The main objective is to study the effect of diabetic nephropathy on pulmonary function and clinical outcomes.  The method is to retrospectively analyze patients with diabetic nephropathy (DN) in our hospital from April 2018 to March 2022 as study subjects. The differences in baseline data, serum indicators, renal function indicators, and pulmonary function of patients at different clinical stages were analyzed and then explored. Finally, logistic regression was used to analyze the risk factors affecting patients' clinical outcomes and to evaluate the diagnostic effects. P < 0.01); multiple logistic regression analysis showed that SBP, HbA1c, FBG, 2hPG, BUN, Scr, TLC, VC, FEV1/FVC, MVV, DLCO, and DLCO/VA were all key factors in the development of clinical outcomes in DN (P < 0.05). ROC analysis showed that all of these important factors had an AUC greater than 0.75 for the diagnosis of DN with high sensitivity and specificity.  Baseline information , serum indicators , renal function indicators , and pulmonary function  were significantly different ( Serum and renal function indices of DN patients gradually increased with stage, accompanied by a decrease in pulmonary ventilation, and diffusion function; SBP, HbA1c, FBG, 2hPG, BUN, Scr, TLC, VC, FEV1/FVC, MVV, DLCO, and DLCO/VA were all key factors affecting the clinical outcome of DN; controlling blood glucose, lipids, improving pulmonary ventilation, and diffusion function can better prevent the occurrence and worsening of DN. Diabetic nephropathy (DN) is a diabetic (DM) lesion involving the kidneys, and approximately 40% of patients develop this microvascular complication, greatly increasing morbidity and mortality in DM patients . DN is aDN is a complex disease influenced by several factors, including susceptibility factors , primary factors , and secondary factors  , 11. TheBased on this, this study used statistical analysis to investigate the impact of diabetic nephropathy on pulmonary function and clinical outcomes and to screen the main influencing factors of clinical outcomes, aiming to provide a laboratory basis for early diagnosis as well as prevention and treatment of the disease. The study is reported as follows.μg/min and exclusion of ketoacidosis, exercise, urinary tract infections, and other renal diseases.A total of 183 children diagnosed with DN in the hospital from April 2018 to March 2022 were recruited as research objects. DM was diagnosed with a random blood glucose (2hPG) ≥ 11.0 mmol/L, fasting blood glucose (FBG) ≥ 7.0 mmol/L, and 2-hour blood glucose (2hPG) ≥ 11.0 mmol/L. DN was defined as more than 2 urinary albumin excretion rates (AER) greater than 20 DN staging criteria (Mogensen staging) were as follows: Stage III: microalbuminuria (early diabetic nephropathy), patients with approximately normal GFR and irreversible renal disease. Stage IV: massive proteinuria, urinary protein >0.5 g/d, late GFR down to 20. Stage V: renal failure, GFR <20, extensive glomerulosclerosis, and rapid deterioration of renal function until renal failure occurs.Inclusion criteria were as follows: all patients met the diagnostic criteria for DN, aged 18–80 years old, and who had completed all index examinations and complete clinical data upon admission. Patients who had been treated with glucose-lowering, antihypertensive, and lipid-lowering drugs within the last month, patients with kidney damage such as urinary tract infections, nephritis, and renal vascular stenosis, and patients with combined cardiovascular and cerebrovascular diseases, tumours, and immune system diseases were excluded. The study was approved by the hospital ethics committee, and all patients signed an informed consent form.Fasting blood samples from patients with DN were collected using EDTA anticoagulation tubes (fasting for at least 8 hours) and centrifuged for 15 minutes at room temperature. The serum was carefully separated and packed into centrifuge tubes and then stored in a refrigerator at 80 degrees. Serum AER, glycosylated hemoglobin (HbA1c), FBG, 22hPG, triglyceride (TG), total cholesterol (TC), and low density lipoprotein (LDLC) were detected by enzyme-linked immunosorbent assay (ELISA). At the same time, renal function indexes, cystatin C (CysC), urea nitrogen (BUN), and serum creatinine (Scr) were measured. In addition, the baseline data of patients with DN were collected, including age, gender, course of the disease, smoking history, drinking history, BMI, systolic blood pressure (SBP), and diastolic blood pressure (DBP).A spirometer was used to measure the pulmonary function parameters of DN patients, total lung volume (TLC), lung volume (VC), exertional expiratory volume in 1 second (FEV1), exertional expiratory volume in 1 second rate (FEV1/FVC), maximum ventilation volume (MVV), maximum expiratory flow in 25% of lung volume (MEF50), 50% (MEF50), 75% (MEF75), exhaled gas 25%–75% mean flow rate of lung volume (MEF25-75), lung carbon monoxide dispersion (DLCO), and carbon monoxide dispersion per alveolar volume (DLCO/VA). The instrument was calibrated before use, and each item was repeated 3 times to obtain the maximum value of the desired curve. All tests were done at 8–10 points and performed by the same operator.n%), and χ2 test was conducted. The measurement data such as different indicators were expressed as mean ± standard deviation (s) using the t-test, with P < 0.05 indicating a statistically significant difference. GraphPad Prism 9 software was used to visualise the results of the statistical analysis. Multiple logistic regression was used to perform risk factor analysis for clinical outcomes in DN. ROC curves were used to analyze the predictive outcomes of the included indicators in DN clinical outcomes, with an AUC >0.75 indicating accurate results.mSPSS 22.0 software was used for statistical processing and analysis. The counting data from baseline data were expressed as percentages (P < 0.05). In addition, there were significant differences in SBP indicators between DN patients with stage IV and stage V. However, there were no significant differences in gender (P=0.44), smoking (P=0.74), and alcohol consumption (P=0.81) among DN patients with stage IV. This suggests that age, disease duration, BMI, SBP, and DBP may influence the development of DN.Baseline data on age, gender, disease duration, smoking history, alcohol history, BMI, systolic blood pressure (SBP), and diastolic blood pressure (DBP) of DN patients are shown in P < 0.5); the indicators of HbA1c, FBG, 2hPG, TG, TC, and LDLC were also significantly higher in patients with stage V DN than in patients with stage IV; similarly, the indicators of renal function CysC, BUN, and Scr also showed the same results. In conclusion, serum indicators HbA1c, FBG, 2hPG, TG, TC, and LDLC and renal function indicators CysC, BUN, and Scr may be key markers for DN staging.To further investigate the changes in indicators in different stages of DN, we mainly measured serum indicators  and renal function indicators . As shown in P < 0.01), and each index was also significantly higher in DN patients with V stage compared to those with IV stage (P < 0.01). This suggests that the involvement of the lungs in DN correlates with the different stages of the disease and that the higher the stage, the more severe the impairment in lung ventilation and diffusion function.To examine the cumulative lung profile of DN, we similarly tested pulmonary function indicators  in patients with different stages of DN, and the results were shown in P < 0.01) for both occurring and nonoccurring clinical outcome events, except for gender (P=0.77), with higher baseline profile levels, serum and renal function indicator levels for occurring outcome events, and lower for pulmonary function indicators. It is suggested that age, disease duration, history of smoking, history of alcohol consumption, BMI, systolic blood pressure, diastolic blood pressure, serum, renal function, and pulmonary function may be risk factors for clinical resolution in patients with DN.To explore the influence of each index on the clinical outcome of patients with DN, the differences in baseline data , serum indexes , renal function indexes , and pulmonary function  were also analyzed. As shown in P=0.028], glycemic index HbA1c , FBG , and 2hPG  BUN , and ScrEXP(B) (95% CI) = 1.956 (1.157–3.065), P=0.041] could significantly improve the incidence of clinical outcomes.To further screen for key factors predisposing to clinical outcomes, we used logistic regression to analyze the correlation between baseline data, serum indices, renal function indices, and pulmonary function and clinical outcomes. The results  showed thttps://www.DeepL.com/Translator(free version), TLC, VC, FEV1/FVC , MVV, DLCO , and DLCO/VA . It can significantly reduce the risk of clinical outcome events. To sum up, SBP, serum indexes , renal function indexes (BUN and Scr), and pulmonary function  may be the key factors affecting the occurrence of clinical outcome in DN.Translated withTo further assess the efficacy of key factors affecting clinical outcomes in DN, we plotted ROC curves for each factor versus clinical outcomes. The analysis results  showed tβ and type IV collagen, with oxidative stress and inflammation. In addition, stage I obesity 1.36 (95% CI 1.10–1.67), stage II obesity 1.43 (95% CI 1.16 CI 1.78), and stage III obesity 1.32 (95% CI 1.05 color 1.66) significantly increased the risk of DN compared to normal BMI. The literature [Abnormalities in blood glucose, blood pressure, and renal function affect the development and progression of DN . Hyperglterature  found thAbnormalities in pulmonary ventilation and diffusion function are associated with the development of DN . DN poseThis study only preliminarily explored the impact of DN on lung function and clinical outcomes at the clinical level, while the mechanisms of DN itself are extremely complex in terms of occurrence and treatment. In subsequent studies, a large number of animal and cellular experiments are needed to explore the regulatory mechanisms of various factors and provide protocols for the personalized prevention and treatment of DN.This study used statistical analysis to investigate the effects of diabetic nephropathy on pulmonary function and clinical outcomes and screened key influencing factors on clinical outcomes. Preliminarily, we obtained that controlling blood glucose, blood pressure, and improving pulmonary ventilation and diffusion function can better prevent the occurrence and deterioration of DN, which is a retrospective study, but this study is a retrospective study and has a small sample size, and a prospective design of a large sample size and multicenter study is needed to verify the correctness of the findings.


