Estimated glomerular filtration rate (eGFR) was recorded preoperatively and at 1 day, 1 month, and 6 months postoperatively.Three hundred thirty-one patients undergoing hand assisted laparoscopic donor nephrectomy (HALDN) were reviewed. MAP2 (range 17.1–39.6) and median age 45 years (range 19–78). MAPd score was 0 for 231 patients (69.8%) and > 0 for 100 patients (30.2%). MAPnd score was 0 for 234 patients (70.7%) and > 0 for 97 patients (29.3%). The median preoperative eGFR was 86.6 ml/min/1.73m2 (range 48.8–138.4). After adjusting for preoperative eGFR, BMI, ASA score, and kidney sidedness, postoperative eGFR was associated with MAP score in the non-donated kidney (p = 0.014) but not in the donated kidney (p = 0.24). Compared to donors with MAPnd = 0, donors with a MAPnd > 0, mean eGFR was − 2.33 ml/min/1.73m2 lower at postoperative day 1 , − 3.02 ml/min/1.73m2 lower at 1 month , and − 2.63 ml/min/1.73m2 lower at 6 months postoperatively .Two hundred females and 131 males were evaluated with median BMI 26.4 kg/mMAP score > 0 in the non-donated kidney is associated with worse renal function in the 6 months following HALDN. Recent studies have evaluated the impact of various preoperative patient-specific and imaging-derived characteristics on postoperative renal function following donor nephrectomy. Examinations of large cohorts of patients suggest that age, male sex, and body mass index (BMI) are predictive of decreased postoperative renal function in patients undergoing donor nephrectomy –4. HowevAdherent perinephric fat (APF) has been associated with surgical complexity and longer operative times in patients undergoing partial nephrectomy . The MayHand-assisted laparoscopic donor nephrectomy (HALDN) was performed as previously described by fellowship-trained transplant surgeons at one institution using a hand-port and two additional trocars , 15. Thed] and non-donated kidneys [MAPnd]), preoperative laboratory values , American Society of Anesthesiologists [ASA] score, sidedness of donor kidney, operative time), and measurement of postoperative renal function  [2 were still considered candidates for donor nephrectomy at our institution based on measured iothalamate or creatinine clearance greater than or equal to the lower 5th percentile when age-adjusted.The data set is similar to that used in our previous manuscript evaluating the relationship between MAP score and operative time in HALDN . Followiquation) . Patientd score was calculated for the patient’s donated kidney and the MAPnd score was calculated for the patient’s non-donated kidney. MAP scores were calculated for every patient utilizing the measurement of posterior renal fat thickness and the measure of severity of perinephric stranding. Perinephric fat thickness was measured at the level of the renal vein for each kidney. Posterior renal fat was measured at this level as a direct line from the level of the renal capsule to the posterior abdominal wall [MAP score was calculated as described in our previous manuscripts evaluating MAP score and its relationship to adherent perinephric fat, renal cell carcinoma progression free survival, and HALDN , 13, 17.nal wall . This vaPerinephric stranding was identified as soft tissue attenuation in the fat surrounding the kidney. This was graded according to severity if present . The MAP score was calculated in each scenario as the sum of the values obtained for posterior renal fat and perinephric stranding to obtain a score 0–5 .d and MAPnd scores were categorized as either 0 or > 0 given the low number of patients with MAP scores of 1–5. All analyses were done separately for MAPd and MAPnd. For cross-sectional associations of MAP score with preoperative eGFR we used linear regression. We used mixed effects regression models with preoperative eGFR as a covariate to evaluate associations of MAP score with postoperative eGFR. Mixed effects models additionally included random patient effects for intercepts and slopes, two indicator variables to represent three postoperative time points, three indicator variables to represent MAP score (> 0 vs. 0) at each postoperative time point. All regression-based models were adjusted for body mass index, ASA score, and sidedness of the donated kidney. Supplementary Table p-values corresponding to the difference in means and difference in slopes were two-sided and based on the t-distribution. P-values less than 0.05 were considered statistically significant. Fitted values obtained from regression models refer to a hypothetical “average” donor where baseline covariates are equal to the mean value of all patients included in the model. SAS statistical software  was used for all statistical analyses.Box plots were constructed to show the distribution of preoperative eGFR according to MAP score. For evaluating associations of MAP score with renal function, MAP2 (range 17.1 to 39.6 kg/m2). A large majority of the patients underwent left-sided donor nephrectomy (89.4%). Two hundred patients were female (60.4%). Of note, patient comorbidities were minimal given the rigorous screening process at our institution prior to consideration of donor nephrectomy. Two hundred and thirty one patients had a MAPd score of 0 (69.8%) and 100 patients had a MAPd score of 1–5 (30.2%). Two hundred and thirty four patients had a MAPnd of 0 (70.7%) and 97 patients had MAPnd of 1–5 (29.3%). Table d and MAPnd scores of the 331 renal donors.A total of 331 patients who underwent HALDN were included in the analysis. Median age was 45 years (range 19 to 78 years) and BMI was 26.4 kg/m2 . The distribution of preoperative eGFR is presented in Fig. d or MAPnd). Associations of MAP score with preoperative and postoperative renal function with adjustment for preoperative covariates are shown in Table d > 0 had a lower mean eGFR by 5.87 ml/min/1.73m2 lower (95% CI 2.02 to 9.71 ml/min/1.73m2) compared to kidney donors with a MAPd = 0 in the donated kidney. When comparing eGFR according to MAPnd score in the non-donated kidney, mean eGFR was 4.59 ml/min/1.73m2 lower (95% CI 0.63 to 8.54 ml/min/1.73m2) in those with a MAPnd > 0 compared to those with MAPnd = 0.Among the entire cohort, the preoperative eGFR ranged from 48.8 to 138.4 ml/min/1.73mn = 10) with a high grade MAPnd score (3 to 5). This cohort had a median preoperative eGFR of 75.3 ml/min/1.73m2  with a median preoperative creatinine of 1.0 mg/dL . At 1 month postoperatively, the median eGFR was 41.6 ml/min/1.73m2  with a creatinine of 1.7 mg/dL . At 6 months postoperatively, the median eGFR was 42.9 ml/min/1.73m2  with a median creatinine of 1.6 mg/dL (range 1.3–1.7 mg/dL). No patient from this high risk group had an eGFR greater than 60 ml/min/1.73m2 at 1 month or 6 months postoperatively.We also investigated the small cohort of patients  but not in the donated kidney . Compared to those with a MAPnd = 0, donors with a MAPnd > 0 had evidence of significantly lower eGFR at POD1 , 1 month follow-up , and 6 months follow-up . We did not find evidence of an association of MAPnd with the change in eGFR from POD1 (slopes) to either 1 month  or 6 month follow-up . Figure We used mixed effects linear regression models to evaluate the impact of MAP score on postoperative eGFR while adjusting for preoperative eGFR and baseline covariates as displayed in Table 2.The MDRD 2006 formula, by definition, inherently demonstrates a correlation between age, sex, and race with eGFR . Six monIn preoperative examination of candidates for donor nephrectomy, assessment of patient-specific factors is crucial in preparation for surgery . Part ofp = 0.014, comparing the full model to the model without MAP score, Table The MAP score serves as a patient-specific and donor site-specific score that is widely applicable to the kidney donor, given that most renal donors have pre-operative cross-sectional imaging (CT scan or MRI). It has also been previously discovered to be an accurate imaged-based predictor of intraoperative APF and postoperative outcomes in patients undergoing laparoscopic and open partial nephrectomy , 12, 18.Additionally, age and male sex have previously been correlated with decreased postoperative donor renal function , 23. By nd scores from 1 to 5 were significantly associated with worse post-donation renal function than patients with MAPnd scores of 0 (p = 0.014). After donor nephrectomy, recovery of renal function is dependent upon adaptive hypertrophy and hyperfiltration of the remaining kidney. This may explain why high MAPnd scores proved to be significantly associated with diminished renal function following HALDN. The MAP score enables evaluation of the thickness and quality of the fat surrounding the non-donated kidney. An evaluation by Yoon et al. demonstrated that an increased area of visceral fat is associated with decreased eGFR and renal function [nd score quantifies the posterior perinephric fat, a quantifiable measure of visceral fat, that may be more specific in predicting remaining renal function in kidney donors compared to BMI. We believe the MAP score may be utilized as an imaged-based adjunct to aid in the evaluation of potential donor renal dysfunction; however larger studies are needed for confirmation.Our study findings show that patients with MAPfunction . The used of 4 and MAPnd of 3. His preoperative eGFR was 76.7 ml/min/1.73m2 with a creatinine of 1 mg/dL. Postoperatively, his eGFR dropped to 41.6 ml/min/1.73m2 at 1 month, 41.5 ml/min/1.73m2 at 6 months, and 32.5 ml/min/1.73m2 at 12 months. All postoperative creatinine measurements were greater than or equal to 1.7. Due to his age, this patient will likely be living with chronic renal insufficiency for many years.We believe the results from this study may contribute to how patients are evaluated for kidney donation in the future. The information may also contribute to patient counseling. For example, a healthy 58-year-old white male included in this study had a MAPnd score (3 to 5) (n = 12), every patient had a preoperative eGFR greater than 60 ml/min. Table 2). However, every patient with a high MAP score had a eGFR less than 60 ml/min postoperatively at 1 month or 6 months. Data available from 8 patients showed no improvement at 12 months postoperatively; no patients had an eGFR greater than 60 ml/min and none improved to within 10% of their preoperative eGFR baseline.When evaluating patients who presented with a high grade MAP 5) n = 1, every pOne limitation of our study is the low number of patients with high MAP scores. This is expected given our otherwise healthy population of kidney donors who are screened for potential diseases or malignancies that could contribute to a higher MAP score. The low number of patients with high MAP scores in this cohort precludes us from evaluating the impact of high MAP scores on postoperative renal function. However, the screening process that limits patients with a high MAP score also removes the potential confounding contribution of additional disease processes such as diabetes and hypertension on overall renal function. We did not have statistics within our dataset regarding smoking status, percentage of patients with diabetes, and other comorbidities that can affect long term renal function. This serves as a limitation to our study. Another limitation of our study is the limited number of females with a MAP score > 0. Previous studies have shown that men tend to have a greater amount of perirenal fat compared to women . In a su2.The MAP scoring system can be universally applied to preoperative imaging in the evaluation of patients undergoing HALDN. Our study suggests that MAP scores greater than 0 in the non-donated kidney aid in estimating postoperative renal function. It is important to note that none of the 10 patients with a MAP score > 2 recovered baseline renal function or had post-donation eGFR > 60 ml/min/1.73mAdditional file 1: Supplementary Figure 1. Estimated glomerular filtration rate (eGFR) after hand assisted laparoscopic donor nephrectomy according to patient sex and Mayo Adhesive Probability (MAP) score in the donated kidney and non-donated kidney. Fitted values of eGFR, measured in units of ml/min/1.73m2, were obtained from mixed effects regression models separately for males and females. These fitted values refer to a hypothetical average patient where covariates  are set equal to their mean values, separately for males and females). Vertical bars represent the 95% confidence intervals.Additional file 2: Supplementary Table 1. Exploration of the impact of preoperative characteristics on the association of Mayo Adhesive Probability score with postoperative renal function.


