal prognosis in men and in patients with VFA ≥100 cm2 may be masked. In the present study, 66.7% of patients with VFA ≥100 cm2 had a V/S ratio ≥0.7; thus, there is a possibility that VFA ≥100 cm2 itself is a risk factor for a poor renal prognosis, and, as a result, sensitive changes in the V/S ratio may lose their meaning. Consistent with this, when stratified by sex, there was a strong association between the V/S ratio and the renal prognosis in women but not in men, whose VFA, V/S ratio, % of V/S ratio ≥0.7 were all greater than those in women . Although there were no comments regarding the influence of the absolute amount of visceral fat accumulation, the Framingham Heart Study [3 vs. 1350 cm3, 0.84 vs. 0.39, respectively). However, we consider the low significance of the V/S ratio in men to be superficial and influenced by high visceral fat accumulation. In fact, in men with VFA <100 cm2, the kidney survival rate was significantly lower in patients with a V/S ratio ≥0.75 than in patients with a V/S ratio <0.75 .In the present study, the V/S ratio was greater in men than in women 1.08 vs. 0.54) and in patients with VFA ≥100 cm vs. 0.54R2 values in our clinical studies, based on the fact that the prognostic abilities of risk factors vary with time [R2 values for the renal outcome is the ability to distinguish between short-term and long-term prognostic power. As we reported in a previous study on IgA nephropathy [R2 value during follow-up or show an increasing pattern in pseudo-R2 values over time are considered useful as medium-term and long-term prognostic factors. Long-term renal prognoses tend to be influenced by lifestyle-related diseases, and generally result in time-series increases in the pseudo-R2 when patients are not treated successfully. The present study is the first to show a difference in the cut-off value for a renal prognostic factor in accordance with sex or the length of the follow-up observation period, using a time series evaluation of the pseudo-R2 values. As the medium-term renal prognosis of patients with CKD has not been previously evaluated by pseudo-R2 values, we attempted to establish indicators for the 6th to 10th years renal prognosis as fixed medium-term indexes that are not influenced by differing follow-up periods in future studies, in order to facilitate comparisons in results between future studies and the present study.The prognostic ability of potential kidney prognostic factors can depend on the length of the follow-up observation period. Therefore, detailed treatments with consideration of both the short-term and long-term prognoses are desired in real clinical practice. However, until recently, time-series changes in the prognostic ability of prognostic factors have not received much attention. We recently decided to evaluate the time-series changes in pseudo-ith time , 21. Thehropathy , short-tR2 values for the renal prognosis showed clear results for men. Furthermore, an interesting pattern in the time-series changes in the pseudo-R2 values was more clearly observed in men than in women . Sex-specific cut-off values are required when there are differences in the average value and distribution of the V/S ratio between men and women. On the other hand, the highest value of the 6Y–10Y Mean of the pseudo-R2 values was obtained with a V/S ratio ≥0.5 for the entire sub-cohort of patients with VFA <100 cm2 and for women with VFA <100 cm2, and with a V/S ratio ≥0.75 for men with VFA <100 cm2. Interestingly, the pseudo-R2 values for a V/S ratio ≥0.5 in men with VFA <100 cm2 showed an increasing pattern after 6 years. Therefore, men with VFA <100 cm2 and a V/S ratio ≥0.5 might have a poor renal prognosis with a much longer follow-up period (more than 10 or 20 years).In the present study, although the multivariate Cox regression analyses failed to show an association between the V/S ratio and the renal prognosis in men, the analysis of the pseudo-2 [2 is a diagnostic criterion for MetS in Japan [2, but not in the sub-cohorts of patients with VFA ≥100 cm2. Furthermore, VFA ≥100 cm2 significantly interacted with the V/S ratio in terms of the renal prognosis. Considering that visceral fat accumulation itself is an important risk factor in MetS, in a sense, it is not surprising that the VS ratio becomes less important as visceral fat accumulation increases. Studies have reported that patients with VFA ≥100 cm2 are at risk for coronary artery diseases [2 are generally considered as low-risk patients (unlike patients with VFA ≥100 cm2), little is known