Accurate diagnosis and assessment of hematuria is crucial for the early detection of chronic kidney disease(CKD). As instability of urinary RBC count (URBC) often results with clinical uncertainty, therefore new urinary indexes are demanded to improve the accuracy of diagnosis of hematuria. In this study, we aimed to investigate the benefit of applying new complex indicators based on random urine red blood cell counts confirmed in hematuric kidney diseases.All patients enrolled underwent renal biopsy, and their clinical information was collected. Urinary and blood biomedical indexes were implemented with red blood cell counts to derive complex indicators. Patients were divided into two groups  based on their renal pathological manifestations. The target index was determined by comparing the predictive capabilities of the candidate parameters for hematuric kidney diseases. Hematuria stratification was divided into four categories based on the scale of complex indicators and distributional features. The practicality of the new complex indicators was demonstrated by fitting candidate parameters to models comprising demographic information.A total of 1,066 cases  were included in this study, with a mean age of 44.9 ± 15 years. In differentiating hematuria-dominant renal histologic lesion from the non-hematuria-dominant renal histologic lesion, the AUC value of “The ratio of the random URBC to 24-h albumin excretion” was 0.76, higher than the standard approach of Lg (URBC) [AUC = 0.744]  0.712 ~ 0.776). The odds ratio of hematuria-dominant renal histologic lesion (Type I) increased from Q2  to Q4 . The predictive model, composed of stratification of new composite indexes, basic demographic characteristics, and biochemical parameters, performed best with AUC value of 0.869 (95% CI 0.856–0.905).The new urinary complex indicators improved the diagnostic accuracy of hematuria and may serve as a useful parameter for screening hematuric kidney diseases. Hematuria is a common urinary abnormality indicative of chronic kidney disease (CKD). In the long asymptomatic early phase of CKD, urinalysis was considered a high priority for evaluating patients with suspected kidney diseases that manifest as hematuria . Urine rA total of 1,066 patients were hospitalized at the Department of Nephrology, Zhongshan Hospital, Fudan University, between August 2018 and July 2021. All patients underwent renal biopsy, and their medical records  were retrospectively retrieved. Inclusion criteria were age > 18 years and had not yet received renal replacement therapy. The exclusion criteria were as follows: transplant recipients, pregnant women, female patients who were menstruating, patients with active tuberculosis, malignancy, acute hemorrhage, an indwelling urinary catheter, infection, or urolithiasis. The study was approved by the Clinical Research Ethical Committee of the Zhongshan Hospital, Fudan University. Informed consent was obtained from all patients. All methods were carried out in accordance with relevant guidelines and regulations.2[kg/m2]), history of diabetes, and hypertension, were retrieved from electronic medical records. Laboratory data from spot urine samples included urinary specific gravity (SG), urinary RBCs, dipstick protein measurements, urinary microalbumin (µmol/L), urinary creatinine level (mg/L), and the percentage of dysmorphic RBCs (%). Quantitative measurements of urine chemistry and protein levels were also collected. Blood chemistry included serum urea nitrogen (mmol/L), estimated glomerular filtration rate (eGFR[ml/min/1.73 m2]), serum creatinine (µmol/L), uric acid (µmol/L), and albumin (g/L] ).Demographic data, including age, sex, height, weight, body mass index . Microscopic urine examination was performed using a bright-field microscope according to the recommendations of the Clinical & Laboratory Standards Institute (CLSI) guidelines as RBC/high-power field (HPF) . MicroscThe urinary albumin-to-creatinine ratio  was calculated as the urinary albumin concentration divided by the urinary creatinine concentration, and the protein-to-creatinine ratio (PCR) was calculated as the urinary protein concentration divided by the urinary creatinine concentration. Estimated GFR (eGFR) was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation. . HyperteUltrasound-guided percutaneous renal biopsy was routinely performed at the core laboratory of Zhongshan Hospital, Fudan University. Renal pathologists collaborated with a nephrologist to make a definitive clinicopathological diagnosis. Renal pathological assessment was performed using light microscopy, immunofluorescence microscopy, and electron microscopy.Based on the pathological lesions detected in renal biopsy combined with clinical manifestations, the spectra of kidney diseases were classified into two types to identify the correlation between RBC measurement in urinalysis and pathological diagnosis. Type I, hematuria-dominant renal histologic lesion; Type II, non-hematuria-dominant renal histologic lesion. Type I features proliferative lesions associated with hematuria and is usually characterized by diffuse mesangial cell proliferation and/or capillary proliferation with or without extensive crescent formation, often with renal interstitial inflammation . SegmentComplex indicators that adjust the parameters for surrogates of routine urinalysis RBC counts were developed to yield hematuria measurements. The relationship between urinalysis results, biochemical indices, and renal pathological classification was analyzed. Urinary parameters included URBC, creatine level, albumin, albumin-creatinine ratio, 24-h urine protein excretion, and 24-h creatinine excretion. The serum biochemical parameters included creatinine, albumin, and urea nitrogen levels. We determined a series of new complex indicators based on the URBC, which included the ratio of random URBC to urinary specific gravity (URBC/SG), the ratio of random URBC to urinary microalbumin (URBC/UAlb), the ratio of random URBC to urinary creatinine (URBC/UCr), the ratio of random URBC to 24-h urinary protein quantification (URBC/24 hUP), and the ratio of random URBC to 24-h urinary creatinine quantification (URBC/24 hUCr).The entire range of parameters was stratified into four equal parts based on the degree of hematuria. Hematuria stratification was defined accordingly, and their correlations with hematuria-dominant renal histologic lesions (Type I) were analyzed. Three models of the new urinary complex indicator (Lg(URBC/24 hUP)), combining diverse factors, were constructed. Models adjusted for demographic characteristics, past medical history, and biochemical data were utilized separately based on hematuria stratification. The relationship between the three models and Type I was analyzed. Model 1 was a univariate model with hematuria stratification alone, Model 2 = Model 1 + demographics  and comorbidities (diabetes and hypertension), and Model 3 = Model 2 + biochemical data .2 test. The differences in the distribution of each urinary index between patients with Type I and Type II were compared. The logarithm of the composite index was analyzed, and a receiver operating characteristic (ROC) curve was drawn. The predictive performance of each new urinary complex indicator for hematuria-dominant renal histological lesions was assessed by calculating the area under the ROC curve (AUC). We classified the composite index into four categories for hematuria stratification. The Cochran-Mantel-Haenszel test was used to evaluate hematuria stratification. Multivariate logistic regression models were fitted to the data to test the relationship