Additionally, 18 patients with chronic kidney disease (CKD) who received renal transplants were enrolled to examine their graft fibrosis and lipid contents via transient elastography. Low-density lipoprotein levels in patients with CKD strongly correlated with lipid contents and fibrosis in grafted kidneys (p < 0.05). Thus, NF may initiate lipogenesis through the SREBP-1/2/AMPK pathway and lipid uptake by CD36 upregulation and aggravate renal fibrosis in vivo. Higher low-density lipoprotein levels may correlate with renal fibrosis and lipid accumulation in grafted kidneys of patients with CKD.Dysregulation of fatty acid oxidation and accumulation of fatty acids can cause kidney injury. Nifedipine modulates lipogenesis-related transcriptional factor SREBP-1/2 in proximal tubular cells by inhibiting the Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) pathway in vitro. However, the mechanisms by which nifedipine (NF) modulates lipotoxicity in vivo are unclear. Here, we examined the effect of NF in a doxorubicin (DR)-induced kidney injury rat model. Twenty-four Sprague–Dawley rats were divided into control, DR, DR+NF, and high-fat diet (HFD) groups. The DR, DR+NF, and HFD groups showed hypertension and proteinuria. Western blotting and immunohistochemical analysis showed that NF significantly induced TNF-α, CD36, SREBP-1/2, and acetyl-CoA carboxylase expression and renal fibrosis, and reduced fatty acid synthase and AMPK compared to other groups ( Lipid accumulation in kidney tissue ,2 causesCalcium channel blockers, such as nifedipine (NF), can ameliorate obesity-induced revascularization impairment by suppressing oxidative stress  and antip < 0.05), with the DR+NF group showing the highest levels (p < 0.05). As shown in p < 0.05) and the DR+NF group showed significantly decreased systolic blood pressure compared to the DR group because of NF’s effect. Thus, renal injury was successfully established in the DR and HFD groups, as demonstrated by complications including high proteinuria and blood pressure, observed starting at week 3.The Sprague–Dawley rats used in this study were divided into four groups: control (fed standard chow), doxorubicin (DR) (DR-induced kidney injury model fed standard chow), DR+NF (DR-induced kidney injury model fed standard chow plus NF), and high-fat diet (HFD) groups . From weeks 1 to 7, the body weight (BW) of the HFD group increased rapidly compared to that of the control, DR, and DR+NF groups. The BW of the DR and DR+NF groups increased slowly compared to that in the control group, and the BW change was similar between the DR+NF and DR groups. Doxorubicin comparably suppressed the BW in the DR and DR+N groups A. Urinart levels B. As shop < 0.05 and < 0.01, respectively) at week 7; in addition, the DR+NF group showed a significantly higher TNF-α level than the DR group (p < 0.01). In contrast, the HFD group showed a significantly lower serum TNF-α concentration  compared to the control. The DR and HFD groups also showed a significant increase in KIM-1 expression in the kidney compared to that in the control group, as indicated by western blot analysis  (p < 0.1 and p < 0.01) (As shown in ctively) B. Especi < 0.01) B,C. In sAs shown in p < 0.01). Cubilin expression was lower in the DR, DR+NF, and HFD groups than in the control group (p < 0.01). Additionally, NF did not cause a further reduction in the cubilin level /ACC and phosphorylated ACL (p-ACL)/ACL expression was higher in the DR+NF group than in the control group  was significantly positively correlated with kidney fibrosis in graft kidneys  or non-dihydropyridines  . All CCBPatients with CKD had a higher probability of developing hypercholesterolemia-related kidney damage, including decreased expression of vascular endothelial growth factor and graft dysfunction , as wellThere were some limitations to this study. First, we did not include an NF-only animal group to observe its lipogenesis effect. This was because normotensive SD rats may suffer from unexpected acute kidney injury following NF use. Second, the study duration was only 5 weeks, following the induction of kidney injury by doxorubicin. A longer follow-up period should be evaluated to determine the long-term effects of NF on creatinine changes in CKD animals.In conclusion, lipotoxicity may be a consequence of AKI, and repeated AKI may induce CKD. Additional studies should focus on lipogenesis and lipotoxicity in the kidney and on pioneer treatments for preserving renal function or detecting AKI in advance to prevent CKD.®, Bayer Taiwan Co., Taipei, Taiwan) corresponding to 0.5 mg/kg/day by referring to the human dose for nifedipine .Twenty-four 4-week-old male Sprague–Dawley rats, obtained from the National Laboratory Animal Center, Taipei, Taiwan, were used in this study. The animals, weighing 200–250 g, were housed in plastic cages at 25 ± 1 °C with a 12-h/12-h light/dark cycle and ad-libitum access to food and water. The rats were randomly divided into the following four groups, with six rats per group: control group, rats fed with standard chow; doxorubicin (DR) group, rats in which the DR-induced kidney injury model was established, rats fed with standard chow; DR+NF group, with the establishment of the DR-induced kidney injury model, fed with standard chow plus NF from week 3 onwards; HFD group, rats were fed with a diet containing 60% of its calories in fat. For comparison of the lipidemic status in the kidneys, an HFD was fed to prepare the obese animal model as a positive control in our design, which also presented kidney injury , lysosomg for 20 min. The serum was collected and assayed immediately, or aliquots were made and stored at ≤−20 °C. The TNF-α concentration was measured using a rat immunoassay . Kidneys, hearts, adipose tissue and livers were rapidly separated, immediately frozen in liquid nitrogen, and stored at −80 °C for later use. All animal studies were approved by the Institution of Animal Care and Use Committee of Taipei Medical University .To measure serum TNF-α levels, blood samples were allowed to clot for 2 h at 36 degrees Celsius before centrifugation at 1000× ™  and VetLab UA (IDEXX). Blood samples were collected once every 3 weeks  and centrifuged at 1500× g for 10 min to obtain the serum. The collected serum was sent for biochemical analyses to determine blood nitrogen urea , creatinine , total cholesterol , and triglyceride  levels. Each rat was housed in a metabolic cage with ad-libitum access to food and water for one day to collect urine for determining its protein content after centrifugation at 1000× g for 1 min.BW at the beginning (W0) of the study and that gained at the end of each week (W1–7) were measured for all animals. Food intake was recorded every 2 days. At W7, blood pressure was measured using the IITC Mouse and Rat Tail Cuff BP System  . The serum and urine samples were analyzed using a VetStatThe rats were anesthetized using 5% isoflurane. The diaphragm was then cut to induce pneumothorax and to permit harvesting of all organs , which were then soaked in 10% formalin fixative for routine histology. Paraffin embedding was performed for further tissue slicing for histology examination. Kidney, heart, adipose tissue, and liver were stored immediately at −80 °C. H & E staining was performed by special technicians from the National Laboratory Animal Center.All rats received an NC3Rs strategic award for humane techniques used for killing lab rodents. In addition to the experimental work, the dissemination of the results of this research forms an important part of our program and, to that end, is supported by the NC3Rs in the Laboratory Animal Center at Taipei Medical University.The paraffin-embedded sections were deparaffinized before staining. Endogenous peroxidase activity was blocked by 3% hydrogen peroxide for 10 min before treatment with antibodies of anti-CD36 , anti-KIM-1  and anti-SREBP . Thereafter, horseradish peroxidase recombinant fusion protein anti-rabbit IgG (1:500) was applied. Finally, DAB chromogen  was used and images were acquired using a fluorescent microscope .The paraffin-embedded tissue section was washed with deionized water for 1–2 min and then treated with Nile red staining dye , followed by examination under fluorescent microscopy.The tissue was harvested from the kidney cortex of the sacrificed animals. Protein was extracted for western blotting from the cortex. The primary antibodies used in this study were Fatty Acid and Lipid Metabolism Antibody Sampler Kit (#8335), anti-TNFR1 (#13377), anti-AMPK (#5832), and anti-p-AMPK (#2535), from Cell Signaling Technology ; anti-SREBP-1 (sc-13551) and anti-SREBP-2 (sc-13552), from Santa Cruz Biotechnology ; anti-CD36 (NB400-144ss), anti-β actin (NB600-501), and anti-α tubulin (NB100-690), from Novus Biologicals ; anti-PPARα (GTX01098), anti-HDAC1 (GTX100513), and anti-histone H3 (GTX122148), from GeneTex ; and anti-KIM 1 . The membrane was then subjected to the secondary antibody, either anti-mouse IgG or anti-rabbit IgG , which was dissolved in 5% skim milk in TBST for 1 h. Next, the membrane was incubated for 1–2 min in enhanced chemiluminescence mixture  for visualization. The western blotting assay was repeated at least three times.