Intracranial pressure (ICP) and ocular perfusion pressure (OPP) are both involved with the pathogenesis of glaucoma. The orbital ICP determines a retrolaminar counter pressure that is antagonistic to the intraocular pressure (IOP). The purpose of this study is to evaluate whether the translaminar pressure difference (TLPD) and the OPP varies in glaucoma patients with different optic disc sizes. In this university hospital-based, observational, cross-sectional clinical study,all patients underwent an ophthalmic evaluation. Blood pressure, height, weight, and the results of retinal nerve fiber layer examination with optical coherence tomography examination were recorded. TLPD and OPP were calculated for each patient using proxy algorithms to attain indirect surrogate parameter values. Patients' eyes were stratified into three quantiles according to optic disc sizes and the differences compared. Data from both eyes were used after using the appropriate correction for inter-eye dependency.PThe sample consisted of 140 eyes of 73 patients with primary open-angle glaucoma and suspects. Patients with large disc size presented with higher TLPD as compared to those with average and small-sized discs (2.4 Glaucoma patients with larger optic discs have higher TLPD. The pathological significance of this finding warrants further investigation. Primary open-angle glaucoma (POAG) is a highly prevalent, sight-threatening, multifactorial disease. Its pathogenesis is associated with both mechanical and vascular factors. Mechanical factors including increased intraocular pressure (IOP) with posterior bulging of the cribriform blade, compression of the nerve fibers, and reduction of the retrograde and anterograde flow and vascular factors including decrease of perfusion pressure in the optic nerve head and deficiency in autoregulation leading to apoptosis of retinal ganglion cells and visual function loss may be involved.,3 From an anatomical perspective, the ICP at the orbit level and the optic nerve tissue pressure determine the retrolaminar counter pressure which is antagonistic to the IOP. Thus, it may be part of the critical translaminar gradient or simply a translaminar pressure difference (TLPD). Presuming that there is a higher difference in the cribrosa translaminal pressure, a marked translaminar pressure gradient may damage the optic nerve, and therefore a low orbital ICP may be associated with the pathogenesis of glaucoma. There has been a debate as to whether this is an epiphenomenon or that there is an actual causal relationship between ICP and glaucoma.Recently, the intracranial pressure (ICP) was thought to be involved in the pathogenesis of POAG. Some clinical and population studies reported that glaucoma patients have a lower ICP compared to that of normal subjects.,6 The underlying pathologic mechanism is related to the reduction in blood perfusion caused by impaired vascular autoregulation. The ocular perfusion pressure (OPP) is a physiologic function that delivers arterial blood to capillary bed for the eye tissues.Several population-based and clinical studies support a strong association between ocular blood flow and the risk of POAG prevalence and progression.,9 There is evidence suggesting that large optic discs may be more susceptible to glaucoma than small discs. Uncertainties regarding whether the TLPD and OPP differ according to the optic disc size and its influence in the glaucoma optic neuropathy exist. This cross-sectional, observational study aimed to assess whether TLPD and OPP vary in glaucoma patients and suspects according to the size of the optic discs.Clinical variables such as TLPD and the OPP are potential players in the glaucoma optic neuropathy. Moreover, the optic disc size can vary substantially in the population.This cross-sectional, observational clinical study was approved by the Committee on Human Research of the institution. The participants were patients from the Glaucoma Service, Santa Casa de Misericordia of Sao Paulo Hospital. The study adhered to the tenets of the Declaration of Helsinki and its late amendments and the Resolution 466/12, National Council of Health, Brazilian Ministry of Health. After explaining the study procedures, all participants signed the informed consent.PPPThe sample included patients who were diagnosed with POAG and met the following inclusion criteria: age After a brief medical interview, patients participated in the study procedures. Demographic data including age, gender, ethnicity, and medical history (comorbidities and previous surgeries) were collected prior to the evaluations. Height (cm) was measured with the patient's back against the wall, without shoes, and feet together using a standard stadiometer. The body weight (kg) was measured on a calibrated manual platform scale with the patient wearing light clothing. The body mass index (BMI) of each participant was determined as the body mass divided by the square of the body height  after taking a drop of fluorescein and proparacaine, gonioscopy with Goldmann goniolens , and optical disc evaluation with the 78D Volk lens  after pharmacological mydriasis with tropicamide eye drops 0.5% and visual field examination. Computerized perimetry was performed with the HFV 750 , SITA standard program 24-2, with appropriate optical correction by a technician.Optical coherence tomography (OCT) was performed with the OCT Angiography RTVueⓇ Avanti XR . The OCT images were obtained at a rate of 26,000 A-scan/s and with a frame rate between 256 and 4096 A-scan/frame. This provided a high tissue resolution (depth resolution of 5.0 μm and transverse resolution of 15 μm). The acquisition of images in all patients followed the same procedure and was carried out by one technician. The retinal ganglion cells in the macular region were assessed using the Nerve Fiber Scan Protocol after pharmacologic dilation of the pupils. Images were excluded if the signal strength index (SSI) The OPP was determined according to the following formula:OPP = [2/3 mean AP] – IOP; where, the mean AP  is 1/3 [SAP – DAP] + DAP. SAP is the systolic arterial pressure and DAP is the diastolic arterial pressure.,12The predictive ICP was calculated according to the equation of Xie et al:ICP = .PThe sample was stratified into three quantiles according to the optic disc size, that is, the disc area (mmP = 0.136). Nevertheless, patients with larger optic disc area presented a higher TLPD as compared to patients with small or average discs  or functional (MD and PSD) variables. The OPP was lower in patients with smaller disc sizes and higher in patients with average discs. However, the difference did not reach statistical significance  is the translaminar pressure gradient. On physiological grounds, the mean IOP is meagerly higher than the mean ICP, which results in a small posteriorly directed translaminar pressure gradient difference of approximately 4 mmHg. An IOP within statistically normal limits in conjunction with a low ICP produce the same pressure gradient across the lámina cribosa (LC) as a high IOP in conjunction with a normal ICP. Changes in the TLPD may cause pathological dysfunction and optic nerve damage attributable to alterations in axonal transportation, LC deformation, changes in blood flow or even all of them in combination.,321,22,,22,23272728]28] A higher IOP, lower ICP, and larger TLPD correlates with enlargement in the C/D ratio and reduction in RNFL thickness.,29 In our study, patients with a larger optic disc area presented with a higher TLPD. For these patients the ganglion cell axons could be more exposed to this pressure gradient. Thus, patients with larger optic discs may be more vulnerable to IOP insults, without simultaneous influence of OPP which did not differ among the three groups. As such, patients with larger discs would be more likely to have glaucoma than patients with smaller optic discs. Interestingly, in cases of progressive optic neuropathies, the optic nerve fiber counts and the anatomic reserve capability are higher in eyes with large optic heads than those with smaller optic discs. Moreover, discs  These characteristics may thwart against the TLPD insult and can work as a compensatory effect.The optic nerve head is located in an area between the high-pressure intraocular space and low-pressure subarachnoid space. Hence, the pressure imbalance between these two spaces can cause damage to the retinal ganglion cell axons that pass through the lamina cribrosa pores. In this model, the TLPD and disc size (radius) were considered as two independent variables of LC stress. If that is the case, larger discs would be vulnerable not only by its anatomic enlarged area but also to a larger TLPD.Recently, Baneke et al have defined the strain in the LC as the function of TLPD times the square of its diameter divided by the square of its thickness [LC stress = (IOP – ICP). LC radius,35,36,37 In contrast, the Beijing Eye Study did not find a clear association between the OPP and the prevalence of glaucoma. In this study, the OPP did not vary according to the optic disc size. Thus, the vascular insult should be the same for all discs, regardless of the disc size, and the higher TLPD could be an isolated aggravating factor and independent of the OPP.A possible association between glaucoma and decreased OPP was demonstrated in several previous studies. It is not certain how different the calculated ICP is from the actual one measured by lumbar puncture. ICP is not only influenced by circadian rhythm, but also by changes in posture, position, and pressure fluctuations in other compartments as in respiratory effort and blood pressure pulsations. Moreover, the production and resorption of cerebrospinal fluid rate are not linear, particularly at different ICP levels. Hence, a linear prediction model for ICP based on Xie's formula may be inaccurate, especially for pathologic conditions. In POAG cases, hemodynamic disturbances are known comorbidities and ICP regulation has been suggested to be abnormal. Moreover, the Cushing reflex or vasopressor response may be affected in these patients and the ICP estimation on BP variation may be too simplistic. Using such a surrogate measure could be misleading. This is a fundamental drawback to the study methodology which limits the generalizability of the finding. However, this same formula has been used in other large population studies.,40 Furthermore, the equation was validated in a cohort of 39 Brazilian patients and showed that the estimated ICP was very close to the measured ICP (95% limits of agreement of –5 to +8 between LP measured and equation-estimated ICP). Moreover, the measurement of ICP by lumbar puncture may be different from the retrobulbar ICP. In general, it is assumed that the lumbar ICP represents the CSF pressure in the optic nerve. However, given the extended length between the lumbar spine and the subarachnoid space of the optic nerve, it is debatable whether this statement is true, particularly in patients with optic nerve sheath diseases and compartmentalization.This study has one important limitation. The measurement of ICP was not performed by the traditional method using lumbar puncture which is an invasive examination, with the risks of spinal cord injury. For ethical reasons, it was not performed for the study purposes without specific medical indications. The estimated ICP was calculated using a mathematical formula based on the BMI and BP values developed in a population study of Chinese individuals.In summary, this study revealed that the TLPD varies according to the optic disc size and that larger discs tend to have a higher TLPD. Although additional studies are still needed to elucidate the possible role of ICP and OPP in the pathogenesis of glaucoma optic neuropathy, we believe that this study contributes to the acumen on how the optic disc size may be important in the pathogenesis of this disease.Nil.The authors declare that they have no conflict of interest.