A prospective study was conducted in the medical intensive care unit. The radial and femoral were simultaneously measured MAP in the patients every hour, for 24 h. In total, 706 paired data points were obtained from 32 patients. MAPradial strongly correlated with MAPfemoral . However, overall MAPradial was significantly lower than MAPfemoral 7.6 mmHg. The bias between MAPradial and MAPfemoral was − 7.6 mmHg (95% limits of agreement (LOA), − 24.1 to 8.9). In the subgroup of patients with MAPradial < 65 mmHg, MAPradial moderately correlated with MAPfemoral (r = 0.63) and the bias was increased to − 13.0 mmHg . There were 414 (58.6%) measurements in which the MAP gradient between the two sites was > 5 mmHg. In conclusion, the radial artery significantly underestimated MAP compared with the femoral artery in patients with refractory shock.Radial and femoral artery catheterization is the most common procedure for monitoring patients with shock. However, a disagreement in mean arterial pressure (MAP) between the two sites has been reported. Hence, the aim of this study was to compare the MAP from the radial artery (MAP Accurate blood pressure monitoring may lead to proper fluid management and decrease unnecessary vasoactive administration.Invasive arterial blood pressure measurement is essential for hemodynamic monitoring in patients with shock admitted to intensive care unit (ICU). Fluid and vasoactive administration are the fundamental management strategies in patients with shock. However, administration of more fluid and large doses of vasopressors are associated with an increased risk of death and organ failure in these shock patients4. The second most cannulated artery is the femoral artery. Theoretically, peripheral sites have greater systolic blood pressure (SBP) and lower diastolic blood pressure (DBP) than more central sites, due to the pulse amplification of pressure waves. However, mean arterial pressure (MAP) remains stable, regardless of the site of the arteries5.Ideally, measurement of central aortic pressures is the gold standard for blood pressure measurement; however, this procedure is invasive and unsuitable for routine clinical practice. Therefore, alternative arteries are used. The most frequently cannulated artery is the radial artery, because of ease of access and fewer complications7, cardiopulmonary bypass10, liver transplantation12, and in septic shock patients14. Previous studies in patients with shock receiving high doses of norepinephrine found that MAP from the femoral artery  was higher than the radial artery , ranging from 4.3 to 15 mmHg and 62–75.4% of cases had a MAP gradient ≥ 5 mmHg15. In contrast some studies in critically ill adult patients17 and pediatric cardiac surgical patients18 reported good agreement between MAP from both sites and concluded that MAPradial was interchangeable with MAPfemoral and should be used for blood pressure monitoring in critically ill patients receiving high doses of vasopressors17.Nevertheless, the difference in MAP between the radial and femoral arteries has been reported in several critically ill patients, such as cardiac surgeryradial and MAPfemoral, as well as the best choice of blood pressure monitoring in patients with severe shock, peripheral or central arterial catheterization, remains controversial. If the MAPradial underestimates the MAPfemoral, it may result in an excess of fluid and vasopressor therapies. In addition, the factors associated with the radial-femoral MAP gradient have never been evaluated. The purpose of this study was to determine the correlation and agreement between simultaneous measurements of MAPradial and MAPfemoral in patients with refractory shock and to explore the clinical factors associated with the MAP gradient between the two sites.Thus, definitive information about the gradient between MAPThis prospective study was conducted in the medical ICU of a university-affiliated, tertiary referral center in Southern Thailand, from; May 2019 to October 2020. The study was approved by the Human Research Ethics Committee of Faculty of Medicine, Prince of Songkla University (REC: 62-008-14-4) and was registered in the Thai Clinical Trials Registry (TCTR20190603002) and was conducted under the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from the next of kin of all the patients before inclusion to the study.20. In this study, we defined patients with refractory shock as those receiving an infusion of ≥ 0.5 µg/kg/min of norepinephrine equivalent 20. The inclusion criteria were as follows: (1) patients with shock who received at least four hours of norepinephrine equivalent ≥ 0.5 µg/kg/min and (2) patients with radial artery catheterization. The exclusion criteria were as follow: (1) contraindication to femoral arterial catheterization, including overlying skin infection, clinical history of severe peripheral vascular disease of the lower limbs, or critical limb ischemia; (2) patients with radial artery catheter malfunctioning, detected by the “fast-flush test” showing overdamping or underdamping of the pressure monitoring systems4; (3) use of intra-aortic balloon counterpulsation; and (4) post-cardiac surgery.There is no definite consensus on the definition of refractory shock. However, in general, it can be summarized as; a shock that does not achieve hemodynamic targets, despite the use of high dose vasoactive agents21. The arterial catheters were connected to non-compliant pressure tubing and two pressure transducers . Both transducers were placed at the same level (phlebostatic axis) and simultaneously zeroed to the atmospheric pressure. The pressure transducer systems were connected to a bedside hemodynamic monitor . A fast-flush test was performed to confirm the adequacy of the frequency response and damping coefficient4.In our ICU, the radial artery was cannulated with a 20G 3.2-cm catheter . For femoral catheterization, a 20 cm 16G single lumen catheter  was used. The catheters were inserted into the femoral artery using the Seldinger technique under ultrasound-guidanceThe following variables were recorded at inclusion were: age, sex, body weight and, height, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, type of shock, type and dose of vasopressor, and types and sites of infection. ICU mortality was also recorded. SBP, DBP, and MAP from two sites, doses of all the vasopressor provided were recorded after femoral catheterization for 10 min and thereafter, every one hour for 24 h by the ICU nurses .The sample size of the study was calculated by assessing agreement between two methods of measurement by Bland–Altman methodCategorical variables are expressed as numbers and percentages. The distribution of variables for normality was tested using the Shapiro–Wilk test. Continuous variables are expressed as mean ± standard deviation (SD) or median and interquartile range (IQR) as appropriate.radial and MAPfemoral. The multilevel mixed-effect model was used to determine the statistical differences between MAPradial and MAPfemoral24. The multilevel model was constructed using the arterial site as a fixed effect with random intercepts for both patients and sequential measurement within the patient levels. Bland–Altman analysis with corrected multiple measurements was used to evaluate the agreement between MAP from both sites25. The bias and 95% limits of agreement (LOA) of the simultaneous measurements were calculated. Bias was defined as the mean difference between MAPradial and MAPfemoral. LOAs were calculated as the mean bias ± 2SD. We also performed a bias plot using the Taffé method27, defining MAPfemoral as a standard reference method, and MAPradial as a new method. Briefly, the bias plot shows the scatter plot of the two measurement methods versus the best linear unbiased prediction (BLUP) with the two regression lines added. Taffé uses an empirical Bayes method to compute the BLUP and uses the reference measurements for each subject to estimate their value27.The Pearson correlation coefficient was used to measure the strength of the linear association between MAPradial and MAPfemoral was defined as  > 5 mmHg17. The correlation and agreement between MAP from two the sites were assessed in each subgroup of MAP levels and norepinephrine doses. Patients were separated to subgroup of MAPradial measurement < 65 or ≥ 65 mmHg. Regarding, norepinephrine dose group, patients were divided into two groups: those receiving maximum dose of norepinephrine < 1 or ≥ 1 µg/kg/min and those receiving maximum dose of norepinephrine < 0.5 or ≥ 0.5 µg/kg/min. Multilevel mixed-effect logistic regression analysis was used to determine the demographic or hemodynamic factors associated with a significant MAP gradient. Statistical significance was set at p-value < 0.05. All statistical analyses were performed using the Stata 15 software.The clinically significant differences between MAPKlebsiella pneumoniae (27.3%), Escherichia coli (18.2%) and Pseudomonas aeruginosa (13.6%). All patients required mechanical ventilator support, and ICU mortality rate was 66.7%.There were 706 paired data obtained from 32 patients, with a mean of 22.1 ± 3.9 data sets per patient. The demographic, clinical characteristics and initial hemodynamic parameters of the patients are shown in Table All the patients received multiple vasoactive agents. Norepinephrine was administered to all patients, 78% and 9.4% of patients received epinephrine and dopamine, respectively. The dosages of each vasopressor are listed in Table radial strongly correlated with MAPfemoral   and 78.8 (95% CI 74.6–82.9) mmHg, respectively. Thus, MAPradial was significantly lower than MAPfemoral by 7.6 mmHg (95% CI 7–8.2) (p < 0.0001)   when MAP dropped from 100 to 60 mmHg.MAP01) Fig. . In the  95% CI 7.6–82.9 mradial < 65 mmHg (35.1% of measurements) and those with MAPradial ≥ 65 mmHg was performed. The MAP was markedly discrepant in cases of MAPradial < 65 mmHg; wherein, most of MAPfemoral were significantly higher than MAPradial. The correlation was fair in group of MAPradial < 65 mmHg   .Subgroup analysis between patients with MAPradial and MAPfemoral in patients receiving norepinephrine lower than 0.5 µg/kg/min and those who received more  and body weight  were associated with significant MAP gradients.There were 414 (58.6%) measurements deviating from the MAP gradient by > 5 mmHg and 235 (33.3%) measurements deviated by > 10 mmHg. The multilevel mixed-effect logistic regression analysis revealed that patients with MAPThe total complications rate were not statistically different between femoral and radial artery catheterization . Bleeding from the femoral arterial puncture site was observed in 6 (18.7%) patients. All of them were easily controlled and none of these patients needed blood transfusion or further intervention to stop bleeding. Two patients (6.7%) developed non-expand small groin hematoma after femoral catheter removal. In contrast, temporary occlusion at radial artery catheter was observed in 4 (12.5%) patients  in septic shock patients14. Previous study in 24 critically ill patients, in mixed ICU found that bias between femoral and radial MAP was 4.3 mmHg 15.Similar to previous studies, this study found disagreement between MAP obtained from the radial and femoral arteries in critically ill patients. Kim et al. demonstrated that the bias between MAPfemoral was higher than MAPradial but was not statistically significant, with a mean bias of 3 ± 4 mmHg 16. A more recent study by Antal et al. also found that MAPfemoral and MAPradial had a good correlation and agreement in sepsis patients, with a bias of 1.4 ± 4.7 mmHg . The difference between our results and those studies may be related to the different study populations and severity of vasopressors used. Patients with refractory shock in this study were diagnosed with septic shock and required a very high dose of vasopressor . However, in the study by Antal et al., only half of their study population was diagnosed with septic shock and they received a lower dose of norepinephrine (0.14 ± 0.17 µg/kg/min) compared to this study.On the other hand, Mignini et al. proposed that measurement of MAP at radial or femoral arteries is clinically interchangeable in critically ill patients. They found that