between the new urinary complex indicators, and Type I and AUC was used to evaluate predictive capacity. Statistical significance was set at p < 0.05 for a 2-sided test.Statistical analysis was performed using Statistical Package for Social Sciences (SPSS), version 25.0 . Qualitative data were presented as numbers and percentages (%). Quantitative data were presented as means with standard deviations (SD) for continuous variables with approximately normal distributions and interquartile ranges (IQR) for non-normally distributed data. All indexes with skewed distributions were log-transformed and dimension-transformed to obtain normal distributions. An independent sample t-test was used to compare the group differences for normally distributed continuous variables. The non-parametric rank-sum test was used to compare group differences for non-normally distributed data. All categorical data were analyzed using the χA total of 1,066 hospitalized patients were included in this study. The mean age was 44.9 ± 15.0 years; men accounted for 59.1% (n = 630). Of these patients, 139 (13.0%) had a history of diabetes, and 552 (51.8%) had hypertension.In the data obtained from the Shanghai Laboratory of Kidney Disease and Dialysis, 872 patients were diagnosed with nephritic glomerular disease , 15 with lupus nephritis, 11 with Henoch-Schönlein purpura, and 3 with hepatitis B virus-related glomerulonephritis. Additionally, 25, 30, 53, and 57 patients were diagnosed with tubulointerstitial nephropathy, hypertensive nephropathy, diabetic nephropathy, and other types, respectively. Of these, 736 (69.0%) patients were classified as hematuria-dominant renal histologic lesions (Type I), and the other 330 (30.9%) patients were classified as non-hematuria-dominant renal histologic lesions (Type II). The clinical and pathological characteristics were described in Table p < 0.001). The 24-h urinary creatinine excretion was higher in Type I  than in Type II. As for patients’ biochemical data, no significant differences in serum creatinine, eGFR, and uric acid were observed between Types I and II kidney diseases (p > 0.05). Serum urea nitrogen  level was higher in Type II kidney diseases than in Type I kidney diseases. In contrast, serum albumin  was lower in Type II kidney diseases than in Type I kidney diseases  was divided into quartiles characterized as Q1 (< 0.85 µL/(g/L)), Q2 (0.85 ~ 1.50 µL/(g/L)), Q3 (1.50 ~ 2.06 (µL/(g/L)) and Q4 (≥ 2.06 µL/(g/L)). The corresponding URBC/24 hUP ratios were < 7 µL/(g/L), 8 ~ 32 µL/(g/L), 33–115 µL/(g/L), and ≥ 116 µL/(g/L) (Table 4 hUP wasCompared with the minimized Lg URBC/24 hUP) level, the odds ratio of Type 1 increased from Q2  to Q4 . There was a 3.72-fold increase in the odds ratio for doubling of Lg (URBC/24 hUP) in the range of 0.85 ~ 1.50. This indicated that a higher quartile of Lg (URBC/24 hUP) facilitated the detection of hematuria-dominant renal histological lesions with higher discrimination  that adjusts 24-h urinary protein quantification for surrogates of random urine RBC count to better reflect hematuria. From our study results, 24-h urinary protein quantification displayed significant distribution discrepancies in the two pathological types and was more related to Type I. Clinical practice guidelines recommend screening for and monitoring albuminuria and incorporating increased albuminuria into the definition and staging of CKD . The 24-In capturing trends in upgrading hematuria stratification-derived AUC values, we observed that patients with a higher URBC/24 hUP showed more specific interactions with Type I changes. Stratification of Lg (URBC/24 hUP) achieved an AUC value of 0.751 . When fitted into the model incorporating demographic characteristics and past medical history, the AUC value increased to 0.866 (95% CI 0.842–0.889). After the integration of biochemical data, the AUC further increased to 0.880 . These findings indicate that new urinary complex indicators corresponded better with Type I in the population at high risk of CKD, such as patients with hypertension and diabetes. For patients in the high-risk group (Q4), 24-h urine collection is a typical method of disease assessment and management. Compared to routine RBCs count based on a single collection, URBC/24 hUP corrects the urine RBC count by “24-h urinary protein quantification,” reflecting a time-accumlation effect.Patients presenting with proteinuria and /or hematuria are usually recommended to have renal biopsy, especially other less invasive procedures are not conclusive enough. Since rThis study had some limitations. First, due to the diversity of renal pathological changes, glomeruli, renal tubules, or interstitium lesions may exist alone or together. Therefore, the corresponding urine abnormalities may interfere with one another. Second, the limited sample size and the unbalanced constituent ratio between Type I and Type II barriers further generalization. Third, a discrepancy between the urinalysis and clinical pathology manifestation existed in some cases, which might be attributed to intermittent onset of hematuria, while other patients who presented with recurrent hematuria and no urinary abnormalities between the hematuric bouts may be recorded in this study as well. As a result, patients with proliferative glomerulonephritis may have negative hematuria, especially in well-rested conditions. Failure of patients to comply with the standards of urine collection or any mistakes in urine sample transport and storage would lead to pre-analytical errors and inaccurate results . HoweverIn combination with clinical information, the accuracy of urine RBC counting could be improved, and the integrity of hematuria diagnosis could also be promoted simultaneously to achieve or approach the non-invasive diagnosis of CKD . This sm


The impairment of kidney function, which occurs in chronic kidney disease (CKD) and acute kidney injury (AKI), promotes specific alterations in nutrient metabolism  and induNutritional management in individuals with impaired kidney function varies depending on the disease severity, nutritional status, cause of disease, comorbidities, medications, and treatment methods. Therefore, understanding the available methods for assessing nutritional status, establishing dietary requirements, and strategies for preventing or treating potential nutritional derangements is essential for optimal care of patients with kidney diseases. This Research Topic focuses on recent studies exploring nutrition and metabolism in CKD.Ramos-Acevedo et al., performed a study in individuals with CKD stages 3–5 without kidney replacement therapy, incorporating measures of nutritional status and other clinical variables. They found good concordance between their models and others validated in CKD. The authors concluded that clinicians should consider using formulas that include nutritional status and other variables, such as weight, fat-free mass, comorbidities, sex, and age, to estimate energy requirements.In individuals with CKD, energy requirements have traditionally been considered to be higher based on early nitrogen balance studies. However, more recent studies have questioned these higher recommendations –5. IndirAbi et al. utilized indirect calorimetry to measure REE in patients with stage 3–5 CKD and assess the relationship with the adipokines leptin, IL-6 and adiponectin in serum. In an initial analysis, the authors found that REE was positively correlated with leptin in males and females and negatively correlated with adiponectin in males only. However, when fat mass was accounted for using a multivariate linear