Background: Thalassemia is the commonest hemoglobinopathy in Southeast Asia. Kidney dysfunction is an underreported sequelae in children with thalassemia. We conducted a retrospective study to identify the prevalence of and predisposing factors for kidney dysfunction in children with transfusion-dependent thalassemia (TDT).Method: Abnormal kidney function was defined as children with a glomerular filtration rate (GFR) of <90 ml/min/1.73 m2 or a decline in GFR of >20 ml/min/1.73 m2 or presence of nephrotic range proteinuria within 3 years of commencing regular (every ≤6 weeks) red cell transfusion. Data analyzed were age at diagnosis of thalassemia, number of transfusion-years, iron chelation therapy, serum ferritin, and pre-transfusion hemoglobin levels.Results: Eighty-one children were studied. Mean age was 11.72 ± 5.275 years. Thirty out of 81 (37%) demonstrated abnormal kidney function. Evidence of glomerular hyperfiltration was seen in 29/81 patients (25.85%) at their last clinic visit. This fraction was doubled [48/81 (59.3%)] when the cohort was tracked back by 3 years from the last clinic encounter. Age at diagnosis  and duration of receiving transfusions  were associated with increased risk of developing abnormal kidney function.Conclusion: Abnormal kidney function in children with TDT may be overlooked by medical personnel without active screening measures. Children receiving regular red cell transfusions require systematic surveillance to enable early detection of kidney dysfunction and timely implementation of appropriate therapeutic interventions. Thalassemia is the commonest inherited hemoglobinopathy, causing premature rupture of the red blood cells and ineffective erythropoiesis. It is estimated that about 8,000 people in Malaysia are living with thalassemia, with more than half (57%) of them dependent on regular blood transfusions .In the absence of hematopoietic stem cell transplantation, red cell transfusion remains the mainstay of treatment in patients with transfusion-dependent thalassemia (TDT). Children with TDT are at risk of transfusion-related complications such as blood-borne infections, allergic reactions, acute lung injury, and circulatory overload , as well2/min is defined as chronic kidney disease. It is pivotal to detect the presence of abnormal kidney function early to prevent disease progression. Undoubtedly, chronic kidney disease in children carries a higher risk of accelerated cardiovascular disease and death  and the oral agents deferiprone  and deferasirox   . Much hazerland) , 18. HowThis was a retrospective cohort study involving two tertiary-level medical institutions in Malaysia. Case note reviews were carried out by members of the clinical team. Patients aged 18 years or younger who had regular red cell transfusions  at either University Malaya Medical Center or Hospital Tuanku Ja'afar between January 2020 to December 2020 were included. We excluded patients with thalassemia who only required periodic red cell transfusions  or newly diagnosed patients with TDT who received <1 year of regular transfusion.Patients' socio-demographic information , anthropometric measurements, blood pressure during blood transfusion, age at diagnosis, months of transfusion, pre-transfusion hemoglobin level, serum ferritin, serum creatinine, urine protein creatinine index, and type of iron chelation utilized were the variables recorded. These parameters were part of standard of care in the management of children with TDT. We used a predefined standardized data collection sheet for extracting data from the medical records. Pre-transfusion hemoglobin and ferritin levels during the preceding 12 months were obtained.0, and at 3 years prior to that, T−3. The average of serum creatinine over a period of 12 months was used to calculate the eGFR. In this study, we defined glomerular hyperfiltration as eGFR of >140 ml/1.73 m2/min .Evaluation of glomerular filtration rate (GFR) is best performed using clearance of inulin, but this method is impractical in day-to-day clinical practice. At the bedside, serum creatinine measurement is a feasible tool . Estimat3 m2/min . Patientt-tests for continuous variables. A multivariate model analysis using logistic regression was performed to determine the predictors of kidney dysfunction. Data were analyzed by using the Statistical Package for Social Science software version 23.0 .Descriptive statistics was performed to describe basic characteristics of the children with kidney dysfunction. We expressed numerical data as means with standard deviations. Categorical variables were expressed as numbers and percentages. Children with kidney dysfunction were compared to those without kidney dysfunction using chi-square tests for categorical variables and independent n = 62; 76.5%) while the remainder were of Chinese descent. Mean age in the study population was 11.72 ± 5.275 years old (2–22 years) and mean age at commencement of regular blood transfusion was 4.79 ± 3.693 years old. Thirty out of 81 (37%) patients fulfilled at least one of the criteria that defines abnormal kidney function: 1/81 had nephrotic range proteinuria (3.33%), 28/81 (34.6%) patients had declined in eGFR of more than 20 ml/min/1.73 m2 and 6/30 patients had established low eGFR of <90 ml/min/1.73 m2 (7.4%). Five patients had more than one abnormal feature. Evidence of glomerular hyperfiltration was seen in 29/81 patients (25.85%) at their last clinic visit (T0) (−3).Characteristics of the 81 patients are presented in sit (T0) . This prUrine protein creatinine index (UPCI) in one patient demonstrated nephrotic range proteinuria, while in others, it was <50 mg/mmol. This patient received deferasirox for 11 years. She had only proteinuria in the nephrotic range without overt nephrotic syndrome and her serum creatinine remained within normal limits. She had a renal biopsy but unfortunately that was suboptimal for diagnosis. After substituting her iron chelation therapy to desferioxamine, her urine protein gradually normalized.We analyzed kidney function in patients with TDT and found that more than a third of our study subjects had evidence of dysfunction. Multivariate analysis showed that duration of exposure to transfusion is associated with the development of abnormal kidney function in children with thalassemia. This observation concurred with evidence in literature .The mechanisms of transfusion-related renal dysfunction in patients with TDT have been reported by various authors. Chronic iron overload and anemia, which often coexist, are postulated to cause glomerular injury and tubular dysfunction. Zhou et al.  studied per se but to “over-chelation,” leading to a relative depletion of iron and reduction in GFR . Ephraim et al.  describeFindings from our cohort reflect the model of glomerular hyperfiltration described by Brenner et al. . The proz-score of height and blood pressure, we were not able to demonstrate a significant association of either parameter in our patients with abnormal kidney function. This suggests that in routine practice, standard parameters like blood pressure and anthropometric measurements are not adequately sensitive to detect subclinical kidney disease.Children with chronic kidney impairment are usually growth retarded and hypertensive. Examining the We acknowledge the limitations within our study. By default, our study was retrospective in nature. Our number of patients was small and requires further validation from other pediatric centers. Analysis of tubular function was also not possible in this study.In conclusion, occult development of kidney dysfunction is seen early in children with TDT patients. Normal creatinine, growth, and blood pressure do not exclude the existence of kidney dysfunction in this group of patients. Careful interpretation of day-to-day clinical assessment will help clinicians to detect patients at risk. The role of kidney-specific biomarkers  and the potential effects of the renin–angiotensin–aldosterone system inhibition when hyperfiltration occurs are potential areas worth exploring. Revisiting the threshold to initiate chelation therapy may be necessary to prevent glomerular hyperfiltration, which may be overlooked by a falsely reassuring serum creatinine level.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 National Medical Ethics Committee (NMRR-20-1849-55951) and Medical Research Ethics Committee at the University Malaya Medical Centre (UMMC) (MREC UMMC ID 2020721-8903). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.KA contributed to the conception and design of the study. NAM, NMZ, CL, SY, NZ, and JF organized the database. NAM performed the statistical analysis. KA, NAM, CE, and HA wrote the first draft and sections of the manuscript. All authors contributed to manuscript revision, read, 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background and Objectives: Angiopoietin-like protein 3 (ANGPTL3) is a secretory protein regulating lipid metabolism. This study evaluated the relationship between serum ANGPTL3 level and peripheral arterial stiffness (PAS) in patients with coronary artery disease (CAD). Materials and Methods: Fasting blood samples were collected from 95 CAD patients. PAS was defined as left or right brachial-ankle pulse wave velocity (baPWV) > 18.0 m/s by an oscillometric method. Serum ANGPTL3 levels were assessed using a commercial enzyme-linked immunosorbent assay kit. Results: Seventeen CAD patients (17.9%) had PAS. Patients with PAS had a significantly higher percentage of diabetes (p = 0.002), older age (p = 0.030), higher systolic blood pressure (p = 0.016), higher fasting glucose (p = 0.008), serum C-reactive protein (p = 0.002), and ANGPTL3 level (p = 0.001) than those without PAS. After multivariable logistic regression analysis, serum ANGPTL3 level (Odds ratio (OR): 1.004, 95% confidence interval (CI): 1.000–1.007, p = 0.041) is still independently associated with PAS in CAD patients. The receiver operating characteristic curve for PAS prediction revealed that the area under the curve for ANGPTL3 level was 0.757 . Conclusions: Serum fasting ANGPTL3 level is positively associated with PAS in CAD patients. Further studies are required for clarification. Coronary artery disease (CAD) remains a leading cause of mortality and morbidity globally despite improvements in preventive, diagnostic, and therapeutic strategies over several decades . IncreasAngiopoietin-like protein 3 (ANGPTL3) is a secretory protein mainly produced in the liver and is known to inhibit lipoprotein lipase, an enzyme that degrades circulating triglycerides in the capillaries of muscle and adipose tissue . IndividPatients with CAD, defined by >50% stenosis in any segment by coronary angiography, was prospectively recruited from August 2020 to December 2020 at a cardiology outpatient department in Hualien, Taiwan. Patients were excluded with an acute infection, acute myocardial infarction, heart failure, aortic aneurysm, dissection, coarctation or malignancy at the time of blood sampling. The medication history in the past two weeks was collected by reviewing medical records. Diabetes mellitus (DM) was defined as two separated blood tests showing either fasting plasma glucose level ≥ 126 mg/dL, or a random glucose level ≥ 200 mg/dL along with classic symptoms of diabetes, or an HbA1c level ≥ 6.5%, or participants using hypoglycemic agents. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg or any prescription of antihypertensive drugs in the past two weeks according to the Eighth Joint National Committee (JNC 8) guidelines. The study was approved by the Research Ethics Committee, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (IRB108-219-A) with informed written consent obtained before study enrollment.All anthropometric measurements were performed by the same operator with the participants in light clothing without shoe. Body weight and height  were recorded to the nearest 0.5 kg and 0.5 cm, respectively. Body mass index was calculated as the weight in kilograms divided by the height in meters squared ,18.g for 10 min. Serum levels of blood urea nitrogen (BUN), creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting glucose, total calcium, phosphorus and C-reactive protein (CRP) were measured by an autoanalyzer  [After overnight fasting for 8–12 h, blood samples of approximately 5 mL were obtained from participants and immediately centrifuged at 3000× Germany) ,18. SeruGermany) ,18. The After blood sampling, the patient was rested in the supine position for ten minutes. The blood pressure was measured for three times by an automatic upper-arm oscillometric device at right brachial artery. The right and left baPWV was assessed by a volume-plethysmographic apparatus  as previously described ,20. The t-tests (two-tailed), whereas continuous variables with non-normally distribution were expressed as medians with interquartile ranges and tested by the Mann-Whitney U test. Categorical variables were tested by the chi-squared test. Nonnormally distributed continuous variables were logarithmically transformed when applied to linear regression analysis. Simple linear and multivariate linear regression analyses were used to analyze the relationship between all variables and left baPWV or right baPWV values in patients with CAD. Significant variables correlated with PAS were tested by multivariable logistic regression analysis. A p value < 0.05 was defined as statistically significant. All analysis was performed using IBM SPSS Version 19.0 .The distribution pattern of the variables was checked using the Kolmogorov-Smirnov test. Continuous variables with normal distribution were expressed as means with standard deviations and tested by the Student’s independent p = 0.030), had higher percentage of DM (p = 0.002), higher SBP (p = 0.016), elevated serum fasting glucose (p = 0.008), CRP (p = 0.002), and ANGPTL3 (p = 0.001) values in comparison to the control group. There were no significant differences between the two groups in terms of sex, hypertension, or anti-hypertension medication used.The demographic, clinical, and laboratory characteristics of the patients are shown in p = 0.041) and age  were independently associated with PAS in patients with CAD (p < 0.001) : 1.004, 95% confidence interval (CI): 1.000–1.007, with CAD . Further< 0.001) .p = 0.047) by simple linear regression analysis , age , log-CRP , and higher log-ANGPTL3 levels  were significantly correlated with left baPWV values, while DM , age , log-CRP , and higher log-ANGPTL3 levels  were significantly correlated with right baPWV values, respectively  and log-ANGPTL3, while negatively correlated with eGFR . Moreoveanalysis . After bectively . To bettThis study found that CAD patients with increased PAS measured by baPWV had concomitant older age, higher prevalence of DM, higher DBP, higher serum fating glucose, CRP and ANGPTL3 levels. Serum ANGPTL3 level and older age were independently associated with PAS in patients with CAD after multivariable adjustment. After adjustment for confounders, the left or right baPWV values were independently positively associated with DM, age, log-CRP and log-ANGPTL3 levels in patients with CAD.Aging is a major determinant of arterial stiffness by reducing the elastin and increasing collagen component as a consequence of repetitive stretched and recoil with each heartbeat ,23. baPWBeyond aging, DM also plays an important role in the pathogenesis of arterial stiffness. First, advanced glycation end products (AGEs), formed between interaction with multiple sugar moieties and the free amino acid residues of proteins, may cause increased collagen component in arterial wall due to pathologic cross-linking with collagen that is resistant to proteolysis . MoreoveVβ3 by the C-domain of ANGPLT 3 promotes vascular smooth muscle cell migration to the intima, foam cell formation, and inflammatory response, which leads to plaque neovascularization [ANGPTL3 is a 460-amino acid liver-derived secretary protein, which is composed of an N-terminal coiled-coil domain involved in inhibition of lipoprotein lipase as well as a C-terminal fibrinogen-like domain affecting angiogenesis ,34. Liporization . A meta-rization . Similarrization . The posrization , but theThere are some limitations in the present study. First, the cross-sectional design with a limited number of CAD patients precludes the confirmation of causality between ANGLPT3 and PAS in patients with CAD. Second, several medications for hypertension and dyslipidemia may affect arterial stiffness through arterial structural and functional alteration and become potential confounders between the association between ANGLPT3 and arterial stiffness . Our resThe present study demonstrated that fasting serum ANGLPT3 level and older age was positively correlated with increased PAS in patients with CAD. Further prospective studies are required to clarify the causal relationship.


Risk of death is high for hemodialysis (HD) patients but it varies considerably among individuals. There is few clinical tool to predict long-term survival rates for HD patients yet. The aim of this study was to develop and validate a easy-to-use nomogram for prediction of 1-, 5-, and 10-year survival among HD patients.n = 438) and validation cohort (n = 205), univariate survival analyses were performed using Kaplan–Meier’s curve with log-rank test and multivariate Cox regression analyses were performed to identify predictive factors, and a easy-to-use nomogram was established. The performance was assessed using the area under the curve (AUC), calibration plots, and decision curve analysis.This study retrospectively enrolled 643 adult HD patients who was randomly assigned to two cohorts: the training cohort , history of emergency temporary dialysis catheter placement, cardiovascular disease (CVD), hemoglobin (Hgl), and no caregiver. The score revealed good discrimination in the training and validation cohort  and the calibration plots showed well calibration, indicating suitable performance of the nomogram model. Decision curve analysis showed that the nomogram added more net benefit compared with the treat-all strategy or treat-none strategy with a threshold probability of 10% or greater.This easy-to-use nomogram can accurately predict 1-, 5-, and 10-year survival for HD patients, which could be used in clinical decision-making and clinical care. The incidence of chronic kidney disease (CKD) is increasing year by year on a global scale and the all-cause mortality in dialysis patients is 6.5–7.9 times higher than in the general population , about 1As a mathematical model to predict the probability of end-point events, risk prediction model has been widely used in the medical field, for example, the EuroSCORE II model for predicting the risk of heart surgery and the Charlson comorbidity index (CCI) for predicting survival of cancer patients ,7. In prn = 438) and a validation cohort (n = 205). The study protocol was approved by the Clinical Research Ethics Committee of The Second Affiliated Hospital of Soochow University and is registered in the Chinese Clinical Trial Registry (no. ChiCTR1900024999).This study enrolled 679 adult HD patients from the Second Affiliated Hospital of Soochow University in China from 31 January 2009 to 31 December 2013. The exclusion criteria were as follows: (1) history of kidney transplantation; (2) chronic peritoneal dialysis (PD); (3) complicated with malignant tumor; after eliminations, 643 subjects were enrolled in our analysis . The finKt/V  multiplied by the dialysis session length (t) divided by the urea distribution volume V). The Kt/V results were obtained by the special HD formula of Kt/V. RKF was estimated from mean values of creatinine clearance and urea clearance.We recorded the following laboratory parameters: creatinine (Cr), hemoglobin (Hgl), albumin (Alb), blood urea nitrogen (BUN), serum uric acid (UA), calcium (Ca), phosphorus (P), potassium (K), low-density lipoprotein cholesterol (LDL), total triglycerides (TGs), total cholesterol (TC), parathyroid hormone (PTH), high-sensitivity C-reactive protein (Hs-CRP), residual kidney function (RKF), and total Demographic variables were included in candidate variables, such as age, smoking, and gender; blood pressure (systolic blood pressure and diastolic blood pressure), height and dialysis dry weight were included as physical examination variables; concurrent disease, including diabetes, hypertension, and cardiovascular disease (CVD). These data were obtained on admission in the diagnostic laboratory of the Second Affiliated Hospital of Soochow University. All data were obtained within 1 months after the patient’s regular HD reached dry body mass. Body mass index (BMI) was calculated according to the height and weight. Diabetes was defined by use of hypoglycemic medications (and/or use of insulin) and/or history of clinical diagnosis. Hypertension was based on at least two separate blood pressure measurements ≥130/80 mmHg or prescription of antihypertensive drugs. History of angina pectoris, myocardial infarction, heart failure, coronary artery bypass, angioplasty, arrhythmia, or stroke taken from clinical records were considered as CVD.Individuals belonging to the training and validation cohort were followed for a median 7.9 years (5.5–10.4 years), for mortality from any cause. The outcome of interest was all-cause mortality which was defined as death due to CVD; cerebrovascular disease; infectious disease; multiple organ failure; secondary malignant neoplasms; other reasons or unknown, as shown in n = 438) and a validation cohort (n = 205). Continuous variables were presented as mean ± SD or median (interquartile range) and compared using an ANOVA or the Kruskal–Wallis test as appropriate. Categorical variables were given as proportions and compared using a χ2 test. The 24-h urine output, age and Hgl were transformed into categorical variables. The remainder of the