MAP14. Kim et al. showed that septic shock patients receiving norepinephrine < 0.1 µg/kg/min had a bias between MAPfemoral and MAPradial of 3 mmHg ; however, the large discrepancies between MAP were found in patients receiving norepinephrine ≥ 0.1 µg/kg/min, with a bias of up to 6.2 mmHg (95% LOA − 6.0 to 18.3). In contrast, other studies have found that norepinephrine dose was not associated with the MAP gradient. Mignini et al. demonstrated that the bias of MAPradial and MAPfemoral was not different between patients receiving high and low dose of vasoactive agents (high vasoactive dose defined as norepinephrine or epinephrine ≥ 0.1 µg/kg/min or dopamine ≥ 10 µg/kg/min). This is consistent with a study in sepsis patients showing that the norepinephrine dose did not the influence the radial-femoral MAP difference17. The results of this study support the statement that norepinephrine dose does not influence the radial-femoral MAP gradient.There were conflicting results regarding the vasopressor dose–effect on the radial-femoral MAP gradients. Previous studies have reported that clinically radial-femoral MAP gradients are commonly observed in patients receiving high doses of norepinephrine administration15. Although, the factors associated with radial-femoral MAP gradients have been extensively investigated, the proper mechanism is still controversial and suggests multifactorial mechanisms for the development of pressure gradients. The radial-femoral MAP gradient may be caused by a decrease in vascular resistance at the level of the hand29, peripheral vasoconstriction30 or a decrease in arterial elastance in the radial artery8. Galluccio et al. determined the demographic or hemodynamic factors driving the radial-femoral MAP gradient in critically ill patients. However, they failed to identify any statistically significant associations, including vasopressor dose or any demographic or hemodynamic data15.This study found a high prevalence of clinically significant MAP gradients between the radial and femoral arteries in patients with refractory shock. This is similar to previous studies reporting that 62% of critically ill patients had a MAP difference of at least 5 mmHg and 27–29% of patients had a MAP gradient ≥ 10 mmHgradial < 65 mmHg had a moderate correlation and increased bias between radial and femoral MAP and were also associated with significant MAP gradients between both sites. These results suggest that, in patients with marginally maintained MAP, measured at the radial artery, femoral artery catheterization should be considered for accurate arterial blood pressure monitoring in patients with refractory shock31. Monitoring MAP at the femoral artery may avoid future fluid administration or increase of unnecessary vasopressor therapy.This study showed that patients with MAP26 and the multilevel mixed-effect model24. However, our study had some limitations. First, most patient with refractory shock in this study had septic shock. Therefore, it may have limited generalizability to other types of shocks. Second, we selected patients with refractory shock who received high doses of vasopressors, which may limit extrapolation for patients with less severe shock. Lastly, the clinical impact of arterial sites on morbidities or mortality was not measure in this study. Therefore, a larger study is required to further investigate the impact of radial and femoral arterial blood pressure monitoring in patients with refractory shock for therapeutic management and patient outcomes.The strength of this study was the use of new statistical analyze to determine bias in the repeated measurement study such as the, bias plot by the TafféThe radial artery significantly underestimated MAP when compared with the femoral artery in patients with refractory shock. More than half of the patients had clinically significant MAP gradients. Patients with refractory shock with borderline blood pressure targets, from the radial artery site, should be considered for femoral artery catheterization to obtain accurate measurements of blood pressure.Supplementary Information.


A clear identification of the etiology of glomerular disease is essential in patients with diabetes. Renal biopsy is the gold standard for assessing the underlying nephrotic pathology; however, it has the risk for potential complications. Here, we aimed to investigate the feasibility of urinary fluorescence imaging using an enzyme-activatable probe for differentiating diabetic kidney disease and the other glomerular diseases. Hydroxymethyl rhodamine green (HMRG)-based fluorescent probes targeting gamma-glutamyl transpeptidase (GGT) and dipeptidyl-peptidase (DPP) were used. Urinary fluorescence was compared between groups which were classified by their histopathological diagnoses  as obtained by ultrasound-guided renal biopsy. Urinary fluorescence was significantly stronger in patients with diabetic kidney disease compared to those with glomerulonephritis/nephrosclerosis after DPP-HMRG, whereas it was stronger in patients with nephrosclerosis than in patients with glomerulonephritis after GGT-HMRG. Subgroup analyses of the fluorescence performed for patients with diabetes showed consistent results. Urinary fluorescence imaging using enzyme-activatable fluorescence probes thus represents a potential noninvasive assessment technique for kidney diseases in patients with diabetes. Diabetes mellitus is the leading cause of kidney disease, and approximately 40% of patients with diabetes develop chronic kidney disease (CKD) . DiabetiAn enzyme-activatable probe was originally developed for the photodynamic diagnosis of cancer . The detFirst, we investigated whether urinary fluorescence can be obtained after incubation with DPP-hydroxymethyl rhodamine green (HMRG) and GGT-HMRG. Urine from a healthy subject underwent fluorescence imaging using an optimized procedure. Although faint autofluorescence was detected in the urine, remarkable fluorescence could be detected after incubation with DPP-HMRG and GGT-HMRG .We included 114 patients in this study; after excluding 12 patients: interstitial fibrosis (n = 7), drug-induced acute kidney injury (n = 2), and not diagnosed (n = 3), the urine samples of 102 patients were analyzed . FluoresNext, we investigated whether the fluorescence intensities of the urine samples could indicate any underlying nephritic pathology. Urine from patients with diabetic kidney disease showed a significantly stronger fluorescence after DPP-HMRG application than urine from patients with nephrosclerosis/glomerulonephritis . MoreoveIn this study, we demonstrated that an HMRG-based activatable fluorescence probe could be used for urine sample analysis. Urinary fluorescence after DPP-HMRG was stronger in patients with diabetic kidney disease than patients with nephrosclerosis/glomerulonephritis, whereas the fluorescence after GGT-HMRG was stronger in patients with nephrosclerosis than those with glomerulonephritis. We propose that urinary fluorescence imaging represents a novel diagnostic method for kidney disease.N-acetyl-β-d-glucosaminidase, β2-microglobulin, and neutrophil gelatinase-associated lipocalin have been used as indicators of kidney injury. However, these are not specific for diabetic kidney disease. Diagnostic methods other than such biochemical analyses have been suggested as candidates for diagnosing diabetic kidney disease [Several urinary biomarkers such as  disease ,7; howevThe feasibility of HMRG-based fluorescent probes for photodynamic diagnosis has mostly been investigated in detecting cancers. Reports using GGT-targeted fluorescent probes have focused on detecting cancers based on the abundant expression of GGT in cancer cells including hepatocellular carcinoma, ovarian cancer, and breast cancer ,8,9. ThiDPP-4 is localized to the glomerular podocytes and brush border of proximal tubular cells . The tubUrinary fluorescence imaging, which uses enzyme-activatable fluorescence probes, can be performed even with a conventional digital camera . MoreoveThis study included only a small sample size; thus, this fluorescence imaging technique requires confirmation with larger studies. The applicability of urinary fluorescence imaging requires setting or investigating the quantitative thresholds along with the standard operating procedures and general inclusion/exclusion criteria in the future. Nevertheless, urinary fluorescence imaging is a potential noninvasive assessment technique for kidney diseases that is applicable for patients with diabetes.p = 0.05; effect size: 0.40). The target number of participants was calculated using software .This study included patients who underwent ultrasound-guided renal biopsy at Tottori University Hospital. The renal biopsies were performed for patients with suspected glomerular diseases ,21. UrinTwo fluorescent probes containing HMRG were purchased  to target DPP and GGT. Both EP-HMRG and GGT-HMRG have a high specificity for DPP and GGT ,5. Each We investigated the optimal conditions for fluorescence imaging. Freeze-thaw cycles of the urine samples and the temperature of incubation did not affect the fluorescence intensities. The fluorescence depended on the concentrations and pHs of the samples. Therefore, urine was adjusted according to the creatinine concentration with phosphate-buffered saline. Stored urine was thawed on ice and diluted in phosphate-buffered saline to a creatinine concentration of 1 μg/μL to equalize urine concentration and pH. In this way, the influence of urine concentration and pH could be minimized sufficiently. The fluorescence solutions were added to each urine sample at a final concentration of 5 µM and incubated for a minute. The fluorescence images were obtained by following an optimized procedure. In brief, the mixture of the sample and the fluorescence probe was exposed to an excitation wavelength of 450 nm, and then the fluorescence images were obtained by a stereomicroscope  equipped with an optical interference filter (~520 nm). Target regions of interest were set for the fluorescent images with digitally obtained images; thereafter, the fluorescence intensities were measured using the ImageJ software .p-value of less than 0.05 was considered statistically significant. GraphPad Prism  was used for the analysis.Continuous variables were expressed as the mean ± standard deviation or median with interquartile range according to the distribution. The Kolmogorov–Smirnov test was used to assess the normal distribution. Correlations between fluorescence intensities and clinical parameters were analyzed by Pearson’s correlation coefficient. Differences between two groups were analyzed using Welch’s t test. Differences between more than three groups were analyzed by one-way analysis of variance with a post-hoc Tukey test. A