regression model, the only significant relationship observed was between REE and leptin in males. This study highlights the importance of considering the degree of adiposity when studying adipokines, as well as the possibility of a sex-specific relationship between adipokines and energy expenditure in CKD patients.Similarly, Wu et al. observed that there was a U-shaped relationship between LDL cholesterol levels and cardiovascular mortality. When a subgroup analysis was performed, this U-shaped relationship only remained significant in those with serum albumin of <36 g/L, used as a biomarker of malnutrition. The authors concluded that nutritional status modifies the relationship between LDL cholesterol and cardiovascular mortality in PD.Cardiovascular mortality is increased in populations with CKD, and there is considerable interest in how commonly assessed lipid risk factors can be utilized to understand and modulate cardiovascular risk . In a laLecamwasam et al. compared clinical and metabolomic data between patients with diabetes and early or late-stage CKD. In this study, the authors found no difference in LDL cholesterol between groups, although low-density lipoprotein triglyceride (LDL-TG) was increased in the late CKD group. The ratio between Apolipoprotein B1 and Apolipoprotein A1 (ApoB/ApoA1), a well-established risk factor for cardiovascular disease  is a uremic toxin which has been implicated in cardiovascular disease  is one of the interventions recommended to manage muscle wasting in patients on maintenance hemodialysis if diet alone does not provide sufficient energy and protein intake . In a raCastle et al. showed this intervention was feasible and acceptable for recent kidney transplant recipients.Obesity is also a critical issue in the CKD population. Post-transplant increases in fat mass are usually associated with insulin resistance and cardiovascular risk factors in kidney transplant recipients . AnotherLiang et al. observed that elderly patients with malnutrition, assessed by the Controlling Nutritional Status score (CONUT score), who underwent percutaneous coronary intervention, had a 2-fold increased adjusted risk of contrast-associated AKI, compared to those with no malnutrition.Malnutrition may also be associated with kidney-related outcomes, such as increased susceptibility to AKI , 14. A sXia et al. investigated the effectiveness of zinc supplementation in 9811 patients with AKI. They found zinc supplementation was associated with improved survival in critically ill patients with AKI. Whilst further study is needed, this study highlights potential benefits of zinc supplementation in critically ill patients with AKI.Zinc is an essential micronutrient involved in numerous metabolic processes. AKI is associated with low plasma zinc , but outSong et al. conducted semi-structured interviews with 23 patients in China on hemodialysis to explore their perceptions and attitudes toward diet. Findings showed diet behavior in Chinese patients undergoing hemodialysis is strongly influenced by culture. Culturally sensitive interventions regarding the improvement of diet intake are urgently needed.Diet management plays a crucial role in treating potential or ongoing nutritional deficiencies and derangements in patients undergoing hemodialysis . HoweverLi et al. explored associations of kidney damage with the interaction of hydration status and physical activity level in 1,914 primary school children from China. They found longitudinal interactions of hydration status and physical activity level on early kidney damage and found increased dehydration among the children over time. These results support the importance of adequate water intake, and suggest that children can be protected from early kidney damage by euhydration, either with sufficient or insufficient physical activity.Healthy lifestyle behaviors, including a healthy diet, weight control and physical activity promote the kidney health of children, reducing long-term kidney damage in adulthood . PhysicaNutrition and metabolism in kidney diseases” enrich our understanding on a wide variety of topics, from nutritional assessment aspects, such as energy expenditure, body composition, bioelectrical impedance analysis parameters, and new and traditional biomarkers evaluation, to nutritional management of the main nutritional disorders in CKD and AKI, including malnutrition, sarcopenia, macro And micronutrients deficiency, and obesity. The articles included in this collection highlight future research directions, assist in the development of novel therapeutic approaches, and contribute to improvements in clinical practice.In summary, the studies included in the Research Topic on “All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Ureteral duplication is a common embryologic abnormality of the kidney with an incidence rate of 0.8% in adults. However, complete duplex ureters opening independently into the urinary bladder are rarely present. We report a 35-year-old female who presented with left flank pain in the last three years. Abdominal CT scan showed left complete duplicated system with lower moiety hydroureteronephrosis and obstructed midureteral stone. The patient underwent left retroperitoneal exploration with complete excision of the hydronephrotic sac. The postoperative course was uneventful without complications. In conclusion, a complete duplex kidney with lower moiety hydronephrosis caused by mid ureteric stone is rare. The renal duplication system should be diagnosed and followed with image guidance periodically as the late diagnosis may have poor outcomes with loss of the kidney or part of it. Ureteral duplications are a common congenital anomaly of the kidney and the urinary tract system , 2. It hGenerally, duplex renal systems are asymptomatic and diagnosed incidentally; however, several conditions requiring treatment have been observed in association with duplex systems: obstruction, reflux disease, and urinary stones are not peculiar but may be commoner in duplex systems .Concerning obstruction, the upper moiety may be at a greater risk caused by ureterocele and lower moiety is at risk of reflux nephropathy , 6. To tA 35-year-old female patient presented with left flank pain in the last three years. The pain was a dull aching type that did not prevent her from accomplishing her daily work and not radiating without aggravating or relieving factors. The patient was visited by a primary health care personnel and diagnosed with renal stone without improvement with medical therapy. The patient had hypertension and was controlled with oral medication ten days ago.On physical examination, her vital signs were normal. In the abdominal examination, she only had mild left costovertebral angle tenderness.Blood tests revealed a total white blood cell count of 9 × 10 [3]/ml, hemoglobin of 14.3 g/dl, blood urea nitrogen of 14 mg/dl, and creatinine of 0.52 mg/dl. Ultrasound of the kidney showed left multiple well-defined anechoic lesions with distal acoustic enhancement (fluid-filled structure) seen on the left kidney mid and lower pole. Computerized tomography (CT) scan of the urinary system (CT urography) showed normal excreting of the right kidney and ureter with no obstruction. The left kidney duplex pelvis with two complete ureters draining into the bladder where the lower kidney draining ureter was dilated to the level of the fourth lumbar vertebrae with obstructed stone measuring 7 mm in diameter .Diagnostic cystoscopy showed a single right ureteric orifice and two left ureteric orifices where the nonobstructed ureteral orifice appears medial where JJ stent