variables were evaluated as linear predictors. The Cox regression model was finally used to determine variable selection and constructed a model for predicting all-cause mortality in the training cohort. The hazard ratio (HR) and the 95% confidence interval (95% CI) were calculated as well. p<.05 was considered statistically significant for tests.The final cohort was randomly divided into a training cohort . Calibration was performed using bootstrapping with 1000 research resamples and assessed utilizing calibration plots, which measured the relationship between predicted probabilities and observed proportions. Decision curve analysis was conducted to determine the clinical usefulness of the survival nomogram by quantifying the net benefits at different threshold probabilities in the cohort. By using recursive partitioning tree analysis to generate the optimum cut of point, patients were categorized as ‘low’ or ‘high’ risk group, and the Kaplan–Meier curves were plotted for these two risk groups. Statistical analyses were performed using the SPSS software  and R software .The baseline characteristics of the two groups are summarized in In training cohort, univariable analysis found 12 candidate predictors that were closely associated with the all-cause mortality , includiMultivariable Cox regression and HRs were calculated for the prognostic factors used to establish the nomogram . In the The performance of the model in the training and validation cohorts was assessed using discrimination and calibration. The model showed good discrimination through ROC curves in two cohorts  and 4. TThe DCA of the nomograms is presented in We developed and validated a easy-to-use nomogram model for all-cause mortality risk among HD patients using seven easily available baseline variables to inform these patients about their future risk up to 10 years, incorporating the result of their clinical features. The prediction nomogram achieved sufficient accuracy and well discrimination which identified that this nomogram can be widely and accurately used for clinical doctors. In addition, the results may be used as guidance for preventive therapy, such as high Hgl and hypoglycemic therapy for patients with a high risk of mortality. However, on the basis of current risk prediction model, comparative studies must be conducted to assess the effectiveness of preventive treatment.Nomograms have frequently been used in cancer prognosis ; howeverWe developed a survival prediction model, which allowed early identification of HD patients at high risk of all-cause mortality. Hence, therapy decisions will be better performed and early interventions will benefit high risk HD patients, and perhaps the most attractive aspect of our nomogram model is its clinical feasibility and simple of use in a wide variety of department of medicine and health. For example, age 80 years who is an HD patient, is nonanemia (Hgl: 120 g/L), nondiabetic, and without CVD, HD was performed using AVF without history of emergency temporary dialysis catheter placement and has a caregiver, will have a total risk score of 54 points, which corresponds to a 1-, 5-, and 10-year probability of survival of 93%, 68%, and 46%, respectively . In contIn this study, we conducted a multivariable analysis of the included variables, and the results showed that age was an independent risk factor for death in HD patients. Elderly patients are prone to severe complications with poor body resistance and cognitive decline, quality of life decreases and mortality increases after initiation of dialysis, in particular, HD patients who lived alone and did not have caregivers during or after the HD treatment had a higher risk of death. As can be seen from the results of this study, the absence of caregivers was also significantly associated with increased mortality in HD patients; therefore, for elderly patients, especially those without caregivers, nurses should be increased to accompany them, meanwhile, doctors need to evaluate the potential complications more closely during dialysis treatment.The results also showed that CVD was an independent risk factor for death, previous studies have reported that CVD is the main cause of death in ESRD patients , our stuAlthough previous studies have done some good predictions of mortality in HD patients, for example, the vascular calcification score (AUC = 0.72), Anker’s model (c-index = 0.72–0.74), and Shastri’s model (c-index = 0.75) performed effective in predicting CVD mortality for HD patients ,24,25, cp< .05 were selected for the Cox analysis, which to some extent lost the related risk factors affecting death, so a larger sample size study was needed to confirm the findings of this study. Last, although the robustness of our nomogram was examined extensively with internally validation using bootstrap testing, the universality was uncertain for other HD patients, it needs to be externally assessed in wider HD populations.However, there are some limitations in this study. First of all, this study is a single-center study with a small sample size, which may increase the possibility of type II errors, and we developed a nomogram for predicting survival, but external validation was absent. At the same time, only those variables with univariate analysis results of This study developed a easy-to-use nomogram with good accuracy for predicting 1-, 5-, and 10-year survivals in HD patients. The simple and reliable score was designed to identify HD who were at high risk of death; therefore, this nomogram suggested treatment of anemia, disordered blood glucose levels, and CVD may be the key points to reduce all-cause mortality risk for HD patients; furthermore, it is also possible to improve the survival rate by reducing the use of semi-permanent dialysis catheter and avoiding temporary dialysis catheter implantation in case of emergency; the planned establishment of AVF prior to dialysis is advocated, in addition, having a caregiver for dialysis patient is also an important way to improve the survival.


Intralesional curettage is a commonly used treatment for primary bone tumors. However, local recurrence of tumors after curettage remains a major challenge.(1) Is blood pressure related to local recurrence after intralesional curettage for benign or intermediate bone tumors? (2) What’s the impact of tourniquet usage on the risk of recurrence from high blood pressure?p-value was < 0.2, variables were included in multivariable analyses to identify independent risk factors for local recurrence. Patients were then stratified by tourniquet usage (use/non-use), and risk from high blood pressure was evaluated in both subgroups.This retrospective study evaluated patients receiving intralesional curettage for primary bone tumors from January 2011 to January 2015. A total of 411 patients with a minimum five-year follow-up were included for analysis. Demographic and disease-related variables were first assessed in univariable analyses for local recurrence risk. When a yielded p = 0.005); tumor type; lesion size ; anatomical site ; and preoperative mean arterial pressure . In subgroup analyses, after adjusting for age, tumor type, lesion size, and anatomical site, tourniquet use modified the preoperative mean arterial pressure - recurrence relationship: when tourniquet was not used, preoperative mean arterial pressure predicted local recurrence ; when tourniquet was used, preoperative mean arterial pressure was not related to local recurrence .At an average follow-up of 6.8 ± 1.0 years, 63 of 411 patients (15.3%) experienced local recurrence. In multivariable analyses, local recurrence was associated with age (OR, 0.96; 95% CI, 0.94–0.99; A high preoperative blood pressure was related to local recurrence after intralesional curettage for primary bone tumors in our study. Tourniquet usage and controlling blood pressure might be beneficial for reducing local recurrence in patients scheduled to receive intralesional curettage for primary bone tumor treatment.Level IV, hypothesis-generating study.The online version contains supplementary material available at 10.1186/s12891-022-05157-4. Patie tumors . Howevere tumors –6.Generally, there are four major steps for intralesional tumor: curettage, high-speed burring, applying an adjuvant substance, and mechanical reconstruction . High-spDuring curettage, intramedullary hemorrhaging is commonly difficult to control when a tourniquet cannot be used, requiring blood transfusion in more than 50% of patients . Hence, However, it was at substantial risks to maintain intra-operative blood pressure at levels much lower than preoperative baseline . It is rWe asked the following research questions: (1) Is blood pressure related to local recurrence after intralesional curettage for benign or intermediate bone tumors? (2) What’s the impact of tourniquet usage on the risk of recurrence from high blood pressure?The study protocol was approved by and under the supervision of our institutional ethics committee . The procedures involved in collecting information from patients were carried out in accordance with all local laws and regulations.n = 162); who, at baseline, lacked magnetic resonance imaging (MRI) and/or computed tomography (CT) (n = 106); whose surgery was not performed by specialists of musculoskeletal tumor surgery (n = 56). The detail flow chart of the study was shown in Fig. We conducted a retrospective study of all patients with primary bone tumors treated between 2011 and 2015 with intralesional curettage at our hospital. In our institutional database, we identified 735 patients who underwent intralesional curettage for primary bone tumors during the study period. We excluded from the analysis patients who had less than 5 years of follow-up  and enchondromas. Cartilaginous tumors were diagnosed with available radiographic imaging by a multidisciplinary team . Other tumor types were diagnosed solely by the pathologists. Anatomical localization was defined by where the proximal tumor margin was rather than by the distal one or center of tumor mass.All surgical procedures were performed in a similar fashion by orthopedic oncology specialists at our institution. Briefly, the lesion-bearing bone was exposed via an appropriate approach, chosen at the discretion of the treating surgeon. A large cortical window was created using a thin oscillating saw. Curettage was performed using a series of straight and angled curettes to remove all visible tumor in the bone cavity. This was followed by high-speed burring and then aggressive curettage with phenol and ethanol to expand the tumor-free margin. Finally, the cavity was filled with allografts, autografts, or polymethylmethacrylate (PMMA) for mechanical reinforcement. The use of allografts, autografts or PMMA was usually chosen by the patient in pre-surgical consultation with surgeons explaining the potential benefits and risks. The treating surgeon determined whether to perform internal fixation and which