The success rate of hemostasis, changes of hemodynamic parameters before and after treatment, and incidence of HRS are compared between the groups. Logistic regression analysis is used to explore the use of propranolol when HRS occurred. NSBBs combined with somatostatin are more effective than somatostatin alone in the treatment of liver cirrhosis complicated with esophageal-gastric variceal bleeding; NSBBs may be associated with the occurrence of HRS.Esophageal-gastric variceal bleeding occurs in 5–15% of patients with liver cirrhosis annually, and the mortality rate is as high as 20% within 6 weeks of the first bleed. The more compromised the liver function, the higher the mortality. Effective control of bleeding is pivotal for reducing mortality in patients with liver cirrhosis. To explore the effect of nonselective  Moreover, the acute attack is sudden and dangerous. The mortality rate of patients is high, and the key to reduce the mortality of patients is to stop bleeding in time –3. Some c output . Additioc output .Although propranolol has the above therapeutic advantages, some patients are still at risk of rebleeding due to a poor response when used alone, with 40% clinical efficacy . In patiThe clinical data of 248 patients with liver cirrhosis complicated with esophagogastric variceal bleeding at our hospital are selected for the study. From March 2016 to April 2019, 112 patients are treated with somatostatin (control group) and 136 patients are treated with somatostatin+propranolol (study group) –19. ExclP > 0.05).The mean age of patients is 64.01 ± 8.29 (range: 45–89) years; 74 patients are men (54%) and 62 are women (46%) in the study group , 21. In Patients are administered treatment including fluid replacement, hemostasis, blood transfusion, and anti-infection after admission. Patients are closely monitored, signs and emergency measures undertaken as required. The control group is treated with somatostatin . First, somatostatin (3 mg) is dissolved in sodium chloride solution . Second, 4.1 mL is injected intravenously with the first dose. Subsequently, the solution is continuously pumped into the vein at a rate of 4.1 mL/h for 5 days.The study group is orally administered propranolol (10 mg) , three times per day, and treated continuously for five days, similar to the control group.The portal vein blood flow, splenic vein blood flow, systolic arterial systolic pressure (SAP), and mean arterial pressure (MAP) before and after treatment are compared between the two groups. Additionally, the success rate of initial hemostasis, the rate of rebleeding, the effective rate of treatment, and the incidence of HRS are compared between the two groups.D) and blood flow velocity (V) of the blood vessels in the breath-holding state after inhalation are measured, respectively, and the blood flow of portal and splenic vein is calculated using the equation Q = 14 π D2 × V × 60.We recorded the values of SAP and MAP by connecting a multifunction detector. In addition, we used B&K3535 ultrasound diagnostic instrument with a probe frequency of 3.5 MHz. The patient is placed in the supine position or left position, the main axis of the portal vein is displayed in the first hepatic hilum, and the measuring point is ~1– 2 cm from the left and right branches of the trunk. The right splenic portal vein is shown in the transverse position, and the probe is adjusted so that the angle between the sound beam and the direction of blood flow is <60°. The internal diameter , basic etiology of liver cirrhosis, liver function Child-Pugh grade, total bilirubin (TBIL), serum albumin (ALB), platelet (PLT), international normalized ratio (INR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin (Hb), serum sodium concentration, serum creatinine (Cr), and model end-stage liver disease (MELD) index for the study and control groups are obtained.The venous blood of patients (5 mL) is collected with an anticoagulant tube, and platelet (PLT) count is detected using the KX-21 automatic hematology analyzer . In addition, the AU5400 automatic biochemical analyzer  is used to determine Hb and serum sodium concentration. INR is measured using theCS-5100 automatic coagulation analyzer .The venous blood of the patients is collected again and centrifuged at the speed of 3000 RPM (revolutions per minute) for 10 min. The upper serum is collected for further evaluation. The levels of ALT, AST, ALB, TBIL, and Cr are detected using the 7020 automatic biochemical analyzer .MELD is calculated as follows: MELD = 9.6 × In (creatinine mg/dL) + 3.8 × In (bilirubin mg/dL) + 11.2 × In (INR) + 6.4 × etiology ; the final result is an integer.Child-Pugh grading of liver function: the TBIL, ALB, PT, ascites, and hepatic encephalopathy of the two groups are graded and scored. TBIL values are counted as 1, 2, and 3 points based on the ranges <34.2 mmol/L, 34.2–51.3 mmol/L, and >51.3 mmol/L, respectively. ALB values are calculated as 1, 2, and 3 points for >35 g/L, 28–35 g/L, and <28 g/L, respectively. The scores of PT are 1, 2, and 3 in terms of 1–3 s, 4-6 s, and >6 s, respectively. The scores of ascites are 1, 2, and 3, respectively, in terms of none, small quantity, and moderate amount of ascites; and 1, 2, and 3 points in terms of none, mild, and moderate hepatic encephalopathy, respectively. The liver function of the two groups is divided into 3 grades according to the total score: 5–6 as good liver function (grade A), 7–9 as moderate liver function (grade B), and ≥10 as poor liver function (grade C).μmol/L, or the Cr value of patients within 7 days of treatment is >1/2 of the baseline value.The diagnostic criteria of HRS are as follows: the increase of Cr within 48 h of treatment is >26.5 t-test is used for between-group comparisons, and the paired t-test is used for comparison before and after treatment in the group. Sex, underlying etiology, Child-Pugh classification of liver function, and other count data are expressed described as percentages, and the χ2 test is used for comparison between groups. The binary logistic forward condition method is used for the analysis of HRS-related factors. Statistical significance is set at P < 0.05.SPSS 21.0 software is used for statistical analysis. In this study, the values for TBIL, ALB, PL, INR, AST, ALT, Hb, and other data in the two groups are first tested by pp or qq graphs. The data with normal or near-normal distribution are expressed as mean ± standard deviation . After treatment, the portal vein blood flow, splenic vein blood flow, SAP, and MAP in the two groups are lower than those before treatment (P < 0.05). The portal vein blood flow, splenic vein blood flow, SAP, and MAP in the study group are lower than those in the control group (P < 0.05) as shown in Before treatment, there is no significant difference in portal vein blood flow, splenic vein blood flow, SAP, and MAP between the study and control groups (P < 0.05). There is no significant difference in the rate of rebleeding between the two groups (P > 0.05). In the study group, somatostatin+propranolol treatment provided a better rate of initial hemostasis and treatment efficiency, with reduced incidence of HRS. The success rate of initial hemostasis, the effective rate of treatment, and the incidence of HRS in the study group are higher than those in the control group (The model is established using the logistic forward condition method, taking HRS as the dependent variable, with NSBB treatment, age, sex, BMI, basic etiology of liver cirrhosis, Child-Pugh grade of liver function, TBIL, ALB, PL, INR, AST, ALT, Hb, blood natrium concentration, Cr, MELD index evaluation, portal vein blood flow, splenic vein blood flow, SAP, and MAP values before treatment as dependent variables. The results revealed that increases in INR, Cr, MELD index, and splenic vein blood flow and a decrease of PLT are all independent risk factors for HRS in patients with liver cirrhosis complicated with esophagogastric variceal bleeding. Liver cirrhosis is a common chronic liver disease in clinic, often combined with other serious complications, with high mortality. Studies have reported that 35–66% of patients with cirrhosis acquire bacterial infections within the first 5–7 days of gastrointestinal bleeding. Infection can exacerbate the disease, increase the difficulty of treatment, and negatively affect the prognosis of patients. Rupture of esophageal and gastric varices is the most serious complication in patients with decompensated liver cirrhosis. The onset of disease is sudden and dangerous, and the patient's mortality rate is high. The key to reducing the patient's mortality rate is to stop the bleeding in time. The clinical manifestations may be melena or hematemesis and in severe cases can lead to hemorrhagic shock and is life-threatening. Therefore, effective measures to treat liver cirrhosis must be undertaken, and it is of vital importance to treat patients with esophageal and gastric varices to reduce the mortality of patients. HRS refers to functional acute renal failure that occurs when severe liver disease occurs, and incidence of the disease is progressively increasing. Approximately 40% of patients with liver cirrhosis and ascites may develop HRS within 5 years, and the survival rate of confirmed patients is low. In cirrhosis of the liver with rupture of esophageal-gastric varices, the peripheral blood vessels of bleeding patients are dilated; the effective circulating blood volume is significantly reduced, resulting in insufficient perfusion of vital organs and tissues; activation of the endogenous vasoconstrictor system occurs, thereby increasing the release of antidiuretic hormone, leading to a decrease in the glomerular filtration rate and renal artery constriction of blood vessels, triggering HRS. Esophageal-gastric floor varicose vein rupture bleeding reduces the effective blood volume and activates the renin-angiotensin-aldosterone system, which significantly reduces renal blood flow, increases sodium storage, decreases glomerular filtration rate, and aggravates renal damage, which is also an important mechanism by which HRS occurs. At present, there is no clear and effective treatment for HRS locally or abroad, and liver and kidney transplantation is the most effective measure.Somatostatin can reduce the blood flow to the gastrointestinal tract, inhibit the release and secretion of acidic substances, and enhance vasoconstriction and thereby stop bleeding. Somatostatin can control bleeding by constricting visceral blood vessels and inhibiting the activity of endogenous vasodilator substances and effectively prevent rebleeding, quickly reduce visceral blood flow and gastric mucosal blood flow, and is particularly effective in reducing portal pressure and atypical venous blood flow. The venous blood flow can also inhibit the secretion of gastric acid and protect the normal physiological functions of the esophagus and stomach and effectively treat the esophagus and stomach fundus variceal bleeding. However, with the increase in drug dose, the effect of somatostatin in reducing portal pressure did not increase and the systemic arterial pressure. There is no significant change in vascular resistance, suggesting that somatostatin cannot be used to increase portal pressure to improve the curative effect and requires a comprehensive treatment plan.β1 and β2 receptors. The β2 receptor reflection of the visceral blood vessels constricts the visceral arteries, thereby lowering the pH, significantly reducing the cardiac output and the pressure of the hepatic portal vein. Studies have also confirmed that it can improve esophageal variceal symptoms of rupture and bleeding, inhibiting the occurrence of bleeding from the esophageal-gastric varices. Traditional NSBBs include propranolol. Propranolol is clinically used as a primary preventive drug to prevent esophageal and gastric variceal bleeding in decompensated cirrhosis. Propranolol can antagonize β1 receptors to reduce heart rate and decrease cardiac output and antagonize β2 receptors to constrict visceral blood vessels. In patients with liver cirrhosis, the hyperdynamic circulation and the gradual decrease of cardiac compensatory reserve will lead to the body's resistance to acute circulatory hypertension, resulting in the adaptation mechanism, which can easily lead to low cardiac output. In patients with liver cirrhosis, the gradual decrease of high power circulation and cardiac compensatory reserve will lead to the adaptation mechanism of the human body to promote acute circulatory hypertension, which easily leads to low cardiac output. Studies have shown that combining drugs can effectively improve their efficacy. Therefore, in this study, somatostatin and propranolol are used as therapeutic drugs to compare the effect of single or combined application of somatostatin and propranolol in liver cirrhosis and their influence on hemodynamics.In addition, NSBBs include aspirin treatment for liver disease, and their mechanism involves inhibition of catecholamine binding to β1 activation. The effect of this mechanism is significantly decreased in patients with esophageal-gastric variceal bleeding, resulting in a further decrease in blood pressure and cardiac output and an increase in the incidence of HRS.Currently, there are few reports about the use of somatostatin combined with propranolol for the treatment of esophagogastric variceal bleeding. The results reveal that the portal vein blood flow and splenic vein blood flow are lower after treatment in both groups compared to pretreatment values. However, the reduction is greater in the somatostatin combined with propranolol group. It promotes bacterial infection, increases the contraction of peripheral