Fr 6 size was placed without difficulty. The obstructed ureteral orifice appears lateral and caudal where the ureteric catheter advanced till to the obstructed part (midureter) due to impacted stone with no association with ureterocele . A diagnPreoperative antibiotic (ceftriaxone: 1 g) was administered. Then, the abdomen was entered through a left subcostal flank incision under general anesthesia. Retroperitoneal space was entered, and the left kidney was identified after Gerota's fascia was opened. The lower pole of the kidney was hydronephrotic and looked like a bag of fluid. The two ureters were identified and found with the upper pole insertion, and the other was draining the lower pole .The lower segment vasculature and upper moiety blood supply were identified, and the left partial nephrectomy was done  . SimilarThe first modality used was ultrasound showing our patient's multicystic mid- and lower pole segments. Later, other imaging modalities used to confirm or rule out conditions must be held. These include voiding cystourethrography, which is used to rule out reflux. Intravenous urography IVP and CT urography to confirm the duplex system and other obstruction causes, and nuclear imaging to realize the split function and level of obstruction , 14. In Another option for clarifying the anatomy of duplication anomalies is preoperative cystoscopy combined with a retrograde ureteropyelogram prior to surgical correction .Management depends on the cause of obstruction and the cortical loss in the renal moiety . The majOur patient might have benefited from a simple endoscopic procedure if the diagnosis had been made sooner. However, her delayed presentation to appropriate care due to her primary healthcare providers' low suspicion index resulted in this unfortunate complete renal moiety parenchymal loss; a similar result was reported by Anyimba et al. The previously asymptomatic duplex renal system may develop symptoms later in life. When identified without symptoms or evidence of renal function compromise, the integrity of the renal moieties may have to be closely monitored for the rest of its life. A thorough evaluation with a high index of suspicion is required in individuals presenting with flank pains to quickly identify missed duplex renal systems and duplex system associated disorders quickly and thus prevent the attendant renal moiety parenchymal loss.


Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin–angiotensin–aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin–angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD. Chronic kidney disease (CKD) is a global public health issue . In ChinThe risk of cardiovascular events is significantly increased under CKD, with cardiovascular diseases representing the major cause of death in patients with CKD . CompareTraditional risk factors such as hypertension, hyperglycemia, and dyslipidemia, as well as non-traditional risk factors such as abnormal calcium and phosphorus metabolism, in addition to inflammation, are all implicated in the high incidence of cardiovascular events in patients with CKD .Hypertension is one of the most common complications in patients with CKD , where tGenerally, the blood pressure target for patients with CKD and hypertension is stricter than that for regular patients with hypertension. The SPRINT study confirmed that intensive blood pressure reduction benefited patients with CKD by alleviating cardiovascular and cerebrovascular events . Based oAntihypertensive treatment for patients with CKD usually includes lifestyle intervention in conjunction with drug treatment . All fivNatriuretic peptides, including atrial, B-type, and C-type natriuretic peptides, are a group of polypeptides with a wide range of physiological effects, including the promotion of natriuresis and diuresis, vasodilation, RAAS inhibition, reduction of sympathetic nerve activity, and the suppression of proliferation and fibrosis . SacubitIn recent years, studies have successively confirmed that the first and so far the only angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure in patients with CKD more effectively than RAAS inhibitors and can improve the prognosis in patients with heart failure . ConsideSuggestion 2.1: When ARNI is used for patients with hypoproteinemia , titration should be started from a low dose. The dosage and frequency that is suitable for patients should then fall within a safe-dose range (see Suggestion 2.2 for hypoproteinemia caused by hepatic dysfunction). (2D)Rationale: ARNI has a high protein binding rate , there is no need to adjust the loading dose, whereas in cases of moderate hepatic impairment (Child–Pugh B), the loading dose should be halved and the dose should be gradually increased to the most suitable dose that the patient can tolerate. ARNI is not recommended for patients with severe hepatic impairment. (1B)Rationale: A pharmacokinetic study in patients with mild to moderate hepatic impairment revealed that, compared with healthy subjects, exposure to sacubitril, LBQ657, and valsartan was slightly increased in patients with mild hepatic impairment . In patients with moderate hepatic impairment, the exposure increased by 3.4, 1.9, and 2.1 times, respectively . Thereafter, depending on the patient's tolerance, the dose should be doubled every 2–4 weeks until the target dose of 200 mg BID is reached. For patients who have previously used ARBs, we suggest converting to the appropriate ARNI dose according to the previous ARB dose. For patients who have used ACEIs, it is necessary to discontinue the drug for more than 36 h before converting to an appropriate ARNI dose with reference to the original ACEI dose.Rationale: For patients with heart failure, it is usually appropriate to start ARNI treatment at a relatively low dose to improve tolerance to the initial treatment. The target dose of 200 mg BID is based on previous studies, which showed that 200 mg ARNI can fully inhibit neprilysin and enhance the activity of natriuretic peptides Rationale: The PIONEER-HF and TRANSITION studies evaluated the benefits of initial ARNI treatment after stabilization of acute heart failure (P < 0.002)   indicate< 0.002) . The TRA< 0.002) . TherefoSuggestion 2.4.1: Concomitant use of ARNI and ACEI should be avoided ((1C) avoided , and it Rationale: The concomitant use of ACEI while inhibiting neprilysin may increase the risk of angioedema Rationale: The mechanisms of action for ARNI and SGLT2i are relatively clear. ARNI acts on the natriuretic peptide system and RAAS, which blocks the adverse effects of the latter, while also enhancing the beneficial effects of the former, thereby playing a role in reversing cardiac remodeling and improving heart failure ( failure . SGLT2i  failure . As ARNI failure . Therefo failure . Moreove failure . Moreove failure . However failure . When usSuggestion 2.4.3.1: ARNI is contraindicated in patients with a previous history of angioedema ((1C)gioedema . (1C)Rationale: Patients with a previous history of angioedema may have an increased risk of angioedema during ARNI treatment ommended . (1C)Rationale: Aliskiren is a direct inhibitor of renin, and its combination with ACEI or ARB may cause dual inhibition of the renin–angiotensin system and increase the risk of poor prognosis .Rationale: ARNI may induce hyperkalemia. In the PARADIGM-HF study, 12% of patients receiving ARNI and 14% of those receiving enalapril developed hyperkalemia. Thus, the concomitant use of spironolactone, amiloride, or potassium salt with ARNI may increase potassium levels in the blood. In severe cases, hyperkalemia can lead to renal failure, muscular