type of implant to use.Postoperative follow-up was recommended at three-month intervals in the initial year and once per year after the initial year. The primary outcome was local recurrence after surgery. Local recurrence was defined by one or more of the following being present: (1) diagnostic histology of suspected tumor tissues obtained from biopsy or re-operation, (2) a static or slow-growing lesion with typical radiological finding(s) of local recurrence when re-operation is not indicated. The anesthesiologist measured intra-operative hemorrhage volume, which was determined by summing the intra-operative suction fluid volume and the volume accumulated from surgical gauzes, according to the gravimetric method . The prep < 0.05, unless otherwise noted. IBM SPSS version 26.0  was used. Univariable comparisons were evaluated with Fisher’s exact test or the Mann-Whitney U test, depending on whether the variables were categorical or continuous, respectively. When a yielded p value in the univariable analysis was p < 0.2, this variable was assessed in multivariable analysis to identify independent risk factors. Comparisons of local recurrence between patients grouped by tourniquet usage (use/non-use) were adjusted for patient- and disease-related variables from the multivariable analysis. Other variables were evaluated using Dunnett’s test for multiple comparisons.Continuous variables were summarized as means ± standard deviation (SD); categorical variables were summarized as counts with percentages (%), unless otherwise noted. All statistical group comparisons were two-sided and were considered significant at n = 163) were the most frequent site of tumors, followed by the distal humerus and more distal locations (n = 95), proximal femur (n = 69), proximal humerus (n = 59), and pelvis (n = 25).Data from 411 patients were available for analysis (Table p = 0.002). Fibrous dysplasia (FD) and giant cell tumor of bone (GCTB) accounted for the largest proportion , and GCTB had the highest local recurrence rate (24.0%). An increasing trend in local recurrence rate was observed with ascending of the blood pressure interval . The Kaplan-Meier survival curve  for recurrence-free survival in patients with high pre-op MAP (> 110 mmHg). Age, tumor type, lesion size, anatomical site, and pre-op MAP yielded p values of < 0.2 and thus were entered as independent variables in the multivariable analyses.Table p = 0.005); tumor type; lesion size ; anatomical site ; and pre-op MAP . The results of single disease analysis  were showed in the Supplementary material , and when age, tumor type, lesion size, and anatomical site variables were statistically controlled for, pre-op MAP , local recurrence risk was significantly related to pre-op MAP , we found that the pre-op MAP–recurrence relationship was modified by tourniquet usage Table . For patThere was evidence in support of our hypothesis that in patients with high pre-op MAP who underwent intralesional curettage without a tourniquet, intra-operative hemorrhage volume and hemorrhage velocity were higher Table . By contIntralesional curettage is a widely used treatment for primary benign bone tumors, while local recurrence of tumors remains a major challenge after curettage , 6. PrevMany previous studies have suggested patients might be at increased risk of local recurrence when the tumor was localized at more proximal sites  –31. As aTourniquet control, if used during intralesional curettage, could create a hemorrhage-free surgical field and thus could potentially modify the risk from high blood pressure. Thus, we further investigated the risk of blood pressure in subgroups of patients according to tourniquet use/non-use and found that the risk of intra-operative blood pressure was derived from cases lacking tourniquet use. It is preferable to maintain intra-operative blood pressure within 20% of preoperative baseline values . Thus, rAnother risk factor for local recurrence in our study was being younger at the time of surgery for intralesional curettage. This finding is consistent with the hypothesis that tumor cells tend to be more active and aggressive in younger patients , 34. AnoThis study was a retrospective evaluation and had several limitations imposed by such a design. First, due to its retrospective design, the possibility of selection bias might be present. However, all patients receiving intralesional curettage for their primary bone tumor during the study period were reviewed and rigorously assessed for eligibility, which should minimize the impact of selection bias. Second, phenol and ethanol for aggressive curettage were the preferred adjuvant treatment in the study period, while other adjuvant such as liquid nitrogen or argon gas for cryoablation was not available in our hospital, and its thermal effect might be neutralized by a continuous heat exchange mechanism of uncontrolled bleeding . There ip = 0.45), similar results could also be found in non-vascularized lesions (Table SAlthough primary or intermediate, inter-tumoral heterogeneity between different tumors inevitably existed for analysis of such different bone tumors. We did not find significant difference among groups of pre-op MAP in the single disease analysis but we could observe an absolute difference in local recurrence rate (e.g. GCTB; < 95 mmHg, 21.6% vs. 95–110 mmHg, 22.9% vs. > 110 mmHg, 40.0%; Finally, as a retrospective study, intra-operative blood pressure was not available in this research and we focused on patients’ pre-op MAP instead, hence the findings in this study might not be so conclusive and further larger prospective study should be needed for validation.In conclusion, a high blood pressure was related to local recurrence after intralesional curettage for primary bone tumors in our study. Tourniquet usage and controlling blood pressure to a reasonably low level might be beneficial for reducing local recurrence in patients scheduled to receive intralesional curettage for primary bone tumor treatment.Additional file 1.


Background and Objectives: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for cardiovascular disease. This study aimed to investigate the relationship between pulmonary hyperinflation and baroreceptor reflex sensitivity (BRS), a surrogate for cardiovascular risk.Methods: 33 patients with COPD, free from clinical cardiovascular disease, and 12 healthy controls were studied. Participants underwent pulmonary function and non-invasive hemodynamic measurements. BRS was evaluated using the sequence method during resting conditions and mental arithmetic stress testing.Results: Patients with COPD had evidence of airflow obstruction  and lung hyperinflation  compared to controls. Spontaneous mean BRS (BRSmean) was significantly lower in COPD, both during rest  and stress testing . Stroke volume (SV) was significantly lower in the patient group . RV/TLC was found to be a predictor of BRS and SV (P < 0.05 for both), independent of resting heart rate.Conclusion: We herewith provide evidence of impaired BRS in patients with COPD. Hyperinflation may influence BRS through alteration of mechanosensitive vagal nerve activity. Chronic obstructive pulmonary disease (COPD) is characterized as a common, preventable disease of the respiratory system, often associated with various extrapulmonary comorbidities like cardiovascular diseases , 2. PrevMoreover, there is evidence of impaired autonomic function and baroreceptor reflex sensitivity (BRS) in patients with COPD –9. ImpaiThus, the aim of the current study was to evaluate the relationship between hyperinflation and BRS in patients with stable COPD. An impairment in BRS compared to healthy controls with further deterioration concomitant to increases in airflow obstruction and hyperinflation was hypothesized.1%) of <50% according to GOLD criteria and a residual volume/total lung capacity (RV/TLC) of at least 50%, compared to healthy individuals  >55 mmHg and a body-mass-index (BMI) >35. All patients had to be ex-smokers with abstinence from smoking for at least 4 months.Patients were recruited from our outpatient clinic, undergoing evaluation for bronchoscopic lung volume reduction. They had to provide high-resolution computed tomography scan as well as echocardiography not older than 6 months and report a history of stable COPD, defined as a disease without exacerbations and changes in respiratory medication during the previous 4 months. Exclusion criteria furthermore were a history of and medication for any cardiovascular comorbidities, severe pulmonary hypertension or diabetes mellitus, a diffusion capacity of the lung for carbon monoxide (DLCO) <20%, giant bullae in the provided computer tomography, alpha-1-antitrypsin deficiency, prior thoracotomy, excessive sputum production, hypercapnia with an arterial partial pressure for carbon dioxide  and diastolic (BPdia) beat-to-beat arterial blood pressure were obtained by using the vascular unloading technique of the finger  . Mean arvice versa, progressive decreases in BPsys followed by a progressive shortening in PI (down-sequences). The slope of each regression line between BPsys and PI changes was taken as an index for the sensitivity of arterial baroreflex modulation of heart rate. Since PI, and not heart rate, is used for calculation, this ensures a positive direction of the slopes, regardless of up- or down-sequences. Only episodes with correlation coefficients greater than 0.95 were selected and from all regression lines a mean slope was calculated to account for BRS, both for up- and down-sequences (BRSup or BRSdown) and for each steady state period . The mean of BRSup and BRSdown was taken to indicate overall BRS (BRSmean), again both for resting condition and arithmetic stress testing. A patient example of BRS measurements was provided in the BRS was evaluated by the Task Force® Monitor using the sequence method –18. ThisSince an inverse relationship between heart rate and BRS had been described , we usedStatistical analyses were calculated using SPSS® . Figures were made using GraphPad Prism® . There was no formal sample size calculation. The number of patients and controls was chosen pragmatically.1/FVC, FEV1%, RV/TLC, FRC, BRSup, BRSdown, BRSmean) were logarithm-transformed. Normally distributed variables were indicated as arithmetic means, logarithmic normally distributed variables as geometric means after back transformation, both with their 95% confidence interval (CI).For descriptive statistics, variables were assessed for normal distribution using normal plots, whereby logarithmic normally distributed variables  was lower in the patient group but paCO2 did not differ. All patients were at least on dual long-acting bronchodilator therapy, 31 used triple therapy with inhaled corticosteroids.The baseline characteristics of the participants are summarized in r = −0.585, P < 0.001, r = −0.533, P < 0.001). Multivariable regression analysis showed lnRV/TLC to be a predictor of SV, independent of heart rate .Patients with COPD had significantly higher heart rate, both during rest and stress, higher blood pressure, lower SV and stroke index (SI) during rest compared to healthy subjects . SV and P = 0.397; P = 0.142). By using parameters of airflow obstruction and hyperinflation as continuous variables, a significant correlation with lnBRSmean during rest , whereby the effect with lnFEV1% diminished  . In a multivariable regression analysis, using lnBRSmean as well as lnRV/TLC as independent variables, this relationship was not significant anymore . LnRV/TLC, however, was found to be a significant predictor of lnBRSmean, independent of heart rate during each condition . Furthermore, there was no relationship between lnBRSmean and arterial blood gases, neither with paO2 nor paCO2 (P > 0.1 for both).