about whether patients with VFA <100 cm2 have renal risk factors associated with metabolic disorder. The results of the present study are meaningful, in that the V/S ratio was shown to be a more important factor for kidney disease progression in patients with VFA <100 cm2 than in patients with VFA ≥100 cm2, suggesting that visceral fat-related renal damage has begun in both sexes, even before apparent metabolic-related systemic complications have emerged. Considering the disease characteristics of CKD, which progress over decades, from a public health perspective, prevention and early intervention based on the V/S ratio will likely reduce the burden of kidney disease.It has been reported that the clustered number of MetS components is greater than 1.0 in Japanese persons with VFA ≥100 cmin Japan , and thein Japan . In the diseases , cardiovdiseases , 49, anddiseases . The con2 than did the women. This may have influenced renal prognosis analyses. Fifth, as it was not possible to collect data on the duration of CKD in the present study, it cannot be ruled out that the duration of CKD may have affected the renal prognosis outcome. Additionally, the sample size was relatively small, and further prospective studies with larger cohorts are required to confirm the impact of the V/S ratio on kidney function decline in patients with CKD. On the other hand, the present study has several strengths. First, this is the first study to evaluate the time-series changes in pseudo-R2 values for the V/S ratio at several cut-off points. Second, the detailed analyses were designed to disaggregate the data stratified by sex and VFA category, which is important for achieving patient-centered medicine [The present study has several limitations. First, the impact of subsequent V/S ratio changes on outcomes was difficult to demonstrate because only baseline laboratory data were used in the analyses. Second, since all the participants were Japanese patients with CKD, the association between the V/S ratio and kidney outcomes may not be generalizable to other populations. Third, a potential selection bias was unavoidable because the patients voluntarily enrolled in this study. Fourth, the men in the present study had lower kidney function and a lower proportion of patients with VFA <100 cmmedicine , 36. Thi2 on the V/S ratio in relation to the renal outcome. The present study found, for the first time, that the V/S ratio is associated with CKD progression, especially in patients with VFA <100 cm2. Furthermore, based on the 6Y–10Y Mean of the pseudo-R2 values, the critical cut-off points of the V/S ratio for the medium-term renal prognosis differed between men and women (V/S ratio: 0.75 in men vs. 0.5 in women).It may be clinically meaningful to consider the influence of sex and an absolute amount of VFA ≥100 cm


This scoping review sought to summarize available data on the prevalence, associated factors, etiology, comorbidities, treatment, cost and mortality of chronic kidney disease (CKD) in Cameroon.We searched PubMed, Scopus and African Journals Online from database inception to 31 March, 2020 to identify all studies published on the prevalence, associated factors, etiology, comorbidities, treatment, cost and mortality of CKD in Cameroon.Thirty studies were included. The prevalence of CKD varied from 3 to 14.1 and 10.0%–14.2% in rural and urban areas, respectively. The prevalence of CKD in patients with hypertension, diabetes mellitus, and human immunodeficiency virus was 12.4–50.0, 18.5%, and 3.0–47.2%, respectively. Hypertension (22.3–59.1%), chronic glomerulonephritis (15.8–56.2%), and diabetes mellitus (15.8–56.2%) were the most common causes of CKD. The cause was unknown in 13.5–17.0% of the cases. Advanced age, hypertension, diabetes mellitus, and obesity were frequent associated factors. Hemodialysis was the main treatment modality in patients with End Stage Renal Disease (ESRD). The monthly cost of management of non-dialyzed CKD was 163 US dollars. The one-year mortality rate of ESRD was 26.8–38.6%.Chronic kidney disease affects about one in 10 adults in the general population in Cameroon. Patients with hypertension, diabetes mellitus, and human immunodeficiency virus bear the greatest burden of CKD in Cameroon. Advanced age, hypertension, diabetes mellitus, and obesity are major factors associated with CKD. Chronic kidney disease in Cameroon is associated with high morbidity and mortality and huge economic cost on the patient. Chronic Kidney Disease (CKD) is an abnormality in kidney structure