paralysis, arrhythmia, and cardiac arrest. Therefore, when using ARNI in combination with any of these three agents, close attention should be paid to serum potassium levels to avoid hyperkalemia.Suggestion 2.4.3.4: ARNI is contraindicated in pregnant women to avoid the risk of teratogenicity at the early stage as well as the inconvenience and risk of subsequent drug adjustment ((2C)justment . (2C)Rationale: The application of ARNI in pregnant women may cause fetal injury. Further, the application of drugs that inhibit the RAAS in the second and third trimesters may affect fetal renal function and increase the risk of illness and death of the fetus and neonate Rationale: When ARNI was taken with a meal, exposure to sacubitril and valsartan was significantly lower, whereas exposure to the active metabolite LBQ657 exhibited no significant change Rationale: The efficacy of ARNI in non-dialysis patients with CKD and heart failure has been confirmed by several studies. Analysis of the CKD subgroup in the PARADIGM-HF study (eGFR: 30–60 mL/min/1.73 m2) revealed that ARNI reduced the risk of cardiovascular events compared with the ACEI-treatment group, with the risk of cardiovascular death decreasing by 24%, the risk of hospitalization owing to heart failure and all-cause death decreasing by 21%, and the risk of preset composite kidney events was reduced by 36%  (2), ARNI treatment significantly reduced the risk of cardiovascular death and hospitalization owing to heart failure (P = 0.011) (2) in the PARAGON-HF study showed that ARNI significantly reduced the risk of the renal composite endpoint by 50% compared with ARB (2), the eGFR under ARNI treatment was significantly higher than that under valsartan treatment (P < 0.01) (disease) , 44. At  failure . In addi= 0.011) . In pati < 0.01) . Further < 0.01) .Suggestion 3.1.2: ARNI is recommended for non-dialysis patients with CKD exhibiting hypertension. (1B)Rationale: ARNI can simultaneously act on the RAAS and natriuretic peptide system, thereby reducing blood pressure via multiple mechanisms and protecting target organs . If the patient can tolerate this dose, the dose should be doubled every 2–4 weeks until reaching the target maintenance dose of 200 mg BID ((2B)0 mg BID . (2B)Rationale: In patients with renal impairment, exposure to sacubitril active metabolite LBQ657 was affected, whereas exposure to sacubitril and valsartan was not affected, and the difference in LBQ657 exposure was not significant under mild renal impairment. However, in patients with moderate, severe, and end-stage renal disease , the exposure increased by 2.29, 2.90, and 3.27 times, respectively . For patients whose blood pressure cannot be sufficiently controlled via a single administration daily, the dose can be increased to 400 mg QD (1B). In patients with CKD, a twice-daily dosage regimen can also be adopted (2C). For patients with mild renal impairment (eGFR 60–90 mL/min/1.73 m2), there is no need to adjust the dose (1B), whereas for those with moderate and severe renal impairment (eGFR 15–60 mL/min/1.73 m2), it is recommended to reduce the loading dose to 100mg QD ((2C). However, considering the minimal experience of patients with end-stage renal disease, these clinical findings should also be considered in this case (2C).100mg QD  (2C). HoRationale: In terms of pharmacokinetics, the half-lives of LBQ657 and valsartan after a single dose of ARNI 200 mg are 11.5 h and 9.9 h (2) were treated with ARNI 100–400 mg QD for 8 weeks according to their blood pressure. At the end of the study, 26 patients received LCZ696 at 200 mg QD, whereas 18 patients received LCZ696 at 400 mg QD. During the eight-week treatment period, no serious adverse reactions were noted. These results indicated that the regimen was generally well tolerated, with no adverse events such as hypotension and angioedema Rationale: In the PARADIGM-HF study, 14% of patients treated with ARNI developed symptomatic hypotension (SBP <100 mmHg), which was slightly higher than the proportion in the enalapril group (9.2%) (p (9.2%) . In a mep (9.2%) . We suggp (9.2%) . If hypop (9.2%) . UsuallySuggestion 3.3.2: For patients with hyperkalemia (≥5.0 mmol/L), we recommend stopping potassium supplementation and MRA, and lowering potassium. If necessary, dose reduction or discontinuation of ARNI may be considered. (1B)Rationale: ARNI treatment may lead to an increase in serum potassium because of its effect on the RAAS (2) was similar  (the RAAS . In the the RAAS . In the  = 0.10) . For pat = 0.10) . The serSuggestion 3.3.3: There are no available clinical trial data regarding the respective evaluation criteria or treatment methods for patients exhibiting a rapid decline in renal function resulting from ARNI treatment. Thus, treatment methods for renal function decline due to RAAS inhibitor treatment can be referred to instead. First, it is necessary to clarify the reasons for the decline of renal function. After excluding renal artery stenosis as the culprit, if the serum creatinine levels increase by <30% compared with the baseline value, ARNI can be used continuously. If serum creatinine levels exceed the baseline level by 30%, the dose should be reduced or ARNI should be discontinued in time, and the underlying reasons should be identified. If serum creatinine levels exceed the baseline level by 50%, it is recommended to discontinue ARNI. (1C)Rationale: Because of its effect on the RAAS, ARNI treatment may lead to an increase in creatinine. In the PARADIGM-HF study, 5% of patients treated with ARNI reported renal failure Rationale: When patients with diabetes exhibit renal insufficiency, renal gluconeogenesis is weakened and the clearance rates of some drugs are reduced, which may in turn increase the risk of hypoglycemia. In addition, some hypoglycemic drugs or their metabolites can accumulate in the kidneys, which further aggravates renal insufficiency. Therefore, it is necessary to select appropriate hypoglycemic drugs and dosage based on the renal function of patients with CKD Rationale: The PARADIGM-HF study showed that, compared with ACEI, ARNI significantly delayed the decline rate of eGFR in patients with HFrEF by 23.5%, and reduced the risk of cardiac and renal adverse events in patients with CKD and HFrEF Rationale: A meta-analysis including five randomized controlled studies confirmed that, compared with ACEI/ARB, ARNI more effectively reduced the mean sitting arterial pressure  and diastolic pressure  ( < 0.01) . An eigh < 0.01) . A meta- < 0.01) .Suggestion 3.4.2.2: For patients with CKD and poor nocturnal blood pressure control treated with ACEI/ARB, we suggest switching ACEI/ARB to ARNI to further improve nocturnal blood pressure control. (1B)Rationale: A randomized controlled study in patients with hypertension in Asia showed that ARNI treatment for 8 weeks effectively reduces nocturnal ambulatory SBP by up to 16.14 mmHg Rationale: The use of ACEI/ARB will decrease potassium excretion through the kidneys and increase serum potassium levels. In the PARADIGM-HF study (which excluded patients with eGFR <30 mL/min/1.73 m2), the serum potassium level was lower in the ARNI treatment group than in the enalapril group, and the incidence of hyperkalemia and severe hyperkalemia was significantly reduced, with even patients treated in combination with MRA exhibiting a significantly lower risk of hyperkalemia (P = 0.048)  . A meta-= 0.048) ; howeverSuggestion 3.4.4: For patients with CKD exhibiting heart failure who are treated with ACEI/ARB and whose serum creatinine has increased substantially (by >50% or ≥266 μmol/L), we recommend discontinuing