= 0.661) . SimilarWe herewith provide evidence of impaired spontaneous BRS in patients with COPD. Furthermore, we were able to detect an independent relationship between hyperinflation and BRS in this report.Although COPD is primarily defined as a chronic inflammatory disease of the lungs, it is accompanied by a variety of systemic features like cardiovascular comorbidities , 2. TherThe autonomic nervous system with its baroreflexes ensures adaptation of blood pressure and heart rate and therefore stability of circulation during activities of daily living . BRS was1% 38.5 ± 15.8) compared to those in the current report and a relationship of BRS with pulmonary function parameters was not tested  on BRS, as all cardiovascular assessments were done post-bronchodilator therapy. Nevertheless, since all COPD patients were at least on dual bronchodilator therapy, the relationship between hyperinflation and BRS appears to be independent of concomitant antimuscarinic or sympathomimetic influences. An important strength of this study, however, is the comprehensive, non-invasive hemodynamic measurement taken by validated testing methods.Our results might have important therapeutic implications. Impairments in autonomic function may be—at least partially—reversible following pharmacological or non-pharmacological reductions in hyperinflation. In fact, improvements in cardiac function have previously been reported in response to volume reduction, by means of inhaled bronchodilators  as well In conclusion, we were able to observe impaired BRS in patients with COPD and hyperinflation compared to healthy controls. Subsequent studies should examine whether lung volume reduction procedures are able to improve baroreceptor function and thus reduce cardiovascular risk in patients with COPD.The original contributions presented in the study are included in the article/Ethical approval was not provided for this study on human participants because according to regulations of the Ethics Committee of the City of Vienna, the Institutional Review Board approved the study. The patients/participants provided their written informed consent to participate in this study.AM contributed to data analysis, statistical evaluations, interpretation and writing of the manuscript, and guarantees for its content. VW, SA, and IS contributed to subject recruitment, data collection, and investigation. G-CF contributed to data analysis and statistical evaluations. MU contributed to graphic design of figures. AV contributed to conceptualization, methodology, data analysis and interpretation, and writing of the manuscript. All authors contributed to manuscript revision, read, 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Diabetes-related kidney disease is associated with end-stage renal disease and a high mortality rate. However, data on risk factors associated with kidney disease in patients with newly diagnosed type 2 diabetes mellitus (DM) remains insufficient. The aim of the present study was to identify the risk factors significantly associated with chronic kidney disease progression in patients with newly diagnosed type 2 DM.We reviewed a total of 254 consecutive patients who were newly diagnosed with type 2 diabetes at Nanjing First Hospital from January to December 2014. They were observed for two years, and baseline and biochemical variables were used to identify significant predictors of kidney failure progression. Kidney failure progression was defined as a ≥ 30% increase in serum creatine level.p = 0.015) and microalbuminuria (p < 0.001) were associated with kidney failure progression in patients with newly diagnosed type 2 DM. Those with lower estimated glomerular filtration rate  at baseline had lower serum albumin levels compared to those of patients with higher eGFR. The albuminuria levels were higher in patients with lower eGFR than in those with eGFR ≥ 90 ml/min/1.73 m2. Receiver operating characteristic curve analysis showed that the area under the curve was 0.754 (95% CI [0.670–0. 0.837]).The mean age of patients was 58.96 years, 37.4% were women, and 57.1% had hypertension. Kidney function progressed in 40 patients (15.75%). Multivariable logistic regression analyses showed that serum albumin (The overall rate of chronic kidney disease progression is relatively high, and low serum albumin and high albuminuria levels are associated with kidney failure progression in newly diagnosed diabetic patients. Diabetes-related chronic kidney disease (CKD) has become more common than CKD related to glomerulonephritis in both the general population and a hospitalized urban population in China . DiabetiDM has approached epidemic proportions over the past decade worldwide. In China, the prevalence of diabetes has sharply increased. In a 2013 survey, 4% of adults have been previously diagnosed with diabetes ; 6.9% ofWe conducted a retrospective analysis on the clinical data of patients who were newly diagnosed with type 2 DM in Nanjing First Hospital from January 2014 to December 2014. Patients were excluded if they had the following: (1) acute complications of DM on admission, such as diabetic ketoacidosis; (2) severe infectious diseases on admission, fever, urinary tract infection, haematuria, glomerulonephritis; (3) severe cardiovascular diseases, such as stroke, myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, and heart failure; (4) severely impaired liver function; (5) psychiatric disorders or were pregnant or planning to conceive; (6) cognitive disorders, alcoholism, or history of drug abuse; (7) acute kidney injury upon admission and/or at the end of follow-up. Patients lost to follow-up or with incomplete data were also excluded. The patients ranged in age from 18 to 86 years. All patients had the same medical team for treatment and care. The study protocol was approved by the Institutional Review Board at Nanjing First Hospital, Nanjing Medical University, which waived the requirement for written informed consent from patients.2) = 175 × SCr-1.234*age-0.179 * 0.79 . Albuminuria levels were measured at the same laboratory by a chemiluminescent method using the IMMULITE 2000XPi immunoassay system . The results were divided into quartiles  and assigned a value . The diagnosis of acute kidney injury was based on a serum creatine level increase of ≥0.3 mg/dL (26.52 μmol/L) or ≥1.5- to twofold from baseline level and a urine output of <0.5 ml/kg/h for more than 6 h.Data from all participants were collected anonymously. Type 2 DM was diagnosed according to the American Diabetes Association 2010 criteria . BiochemKidney function decline was defined as a ≥ 30% increase in serum creatinine level. Patients whose serum creatine levels were increased because of acute kidney injury were excluded.p-value < 0.1 in the univariate analysis were then entered into a multivariable logistic regression analysis model to determine their net effects on kidney function decline. Odds ratios and their 95% confidence intervals (CIs) were used to assess the independent contribution of prognostic factors. A p-value < 0.05 was considered statistically significant.Data were analysed with PASW Statistics18 software (SPSS (Hong Kong) Ltd., Hong Kong, China). Continuous variables were expressed as mean ± standard error of the mean. Statistical significance of differences between groups were determined by t-test or one-way analysis of variance. Ordinal data were expressed as M , and a Wilcoxon rank sum test was used for comparisons between the two groups. Proportions were compared using the chi-squared test and Fisher’s exact test when the numbers were small. All variables were first analysed using univariate analysis. Variables with a n = 40). The baseline demographics and clinical characteristics of the patients are listed in n = 159). The mean body mass index of all enrolled was 25.21 ± 3.53, and 57.1% (n = 145) of them had a history of hypertension. Kidney function decline was more likely among patients with a history of hypertension and a larger hipline measurement.The incidence of kidney function decline was 15.75%  at baseline had lower serum albumin compared to those of patients with an eGFR 60–90 ml/min/1.73 m2 and eGFR ≥ 90 ml/min/1.73 m2 (2 (Those with lower eGFR level (30–60 ml/min/1.73 m/1.73 m2 . The alb73 m2 (2 .An ROC curve was created by plotting sensitivity against specificity at various threshold settings. The x-axis represents 1-specifity, and the y-axis represents sensitivity, the model was well calibrated, and the area under the ROC curve is shown in The present study was undertaken to investigate the risk factors associated with kidney function decline in newly diagnosed type 2 DM patients. A few studies had examined the risk factors for CKD progression in diabetic patients . HoweverIn the present study, we observed an association between albuminuria and kidney function decline in type 2 DM patients, and the predictive power of albuminuria for progressive kidney disease has previously been shown in diabetic patients . SeveralWe found that serum albumin was associated with kidney function decline in newly diagnosed diabetic patients independent of albuminuria. Previous studies have shown that low albumin levels are strongly associated with cardiovascular disease, heart failure, and mortality in vulnerable populations . LimitedOnly a few studies have so far reported that other risk factors independently predict CKD progression in diabetic patients. Our study has several limitations. First, the study was a retrospective, single-centre study, thus making it prone to bias. Second, there was sample size inequality between the groups, and accordingly, the observed significant differences may have been due to the small number of patients in the progression group.Low serum albumin and high albuminuria levels are strongly associated with CKD progression in patients with newly diagnosed type 2 DM. Additional prospective studies in humans are required to confirm this relationship and to understand the underlying mechanisms.10.7717/peerj.11735/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.11735/supp-2Supplemental Information 2Click here for additional data file.