® examination was performed on the kidney. We also performed TE and controlled attenuation parameter (CAP). Biochemical analyses were carried out to determine blood nitrogen urea, creatinine, LDL, and protein levels in the urine.The study recruited patients with CKD who underwent kidney transplantation from the out-patient department at Taipei Medical University Hospital. This study involving human subjects was reviewed by the institutional review board committee of Taipei Medical University Hospital. (No. 201707021). The exclusion criteria were age >90 years or patients with discomfort who could not tolerate sonography examinations. Eighteen patients were enrolled and provided signed informed consent. Of the enrolled patients, the average age was 59.4 years, average blood urea nitrogen was 21.5 mg/dL, average creatinine was 1.27 mg/dL, and average daily urine protein was 335 mg per day. Seventy-two percent had hypertension under anti-hypertensive agents, and no patients were currently being administered nifedipine. Their demographic biochemistries were recorded and FibroScan® device pulse–echo ultrasound acquisition was used to follow the propagation of the shear wave and to measure its velocity, which is directly related to tissue fibrosis . The detailed procedure has been described previously [TE was performed on patients at baseline. The FibroScaneviously . TE witheviously . A pioneeviously . All meap-values ≤ 0.05 were considered statistically significant. The meaning of the different asterisks is described in the relevant figure legends. We used Spearman’s test to find the associations between the non-pyramid distribution of continuous variables such as LDL, elasticity, CAP, and serum creatinine. Analysis of variance is used to test variation among and between groups for more than 3 variables in a group.Analysis of variance and post-hoc tests using SPSS 14.0  were used to statistically evaluate the data, and results are presented as the mean ± standard deviation. Analysis of variance was chosen to test the difference between four study groups with post-hoc analysis. Two-tailed In this study, we demonstrated that nifedipine may induce renal fibrosis and lipogenesis in a CKD animal model with a higher expression of CD36/SREBP-1/2 signals. Interestingly, hypercholesterolemia, as represented by high LDL levels in patients with kidney transplantation and CKD, was significantly associated with kidney fibrosis and lipid accumulation. Therefore, NF use and lipid content should be closely monitored in patients with CKD.


Background: Phenylephrine and atropine can cause serious adverse effects when applied in combination. We investigated the effect of phenylephrine eye drops combined with intravenous atropine on the cardiovascular system in patients under general anesthesia undergoing intraocular surgery.Methods: The effects of the drugs were observed through clinical study. Thirteen patients undergoing intraocular surgery under general anesthesia were observed in this study; all were injected intravenously with atropine due to the oculocardiac reflex during surgery. To study the combination of drugs, an in vivo study was performed on rats. Seventy-two standard deviation rats that received phenylephrine eye drops and intravenous atropine treatment under general anesthesia were assessed, of which 18 treated with these drugs simultaneously were administered normal saline, neostigmine or esmolol. Blood pressure and heart rate were recorded and analyzed.Findings: The age of the patients ranged from seven to 14 years old with an average age of 10.7 years old, and 11 patients were male. In patients, 5% phenylephrine eye drops combined with intravenous atropine led to a significant heart rate increase and the increase lasted 20 min. The significant increase in diastolic blood pressure and systolic blood pressure lasted for 15 and 25 min, respectively. From five to 25 min after intravenous atropine treatment, the systolic blood pressure and diastolic blood pressure were both more than 20% higher than that at baseline. In rats, the changes in blood pressure and heart rate were independent of the phenylephrine and atropine administration sequence but were related to the administration time interval. The neostigmine group showed a significant decrease in blood pressure after the increase from the administration of phenylephrine and atropine.Interpretation: Phenylephrine eye drops combined with intravenous atropine have obvious cardiovascular effects that can be reversed by neostigmine. This drug combination should be used carefully for ophthalmic surgery, especially in patients with cardio-cerebrovascular diseases. Agonism of alpha 1-adrenoceptors in the iris dilator leads to mydriasis. Phenylephrine is a selective alpha 1-adrenergic agonist. It can produce prompt and transient mydriasis without increasing the intraocular pressure or affecting the accommodative ability of the eye (cycloplegia) . PhenyleOphthalmic surgery operations that stimulate eyeball or ocular tissue can induce the oculocardiac reflex (OCR) directly, and OCR incidence is high during surgery . SeriousPhenylephrine eye drops and intravenous atropine treatment are often used together in ophthalmic surgeries while patients are under general anesthesia in clinical practice. Although adverse cardiovascular reactions following phenylephrine instillation or intravenous atropine treatment have been reported, the adverse effects and interaction mechanisms of the combination of the two drugs are unclear. Notably, we first noticed a phenomenon in clinical practice where concurrent application of phenylephrine eye drops and intravenous atropine during eye surgery can cause clinically significant increases in heart rate and blood pressure, which could even be life-threatening without intervention. This phenomenon prompted us to think and consult the relevant literature. Keys and Violante reported that subcutaneously injected atropine followed by subcutaneously injected phenylephrine caused a higher blood pressure and heart rate than phenylephrine alone due to atropine enhancing the pressor effect of phenylephrine . Levine This retrospective analysis included 13 patients who received 5% phenylephrine eye drops combined with intravenous atropine administration during intraocular surgery while under general anesthesia at the Zhongshan Ophthalmic Center from 2016 to 2019. The studies were reviewed and approved by Medical Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University. The age of the patients ranged from seven to 14 years old with an average age of 10.7 years old, and 11 patients were male. The induction of general anesthesia was performed using midazolam (0.03 mg/kg), fentanyl (1 μg/kg), atropine (5 μg/kg), propofol (2–3 mg/kg), and vecuronium (0.6 mg/kg). A tracheal tube was inserted approximately 5 min after induction, and propofol (150–200 μg/kg/minute) and remifentanil (0.2 μg/kg/minute) were used to maintain anesthesia. Eye surgery began approximately 10 min after the instillation of 10–20 mg phenylephrine eye drops. The traction of extraocular muscles or compression to the eyeball can cause a temporary decrease in heart rate, known as OCR. If the heart rate  decreases by more than 10% from the base heart rate, surgical procedures should be stopped, and the traction of the extraocular muscles or compression of the eyeball should be relaxed . If the In our study, the heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) of all patients were recorded at different points, namely, before anesthesia, immediately after anesthesia induction, and 5, 10, 15, 20, 25, and 30 min after intravenous atropine treatment.A 0.9% sodium chloride injection (lot number: C180705D) was purchased from Hubei Kelun Pharmaceutical Co., Ltd . Pentobarbital sodium  was purchased from Tocris Cookson Ltd . The 5% phenylephrine eye drops (lot number: 180605) were purchased from Zhongshan Ophthalmic Center, Sun Yat-sen University . Atropine sulfate injection (lot number: 1802024) was purchased from Henan Runhong Pharmaceutical Co., Ltd. . Tetracaine hydrochloride eye drops (lot number: 180524) were purchased from Zhongshan Ophthalmic Center, Sun Yat-sen University . Esselor hydrochloride injection (lot number: 7B0062005) was purchased from Qilu Pharmaceutical Co. Ltd . Neostigmine methylsulfate injection (lot number: 1710605) was purchased from Shanghai Xinyi Jinzhu Pharmaceutical Co., Ltd .Seventy-two wild-type Sprague-Dawley (SD) rats with body weights ranging from 180 to 250 g were purchased from Hunan SJA Laboratory Animal Co., Ltd . The use of experimental animals in this study complied with the animal ethics principles, and the protocol was approved by the laboratory animal ethics committee (No. 00201878). Based on previous research and animal welfare, we tried to reduce the number of animals we used as long as we could achieve our experimental objectives. To obtain accurate analysis and minimize the number of experimental animals, a proper number of experimental animals was used. The experimental rats were randomly divided into 12 groups using a random number table, with six rats in each group. Specifically, group A received 5% phenylephrine eye drops only; group B received intravenous atropine administration only; group C received phenylephrine and atropine simultaneously; groups D, E, and F received 5% phenylephrine eye drops first and then received intravenous atropine treatment five, ten, and 15 min later, respectively,; groups G, H, and I received intravenous atropine administration first followed by 5% phenylephrine eye drops 5, 10, and 15 min later, respectively,; group J received phenylephrine and atropine simultaneously followed by intravenous saline treatment 1 min later; and groups K and L received phenylephrine and atropine simultaneously followed by 0.15 mg/kg neostigmine and 1.0 mg/kg esmolol treatment 1 min later, respectively.The rats were anesthetized with an injection of 1% pentobarbital sodium (50 mg/kg). Before the procedure, all catheters were heparinized with 1000 IU/ml heparin to empty the air in the device. The left common carotid artery was isolated while the rats were in the supine position. Arterial cannulas were placed in the common carotid artery of rats and connected to a physiological monitor. Parameters were measured in this study using the BL-420 F biological signal acquisition and analysis system (Chengdu Taimeng Science and Technology Co. Ltd.). After surface anesthesia of the right eye with tetracaine hydrochloride eye drops, a T-shaped incision of conjunctiva approximately 2 mm away from the corneal rim was created by creating an incision approximately 0.3 cm along the corneal rim and then cutting approximately 0.3 cm away from the cornea. Finally, one 5% phenylephrine eye drop was added to the