blood vessels, and reduces cardiac output, resulting in damage to the body due to hemodynamic changes in patients. The increase in circulatory power and the decrease in cardiac reserve capacity stimulate the adaptive mechanism of the body to high pressure and increase the probability of spontaneous peritonitis, which leads to splenic and portal hypertension and hemodynamic abnormalities. A significant decrease in cardiac output significantly increases the incidence of HRS. This study is conducted to determine whether NSBB treatment can maintain circulatory reserves. The important adaptive mechanism of NSBB treatment involves promotion of an increase in the heart rate by β receptors, reduce the heart rate, inhibit cardiac contraction, significantly slow atrioventricular conduction, and effectively reduce blood volume and portal vein pressure. Moreover, propranolol can also bind to the β2 receptor, significantly activate visceral vascular α receptors, enhance the contractile ability of the visceral artery, reduce intrahepatic sinusoidal pressure, effectively reduce blood flow, and promote hemostasis.The SAP and MAP values measured in the study group after treatment are lower than those recorded before treatment. In addition, the values in the study group are lower than those in the control group. Propranolol can inhibit the effect of myocardial Some scholars have reported a positive correlation between portal vein pressure and the MELD score. Physiologically, platelets affect coagulation and hemostasis, and PLT and the INR are the main factors that determine the prognosis of patients with liver cirrhosis. In addition, the Cr level can reflect the renal function status and is also closely associated with the prognosis of patients. The Child-Pugh liver function classification is also a common evaluation index of liver function. The study results revealed that an increase in the INR, a decrease in PLT, and increases in the Cr, MELD index, and splenic vein blood flow are independent risk factors for HRS.Peripheral vasodilation and effective circulatory blood volume are significantly decreased in patients with liver cirrhosis complicated with esophageal-gastric fundus variceal bleeding. This condition results in insufficient perfusion of important organs and tissues and activation of the endogenous vasoconstriction system. In addition, it results in increased release of antidiuretic hormone and decreases in the glomerular filtration rate and renal artery vasoconstriction, leading to HRS. Esophageal-gastric variceal bleeding can reduce the effective blood volume, activate the renin-angiotensin-aldosterone system, significantly reduce renal blood flow, increase sodium storage, reduce the glomerular filtration rate, and aggravate renal damage, which is also an important reason for the occurrence of HRS.The occurrence of HRS is multifactorial. In addition, the mechanism in patients with liver cirrhosis complicated with esophageal-gastric variceal bleeding is more complicated. There are few reports of the effects of somatostatin and propranolol on the incidence of HRS in patients with liver cirrhosis complicated with esophageal-gastric varices at present. This study explored the therapeutic effect of NSBBs combined with somatostatin. However, a limitation is that the number of cases included is insufficient, and the experimental results have not been fully ascertained based on the uniqueness of this case. Therefore, further confirmatory studies are required.Generally, NSBBs combined with somatostatin are more effective in the treatment of liver cirrhosis complicated with esophageal-gastric variceal bleeding than somatostatin alone. NSBBs may have a significant effect on the hemodynamic parameters of patients. However, the relationship between HRS and somatostatin is not confirmed in this study.


Irrational prescription has a lion share for uncontrolled blood pressure. There is no study assessing prescription pattern among hypertensive patients at the study sites. Therefore, the objective of the current study was to evaluate prescription patterns for hypertension and blood pressure (BP) control at randomly selected hospitals of South Gondar Zone.A hospital based cross sectional study was conducted from December 1, 2020 to February 30, 2021. Hypertensive patients were selected by systematic random sampling proportionally from study hospitals. Structured questionnaires were used to collect socio-demographic chacteristics and adherence. Data abstraction form was used to collect prescription patterns, BP level and other necessary information. The association of prescription patterns and other variables with blood pressure control was determined by using binary logistic regression.All recruited 423 patients were included in data analysis. Among prescriptions for hypertension, on average 93.5% were found to be in line with WHO guideline. About 53% of prescriptions for hypertension were monotherapies. Patient level low medication regimen complexity, and monotherapy were associated with blood pressure control . Patients with inappropriate drug selection, and non-adherence were less likely to have controlled BP . Moreover, patients who didn’t have health insurance and follow regular aerobic exercise were less likely to have controlled BP .Diuretics were the most frequently prescribed drug in monotherapy and in combination with calcium channel blockers (CCBs) as dual therapy. On average, more than 90% of prescription was in accordance with WHO guideline and around one-third of participants experienced at least one moderate or major drug-drug interaction. Patient level low medication regimen complexity and monotherapy were positively associated with BP control whereas, non-adherence, inappropriate drug selection, having no health insurance, and didn’t follow regular aerobic exercise were negatively associated with BP control. Clinicians should be adherent to treatment guidelines and focus on modifiable factors to improve BP control. Hypertension can be defined as average systolic and/or average diastolic blood pressure levels equal and greater than 140 mmHg and 90 mmHg, respectively or reported use of antihypertensive drugs. Hypertension is a major public health problem that considerably increases the risk of heart, brain, kidney and other disease. Worldwide, around 1.4 billion people were estimated to have high blood pressure . HyperteAntihypertensive drugs are known to have clear benefits in reducing the rate of cardiovascular complications and risk of adverse health problems . The useCurrent Ethiopian treatment guideline recommends thiazide and thiazide like diuretics (TLDs), calcium channel blockers (CCBs), angiotensin convertase enzyme inhibitors (ACEIs) or Angiotensin II type 1 receptor blockers (ARBs) as preferred first line agents for patients with hypertension, which is in line with current World Health Organization (WHO) and Joint National Committee-Eight (JNC-8) recommendations. The treatment can be stepped up further in terms of dose and combination of drugs from different classes if blood pressure is not under control , 16, 17.To date, there is paucity of data regarding prescription pattern of antihypertensive drugs in Ethiopia. This is a major concern considering hypertension is a big public health problem in Ethiopia and consequence of poor blood pressure control , 12. As The study areas were four randomly selected hospitals which are found in South Gondar Zone, Amhara Regional State, Ethiopia. Eleven administrative zones are found in this Zone and the health services have been provided with 1 Comprehensive Specialized Hospital, 7 primary hospitals and 95 health centers in this zone. Above 2 million people was living in this zone according to the 2007 national census conducted by Central Statistical Agency (CSA) of Ethiopia .The study design was a hospital base cross sectional study which was conducted from December 1, 2020 to February 30, 2021.The source population was all hypertensive patients who have follow-up and attending the selected hospitals. Patients who fulfilled the inclusion criteria and receiving anti-hypertensive drugs were considered as the study population.The single population proportion formula was employed to determine the sample size as shown below:p value of 0.5 was used. Then, the sample size was determined as, n= (1.96)2 *0.5*((1–0.5)/(0.05)2 = 384. After adding 10% for non-responding rate, the final sample size was found to be 423. Debre Tabor Comprehensive Specialized Hospital was selected purposively as it is the only Comprehensive Specialized Hospital of this zone. Random was employed to select 3 primary hospitals which were Addis Zemen, Mekane Eyesus, Nifas Mewcha. Then, 423 study participants were interviewed and their charts were reviewed by employing systematic random sampling and proportional allocation to study hospitals  scale and those patients with MAS score of 8 was considered as adherent to their medication .Regular aerobic exercise was considered for patients engaged in moderate aerobic exercise such as walking briskly, recreational swimming, riding bicycle, and tennis for at least 150 min per week (30 min per day for 5 days per week) .Adherence of prescribers to guideline was assessed based on the recommendation of WHO guideline for hypertension management, and adherence to guideline was considered when prescribers follow 100% of the guideline recommendations .Socio-demographic, Clinical data, and patients’ details of current medications were gathered from the chart. Socioeconomics, adherence to medication, and other required data that were not found from the chart were collected by interviewing the patients using structured questionnaire. The questionnaire was translated to Amharic language and back to English in order to maintain its consistency.Adherence to medication was evaluated by using an eight item medication adherence scale (MAS-8). For the first seven items, the value for “Yes” = 0 and “No” = 1 was given whereas for item number five, the values for “Yes” and “No” are reversed and for the last item a five-point likert response are used with options “never”, “once in a while”, “sometimes”, “usually”, and “always” . A recenhttp://www.micromedexsolutions.com ). This result is in accordance with finding of a meta-analysis which concluded that aerobic exercise reduces blood pressure .In the current study, not having health insurance was negatively associated with optimal blood pressure control compared to those who had health insurance (AOR = 0.420.26–0.68]). This finding is in line with the finding of the study conducted in United States [–0.68). TThis study has provided information regarding the prescription patterns of antihypertensive drugs with respect to the level of BP control. It is a multi-center study and it will help prescribers to focus on specific factors that affect BP control. But, it has some limitations. First, it is a cross sectional study. Second, data were collected by chart review and patient interview, so prescribers were not involved to give information about their attitude towards compliance to treatment guideline and factors affecting it. Hence, a prospective study having discussion with prescribers is needed to ascertain factors affecting adherence to treatment guidelines and blood pressure control. In addition, inappropriate prescriptions might be overestimated by our study as pharmacists might have responded for some inappropriate prescriptions after prescription.The finding of the present study showed that on average prescribers adherence to WHO guideline was not 100%. Inappropriate drug selection was the main contributing factor for violation of the guideline recommendation. High drug-drug interactions (one-third of participants) were found. Patient level low MRCI and monotherapy were positively associated with BP control whereas, non-adherence, inappropriate drug selection, having no health insurance, and didn’t follow regular aerobic exercise were negatively associated with BP control. Clinicians should adhere to treatment guidelines and focus on modifiable factors to improve BP control. Ethiopian heath minster and Health bureau shall identify the gaps why prescribers do not adhere to guidelines and design interventions.