According to the ROC curve, baseline NGAL levels performed better than eGFR to predict CI-AKI (AUC 0.753 vs. 0.604), with the optimal cutoff value for baseline NGAL to predict CI-AKI being 127 ng/mL . In a multivariate logistic regression model, the NGAL level >127 ng/mL ng/mL was independently associated with CI-AKI . Conclusion: Baseline serum NGAL levels in CKD patients may identify a high-risk population for CI-AKI following PCI. Further studies on larger populations are required to validate the potential utility of NGAL measurements in monitoring specific CKD-associated conditions.Background: The risk of contrast-induced acute kidney injury (CI-AKI) following coronary intervention is particularly high among patients with chronic kidney disease (CKD). Among these patients, baseline neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular damage, reflects the severity of renal impairment. We evaluated whether the baseline serum NGAL level may be a marker for the development of CI-AKI following percutaneous coronary intervention (PCI). Methods: Eighty-eight CKD patients treated with PCI were included. Serum NGAL levels were drawn upon hospital admission. Receiver operator characteristic (ROC) methods were used to identify the optimal sensitivity and specificity for the observed NGAL level compared with the estimated glomerular filtration rate (eGFR) calculated for patients with CI-AKI. Results: Overall CI-AKI incidence was 43%. Baseline serum NGAL levels were significantly higher in patients with CI-AKI than in patients without CI-AKI (150 vs. 103 ng/mL,  Contrast-induced acute kidney injury (CI-AKI) is a common complication among patients undergoing percutaneous coronary intervention (PCI). Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein stored in granules of mature neutrophils released by renal tubular cells following acute tubular damage ,2,3. In We performed a prospective, observational, open-label trial at the Tel Aviv Medical Center. We included patients with CKD admitted to the cardiology ward following PCI between December 2018 and March 2020. The presence of baseline CKD was determined based on past laboratory data and medical reports, as well as admission serum creatinine, and was available for all included patients. Based on the availability of NGAL kits, the study population consisted of 88 patients undergoing PCI. Iodixanol was used as a contrast agent . Physiologic normal saline (0.9%) was administered intravenously at a rate of 1 mL/kg/h for 12 h following exposure to contrast material, although for patients with overt heart failure The hydration rate was reduced for patients with overt heart failure at the physicians’ discretion. The study protocol was approved by the local institutional ethics committee .Serum samples for baseline NGAL were collected within 12 h following hospital admission. Samples were centrifuged within 10 min of collection using a cooled centrifuge, and plasma and serum were stored at −20 °C. NGAL levels were analyzed using NGAL rapid turbidimetric immunoassay .2 based on past laboratory reports, admission blood samples, and patient data. CI-AKI was defined using the KDIGO criteria as either: an increase in sCr by 0.3 mg/dL or more within 48 h following PCI or an increase in sCr above 1.5 times the baseline within seven days of PCI [Baseline venous blood samples were used for sCr and high sensitivity C-reactive protein (CRP) level measurements. sCr was also tested repeatedly on a daily basis during hospitalization for all included patients. CRP levels were analyzed quantitatively using the Bayer wide-range assay. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation . CKD wass of PCI .t-test for normally distributed data and the Kruskal–Wallis test for non-normally distributed variables. Spearman’s rank correlation was used to measure the correlation between the logarithmic transformations of NGAL and eGFR. Receiver operator characteristic (ROC) curve analysis was performed to identify the optimal cutoff point of serum NGAL levels and eGFR  for the prediction of CI-AKI. The area under the curve (AUC) was calculated as a measure of the accuracy of the tests. A multivariate logistic regression model was used to assess the association between serum NGAL levels and AKI, as well as control potential confounders. Initially, univariate regression was employed, and variables with a p-value < 0.1 were included in the multivariate binary logistic regression model. A two-tailed p-value < 0.05 was considered significant for all analyses. All statistical analysis was performed using R statistical software .Categorical variables were expressed as frequencies and percentages. The distribution of continuous variables was assessed using histograms and quantile–quantile plots. Normally distributed continuous variables were displayed as means (± standard deviations), and non-normally distributed variables were displayed using median and interquartile range (IQR). Fisher’s exact test was used to evaluate the association between categorical variables. Continuous variables were compared using the independent sample p < 0.001). Serum NGAL was significantly and inversely correlated with eGFR , 38 (43%) of whom developed CI-AKI throughout hospitalization. Baseline characteristics and laboratory results for CKD patients with vs. without CI-AKI are presented in p < 0.001)  with the optimal cutoff value for baseline NGAL to predict CI-AKI being 127 ng/mL  .p = 0.01). Other factors associated with CI-AKI included age, smoking history, and CRP.Hazard ratios with corresponding 95% confidence intervals of the univariate and multivariate binary logistic regression for the development of CI-AKI are summarized in We demonstrated for the first time that, among CKD patients undergoing PCI, baseline NGAL levels were inversely correlated with eGFR. Furthermore, baseline NGAL performed better than eGFR as a marker of CI-AKI, with levels >127 ng/mL independently associated with CI-AKI.CI-AKI following PCI is common, and even minute increases in sCr are associated with longer hospitalizations and unfavorable in-hospital and long-term outcomes. Among the various risk factors for CI-AKI, CKD ranks highly, with up to 50% of CKD patients developing this complication following contrast exposure ,14. TherNGAL, a 25-kDa protein covalently bound to gelatinase proteins in human neutrophils, was reported as an early marker of kidney tubular injury in various patient populations and hence was nicknamed “kidney troponin” ,7,8,9. PNGAL was originally isolated from the supernatant of activated human neutrophils but is also expressed at a low level in other human tissues, including the kidney . NGAL isWorsening renal function may enhance overall inflammatory responses due to the decreased renal clearance of various factors directly or indirectly involved in the inflammatory cascade. In humans, deteriorating renal function may also affect the levels of additional inflammatory markers . In the Our findings suggest that the measurement of baseline plasma NGAL levels can assist in the stratification of those at high risk of further deterioration, as nearly 50% of patients with CKD demonstrated acute on chronic renal impairment. This type of patient profile is increasingly frequent among patients undergoing PCI, and, for these high-risk patients, preventive measures could help to limit renal damage and reduce mortality, as the available treatments for CI-AKI, once diagnosed, are limited. In these patients, in addition to pre-PCI hydration, one may consider deferring the use of drugs that may be potentially nephrotoxic  and monitoring post-PCI serum NGAL for the early detection of early subclinical renal insult.The current study has notable limitations. This is a single-center study with a modest sample size. In addition, our study is based on measurements of serum NGAL. The addition of urinary NGAL measurements to the analysis would have strengthened our conclusions; however, kits for measurements of urinary NGAL were not available for our institution. In patients with chronic renal insufficiency, urinary NGAL did not appear to have any predictive value for identifying those who would go on to develop CI-AKI ,25. BaseAmong CKD patients, baseline NGAL levels may identify a population with a high risk for the development of CI-AKI. Further studies on larger populations are required to validate our reports and evaluate the potential utility of NGAL measurements in monitoring specific CKD-associated conditions.