incision. In addition, 0.06 mg/kg atropine, 0.15 mg/kg neostigmine and 1.0 mg/kg esmolol were administered via tail vein injection. For simultaneous administration of phenylephrine and atropine, the right eye was anesthetized and operated first, followed by 0.06 mg/kg intravenous atropine treatment and the administration of one 5% phenylephrine eye drop.The operations were performed according to the corresponding time intervals based on different groups. The blood pressure and heart rate were recorded 5 min before any treatment until 40 min after treatment.p value was considered statistically significant when it was less than 0.05.Data are all shown as the mean ± standard deviation (SD). The statistical methods used in this study were an analysis of variance (ANOVA) for the comparison of means among groups and Student's t test for the comparison of means between two groups. SPSS 26.0  was used to analyze the data, and all experiments were blinded. A p = 0.0008). The peak heart rate occurred 15 min after intravenous atropine treatment  and slowly decreased until 30 min after treatment, but the heart rate was still significantly higher than that at baseline   = −60.39 to −16.22 bpm,  0.0311) . Topical 0.0311) .p = 0.0014). The highest SBP occurred 10 min after intravenous atropine treatment  and decreased slowly through 30 min after the treatment. SBP was still significantly higher than that before anesthesia . SBP increased from 103.15 ± 11.38 mmHg before anesthesia to 162.15 ± 26.42 mmHg 10 min after intravenous atropine treatment. (p = 0.0004). The highest DBP appeared 10 min after administration of the medication , decreased gradually to the baseline level at 25 min with no difference  and remained stable at 30 min after administration of medication. Intravenous atropine treatment caused DBP to increase to the highest level, reaching 109.08 ± 20.41 mmHg from 60.46 ± 7.61 mmHg before anesthesia.  = 8.33, p = 0.4019) , or heart rate among the groups  . The blo 0.4019) . After a 0.4019) . After i 0.4019) . However 0.4019) . The inc 0.4019) . With th 0.4019) , Figure2 0.4019) . The resp = 0.8065; ANOVA, F = 0.57, p = 0.5773; ANOVA, F = 0.4008, p = 0.6767; ANOVA, F = 3.356, p = 0.0624) . The mean heart rate decreased in the neostigmine group     . Comparene group . However 0.2174) . Compare 0.9038) . Compare 0.4110) . The hea 0.4110) .Based on clinical observations and animal experiments, we found hazardous effects of the combination of topical phenylephrine and intravenous atropine treatment on blood pressure and heart rate. In pediatric patients, five to 25 min after intravenous atropine treatment SBP and DBP were more than 20% higher than the baseline blood pressure level. Acute elevated blood pressure  during the intraoperative period can be considered a hypertension emergency . A hyperHypertensive emergencies usually require the intravenous administration of antihypertensive drugs . EsmololHowever, our clinical study had several limitations. A small sample size and the single-centred retrospective study are the major limitations of our study. In addition, this study only focused on pediatric patients and had a limited number of patients (more boys), resulting in considerably biased clinical features. A further retrospective study is needed in multiple centers with a large sample to observe the adverse cardiovascular effects of phenylephrine eye drops combined with intravenous atropine in patients.1.The combined use of phenylephrine and atropine eye drops should be avoided.2.Intravenous atropine can be used only for blunting OCR after a certain time interval, usually more than 10 min, after using phenylephrine eye drops.3.The patient can be rescued with neostigmine if the concurrent use of intravenous atropine and phenylephrine eye drops results in clinically significant high blood pressure and heart rate.We suggest the following recommendations for the clinical use of atropine and phenylephrine in pediatric patients:1.Patients must be asked about their medical history and drug allergy history. Patients with cardiovascular disease should be treated with caution.2.The nasolacrimal passage should be compressed for 60 s immediately following topical administration of compound tropicamide eye drops to minimize drainage.3.Patients should be closely observed for systemic adverse reactions.To avoid serious adverse reactions, the following points should be noted for the clinical use of compound tropicamide eye drops:The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by Medical Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements. The animal study was reviewed and approved by The laboratory animal ethics committee of Drug Evaluation Center, Guangzhou Boji Pharmaceutical Biotechnology Co., Ltd (No. 00201878).WG conceived and designed the study and provided the clinical data. YG, YW, and HZ performed the animal experiments. YG, QL, SZ and JT performed the analyses. YW, JP, and XY conducted the analyses. QL and YD wrote the paper. WG and WC reviewed and edited the manuscript. All authors read and approved the manuscript.This work was supported by the Science and Technology Program of Guangzhou of Wei Chi (No. 201804010415).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


There is evidence that mild cognitive impairment (MCI) or Alzheimer's disease (AD) is accompanied by alterations in the retina. The current study was performed to investigate structural and functional changes in patients with systemic neurodegenerative disease.A total of 47 patients with either MCI or AD and 43 healthy age‐ and sex‐matched control subjects were included. Inclusion criteria for MCI were abnormal memory function and a mini‐mental state examination (MMSE) score >26 points, for patients with AD a diagnosis of probable AD of mild to moderate degree and an MMSE score in the range of 20–26. Retinal blood flow was measured using a Doppler optical coherence tomography (OCT) system. Retinal vessel diameter, oxygen saturation and flicker‐induced vasodilatation were measured using a Vessel Analyzer. Retinal nerve fibre layer thickness (RNFLT) was assessed using an OCT system.Global RNFLT was lower in patients compared to healthy controls . The same was found in regards to retinal arterial blood flow, which was 9.3 ± 2.4 and 12.3 ± 3.2 μl/min in the patient and control groups, respectively (p < 0.001). Mean retinal arterial diameter was reduced in patients . Arteriovenous difference in oxygen saturation was lower in patients . No difference in the flicker response was observed.In patients with MCI and AD, arteriovenous difference in oxygen saturation, retinal blood flow and arterial vessel diameter was reduced. No difference was found in flicker response between groups. This indicates alterations in retinal oxygen metabolism in patients with neurodegenerative disease. Alzheimer’s disease (AD) is a major cause of dementia and a considerable healthcare problem worldwide  angiography studies show alterations in the retinal microcirculation of subjects with preclinical and manifest AD . Healthy subjects were recruited at the Department of Clinical Pharmacology. Subjects were only included after having provided written informed consent following a detailed explanation of the study procedures. Before the study, subjects passed a screening examination that included physical examination, mini‐mental state examination (MMSE), assessment of visual acuity, slit lamp biomicroscopy, funduscopy and measurement of intraocular pressure (IOP) using Goldmann applanation tonometry.Inclusion criteria for patients with AD were confirmed diagnosis of AD of mild to moderate degree based on the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria and MMSE score between 20 and 26 points. Mild cognitive impairment (MCI) was defined as memory complaint, corroborated by an informant, abnormal memory function, documented by delayed recall of one paragraph from the Logical Memory II subtest of the Wechsler Memory Scale‐Revised, MMSE score >26 points and being not sufficiently impaired to meet the NINCDS/ADRDA criteria, as judged by an experienced AD research clinician. The Hachinski Ischemia Scale was used to distinguish AD and MCI from multi‐infarct dementia.Ophthalmic inclusion criteria were visual acuity of 20/40 or better, IOP < 21 mmHg and normal findings from slit lamp biomicroscopy and funduscopy. Patients were only included if no abnormalities in the ophthalmic examination were found. Exclusion criteria were ametropia ≥6 dioptres, untreated arterial hypertension, history or family history of epilepsy, and any clinically relevant illness as judged by the investigators. Participants had to abstain from beverages containing alcohol or xanthine derivates in the 12 hr before the study day.The study eye was dilated with a drop of tropicamide . This was followed by a resting period of at least 20 min to ensure full development of mydriasis and stabilization of blood pressure. Thereafter, retinal blood flow was measured using the custom‐built dual‐beam bidirectional Doppler Fourier‐Domain OCT. Fundus photographs were taken using a Retinal Vessel Analyzer  in order to quantify the retinal oxygen saturation. Blood pressure and pulse rate were measured non‐invasively.Intraocular pressure was measured using a Goldman applanation tonometer. Systolic, diastolic and mean arterial blood pressures  were measured on the upper arm by an automated oscillometric device . The same device was used to record pulse rate. Ocular perfusion pressure (OPP) in the sitting position was calculated as OPP = 2/3*MAP − IOP . A circular scan with a 3.46 mm‐diameter centred on the optic disc was performed and RNFL thickness values were provided for four quadrants, six sectors and an overall average over the entire 360 degrees. These average RNFL thickness measurements derived from SPECTRALIS RNFL analysis report were used for the present study. In addition, central retinal thickness was assessed using the standard scanning protocol for the macula .