The advances in transplant immunosuppression have reduced substantially the incidence of kidney graft rejection. In recent years, the focus has moved from preventing rejection to preventing the long-term consequences of long-standing immunosuppression, including nephrotoxicity induced by calcineurin inhibitors (CNI), as well as infectious and neoplastic complications. Since the appearance in the late 1990s of mTOR inhibitors (mTORi), these unmet needs in immunosuppression management could be addressed thanks to their benefits . However, management of side effects can be troublesome and hands-on experience is needed. Here, we review all the available information about them. Thanks to all the basic, translational and clinical research achieved in the last twenty years, we now use mTORi as de novo immunosuppression in association with CNI. Another possibility is represented by the conversion of either CNI or mycophenolate (MPA) to an mTORi later on after transplantation in low-risk kidney transplant recipients. The landscape of kidney transplantation has changed notably, moving from an incidence of acute kidney graft rejection of >80% in the early ages to <10% nowadays, as a result of the advances in transplant immunosuppression. Initially, it was based on steroids and azathioprine (AZA), but the current gold standard, also recommended by the KDIGO guidelines, includes first-line induction therapy with basiliximab in association with a calcineurin inhibitor (CNI)  and an antiproliferative agent , with the possibility of early steroid withdrawal in low-risk recipients. In recipients with a high immunological risk, the suggested first-line induction therapy is represented instead by lymphocyte-depleting agents ). Patients treated with mTORi had a higher risk of New-Onset Diabetes After Transplantation (NODAT), dyslipidemia, edema, lymphocele and thrombocytopenia, but a lower risk of CMV infection, malignancy and leucopenia .It should be remarked that transplant physicians’ lack of experience with mTOR and the fact that in some trials CNI were not minimized could be responsible for these disappointing results in terms of renal function and graft survival. As a matter of fact, when EVL was used with optimal trough levels (3–8 ng/mL) in association with reduced-dose CNI, there was absolutely no difference in terms of hard outcomes and renal function .Finally, this approach has been recently validated in the TRANSFORM trial, the largest trial ever performed in kidney transplantation. In this study, low-risk kidney transplant recipients were randomized to receive the mTORi Everolimus (EVL) or MPA in combination with a CNI  and prednisone . Inducti2, respectively) [Reduced rates of infections were noted in the EVL group, especially CMV and BK. Two-year results of the trial were recently published, confirming the non-inferiority of the CNI/EVL regimen and also observing a reduced incidence of de novo DSA in the on-treatment population. Renal function was also not different between groups (52.6 versus 54.9 mL/min per 1.73 mctively) . When usctively) .n = 205), TAC/EVL (n = 199) or CsA/EVL (n = 208), along with steroids and basiliximab induction. In contrast with the TRANSFORM, tacrolimus trough levels were not minimized in the EVL group . The efficacy endpoint  was 13.0%, 24.6% and 9.8% for the TAC/EVL, CsA/EVL and TAC/MPA combinations, respectively (p = 0.260 for EVR/TAC and p < 0.001 for EVR/CsA versus MPA/TAC). Renal function endpoint revealed worse results for the two EVL groups in comparison with the MPA group (EVL/TAC 62.2 mL/min versus EVL/CsA 58.4 mL/min versus MPA/TAC 67.8 mL/min). While the results for CsA are not surprising, lower GFR in the EVL/TAC group was disappointing. A possible explanation given by the authors for this result is that TAC minimization was not planned in the EVL group. As a matter of fact, in the TRANSFORM trial there were no differences in 12-month renal function between groups. In a post-hoc analysis, the authors of the ATHENA study demonstrated that, indeed, EVL patients with low exposure to TAC (<5 ng/mL)did not have inferior renal function compared to the MPA group [Another two recently published studies that deserve attention are the ATHENA and the US92 ,78. In tPA group .p < 0.05), while graft loss  and combined graft loss/death/loss at follow-up  were significantly lower in the EVR/TAC group, with no differences in renal function. The authors explained this difference in treated BPAR with low exposure to EVL during the first two weeks after kidney transplant. Incidence of BPAR was indeed higher in those centers in which patients were under-exposed to the drug. Another difference with respect to the TRANSFORM trial was that high immunological risk was not an exclusion criterion [In the U292 trial, Qazi et al. essentially used the same approach of the TRANSFORM study in an American cohort of patients . The pririterion ,78. ProbThe results of the last trials changed the perspective about the use of mTORi in kidney transplantation and the most recent meta-analysis confirmed that there are no differences for hard outcomes, including BPAR, patient and graft survival, in comparison with MPA . These rn = 186) had very similar results to that of the original trial, with no differences in terms of 1-year and last follow-up graft rejection and survival between the MPA and mTORi group. On the other hand, patients that could not have participated in the trial (n = 215), had better results for both outcomes. Another strong point in favor of mTORi was the evidence in all groups of better 1-year and last follow-up patient survival. A reduced rate of infection-related hospitalizations during the first year could partially justify this finding. On the other side, a higher incidence of drug discontinuation was observed in the mTORi group due to classical side effects, including hypercholesterolemia, proteinuria, surgical-associated complications, etc., as well as beneficial effects .All the lessons learned by all these randomized clinical trials taught the transplant community how to take advantage of the benefits of mTORi , without paying an excessive price for their side effects. It is also important to bear in mind the strict inclusion criteria of the TRANSFORM trial. Patients at high immunological risk were discarded, as well as recipients of a Donors after Circulatory Death (DCD), which represent a valuable source of donors in many countries. In this field, a single-center propensity score analysis published in 2020 by our group  verifiedA difference worthy to mention with respect to the TRANSFORM trial was the higher trough levels of TAC in patients treated with mTORi; this may also justify the decreased incidence of rejection in this group. This different attitude about TAC/mTORi trough levels was not associated with a worse 1-year renal function and higher chronicity scores at protocol renal biopsy .n = 71), the combination TAC + mTORi was associated with better results in terms of 1-year rejection-free survival compared to TAC + MPA  [In a sub-analysis of the same population focused on high immunological risk patients, defined as a baseline cPRA ≥ 50% (ctively) . This stctively)  is probactively) ,81. ThisThe two mTOR inhibitors commercially available and approved for use in kidney transplantation can be started soon after surgical intervention at a dose of 1–2 mg qd  or 1–1.5 mg bid , with the aim to reach trough levels of 3–8 ng/mL. During the first weeks after kidney transplant, it is advisable, however, to maintain trough levels in the range of 3–5 ng/mL.In our center, SRL and EVL are associated with TAC in order to reach a sum (TAC + mTORi) of trough levels of 8–12 ng/mL ,81. ThisInduction should be based on individual risk assessment depending on the immunological risk .Contraindications for the start of de novo mTOR inhibitors in kidney transplantation include: a previous history of intolerance or side effects with mTORi, chronic obstructive pulmonary disease, central obesity that could impair surgical wound healing, thrombotic microangiopathy as the cause of end-stage renal disease, and any patient at risk of surgical complications and possibly re-intervention. Patients that could benefit most from the use of mTOR inhibitors are those with a history of virally induced cancers and who are at risk of developing CMV disease or BK nephropathy.Advantages for the use of mTOR inhibitors in comparison with MPA include, undoubtedly, less incidence of viral infections , less neutropenia and low blood platelets, and a possible reduction in long-term incidence of solid neoplasia, especially for non-melanoma skin cancer in which the evidence is more convincing ,6. MoreoThe most common side effects associated with the use of mTOR inhibitors are listed in In conclusion, mTORi provide a valuable solution in today’s landscape of kidney transplantation as a first-line de novo therapy. They also represent a valuable option for replacing either TAC or MPA in stable kidney transplant recipients at low risk of rejection with immunosuppression-related side effects. Incidence of side effects has decreased in recent years, thanks to lower trough levels and hands-on experience. It should also be highlighted that, in most cases, side effects of mTORI can be easily managed, in the same way kidney transplant physicians are used to doing when managing the side effects of either TAC or MPA.