ACEI/ARB, monitoring renal function, and switching to ARNI after renal function stabilizes or improves, so as to reduce the risk of entering end-stage renal disease. (1B)Rationale: A review published in 2021 noted that the sympathetic system was strongly activated in patients with heart failure, and using a RAAS inhibitor alone to dilate efferent arterioles could significantly reduce the hydrostatic pressure in capillaries, resulting in an increase in creatinine. When ARNI was used instead of RAAS inhibitors, efferent and afferent arterioles were dilated synchronously, the renal plasma flow increased, the effective filtration area increased, and the filtration permeability of mesangial cells increased, thus improving eGFR (P = 0.002) (ing eGFR . In the = 0.002) .Suggestion 3.4.5: For patients with CKD who still exhibit overhydration after treatment with ACEI/ARB, we suggest switching ACEI/ARB to ARNI to improve volume control. (2C)Rationale: ARNI not only inhibits the RAAS system, but also inhibits enkephalinase and enhances the natriuretic peptide system. The natriuretic peptide system is a potential target for renal disease treatment, which can promote natriuresis and diuresis, help reduce sodium as well as water retention, and improve volume control Rationale: Subgroup analysis of the PIONEER-HF study confirmed that direct initiation of ARNI had more clinical benefits than switching from ACEI to ARNI. Further, the benefits were consistent among all patients in the high-risk subgroup Rationale: Data exist on the use of ARNI in patients with heart failure undergoing maintenance dialysis. A clinical study conducted in hemodialysis patients in China showed that, when ARNI 100 mg BID was used to treat hemodialysis patients with HFrEF or heart failure with midrange ejection fraction, the maximum blood concentration of LBQ657 was within the safe drug concentration range, and ARNI effectively improved their left ventricular ejection fraction (P < 0.05) ( < 0.05) . Another < 0.05) . A Chine < 0.05) .Suggestion 4.1.2: ARNI can be used in patients with hypertension undergoing maintenance dialysis to lower blood pressure, protect cardiac function, and reduce the risk of cardiovascular events. (2D)Rationale: Approximately 90% of dialysis patients in China have hypertension olerance . (1C)Rationale: When used reasonably, ARNI is well tolerated in dialysis patients. In a retrospective study, 23 patients who were switched from ACEI/ARB to ARNI treatment exhibited an average dose of ARNI at the baseline of 90 ± 43 mg/d. After a follow-up period with a median length of 132 days, the dose at the last follow-up was 123 ± 62 mg/d. The most common adverse reaction during treatment was hypotension (SBP <100 mmHg), which usually occurred during or immediately after hemodialysis. During treatment, the dose of ARNI was reduced for approximately 21.7% of patients because of adverse reactions; however, these reactions did not lead to drug discontinuation (inuation . Therefoinuation , 81.When using ARNI in patients with CKD, its dosage and frequency should be determined according to renal function, cardiac function, and the occurrence of hypoproteinemia or abnormal liver function. Whether it is necessary to start with a low dose in patients with moderate and severe renal impairment should be further addressed . AlthougAll authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background and Objectives: StoreProtect Plus® is a preserving solution for cold organ storage, with a composition identical to Institute Georges Lopez (IGL-1) solution. The aim of this single center study was to compare the clinical performance of StoreProtect Plus with the generic counterpart of University of Wisconsin preservation fluid, named SPS-1®. Materials and Methods: The clinical outcomes of 168 consecutive organs preserved with StoreProtect Plus solution and 167 organs preserved with SPS-1 solution were compared. During an 18-month post-transplant follow-up period, kidney graft function, the frequency of acute rejection, post-transplant diabetes, and infectious complications, as well as patient and graft survival were analyzed. Results: There was significantly more immediate graft function (IGF)  and less slow graft function (SGF)  in the StoreProtect Plus group in comparison with the SPS-1 group, whereas the occurrence of DGF was similar in both groups. Long-term kidney graft function was comparable. Multivariate regression analysis showed that the use of StoreProtect Plus vs. SPS-1 solution  and the amount of residual diuresis  independently increased the occurrence of IGF, whereas Scr > 1.5 mg/dL prior to organ procurement , longer CIT , and CVD donor death  were associated with SGF. Conclusions: The higher occurrence of IGF was found in kidney transplant recipients whose organs were preserved using StoreProtect Plus solution as compared with SPS-1 solution. The two groups did not differ in kidney graft function, the frequency of post-transplant complications, as well as patient and graft survival. In kidney transplantation, organ preservation solutions have been developed to reduce ischemia/reperfusion tissue injury during cold storage and, in consequence, to improve early graft function and its long-term survival . The aimIn recent years, the use of generic preservation solutions has been increasing as a result of a worldwide transplant cost-saving strategy. However, although the fluid composition of a generic product should be the same as in the original solution, other factors, including the purity of the components used, the performance/quality of the bags, and storage conditions, could affect the graft viability and, in consequence, worsen the clinical outcomes of organ transplantation . It is w® is a solution for the perfusion and cold storage of organs for transplantation, produced by Carnamedica  and marketed since 2017 (ID: 9619 7077 2240). Its composition is identical to IGL-1 solution. It meets the requirements of the European Medical Devices Directive (MDD) and is certified by the Notifying Authority No. 2274. From December 2018, it has been constantly used in our center for organ preservation during kidney, liver, and simultaneous pancreas–kidney transplantation. Taking into account that the original UW solution  was used in our center over a decade ago, with different characteristics of both recipients and donors, as well as markedly different immunosuppression and induction therapy protocols, we decided to perform a retrospective comparison of the generic UW solution  with the generic IGL-1 solution (StoreProtect Plus) in aspects of early post-transplant graft function and also midterm follow-up patient and graft clinical outcomes.StoreProtect Plusn = 7) and simultaneous pancreas–kidney transplant patients (n = 10) were not included in the analysis. All organs were preserved in cold storage and all donors and recipients were Caucasian.In the period from December 2018 to December 2020, 168 consecutive organs were transplanted and preserved with StoreProtect Plus preservation fluid. The control group consisted of 167 consecutive kidney transplantations between May 2015 and November 2016, with organs preserved with SPS-1 solution. Due to the potential risk of bias caused by the relatively short cold preservation time, the recipients of organs from living donors , ECD status, the Kidney Donor Risk Index (KDRI) value, the occurrence of hypertension, the serum creatinine level prior to organ procurement, and the cause of death. There were no diabetic donors in the analyzed cohort. The study protocol was reviewed by the Bioethical Committee of the Medical