Δ∝to overcome the problem of angle‐ambiguity. Two spectrometers collect the spectral information of the two orthogonally polarized laser beams and two OCT images are formed under two different angles of incidence. The phase changes in these channels are different according to the different Doppler angles. The central wavelength of the laser is atλ0 = 838.8 nm with a spectral bandwidth of 54.0 nm. This results in an axial resolution in tissue of approximately 6 µm. The lateral resolution of the system is approximately 20 µm.For the measurement of retinal blood flow, we used a custom‐built dual‐beam Doppler Fourier‐Domain OCT system coupled to a fundus camera. This system has been described in detail previously  of the blood in the vessel can be calculated asΔαis small. In this equationΔΦ=Φ1-Φ2, λ is the central wavelength of the light source, β is the angle between the plane spanned byκ1→andκ2→and the velocity vector, and n is the group refractive index of blood.In this equation, In the present study, we have used a slightly different novel approach to calculate the absolute blood velocity. The phase shifts in the two channels can be written as follows . As such, V was used to calculate blood flow in retinal arteries and veins. The advantage of this novel was to calculate absolute blood velocity is that it is less sensitive to poor signal quality in one of the channels. In addition, it introduces on objective criterion for quality control.In this equation, the angle QA=VA·dA2·π4andQV=VV·dV2·π4 needs to be calculated. For this, we followed an approach described in Fondi et al.  that useIn all study participants, measurements were obtained from one major temporal retinal artery and vein approximately one disc diameter from the ONH.For the assessment of flicker‐induced vasodilatation, a commercially available Dynamic Vessel Analyzer  was used. This device comprises a fundus camera, a video camera, a real‐time monitor and a personal computer with an analysing software for the determination of retinal arterial and venous diameters .All outcome parameters were checked for normality using the Shapiro–Wilk test. Un‐paired t‐tests were used to compare groups. Flicker‐induced vasodilatation was calculated as per cent change over baseline. In addition, correlation analyses were performed for global RNFL thickness as a structural parameter with vascular functional parameters . Data are presented as means ± SD. A p‐value < 0.05 was considered the level of significance. Statistical analysis was carried out using CSS Statistica for Windowsn = 23) or MCI (n = 24) and 43 were healthy control subjects. All subjects were of Caucasian ancestry. A demographic overview is given in Table A total of 90 subjects were included in the present study, of which 47 were patients with either a diagnosis of AD , while no difference in venous diameter was found between groups .While retinal arterial oxygen saturation was similar between groups , venous oxygen saturation was significantly higher in patients compared to controls . This is reflected in the arteriovenous difference in oxygen saturation, which was found to be significantly lower in patients with neurodegenerative disease compared to healthy controls . In retinal veins, an increase of +3.5 ± 2.1% and of +3.7 ± 2.5% was seen in patients and controls, respectively (p = 0.63 between groups).Correlation analysis between global RNFL thickness and the vascular functional parameters such as flicker response, retinal blood flow and A‐V difference, revealed no statistically significant correlations .Click here for additional data file.


Background: Malnutrition is associated with poor outcomes in patients with cancer, heart failure and chronic kidney disease. This study aimed to investigate the predictive value of the Controlling Nutritional Status (CONUT) score in coronary artery disease (CAD) patients. Methods: We recruited a cohort of 3118 patients with CAD undergoing percutaneous coronary intervention (PCI) from 2005 to 2015. Nutritional status was evaluated using the CONUT score, with higher scores reflecting worse nutritional status. Results: After adjustment for comorbidities and medication, an increased CONUT score was independently associated with a higher risk of acute myocardial infarction (AMI) , cardiovascular (CV) death , congestive heart failure (CHF) , a major adverse cardiovascular event (MACE) , and total CV events . The subgroup analyses demonstrated that the association of the CONUT score existed independently of other established cardiovascular risk factors. In addition, CONUT significantly improved risk stratification for myocardial infarction (MI), cardiac death, CHF, MACEs and total CV events compared to conventional risk factors in CAD patients by the significant increase in the C-index (p < 0.05) and reclassification risk categories in cardiac death and MACEs. Conclusions: The CONUT score improved the risk prediction of adverse events compared to traditional risk factors in CAD patients after percutaneous coronary intervention (PCI). Cardiovascular disease remains one of the leading causes of death worldwide despite improvements in evidence-based management ,2. CardiMalnutrition is known to be associated with worse clinical outcomes in patients with heart failure, ischemic stroke, cancer and chronic kidney disease ,4,5,6,7.A total of 3118 patients with symptomatic CAD who received coronary intervention at the Taipei Veterans General Hospital between 2005 and 2015 were enrolled in this study. CAD was diagnosed by at least one of the following modalities: (1) a history of myocardial infarction as evidenced by ischemic change in a 12-lead electrocardiography (ECG) and elevated cardiac enzymes; or (2) a history of angina with ischemic ECG changes, a positive response to a stress test, or the presence of a significant stenotic lesion on a coronary computed tomography angiography (CCTA). CAD patients who fulfilled the above criteria and received a coronary intervention (percutaneous coronary intervention (PCI)) with either coronary stenting or balloon angioplasty were enrolled. This work was a retrospective observational study that complied with the Declaration of Helsinki and was approved by the appropriate Health Authorities, Independent Ethics Committees, and Independent Review Boards in Taipei Veterans General Hospital (2016-03-014CC). Baseline characteristics and risk factors, including a history of hypertension, diabetes and smoking, as well as medication history, were collected. In addition, biochemical profiles including albumin, blood profiles, lipid profiles, renal function parameters and parameters related to coronary intervention were collected. Nutritional status was evaluated using the CONUT score, which takes into account serum values of albumin (g/dL), total cholesterol level (mg/dl), and total lymphocyte count (/mL), with a score ranging from 0 to 12 ,13. HighThe study patients resumed outpatient clinic visits within two to four weeks of discharge. After their first return visit, they were regularly followed up at one- to three-month intervals. Data for follow-up were retrospectively obtained from hospital records and chart reviews. The primary endpoint was major cardiovascular events including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and revascularization procedures including coronary intervention and bypass surgery. Myocardial infarction was confirmed in patients presenting with ischemic symptoms with elevated serum cardiac enzyme levels and/or characteristic ECG changes. Coronary revascularization procedures with either coronary intervention or coronary artery bypass grafting surgery were confirmed by medical record review. Stroke was confirmed if there was a new neurologic deficit lasting for at least 24 h with definite imaging evidence of cerebrovascular accident by either MRI or CT scan. Major adverse cardiovascular events (MACEs) included cardiac death, non-fatal myocardial infarction (MI) and ischemic stroke. The protocol for cardiovascular (CV) event follow-up was similar to that previously reported ,15. 2 or Fisher’s exact test. The primary and secondary outcomes were described as overall percentages and expressed as means of proportions with a 95% confidence interval (CI). The event-free survival rate was calculated using the Kaplan–Meier method, with the significance evaluation using log rank tests. The primary analysis used an unstratified log-rank test to compare the overall survival between variable CONUT groups. Multiple regression analysis was carried out using Cox proportional hazard regression analysis adjusted for age, gender, BMI, history of hypertension, diabetes, medications including statins, LDL and HDL to evaluate whether the CONUT score was an independent factor in determining the occurrence of acute myocardial infarction, congestive heart failure (CHF), CV death, major cardiovascular events, and total CV events. Subsequent subgroup analysis was performed to investigate the effects of the CONUT score among other risk factors for cardiovascular events, such as age, gender, history of diabetes mellitus, hypertension, LDL and HDL. To assess whether the accuracy of predicting adverse cardiac events would improve after the addition of CONUT to a baseline model with established risk factors , the C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated. A similar analysis has been used in our previous work [http://www.R-project.org/; R Foundation for Statistical Computing, Vienna, Austria). In all of the tests, the two-tailed alpha significance level was 0.05. The baseline characteristics of patients according to baseline CONUT score categories were compared. The occurrence of future adverse outcomes including non-fatal stroke, non-fatal myocardial infarction, repeat revascularization, and total CV events during the follow-up period was compared between groups. Quantitative variables were expressed as the mean and standard deviation in the presence of a normal distribution, or as the median and interquartile range in the