The aim of this study was to assess whether hematological indices of the peripheral blood are associated with revision surgery in patients with chronic rhinosinusitis (CRS) undergoing endoscopic sinus surgery (ESS).This retrospective, cross-sectional, single-center study included 541 CRS patients that underwent ESS. Demographics and laboratory parameters were retrieved, and group comparisons were performed. We computed binary logistic regression models to associate clinical characteristics , absolute blood counts of different leukocyte types , and hematological indices of the peripheral blood  with revision surgery as outcome.p < 0.001). Binary logistic regression analysis revealed higher odds for revision surgery in patients higher in age , with presence of aeroallergen allergies , presence of asthma , higher preoperative eosinophil counts , and higher ELR .The study population included 435 primary surgeries and 106 revision cases. Patients undergoing revision ESS showed significantly higher absolute preoperative eosinophil counts (381.6 ± 265.6 per µl), ELR (0.205 ± 0.195), and ENR (0.105 ± 0.074) compared to primary cases (all We found that higher peripheral eosinophil count and higher ELR were associated with revision ESS in CRS patients. Preoperative assessment of hematological indices of the peripheral blood might be a valuable indicator of disease severity, thus facilitating better treatment selection. Chronic rhinosinusitis (CRS) is a common global disease caused by inflammatory processes of the nose and the paranasal sinuses. The main treatment goal of CRS is the reduction of local inflammation, infection control, and the restoration of sinonasal mucociliary clearance. For patients that fail appropriate medical therapy, endoscopic sinus surgery (ESS) represents an appropriate treatment option . HoweverWhen pathogens enter the mucosal barrier, patients showcase different inflammatory endotypes, with type 1 being targeted at viruses, type 2 at parasites, and type 3 at fungi and bacteria . Type 2 Hematological indices of the peripheral blood, such as increased neutrophil-to-lymphocyte ratio (NLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR), were previously described as potential markers for disease recurrence in CRS patients , 13. HowThis study followed a cross-sectional, single-center design and was approved by the Ethics committee of the Medical University of Vienna (EK-Nr.: 1736/2020). The study was conducted at the Department of Otorhinolaryngology at the Medical University of Vienna (MUV). We retrospectively included 541 patients diagnosed with CRS based on EPOS established criteria who underwent ESS at the MUV between 01.01.2012 and 31.12.2015 [All patients provided a routine blood test  preoperatively (0–45 days before surgery). On average, the peripheral blood samples were taken 8.8 days (SD = 6.2) prior to surgery. Blood samples were taken at a single point in two groups – prior to primary ESS in naïve cases and prior to revision ESS in recurrent cases. The absolute serum counts of lymphocytes, neutrophils, basophils, and eosinophils were obtained (absolute number/µl) and used to calculate the neutrophil-to-lymphocyte ratio (NLR), basophil-to-lymphocyte ratio (BLR), eosinophil-to-lymphocyte ratio (ELR), and eosinophil-to-neutrophil ratio (ENR).t-tests to facilitate mean comparisons for the hematological indices of the peripheral blood and other normally distributed continuous variables. We applied Chi-squared tests (χ2-test) for group comparisons of binary categorical variables.We performed statistical analyses using SPSS . Continuous variables, such as eosinophil count (absolute number/µl) and ELR, were presented as mean ± standard deviation (SD). Categorical variables were presented as absolute numbers (percentages). We first divided our patients into two groups to further elucidate differences between patients who had not undergone ESS (primary surgery) and patients who had already received surgical treatment of the paranasal sinuses (revisions). We used two-tailed unpaired β) and 95% confidence intervals (CI) were calculated for each variable. The level of significance was set at 0.05.We performed univariate binary logistic regression analysis with revision surgery as the outcome and the factors of age (in years), gender , smoking (reference: non-smoker), aeroallergen allergies (reference: not present), asthma (reference: not present), presence of nasal polyps (reference: not present), lymphocyte count (absolute number/µl), neutrophil count (absolute number/µl), basophil count (absolute number/µl), and eosinophil count (absolute number/µl) as explanatory variables. Two multivariable binary logistic regression models with revision surgery as outcome were computed: the first model included the different counts (absolute number/µl) of leukocytes  and clinical characteristics  as predictive variables, while the second model included the hematological indices of the peripheral blood  and clinical characteristics  as predictive variables. The adjusted odds ratios . χ2-test further revealed that patients undergoing revision surgery more frequently reported aeroallergen allergies , physician-diagnosed asthma , and the presence nasal polyps .Five hundred and forty-one patients who underwent ESS at the MUV were eligible for this study throughout the observational period. This study population was partly included in an earlier study . Four huIn a first step, we were interested to know whether there were differences in preoperative peripheral blood counts of lymphocytes, neutrophils, basophils, eosinophils, NLR, BLR, ELR, and ENR between patients undergoing primary surgery and those undergoing revision ESS. We, therefore, performed unpaired t-tests between the primary and revision group.t-tests revealed that the eosinophil-count was significantly higher in patients requiring revision ESS  . Furthermore, the ENR was also significantly higher in patients undergoing revision surgery . We found no significant differences in the NLR and the BLR between patients undergoing primary and revision ESS , presence of aeroallergen allergies , asthma , and nasal polyps  to be significantly associated with higher odds for revision surgery. Furthermore, higher peripheral blood eosinophil counts , higher ELR , and higher ENR  were also significantly associated with revision ESS , aeroallergen allergies , physician-diagnosed asthma , and higher eosinophil count  were associated with revision surgery. The other model including age, gender, smoking status, presence of aeroallergen allergies, presence of physician-diagnosed asthma, presence of nasal polyps, and the hematological indices of the peripheral blood  revealed that higher age , aeroallergen allergies , physician-diagnosed asthma , and higher ELR  were associated with higher odds for revision ESS.As we found significant associations in univariate analysis, we next wanted to know which variables remained associated in multivariable analysis after controlling for demographics and clinical characteristics. In the multivariable model including age, gender, smoking status, presence of aeroallergen allergies, presence of physician-diagnosed asthma, presence of nasal polyps, absolute count of lymphocytes, neutrophils, basophils, and eosinophils we found that higher age  , 14. CRSThe present study revealed that patients undergoing revision ESS showcased significantly elevated peripheral eosinophil blood counts and ELR compared to patients undergoing primary surgery. These findings align with previous studies, which reported that tissue eosinophilia was associated with increased disease severity and recurrence in CRS patients , 16. TheOur findings did not reveal significant differences between primary surgeries and revisions for the other hematological indices of the peripheral blood . However, a previous study reported higher NLR and BLR in CRS patients with nasal polyps and disease recurrence, as elevated neutrophils and lymphocytes are indicators of inflammatory processes and basophils have been associated with inflammatory exacerbations . A possiRegarding demographics, higher age was another factor that had a significant association with revision surgery, which is in accordance with previous studies that reported higher age as a risk factor for revision ESS in CRS patients . HoweverConcerning the impact of aeroallergen allergy, we found that patients undergoing revision ESS reported aeroallergen allergies significantly more frequently than patients undergoing primary surgery. This finding was not surprising, as aeroallergen allergies have previously been associated with disease recurrence in CRS patients . FurtherAlthough group comparisons and univariate binary logistic regression analysis revealed a significant association between the presence of nasal polyps and disease recurrence, this factor failed to reach significance in our multivariable binary logistic regression model. Nevertheless, the EPOS guidelines and previous studies list nasal polyposis as an essential risk factor for disease recurrence and the demand for revision ESS , 8. ThisThis study provides further evidence for the prognostic validity of the preoperative evaluation of hematological indices of the peripheral blood, such as the ELR for CRS patients and allowed for an assessment of potential risk factors for a relatively large cohort of CRS patients undergoing primary and revision ESS. However, the limitations of this study include the single-center and cross-sectional design, which did not allow the inclusion of patients undergoing revision ESS at other hospitals throughout the observational period and beyond. As this study followed a cross-sectional design, we only observed patients at a single point  and did not gain insight into, whether the patients required revision surgery or experienced disease recurrence after the study period. Future studies could follow a longitudinal design and would contribute to our current level of knowledge by further investigating the individual patient’s course of disease and revision rates. However, using revision surgery as the outcome implies a certain bias in itself, as some patients experience disease recurrence, but abstain from undergoing revision surgery or undergo surgery with significant time delay because of risk or fear of complications, inability to undergo anesthesia, due to medical conditions, or other reasons. Nevertheless, we obtained further insight into the validity of preoperative hematological indices of the peripheral blood and identified the ELR as a possible future predictor of disease severity and recurrence in CRS patients.We found that peripheral eosinophil count and ELR were significantly higher in patients experiencing disease recurrence, suggesting that these parameters could serve as indicators for severe cases of CRS. Our results suggest that the routine evaluation of peripheral eosinophil counts and the calculation of the ELR could be used to adapt treatment to the individual CRS patient’s demand and facilitate a better selection of treatment options, including biological agents targeted to suppress type 2 inflammatory patterns.


Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs  and derived a new PRS to predict the short-term prognosis in ADHF.A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer–Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS.9/L) + 1 × (creatinine > 80 μmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64–0.70) and a good calibration . The results in validation cohort verified these findings.The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53–0.57), 0.54 (95% CI 0.53–0.56), and 0.56 (95% CI 0.54–0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 10The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients. Acute decompensated heart failure (ADHF) is a prevalent clinical syndrome with a poor prognosis in internal medicine and emergency department, and the majority of ADHF patients require hospitalization for further treatment , 2. DespIt is critical to accurately predict prognosis in patients with ADHF during and after hospitalization to optimize treatment decisions, thereby reducing readmissions and deaths . For theAmong the previously published PRSs, the 3A3B score is developed for the Japanese HF preserved left ventricular ejection fraction (LVEF) (HFpEF). From a total of 14 covariates, age, albumin, anemia, BMI, BNP or NT-proBNP, and BUN were selected as long-term prognostic variables . The preThe AHEAD score is a simple tool based on 5 comorbidities , Elderly, Abnormal renal parameters (creatinine), and Diabetes mellitus) used to predict the short and long term prognosis of hospitalized patients with acute HF (AHF) in the European population. It was derived from a prospective multicenter registry. The score was externally validated in the GREAT registry consisting of nine AHF cohorts from Italy, Spain, France, Argentina, Finland, Switzerland, the USA, Tunisia, and Austria . NeverthThe OPTIME-CHF score has been suggested as a way to predict the risk of 60-day mortality for hospitalized patients with decompensated HF. Using data from a cohort from the United States, 5 routine variables on admission, including