University of Silesia (PCN/CBN/0052/KB/128/22). Initial graft function was defined based on the serum creatinine (Scr) level at post-transplant day 3 and the need for dialysis therapy during the first week after transplantation. Patients with immediate graft function (IGF) were characterized by Scr < 3 mg/dL at day 3; slow graft function (SGF) was defined as Scr above 3 mg/dL at day 3, and delayed graft function (DGF) was recognized in patients who required dialysis therapy after transplantation. The latter category was also used in cases of ineffective post-transplant diuresis  during the first postoperative days, which however, usually enables those patients not to be dialyzed due to the lack of overhydration and hyperkalemia. Primary graft nonfunction (PGN) was attributed to those kidney grafts which had to be removed during the first post-transplant hospitalization.Scr was analyzed at postoperative (POD) day 3 and 7, and at the day of discharge from the hospital. In patients with DGF, the morning predialysis Scr values were analyzed. In the follow-up period, Scr was analyzed 3-, 6-, 12-, and 18-months post-transplantation. The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula.During the 18-month follow-up period, patient and graft survival were analyzed. Additionally, we analyzed the frequency of acute rejection (AR) episodes, post-transplant diabetes mellitus (PTDM), and infectious complications, including CMV infection.t-test (for quantitative variables) or the χ2 test  was used. Variables with nonparametric distribution were compared using the Mann–Whitney U test. Correlations were calculated using Spearman. Stepwise multivariate regression analysis was performed for IGF as the dependent variable, including dialysis vintage, residual diuresis, cold ischemia time (CIT), the use of induction therapy, the type of preservation solution used (StoreProtect Plus vs. SPS-1 solution), donor BMI, hypertension, and last donor Scr prior to organ procurement > 1.5 mg/dL as potential independent variables. The model included all variables selected in the univariate analysis, CIT as a traditional well-established risk factor, and the type of preservation solution used. In all the statistical tests, ‘p’ values below 0.05 were considered statistically significant. Statistical analyses were performed using STATISTICA 13.3  and MedCalc 18.6 . Data were presented as means with a 95% confidence interval (CI), medians with Q1–Q3 values, or frequencies. For the comparison of study groups, the Student n = 335), the causes of chronic renal disease were as follows: chronic glomerulonephritis (38.8%), interstitial nephritis (7.5%), polycystic kidney disease (16.1%), diabetic nephropathy (8.1%), hypertensive nephropathy (11.6%), and other disease and unknown conditions (17.9%). The final analysis included 168 KTRs who received organs preserved with StoreProtect Plus and 167 KTRs who received organs preserved with UW. The 18-month results were available for the entire study cohort. In the whole study group . Both analyzed groups did not differ in regard to age, sex, BMI, primary kidney disease, HLA mismatch, CIT, and the percentage of repeated transplantations   or polyclonal  antibodies. There was a higher percentage of patients with induction therapy in the StoreProtect Plus group as compared with the SPS-1 group  .p < 0.05; StoreProtect Plus group: 47.3 vs. 23.2%; p < 0.01). Interestingly, the percentage of SGF was similar after SCD and ECD transplantations, whereas the significant impact of ECD status on DGF occurrence was shown .No significant difference was found in the occurrence of DGF between the two study groups. Importantly, there was significantly more IGF and less SGF in the StoreProtect Plus group than in the SPS-1 group . The frep = 0.60). As expected, donor Scr was associated with recipient Scr during the hospital stay . Additionally, in the StoreProtect Plus group, there were significantly lower median serum creatinine levels measured at the 3rd, 7th, and discharge day as compared with the SPS-1 group . Of notepartial = 0.217; p < 0.001) and residual diuresis  independently increased the occurrence of IGF, whereas Scr > 1.5 mg/dL prior to organ procurement , longer CIT , and CVD donor death  were associated with slower graft function. The rest of the potential explanatory variables were removed from the final model.Stepwise multivariate regression analysis revealed that the use of StoreProtect Plus vs. SPS-1 solution (rp = 0.39). The structure of death causes was comparable, with 50% infectious death in each group and 21.5 vs. 30% CVD death, respectively (p = 0.64). The 18-month follow-up data were available for all the patients in the SPS-1 group and for 164 (97.6%) patients in the StoreProtect Plus group. During this period, there were six graft losses (3.6%) in each group. Fourteen patients (8.4%) died in the SPS-1 group and 10 patients (6.0%) died in the StoreProtect Plus group (p = 0.84). In addition, the percentage of patients with PTDM was comparable . Finally, the rate of all infectious complications during the first 18 months post-transplantation, including CMV episodes, did not differ between groups . The incidence of AR during the follow-up period was similar in both groups (23 vs. 22 events; Kidney graft function did not differ between the groups up to the 18-month timepoint . In the In the present analysis, it was found that the clinical performance of the generic preservation solution, StoreProtect Plus, is not inferior to the previously used generic SPS-1 solution, when taking into account both early post-transplant kidney graft function and the 18-month follow-up observation. There was a substantially higher occurrence of IGF in the StoreProtect Plus group. Importantly, the 12-month kidney graft function in both the analyzed groups was satisfactory and comparable to the previously reported data from the modern immunosuppression era ,11. Our current results regarding the clinical effectiveness of two different generic organ preservation solutions are similar to the previous reports, comparing the efficacy of their original counterparts ,8 in kidIt is worth noting that several different SGF definitions were used in previous studies, being generally based on the Scr level measured at POD 5, 7, or even 14, or on the inadequate Scr reduction rate over a given period . TherefoIn contrast to the abovementioned most common SGF definition, our transplant center adopted the stricter criterion of Scr > 3 mg/dL at POD 3, which resulted in the relatively low IGF percentage reported in the present study compared to others ,14,15,16The main limitation of this study is its retrospective character. However, due to the internal regulations, the type of preservation solution used during the given time period was chosen independently by our hospital supply department, and so it is difficult to plan prospective pair-to-pair comparison. Nevertheless, it is the first clinical study to analyze and compare the results of kidney transplantations using two generic preservation fluids, based on the UW and IGL-1 original solutions. Another limitation is the fact that both investigated groups of KTRs were not transplanted contemporarily.To conclude, the higher occurrence of IGF was found in kidney transplant patients whose organs were preserved using StoreProtect Plus solution as compared with SPS-1 solution, whereas the occurrence of DGF was similar. However, the two analyzed groups did not differ in kidney graft function, the frequency of post-transplant complications, as well as patient and graft survival during the 18-month follow-up period.