presence of an asymmetric distribution. Qualitative variables were presented as both absolute frequencies (number of patients) and relative frequencies (percentage). Comparisons of continuous variables between groups were performed by an ANOVA test, while subgroup comparisons of categorical variables were assessed by a χous work . Statistp for trend < 0.05). In addition, patients with worse nutrition had more underlying comorbidities including congestive heart failure, chronic kidney disease and more extensive coronary artery disease. A total of 3118 patients who underwent percutaneous coronary intervention were enrolled in this study. The baseline characteristics of the participants according to CONUT score categories are shown in p < 0.001), AMI (log-rank p < 0.001), cardiovascular death (log-rank p < 0.001), CHF (log-rank p < 0.001) and total CV events (log-rank p < 0.001). This suggests that a higher CONUT category (poor nutrition status) was associated with an increased risk of future adverse events in CAD patients after coronary intervention.p = 0.008), CV death , CHF , MACEs  and total CV events . The trends toward increased risks of AMI, CV death, CHF, MACEs and total CV events were significant across worse CONUT categories , nonfatal MI (p = 0.0483), CHF (p = 0.001), MACEs (p < 0.001) and total CV events (p = 0.0053), as shown by the significant increase in the C-index (p < 0.001) with a 12.29% increase in net reclassification improvement (NRI) (p = 0.0151) in cardiac death and MACEs . This suggests that adding the CONUT score could provide significantly better predictive value than traditional risk factors for CAD patients after PCI, especially for cardiac death and major adverse events.Adding the CONUT score to a baseline model improved the prediction of cardiac death , suggesting that CONUT independently represents a useful predictive value regarding the long-term outcomes of CAD patients. Subgroup analyses emphasized that the CONUT score is an independent marker for risk stratification after adjusting for other cardiovascular risk factors in high-risk CAD populations. In addition, the CONUT score significantly improved the risk stratification of cardiac death and MACEs compared to conventional risk factors in CAD patients. This indicates that the CONUT could be used as an easy and practical indicator for identifying high-risk CAD patients who will develop major events after PCI.Nutrition status plays an important role in maintaining vital organ function in the human body ,18. MalnThe CONUT score consists of three laboratory markers: albumin, cholesterol and lymphocyte count. Albumin levels are not related solely to nutritional status. They are also related to the acute phase reaction. Albumin is a serologic marker of inflammation superimposed on malnutrition, which has inflammatory effects on the vascular endothelium and lipoprotein structure . Lower aRecently H. Wada et al. disclosed that nutritional status as assessed by the PNI is useful in predicting long-term cardiovascular outcomes in stable CAD patients that underwent elective PCI . In thisThe mechanism linking poor nutrition to worse adverse outcomes is considered to be multifactorial. Malnutrition may decrease underlying fibrinolysis ability, platelet inhibition and antioxidant capacity and increase blood viscosity, leading to the occurrence of adverse outcomes. Our study is consistent with the finding of M. Yokoyama who reported the independent predictive value of CONUT score-based malnutrition status in peripheral arterial disease . In addiThis study has several potential limitations due to its retrospective nature and patient enrollment at a single institution. The study period is quite long, and the treatment of coronary artery disease including the statin intensity and prescription practice has changed during this period. Additionally, due to a lack of data, we could not determine the effects of the serial changes in nutritional status. However, we showed that malnutrition is common in patients with coronary artery disease, which could add as a prognostic factor for clinical outcomes in addition to the established risk factors. The use of the CONUT score, which comprises cholesterol levels, might be affected by the use of statins, which is common in patients with coronary artery disease. This issue has been adjusted for by considering statin use in the Cox regression analysis in Model 2 and Model 3 as shown in This study shows that the CONUT score is an independent predictor of long-term cardiovascular disease to identify outcomes in patients with coronary artery disease, including those presenting with acute coronary syndromes. This suggests the usefulness of the CONUT score, in addition to the well-established cardiovascular risk factors, for risk stratification in these patients prior to PCI.


We aimed to examine the risk factors for chronic kidney disease (CKD) stage 3 among adults with ASK from unilateral nephrectomy.We retrospectively collected data from adult patients with ASK between January, 2009 and January, 2019, identified from a tertiary hospital in China. The clinical data were compared between patients who developed CKD stage 3 and those who did not develop CKD stage 3 during follow-up.p < 0.001), diabetes , hyperuricemia , a history of cardiovascular disease (CVD) , and ASK due to renal tuberculosis  were independent risk factors for developing CKD stage 3 among patients with ASK.In total, 172 patients with ASK  were enrolled, with a median follow-up duration of 5.0 years. During follow-up, 91 (52.9%) and 24 (14.0%) patients developed CKD stage 3 and end-stage renal disease, respectively. Multiple regression analyses showed that age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.039–1.115, Regular follow-up of renal function is needed among adult patients with ASK. Optimal management of diabetes, hyperuricemia, and CVD may reduce their risk of CKD stage 3, especially among those that undergo unilateral nephrectomy for renal tuberculosis. These adaptive changes may have short-term benefits, but the long-term effect can be harmful to the solitary kidney [. Although the risk of impaired renal function in the solitary kidney has been studied before, available reports predominantly focus on patients with CSK or those who are kidney donors [The origin of solitary kidney can be congenital or acquired. Congenital solitary kidney (CSK) is mainly due to unilateral renal agenesis, while acquired solitary kidney (ASK) after unilateral radical nephrectomy in adults is frequently the result of treatment for renal tumors, severe parenchymal renal infections, renal trauma, and kidney donation. Patients with a solitary kidney have by definition renal mass reduction, which leads to functional and structural changes among the remaining glomeruli, followed by compensatory glomerular hypertension, hyperfiltration, and hypertrophy . These ay kidney . Althougy donors –7.Existing studies consistently indicate an increased long-term risk of end-stage renal disease (ESRD) and higher mortality among live kidney donors. A population-based study showed that the estimated risk of developing ESRD 15 years after donation was 30.8 and 3.9 per 10,000 patients among live kidney donors and matched healthy persons, respectively, and the estimated lifetime risk of developing ESRD was 90 and 14 per 10,000, respectively . A meta-The current study aimed to identify important risk factors associated with the development of CKD stage 3 among adults with ASK and to examine the renal outcomes. The information gleaned from this study will help provide optimal management for patients with ASK through protecting their renal function.2 or a history of CKD before nephrectomy, and those who were pregnant. We also collected their clinical and laboratory data, including age, gender, smoking status, history of cardiovascular diseases, years after nephrectomy, body mass index (BMI), blood pressure (BP), comorbidities such as hypertension and diabetes, serum creatinine, urea, uric acid, fasting glucose, total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and spot urine and/or 24-h urine protein levels. Cardiovascular diseases included myocardial infarction, stroke, transient ischemic attack, intermittent claudication, prior revascularization, and/or amputation due to peripheral vascular disease. BMI was calculated based on their weight in kilograms divided by the square values of height in meters. Serum creatinine and uric acid concentrations were measured by the picric kinetic method and the enzymatic method, respectively. Their estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [This retrospective study was conducted in the Lanzhou University Second Hospital, a 3000-bed university-affiliated and tertiary care referral hospital in GanSu, China. We identified patients with an international classification of disease – 10th version (ICD-10) code of Z90.5 (solitary kidney) or Q60.0  between January 2009 and January 2019 from the electronic medical records, and included those older than 18 years old who underwent unilateral nephrectomy. The exclusion criteria consisted of individuals with abnormal proteinuria and eGFR greater than 60 ml/min/1.73 m2 according to the Asian-specific criteria [2 and/or the presence of proteinuria and/or the presence of hematuria in two or more tests at the end of follow-up. The staging of CKD was performed according to the 2012 Clinical Practice Guidelines for the Global Prognosis of Kidney Disease. ESRD was defined as having an eGFR less than 15 mL/min/1.73 m2, the initiation of chronic dialysis, or receiving a kidney transplant.Hypertension was defined as having a systolic and/or diastolic BP ≥ 140 and 90 mmHg, respectively, a history of hypertension, or the use of any antihypertensive medication. Diabetes was defined as having a fasting glucose ≥7.0 mmol/L, a history of diabetes, or the use of any antidiabetic medication. Hyperuricemia was defined as having a serum uric acid ≥420 μmol/L  or 360 μmol/L . Dyslipidemia