or function assessed using a matrix of variables including glomerular filtration rate (GFR), thresholds of albuminuria and duration of injury . The gloChronic kidney disease disproportionately affects low-income and middle-income countries (LMICs) with a prevalence that is 15% higher than that in high-income countries . In addiHigh-risk groups for CKD include persons living with hypertension, diabetes mellitus, overweight, obesity , 12 and The prevalence of CKD in adult Cameroonians varied between 11 and 14.2% . The preThis review sought to assess the burden of CKD in Cameroon. Specifically, we summarized data on the prevalence, incidence, risk factors, treatment, cost of treatment, and outcome of patients with CKD in Cameroon. Furthermore, we aimed to describe the economic burden and comorbidities of patients with CKD, and to identify research gaps.This scoping review was conducted according to the approach proposed by Arsksey and O’Malley .PubMed, Scopus and African Journals Online were searched without language restriction to retrieve all publications on the prevalence, the incidence, comorbidity, risk factors, treatment, economic burden and outcome  of CKD in Cameroon from database inception to March 31, 2020. Table 2 using either the Modification of Diet in Renal Disease (MDRD) study equation, the Cockcroft-Gault (CG) formula, or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations or proteinuria ≥1+  or patients with known CKD on RRT [Cross-sectional, cohort, case-control studies and systematic reviews that reported relevant data on CKD in Cameroon were considered for inclusion. For this review, CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73mD on RRT . LettersTwo authors independently screened abstracts and citations retrieved from the online search and assessed the full texts of the relevant citations for inclusion in the review, Fig. Relevant data were extracted with the aid of pre-structured abstraction sheets. We abstracted the following information from eligible articles: the surname of the first author of the article, publication year, study design and population studied, study setting , study area , percentage of males included in the study, mean or median age of the participants, sample size, measure used to assess kidney damage or function and if these measures were reassessed after 3 months of measurement, prevalence, comorbidity, treatment rate, median duration of hospital stay and mortality rate of CKD.In total, 122 records were retrieved from bibliographic searches. After screening titles and abstracts, 42 full-text papers were assessed for eligibility and 29 studies were retained for this review , 24–49.Table Overall, the prevalence of CKD in the general population ranged from 10.0–14.2%, , 17, 31.The prevalence of CKD among patients with hypertension ranged from 12.4–52.1% , 28, 30,The prevalence of CKD among sugarcane plantation workers was 3.4% . The preTable Eight studies reported on the etiologies of CKD in Cameroon, Table Thirteen studies discussed the comorbidities of CKD in Cameroon, Table Most of the CKD patients required hospitalization and eventual dialysis. The hospitalization rate was 42.2% in patients who were referred late to the nephrologist, and 33.6% of these late referrals were proposed emergency dialysis . EmergenData on the economic burden of CKD is scarce in Cameroon. In a one-month retrospective cost analysis of non-dialysis CKD stage 3–5 patients, the total cost for management of CKD was 163 USD, 86.4% of which was from direct medical cost . MeanwhiThe mortality rate of CKD in Cameroon ranged between 26.8 and 58.0% during a period of 1 to 10 years of follow up, Table This scoping review systematically summarizes data on the prevalence, associated factors, etiology, comorbidities, treatment and its cost, and mortality of CKD in Cameroon. The prevalence of CKD was high, ranging from about 1 in every 10 people in the general population to about 1 in every 2 persons in high-risk groups. Hypertension, diabetes mellitus and chronic glomerulonephritis were the most common causes of CKD, while the cause was unknown in a significant proportion of patients. Hypertension, diabetes mellitus, obesity, advanced age and female gender were some factors associated with developing CKD in Cameroon. The treatment of CKD involved the management of comorbidities, progression factors, and hemodialysis in those with ESRD. Despite these treatment measures, mortality from CKD remains high with a 1-year mortality rate of more than 25% among