age, SBP, sodium, New York Heart Association (NYHA) class IV, and BUN, were found to be independently associated with the prognosis. The discrimination of the current score was excellent (c-index = 0.77). The authors further developed a nomogram based on each factor for bedside application , which, Considering the research context (population and regions), as well as the availability of variables, we selected the 3A3B , AHEAD , and OPTThe study population consisted of hospitalized patients with ADHF enrolled in the Hebei Acute Decompensated Heart Failure (Heb-ADHF) registry (ChiCTR-POC-17014020) database, a prospective, multicenter, open study designed in real-world to assess risk predictors of influencing comprehensive treatment and short-term prognosis in patients with ADHF. From March 2016 and December 2018, patients were consecutively recruited in 13 tertiary hospitals in Hebei Province, China.ADHF was defined as new-onset AHF or decompensation of chronic HF (CHF) . All of 2; length of hospital stay (LoHS), 10 days; systolic blood pressure (SBP), 130 mmHg; diastolic blood pressure (DBP), 80 mmHg; anemia, < 13.0 g/dL in men or < 12.0 g/dL in women; red blood cells (RBC), 4.15 × 1012/L; neutrophil, 4.37 × 109/L; lymphocyte, 1.11 × 109/L; platelet, 155 × 109/L; total cholesterol (TC) 3.6 mmol/L; low density lipoprotein cholesterol (LDL-C), 2.0 mmol/L; creatinine, 80 μmol/L; blood urea nitrogen (BUN), 21 mg/dL; aspartate aminotransferase (AST), 32 U/L; alanine aminotransferase (ALT), 59 U/L; QRS fraction, 55%; left ventricular ejection fraction (LVEF), 36%; left atrial diameter (LAD), 41 mm. Phase values were used for BNP (NT-proBNP), 100 to < 500 (300 to < 2500), 500 to < 1500 (2500 to < 7500), and ≥ 1500 (≥ 7500) pg/mL, respectively. QRS fraction is defined as the sum of the R-wave amplitudes of the standard 12 leads (ΣR) divided by the sum of the absolute values of the QRS wave amplitudes of the 12 leads (ΣQRS) in electrocardiogram, i.e. (ΣR/ ΣQRS) × 100%. All cut-offs were calculated based on the predictive power of each variable for the outcome event.We recorded the following clinical data on admission of each enrolled patient: (1) demographic characteristics; (2) clinical history; (3) physical examination; (4) laboratory tests; (5) chest radiography (6) electrocardiogram; (7) echocardiography; and (8) medical treatment. Variables analysis of the outcome events group revealed the following cut-offs: age, 65 year-old; body mass index (BMI), 24 kg/mThe primary endpoint was the composite of in-hospital all-cause mortality, 30-day all-cause readmission, or 30-day all-cause mortality after discharge. The follow-up programs for all patients were carried out according to the original plan of the Heb-ADHF study via medical records, physician’s office visits, or telephone interviews from admission to 30 days after discharge.n) and proportions (%). The few missing data are replaced by the expectation–maximization method. The Student t-test or Mann–Whitney U test was used to evaluate differences between groups for continuous variables and the Chi-square (χ2) test for categorical variables whenever appropriate. The discrimination of each PRS was evaluated by the area under the receiver operating characteristic curve (AUROC) with a 95% confidence interval (CI) to assess ability to predict the endpoint. To begin, univariate logistic regression analyses were used to identify risk factors associated with outcome events. Variables with P-values of < 0.2 in univariate analyses were entered into the multivariable analysis. Then, variables with P-values of < 0.05 in the multivariate logistic regression were considered as independent variables for the new PRS. Odds ratios (ORs) with 95% CIs were calculated for the logistic regression analysis. The relative significance of each predictor within the final PRS model was assessed by the value of the partial Wald χ2 statistic minus the degrees of freedom (df) of predictors (χ2-df). In the new PRS model, we assigned the scores (points) for each independent variables based on their value of (χ2-df): (χ2-df) ≤ 5.0 assigned as 1 point, 5.0 < (χ2-df) ≤ 10 assigned as 2 points, 10 < (χ2-df) ≤ 15 assigned as 3 points, and (χ2–df) > 15 as 4 points. The Hosmer–Lemeshow goodness-of-fit test was used to assess calibration. Using the Z test, we also compared the predictive accuracy of new PRS with that of the 3 previously published PRS by AUROCs. The correlation between different score points and different outcome events was analyzed by Mantel–Haenszel trend test and Pearson correlation test. Two-sided P < 0.05 was deemed statistically significant. Statistical analyses were performed using SPSS software (version 26.0) and the AUROC curves were conducted using the Medcalc software (version 20.0.3).Continuous variables are presented as means ± standard deviations or medians with interquartile range whenever appropriate; categorical variables are presented as frequencies (P > 0.05). The clinical characteristics of derivation and validation cohorts are summarized in Table Patients including 43 discharged within 24 h, 1 with heart transplant, 11 with renal replacement, 2 with massive stroke, 4 with malignant tumors, and 135 lost to follow-up were excluded. Finally, a total of 4550 patients from the Heb-ADHF registry were enrolled in this study, who were randomly divided into the derivation cohort  and the validation cohort  at a ratio of 3:2. The incidence of the composite of outcomes was 13.9% (381/2745) in the derivation and 13.9% (249/1805) in the validation cohorts. For both cohorts, the age, male, BMI, smoking, drinking, HF duration, number of hospitalizations for heart failure (NH-HF), LoHS, SBP, DBP, heart rate, etiology, heart function, comorbidities, urine protein, laboratory blood tests, chest radiography, electrocardiogram, echocardiography, medical treatment, and risk of outcome events were comparable without significant difference , 0.54 (95% CI 0.53–0.56), and 0.56 (95% CI 0.54–0.57), respectively. Only the specificity of 3A3B score was acceptable (85.3%), but the sensitivity was unsatisfactory (22.0%).P < 0.2) entered into the multivariable analysis: sex , BMI, LoHS, DBP, anemia, RBC, neutrophil, lymphocyte, platelet, TC, LDL-C, creatinine, BUN, AST, ALT, cTnI/T, BNP (NT-proBNP), QRS fraction, pulmonary congestion (X-ray), LVEF, LAD, ACEI/ARB, β-blocker, Tolvaptan, recombinant human brain natriuretic peptide (rhBNP), calcium channel blockers, and Statin. However, multivariate analysis revealed that only 8 variables (P < 0.05)  maintained an independent correlation with the composite endpoint, which were included into the development of the final model.Logistic regression analysis was performed in the derivation cohort Table . Followiχ2-df)  value of each independent predictor  Fig. . The sco9/L) + 1 × (creatinine > 80 μmol/L) + 2 × (BUN > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used).1 × (DBP < 80 mmHg) + 2 × . The discrimination was validated by the AUROC for the validation cohort [0.65 (95% CI 0.61–0.69)] . In addition, the AUROCs of the new PRS in both the derivation and validation cohorts were the highest compared with the 3A3B, AHEAD, and OPTIME-CHF score systems  for the derivation cohort Fig. A, and a Mantel–Haenszel test revealed a linear trend between the risk stratification and the incidence of outcomes events . Pearson correlation test indicated that the incidence of outcome events increased with the increase of the risk stratification .The new PRS was then used to classify patients into 3 groups: 0–4 points, low-risk group; 5–8 points, medium-risk group; ≥ 9 points, high-risk group. The incidence of in-hospital all-cause mortality in low-, medium-, and high-risk groups was 1.86% (14/754), 4.07% (74/1820), and 5.57% (110/1976), respectively , QRS fraction of electrocardiogram, and ACEI/ARB were included in the final scoreing system Table , which w1 × Anemia + 2 × (cTnI/T elevated) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 2 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 1 × (ACEI/ARB not used).Hosmer–Lemeshow test χ2 = 10.270, P = 0.247).The discrimination ability of the PRS model without rhBNP was suitable, whose AUROC for the derivation cohort was 0.66 (95%CI 0.63–0.70) with good calibration  to predict the composite of in-hospital all-cause mortality, 30-day all-cause readmission, or 30-day all-cause mortality after discharge in patients with ADHF. The current findings revealed that all the 3 models performed poorly. We also developed a new PRS based on clinical characteristics on admission. The new scoring system comprised a combination of variables, including DBP, lymphocyte, creatinine, BUN, BNP (NT-proBNP), QRS fraction, ACEI/ARB, and rhBNP. We found that the new PRS outperformed the 3A3B, AHEAD, and OPTIME-CHF score in terms of predicting the short-term prognosis. More importantly, we first demonstrated that the QRS fraction is an independent predictor for the short-term prognosis of patients with ADHF. In addition, it was interesting that low DBP, lymphocyte count and rhBNP used were positive predictors of poor short-term outcomes in patients with ADHF in our study.The short-term risk of death or readmission for ADHF was 13.9% in our study, which was somehow lower than the previous literature . The reaP-for-trend < 0.001), namely high-risk stratification increased the incidence of in-hospital all-cause mortality, 30-day all-cause readmission, 30-day all-cause mortality after discharge, or the composite outcomes. Although the discrimination (AUROC) results were not deal, it still has potential predictive value. In particular, our PRS contained some specific predictors with independent predictive value for the endpoint, such as the DBP, lymphocyte, rhBNP, and QRS fraction.In our study, the new PRS got a better predictive value than the 3 previous scoring systems in predicting the composite outcomes. Furthermore, our findings suggested that there was a linear correlation between the new PRS and outcome events. The higher the risk stratification, the higher the incidence of adverse outcome events (χ2-df) value]  will occur in the future” . Therefoue] Fig. . AdditioMore intriguing and meaningful, rhBNP used and low QRS fraction were also predictors of related adverse events. It is known that rhBNP is a synthetic drug frequently used in the clinical treatment of patients with ADHF and recommended by some guidelines , 34. rhBThe QRS fraction included in our PRS as a novel independent predictor for the endpoints was a rather novel finding of our study. Prior published QRS scoring systems have been proved to be related to left ventricular function –42, but 2DS2-VASc score in atrial fibrillation [In fact, using PRSs for ADHF in clinical practice is far from enough. A single PRS is unlikely to apply to all ADHF populations. However, if effective and simple PRSs are actively applied in daily clinical work and incorporated into electronic health records like the application of CHAillation  or GRACEillation , we beliThere exist several limitations in the present study. First, patients' socio-economic background may strongly influence treatment. Some diagnostic and therapeutic approaches such as the detection of interleukin-1 receptor-like 1 (ST2), the use of angiotensin receptor-neprilysin inhibitor (ARNI), and the use of implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D), etc. were less common in the our study population, which may have influenced the inclusion of valuable variables and the discrimination for our new PRS. In the future, it will be necessary to include more updated variables to improve predictive accuracy. Second, because our study was conducted in multi-centers, some only tested BNP, while others only tested NT-proBNP, which may have a certain impact on the results. Third, other than the 3A3B, AHEAD and OPTIME-CHF scores, we have considered comparing the predictive accuracy of the new PRS with other scores in our population. Unfortunately, we failed since our cohort lacked key variables contained in other scores. Fourth, the clinical data were collected for patients on admission without considering pre-hospital management and there was a small amount of data missing, which could have influenced the results. Besides, our PRS still needs external validation.Collectively, the present study validated 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients from the Heb-ADHF registry, but their discriminations were all poor to predict the composite of in-hospital all-cause mortality, 30-day all-cause readmission, or 30-day all-cause mortality after discharge. We proposed a new short-term PRS , QRS fraction, ACEI/ARB, and rhBNP) that showed moderate predictive capability with the larger AUROC than the 3A3B, AHEAD, and OPTIME-CHF scores. The newly found QRS fraction is an easy to obtain and practical parameter employed in daily clinical practice. When the risk score reaches ≥ 9 points, special attention must be paid and clinical decision-making must be formulated and adjusted more actively. More new variables and larger multicenter studies are required to make our PRS become a practical and reliable tool for evaluating the short-term adverse events for ADHF patients.