was defined as having TC ≥ 6.2 mmol/L, LDL cholesterol ≥4.1 mmol/L, HDL cholesterol < 1.0 mmol/L, and/or triglycerides ≥2.3 mmol/L. Obesity was defined as having a BMI ≥ 25 kg/mp value < 0.05 was considered statistically significant in all analyses.All statistical analyses were performed using SPSS version 25.0 . To identify independent risk factors for the development of CKD stage 3, we compared clinical parameters between patients who developed CKD stage 3 and those who did not develop CKD stage 3 during follow-up. Continuous variables were expressed as means ± standard deviation and categorical variables as numbers with percentages. A Shapiro-Wilk test was used to analyze the normality of the data distribution. Non-normally distributed data were expressed as medians with interquartile ranges. We used the Student’s t-test or the Mann-Whitney test and the Chi-square test or the Fisher’s exact test to compare continuous and categorical variables, respectively. We used the Pearson’s parametric test or the Spearman non-parametric test for correlation analyses. We used the logistic regression analyses to identify independent factors associated with the development of CKD stage 3. A We summarized the clinical characteristics of the patients in Table n = 72; 41.9%) and renal tuberculosis . The proportion of patients with ASK that received nephrectomy for renal tuberculosis was significantly higher than those with other conditions among the patients who developed CKD stage 3  (Table p < 0.001) than those who did not, and had a significantly higher proportion of ASK related to nephrectomy for renal tuberculosis  , hyperuricemia , and history of CVD  was also higher among those that developed CKD stage 3 compared to those that did not  , diabetes , hyperuricemia , history of CVD , and having ASK from unilateral nephrectomy for renal tuberculosis  were independent risk factors for developing CKD stage 3 among the included patients with ASK  .China has the third largest number of patients with tuberculosis worldwide, with an estimated incidence of 68 per 100,000 population in 2014 . UrogeniA robust association exists between CKD and cardiovascular diseases (CVDs) . PatientWe discovered that higher age was an important risk factor for CKD stage 3 among patients with ASK, and that there was a trend toward a negative association between patients’ eGFR and the duration after nephrectomy. Higher age is accompanied by eGFR decrease , and renHyperuricemia is also an independent risk factor for rapid CKD progression among children and adults , 31. TheDiabetic nephropathy is the most common cause of ESRD globally, and the presence of diabetes increases the risk of CKD, ESRD, and death . Poor glHypertension is also a well-known risk factor for CKD. However, we did not find patients with CKD stage 3 having a higher prevalence of hypertension, nor was hypertension independently associated with CKD stage 3. It is possible that disparities in the regulatory pathways of fluids, electrolytes, and vasoactive hormones in those with solitary kidney account for this phenomenon. Studies with a larger sample size may be needed for confirmation. Obesity is another predisposing factor for glomerular hyperfiltration and glomerular hypertension, both of which exacerbate CKD progression . A recenGender difference in the risk of CKD has been documented in the general population, with men at a greater risk of developing kidney disease and having unfavorable outcomes . EstrogeSmoking is a known risk factor for many pathologies including CKD and may worsen CKD progression , 42. ExpOur study has several limitations. First, our study was retrospective in nature, and laboratory data were missing for some of the patients. This study could not show the negative effects of AKI on long-term renal outcomes after nephrectomy, and whether urgent or elective nephrectomy influences renal outcomes remains unclear. Second, we used the CKD-EPI formula to calculate eGFR as recommended by the Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines . HoweverIn conclusion, adults with ASK are at risk for developing CKD stage 3, and regular follow-up of their renal function is needed, especially among those with ASK who are elderly, with diabetes, hyperuricemia, or a history of cardiovascular diseases, and those that undergo unilateral radical nephrectomy for treating renal tuberculosis. Optimal clinical management of diabetes, hyperuricemia, and cardiovascular diseases among patients with ASK may reduce their risk of developing CKD stage 3.


Background: The prevalence of hypertension is increasing particularly among obese children and adolescents. Obese children and adolescents with hypertension are likely to remain hypertensive as they reach adulthood and hypertension is linked to an increased risk for cardiovascular disease. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has become one of the most important tools in diagnosing hypertension in children and adolescents and circadian patterns of blood pressure may be important disease-risk predictors.Methods: A retrospective chart review was conducted in patients aged 6–21 years who underwent 24-h ABPM at Kentucky Children's Hospital (KCH) from August 2012 through June 2017. Exclusion criteria included conditions that could affect blood pressure including chronic kidney disease and other renal abnormalities, congenital heart disease, cancer, and thyroid disease. Subjects were categorized by body mass index into normal (below 85th percentile), overweight (85th−95th percentile), stage I obesity (95th−119th percentile), stage II obesity (120th−139th) and stage III obesity (>140th). Non-dipping was defined as a nocturnal BP reduction of <10%.Results: Two hundred and sixty-three patients  were included in the analysis, of whom 70 were normal weight, 33 overweight, 55 stage I obesity, 53 stage II, and 52 stage III obesity. Although there was no significant difference between normal weight and obese groups for prevalence of hypertension, there was a greater prevalence of SBP non-dipping in obese patients as BMI increased (p = 0.008). Furthermore, non-dippers had a significantly elevated LVMI as well as abnormal lab values for uric acid, blood lipid panel, creatinine, and TSH (p < 0.05).Conclusions: These findings demonstrate that obese children and adolescents constitute a large proportion of hypertensive children and adolescents and the severity of pediatric obesity is associated with nocturnal BP non-dipping. Additionally, obesity in children is linked to several cardiovascular risk factors including left ventricular hypertrophy, dyslipidemia, and elevated uric acid levels. Further studies utilizing ABPM measures on risk stratification in this very high-risk population are warranted. Childhood obesity and associated cardiometabolic disease including hypertension are increasing at an alarming rate worldwide. Currently 18.5% of children and adolescents (~13.7 million) are obese in the United States with rates of obesity increasing in all age groups in the pediatric population . AccordiPediatric hypertension has been associated with target-organ damage including left ventricular hypertrophy (LVH) , impaireAmbulatory blood pressure monitoring (ABPM) provides a comprehensive assessment of blood pressure over a 24-h period and is recommended by the 2017 AAP CPG for the confirmation of the diagnosis of hypertension. Additionally, ABPM is recommended for the evaluation for masked hypertension, suspected white-coat hypertension, risk for hypertensive target organ damage, evaluation of hypertension in children with obstructive sleep apnea syndrome, secondary hypertension, chronic kidney disease or structural renal abnormalities, type 1 and type 2 diabetes, history of solid organ transplant, history of pre-maturity and evaluation of non-dipping status, as well as patients with history of aortic coarctation repair, in addition to assessment and monitoring of treatment effectiveness of antihypertensive medications . Strojny2 . Within the previous two decades, there has a been a significant increase in the prevalence of extreme obesity as defined by a BMI of at least 99th percentile on the CDC growth charts . Due to 2 . Cardiov2 .2.7 for children older than 8 years of age and recommends echocardiograms be obtained when the initiation of antihypertensive medication is considered to assess target organ damage (Left ventricular hypertrophy (LVH) is readily assessed by echocardiography and is a form of target organ damage . The AAPn damage . ABPM han damage . LVH hasn damage .The aim of this study was to evaluate relationships of elevated blood pressure and several established markers of cardiovascular and metabolic disease among patients stratified according to obesity and treated at the KCH Pediatric Nephrology Clinic. Furthermore, this study tests the hypothesis that severity of obesity correlates with increased cardiovascular risk including non-dipping and left ventricular hypertrophy.This study was conducted as a retrospective chart review in children who were referred to the KCH Pediatric Nephrology Clinic with elevated blood pressure who underwent a first time 24-h ABPM between August 2012 through June 2017. This study evaluates the relationship between blood pressure and several established markers of cardiovascular and metabolic disease based on severity of obesity. This study was approved by the University of Kentucky Institutional Review Board.via the electronic medical record to identify those patients who underwent a 24-h ABPM from KCH during the study timeframe. Exclusion criteria included conditions that could affect blood pressure including chronic kidney disease, congenital heart disease, cancer patients, patients with ADHD on stimulant medication, and thyroid disease. Data collected included demographic  and diagnostic evaluation  from the electronic medical record.Patients were selected All ABPMs were performed using Spacelabs  90217 monitor or an Oscar 2 ABPM Monitor by SunTech Medical which are validated by the Association for the Advancement of Medical Instrumentation for use in children. The monitor was placed by trained nursing staff at the time of clinic visit with an appropriate cuff size. Readings were taken every 30 min while awake and every 60 min while asleep. Patients were asked to record sleep and wake times during the 24-h period and were instructed to mail this information along with the device back to our office for interpretation of results. Patients were advised to follow routine daily activities but avoid vigorous exercise and to relax the arm during inflation and deflation of the cuff. The adequacy of the study was determined by the interpreting physician at the time of ABPM evaluation according to the Ambulatory Blood Pressure Monitoring in Children and Adolescents: Recommendations for Standard Assessment and included at least 65% successful readings , overweight (85th−95th percentile), stage I obesity (95th−119th percentile), stage II obesity (120th−139th) and stage III obesity (>140th) based on the updated CDC growth charts.via echocardiogram to determine evidence of target organ damage was reported as well. Left ventricular hypertrophy (LVH) was defined as LV mass indexed to height in meters to the 2.7 power that is greater than the 95th percentile for age and sex , hemoglobin A1c, uric acid, and renin-aldosterone-cortisol, and thyroid levels were obtained retrospectively. Cardiac imaging  and sex .via IBM SPSS Statistics version 25.  