hemodialyzed patients. The cost of non-dialysis treatment was high relative to the monthly income of patients with CKD.The prevalence of CKD was reported in both the general population and in high-risk populations  applying various estimators of GFR. The prevalence of CKD in the general population ranged from 10 to 14.2%, which is similar to the overall prevalence of 15.8% in the African adult population . In ruraAbout a third to half of patients with hypertension in Cameroon had CKD , this waAdvanced age and hypertension were common factors associated with CKD in Cameroon and this was similar to other African settings , 53. OveThe most common comorbidities among patients with CKD in our review were hypertension, diabetes mellitus, anemia, obesity, and cardiac diseases. This was similar to the findings of Fraser and colleagues who highlighted hypertension, diabetes mellitus, anemia and ischemic heart disease as common comorbidities associated with CKD . WhetherHepatitis B virus, hepatitis C virus, and HIV were found to be common comorbidities in hemodialysed CKD patients , 41. TheThe growing burden of CKD is paralleled by the need to curtail those who end up in ESRD requiring renal replacement therapy (RRT). Effective and practical therapies for CKD remain a challenge even in developed countries . Little Chronic kidney disease has a high mortality rate among patients with ESRD. Over a quarter of patients starting hemodialysis die within the first year, with about half within the first six months. Chronic kidney disease patients with co-existing hypertension and diabetes mellitus conveyed the poorest prognosis. Late presentation of CKD and affordability were cited as major drivers of high early mortality . SlowingOur review had some key limitations. The prevalence of CKD reported by studies using a single time-point assessment of kidney function or damage are likely to be biased estimates of the true prevalence. Since serum creatinine has a high intraperson variability, a single time point measurement would lead to random misclassification of participants as cases or non-cases of CKD. This error is worse in small studies. Having a large enough sample size with control measurement of serum creatinine levels after three months is important to account for this random error by regression to the mean. The fact that the formulae used to estimate glomerular filtration rate have not been validated in the African population further complicates efforts to estimate the incidence and prevalence of CKD in this population. In addition, limited financial and human resources are major barriers to ascertain the diagnosis of CKD in epidemiological studies, especially in Cameroon. There was a substantial degree of heterogeneity across study participants in the studies included in this review. Studies reporting on the causes of CKD were cross-sectional, which do not provide evidence of temporality. Therefore, it is impossible to know if, for example, hypertension in a given patient is a cause or consequence of CKD. These limitations highlight the need for collaborative efforts to better understand the epidemiological profile of CKD in Cameroon.Chronic kidney disease represents a significant cause of morbidity and mortality in Cameroon. The prevalence of CKD was highest among patients with hypertension, diabetes mellitus, and HIV. The main causes include hypertension, diabetes mellitus, chronic glomerulonephritis, HIV and unknown in some cases. Potential actions to curb the burden of CKD in Cameroon include raising public awareness about the disease, encouraging timely referral from general practitioners to nephrologists, increasing the availability of treatment centers, and encouraging health insurance to cover some of the cost of care.There is limited data on the incidence and prevalence of CKD in the general population. Factors associated with CKD has been generated mostly from cross-sectional studies with possibility of reverse causation. There is a need for population-based cohort studies to assess the incidence and risk factors of CKD in Cameroon. A less costly approach to assess the risk factors of CKD would be to conduct a case-control study using population-based controls. In addition, more research is needed to assess the mortality rate of CKD and its predictors in patients with ESRD. Studies evaluating the economic burden of CKD in Cameroon are warranted. Creation of a national registry for CKD patients may help foster research in CKD in Cameroon and improve on its management and survival rate.