Lower blood pressure (BP) levels are linked to a slower decline of kidney function in patients with chronic kidney disease (CKD) without kidney replacement therapy. However, there are limited data on this relation in peritoneal dialysis (PD) patients. Here we evaluated the association of BP levels with the decline of residual kidney function (RKF) in a retrospective cohort study.3M) into four groups  according to the 2018 European Society of Cardiology and European Society of Hypertension Guidelines for the management of arterial hypertension.We enrolled 228 patients whose PD was initiated between 1998 and 2014. RKF was measured as the average of creatinine and urea clearance in 24-hr urine collections. We calculated the annual decline rate of RKF by determining the regression line for individual patients. RKF is thought to decline exponentially, and thus we also calculated the annual decline rate of logarithmic scale of RKF (log RKF). We categorized the patients’ BP levels at 3 months after PD initiation (BP3M levels (P for trend <0.01). Compared to those of the Optimal group, the multivariable-adjusted odds ratios  for the faster side of the median decline rate of RKF and log RKF were 4.04 (1.24–13.2) and 5.50 (1.58–19.2) in the Grade 2 and 3 hypertension group, respectively (p<0.05).The unadjusted, age- and sex-adjusted, and multivariable-adjusted decline rate of RKF and log RKF decreased significantly with higher BPHigher BP levels after PD initiation are associated with a faster decline in RKF among PD patients. Regardless of the dialysis modality, the preservation of residual kidney function (RKF) is an independent predictor of survival in patients with chronic kidney disease (CKD) G5D –6. Even II receptor blockers (ARBs) slowed the decline of RKF [Several factors that influence the decline of RKF during PD therapy have been revealed. Increased proteinuria  and hypee of RKF . TherapeHypertension is a strong risk factor for the progression of CKD , and thuThe subjects were 178 patients who began PD therapy at Munakata Medical Association Hospital and 89 patients at Kyushu University Hospital between August 1998 and March 2014 , whose data was obtained from the records in March 2016. None of the patients had undergone kidney transplantation or had switched from hemodialysis to PD. Four patients who were followed-up for <6 months were excluded. Thirty-five patients were excluded because of inappropriate data or because RKF measurement was obtained less than twice. As a result, 228 patients were included in this study. The study protocol was approved by the Local Ethics Committee of Kyushu University Hospital (No. 21–16) and was registered at the University Hospital Medical Information Network (UMIN000018902). For those who could be contacted, written consent was informed. However, for those who could not be contacted because of the end of hospital visit or death, written consent was not informed. For those who could not, we applied opt-out method on this retrospective study. The ethics committee specifically approved our opt-out method of consent for patients who were not reachable, which contents are specified in the research proposal. And also, the analysis used anonymous clinical data.−1.094 × age−0.287  [The following demographic, clinical, and biochemical parameters were assessed just before the start of each patient’s dialysis therapy: age, sex, presence/absence of diabetes mellitus, body mass index (BMI), previous history of cardiovascular disease (CVD), blood hemoglobin, serum albumin, and serum creatinine. The BMI was calculated as the weight in kilograms divided by the square of height in meters. The estimated glomerular filtration rate (eGFR) was calculated using the equation developed by the Japanese Society of Nephrology: eGFR = 194 × sCr3M). BP measurements were obtained using a standard mercury sphygmomanometer or an automated device. Subjects were categorized into the following four groups according to the 2018 European Society of Cardiology and European Society of Hypertension Guidelines for the management of arterial hypertension [BP was assessed with the patient in the sitting position during routine examinations at our outpatient department at the time point of 3 months after PD initiation . Results are expressed as the numbers of patients (percentages) or frequencies, or as the median and interquartile range (IQR) (first to third quartiles) for continuous variables. The linear trends in the means and the frequencies of risk factors across BP categories were tested using a linear regression analysis and Cochran-Armitage trend test, respectively. The multivariate-adjusted means of the decline rates of both RKF and log RKF according to BP levels were calculated with an analysis of covariance (ANCOVA) and compared with Dunnett’s t-test. The odds ratio (OR) with the 95% confidence interval (CI) for a faster decline in RKF  was analyzed by univariate and/or multivariable-adjusted logistic regression. The OR for a faster log RKF decline rate was analyzed in the same manner as the RKF decline rate. The variance inflation factor (VIF) of all parameters was checked in all multivariate analyses in order to avoid multicollinearity. Values of p<0.05 were considered significant in all analyses.2/year and −0.54 (−1.08– −0.23) log(ml/min/1.73m2/year), respectively. The median age of patients was 62 (52–72) years. There were 147 males (64.5%) and 78 diabetics (34%). The baseline subject characteristics according to BP categories are shown in 3M levels. The uses of RAS inhibitors and diuretics were not different between 1 month and 3 months after the initiation of PD.The overall median (IQR) decline rate of RKF and that of log RKF were −1.09 (−1.93– −0.59) ml/min/1.73m3M levels were analyzed. The unadjusted and the sex- and age-adjusted decline rates of RKF gradually decreased with higher BP3M levels  to the same analysis as the BPM levels  Figs. ThM levels , but the3M. Among the patients in the original Optimal group, patients with systolic blood pressure < 100 mmHg were regrouped as Optimal 1 (O1) and the others were classified as Optimal 2 (O2). We also analyzed the five groups of O1, O2, N, G1, and G2-3. Only five patients were included in O1 group; the remaining 22 patients were in the O2 group. The mean RKF decline rate was lower in the O1 group compared to the O2 group, but this association disappeared in the log RKF decline rate. There were no significant differences between the O1 and O2 groups in RKF or log RKF decline rate . The multivariable-adjusted OR for a faster decline in RKF was 4.04 (95% CI: 1.24–13.2) in the G2–3 group compared to the O group.We assessed the OR for a faster decline in RKF, which we defined as the faster side separated by the median decline rate of RKF . The incWe performed the same analysis for a faster decline in log RKF. The incidence of a faster decline in log RKF was 25.9% for O, 35.1% for N, 57.3% for G1, and 63.8% for G2–3 patients, with a linear trend (p for trend <0.001). This association remained unchanged after adjusting for the confounding factors. The multivariable-adjusted OR for a faster decline in log RKF was 5.50 (1.58–19.2) in the G2–3 group compared to the O group.3M levels, or between the decline rate of log RKF and BP3M levels .We assessed the multivariable-adjusted mean decline rate of RKF and that of log RKF with the 95% CI in the subgroups stratified by sex, age, and presence/absence of diabetes Tables  and 4. TThe VIF of all parameters was <2.1, which indicated that there was no multicollinearity.3M levels. This association remained unchanged even after adjustment for the confounding factors. In the multivariable-adjusted logistic regression analysis, the OR for a faster decline of RKF gradually increased with higher BP3M levels. The same relationship was observed between the OR for a faster decline of log RKF and higher BP3M levels. This indicates that the higher the BP3M level is, the faster the decline of RKF is. We therefore speculate that optimal BP control is important for the preservation of kidney function not only before dialysis therapy but also after PD initiation. Our results indicate that the 2018 ESC/ESH classification of office BP and definitions of hypertension grade can be applied to PD patients in terms of RKF preservation.Our analyses revealed that the decline rate of RKF was negatively correlated with BPHypertension is a strong risk factor for the onset and deterioration of CKD , and thuWe used the parameter of blood pressure after 3 months of PD initiation as a predictor of RKF decline, and our findings revealed that this parameter was significantly associated with the decline rate of RKF. However, blood pressure just before PD initiation was not associated with the decline rate of RKF, which was also reported in several previous investigations , 27, 28.The International Society for Peritoneal Dialysis (ISPD) guidelines indicate that control of volume overload is the first line of hypertension treatment in PD patients . Therefo3M levels, as did the decline rate of RKF. Several studies have reported that the decline rate of RFK is exponential rather than linear [3M levels remained associated with not only the decline rate of RKF but also that of log RKF. There is a possibility that the decline rate of log RKF represents the decline of RKF more accurately in PD patients. In other cohort studies, the decline of RKF was assessed based on kidney survival before the patient’s urine volume decreased to a specific volume or less . Therefore, the interval until an endpoint is reached can be shortened in patients with delayed PD initiation. If a decrease in urine volume is established as an outcome of a kidney survival analysis, a low eGFR might become a risk factor. We therefore did not use the urine volume as an outcome.We calculated the decline rate of the logarithmic scale of RKF and analyzed it in the same way as the decline rate of RKF. A faster decline rate of log RKF remained associated with higher BPn linear , 23, 24.n linear , 27, 31.Many studies have consistently shown a J-shaped relationship between mortality and lowest and highest BP in CKD G5D patients . This re3M levels were measured only once during the outpatient visit. Since these levels were not measured multiple times, they may not reflect the accurate BP levels. Fourth, the parameters used in multivariable-adjusted analysis did not include parameters related to fluid volume, such as the cardiothoracic ratio or echocardiography findings.This study has several limitations. First, it was a retrospective observational study with a small number of samples, and the data were obtained from two hospitals. Confounding factors might also have influenced the results. It might not be possible to apply our findings to PD patients from other hospitals. In the future, the decline rate of RKF should be evaluated in a large, multicenter, prospective study. Second, there might have been inter-individual differences in the accuracy of the RKF slopes, because neither the follow-up period nor the frequency of RKF measurement was standardized among the patients when we calculated the RKF slope. These two parameters should be standardized among subjects to produce accurate RKF slope data. In addition, almost all of the samples examined herein were brought to the outpatient clinic. Although it is probable that most patients were able to store urine correctly based on the detailed explanation of urine collection that were given, it cannot be denied that urine may not have been stored accurately in some samples and patients. Third, the patients’ BPIn conclusion, our study revealed for the first time that a higher blood pressure level, not just before PD initiation but after 3 months of PD initiation was associated with a slower RKF decline. Appropriate blood pressure control might be important for maintaining RKF not only before dialysis therapy but also after PD initiation.S1 FigA: The unadjusted decline rate of RKF among the preBP groups. B: The sex- and age-adjusted decline rate of RKF among the preBP groups. C: The multivariable-adjusted decline rate of RKF among the preBP groups. *p<0.01 vs. O. Adjusted covariates are as in (TIF)Click here for additional data file.S2 FigA: The unadjusted decline rate of log RKF among the preBP groups. B: The sex- and age-adjusted decline rate of log RKF among the preBP groups. C: The multivariable-adjusted decline rate of log RKF among the preBP groups. Adjusted covariates are as in (TIF)Click here for additional data file.S3 FigA: The unadjusted decline rate of RKF among the BP3M groups. B: The sex- and age-adjusted decline rate of RKF among the BP3M groups. C: The multivariable-adjusted decline rate of RKF among the BP3M groups. *p<0.01 vs. O2, †p<0.05 vs. O2. Adjusted covariates are as in (TIF)Click here for additional data file.S4 FigA: The unadjusted decline rate of log RKF among the BP3M groups. B: The sex- and age-adjusted decline rate of log RKF among the BP3M groups. C: The multivariable-adjusted decline rate of log RKF among the BP3M groups. *p<0.01 vs. O2. Adjusted covariates are as in (TIF)Click here for additional data file.