with significance set at an alpha level <0.05. Modeling was performed in SAS version 9.4 . Continuous variables including lab values such as blood lipid panel, hemoglobin A1c, uric acid, thyroid, renin-aldosterone-cortisol, and LVMI were analyzed using ANOVA utilizing a post-hoc pairwise comparison with a Bonferroni correction and independent samples t-test. Categorical and ordinal variables including gender, BMI stage, blood Pressure stage were analyzed using Pearson's chi-square while non-dipping prevalence were analyzed through Somer's D-test. Additionally, a generalized linear multivariate model was used to examine the interaction of BMI stage and gender on LVMI with significance set at an alpha level <0.05.Bivariate statistical analyses were performed n = 259) 18 years or younger, 40% are female and there were no significant differences among gender and age in each obesity class. Demographics including age, gender, race, and mean BMI are found in A total of 496 completed ABPMs were identified during the study period August 2012 through June 2017; 100 were excluded due to an underlying chronic condition as described in the methods section, an additional 46 of these were repeat ABPMs, and 87 were excluded due to inadequate sample collection (completed readings below 65%). Of those remaining, 263 ABPMs and associated patient data were included in the analysis, of whom 70 (27%) were normal weight, 33 (13%) were overweight, 55 (20%) were class I obesity, 53 (20%) were class II obesity, and 52 (20%) were class III obesity. The mean age was 13.9 ± 0.17 with 98% patients (p = 0.161). The different stages of hypertension as defined by ABPM which takes into account the mean ambulatory systolic blood pressure and load were not significantly different among obesity classes  in addition to significant increases in serum triglyceride . Levels of uric acid were found to be significantly elevated with stage II and III obesity (p < 0.001). HgbA1c was measured in 109 patients and found to be elevated in overweight and obese groups compared to normal weight groups . Of those patients who underwent ABPM measurement and included in analysis, 197 patients underwent echocardiogram  with 6% (n = 11) diagnosed with LVH. Left ventricular mass index assessed via echocardiogram revealed a significant elevation with severity of obesity  or non-dipping . When we further analyzed the difference in LVMI, we found an interaction between LVMI and gender. Although normal weight girls have a lower LVMI than normal weight boys, LVMI has higher values for girls in stage III obesity than boys .Of the patients who underwent ABPM measurement and included in analysis, 234 patients had a renal function panel measured and 178 had lipid panel measured. Total cholesterol was significantly elevated as severity of obesity increased (This study examined several hemodynamic and biochemical markers of cardiovascular risk with respect to obesity class and demonstrated that the prevalence of non-dipping during 24h BP monitoring was more prevalent with increasing severity of obesity. Furthermore, several cardiovascular risk markers including total cholesterol, triglycerides, uric acid levels, and LVMI were significantly associated with severity of obesity. We found a potentially important trend of increased prevalence of non-dipping and greater left ventricular mass in the most severe obesity classes.Nocturnal dip is defined as a nocturnal blood pressure reduction of <10% from mean systolic and diastolic awake BP during the nighttime. The relationships between non-dipping status and target organ damage and cardiovascular morbidity is well-established in adults. Non-dipping in the pediatric population has been less studied but reveals associations with target organ damage such as LVH in diabetic populations  and a loSimilar to our findings, the ERICA study from Brazil reports an increase in prevalence of several cardiovascular risk factors including total cholesterol, LDL cholesterol, low HDL levels, and HgbA1c in relation to severity of obesity in addition to blood pressure . SkinnerPublished findings in adult populations have demonstrated an association between serum uric acid and increased CVD mortality independent of traditional risk factors . A prosp2.7 (The level and duration of BP elevation that result in target organ damage in children and adolescents remain poorly defined; however, LVH has been noted in this population with even mild blood pressure elevation and is probably the most well-studied marker of target organ damage because of the wide availability of echocardiography. In hypertensive children, the prevalence of LVMI ranges from 4.8 to 50% and can be even higher in children on dialysis –39. Dani2.7 . In a Eu2.7 , 41. Sim2.7 . In a di2.7 . However2.7 . Additio2.7 . We noteSeveral studies have demonstrated that childhood cardiovascular risk factors carry forward into adulthood. A meta-analysis that examined the association between childhood obesity and cardiovascular risk in adulthood found a significant and positive association in regard to adult systolic blood pressure, diastolic blood pressure, triglycerides, and negatively associated with adult HDL . FurtherOur study has several limitations including that it is a single center retrospective experience and a cross-sectional design. Since this study is cross-sectional and included a single time point per study participant as a retrospective study we cannot infer causality between different variables examined; rather these relationships can guide additional prospective studies. In addition, we did not collect parameters related to sodium intake or physical activity patterns, which could affect blood pressure findings. All of our patients were referred to our clinic for hypertension evaluation, which may reduce the generalizability to the pediatric population. An additional factor is the tolerability to wearing the 24 h blood pressure monitor as it has been reported that obese adolescents have less successful readings and are thus more intolerant to ABPM . This coPediatric obesity is a major health concern and obese children are at a high risk of early cardiovascular disease. Recent strategies to stratify severity of obesity may provide opportunity to identify patients at highest risk. Our investigations of several hemodynamic and biochemical markers of cardiovascular risk with respect to Obesity Class provided the following insights: the frequency of systolic or diastolic hypertension was not different among obesity severity, but the prevalence of non-dipping during 24h BP monitoring was more prevalent with severity of obesity. Several well-recognized markers of cardiovascular risk are related to severity of obesity. Blood lipid panels demonstrated elevation in total cholesterol with a reduction in HDL, and elevation in triglycerides in relation to severity of obesity. LVMI was significantly associated with severity of obesity and this was found to be more prominent in girls than boys. Our data suggests that there may be a sex-specific target organ response and that obesity class may help to identify the most at-risk children at the earliest times. We found a potentially important trend of increased prevalence of non-dipping and greater LV mass in the most severe stages of obesity. Our studies support the use of ABPM in the evaluation of pediatric hypertension as well as the need to examine additional cardiovascular risk factors at the time of evaluation. Further studies to develop easily implemented and cost-effective risk stratification methods are clearly warranted as are studies to define relationships among blood pressure variables and cardiac structure and function in high-risk obese children.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by University of Kentucky Institutional Review Board. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.MM designed the study, collected data, created figures after analysis, drafted the initial manuscript, and reviewed and revised the manuscript. AC and SK also assisted in the design of the study and collection of the data. HH, MM, JB, and JC oversaw the design and analysis of the study as well as supervising data analyses, review, and revision of the manuscript. AS provided statistical analysis support and reviewed the manuscript. SK designed the study, supervised the data analyses, and critically reviewed and revised the manuscript. All authors contributed to the manuscript review and revision and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.