Treatment of asthma implies inhalation of specific drugs to reach high concentrations in the respiratory tree and ensure low drug bioavailability and few adverse effects. This study aimed to evaluate the effectiveness of the inhalation technique among outpatients with asthma. Tertiary-care hospital-based cross-sectional study in Rio de Janeiro. We evaluated inhalation practices in a convenience sample. A questionnaire was used to investigate sociodemographic data and assess disease control level, duration of use of the inhalation device, length of treatment and previous instructions provided by the prescribing physician. Patients demonstrated their inhalation technique using empty devices, and their technique was considered correct when all steps were appropriately performed or when errors did not interfere with the treatment outcome. Among the 71 participants, 53 (74.7%) had been using the same inhaler device for at least two years and 41 (57.8%) had been under treatment for two years or more. Twelve (17.1%) said that they had been taught once and 57 (81.4%) at least twice, while one (1.4%) reported not having received any guidance regarding use of inhaler devices. Eighteen patients (25.3%) presented controlled asthma and 28 (39.5%) performed the inhalation technique correctly. Incorrect technique was associated with fewer evaluations of the inhalation technique (P =0.04) and uncontrolled asthma (P = 0.01). Less than half of the sample performed the inhalation technique correctly. Incorrect inhalation technique was related to lower number of evaluations of the use of the inhalation device and uncontrolled asthma. Asthma affects up to 300 million people worldwide,,,,,Use of inhaler therapy allows drugs to rapidly reach high concentrations in the airways, with therapeutic effects even with low drug bioavailability and few adverse effects. Inhaler devices are therefore the main route of administration for treatments for asthma.,,The guidelines recommend regular monitoring of the inhalation technique.This study aimed to evaluate the effectiveness of the inhalation technique among outpatients with asthma.This was a cross-sectional observational study on a convenience sample of patients with bronchial asthma who were being treated at one of the outpatient clinics of the Antônio Pedro University Hospital  in Niterói, state of Rio de Janeiro, Brazil. This study was approved by the local ethics committee of our institution , under the number CAAE 56248816.1.0000.5243. Patients signed informed consent forms for their participation in this study.Patients were eligible if they were 18 years of age or older, were not at their first medical appointment and were using the following inhaler devices containing any corticoids, long-acting bronchodilators (or combinations of them) or even a short-acting bronchodilator: Aerolizer, Aerocaps, Diskus and metered-dose inhaler (MDI), without the aid of a spacer. Patients in a phase of exacerbation of symptoms were excluded and referred to the emergency room for immediate treatment. Patients whose diagnoses of asthma were not confirmed during the treatment and those who regularly received any help from others for using the inhaler device were also excluded.Recruitment was performed sequentially, according to the scheduling dates of patients’ medical appointments. After signing an informed consent form, patients gave responses to a self-administered questionnaire that sought sociodemographic data. They had to demonstrate to researchers how they used the device.Patients’ degree of disease control was evaluated in accordance with the Global Initiative for Asthma (GINA)In our outpatient clinic, patients are given guidance for the inhalation technique, reinforced at all visits. The physician always demonstrates the technique using an empty device equivalent to the one used by the patient. It is always requested that patients should bring their empty devices for training, and when they do, they can practice the inhalation technique in front of the physician, and if there are any errors, these are always corrected.The inhalation technique was assessed according to the following check-list: for Diskus users, the user was required to open the inhaler, push the lever back completely, exhale to residual volume, inhale deeply, hold breath for 10 seconds, exhale away from mouthpiece and close the inhaler. For MDI users, it was necessary to remove the mouthpiece cover, hold the inhaler upright, exhale to residual volume, press the canister and inhale deeply, hold breath for 10 seconds, exhale away from the mouthpiece and close the inhaler. For Aerolizer or Aerocaps users, it was necessary to remove the inhaler cover, open the capsule compartment, place the capsule in the appropriate chamber, close the capsule compartment, press the button(s) of the inhaler, exhale to residual volume, inhale deeply, hold breath for 10 seconds, exhale away from the mouthpiece and close the inhaler.Only the inhalation technique that was performed using the device that patients considered to be their main device was evaluated in this study. The patients demonstrated their technique using empty devices, to at least two evaluators . The inhalation technique demonstrations were filmed for reevaluation, for the eventuality of any disagreement among the evaluators. In such cases, evaluation by a third evaluator was mandatory.The evaluation of the inhalation technique was based on the leaflet provided by the producer of each device. The technique was considered correct when all steps were performed properly or when the misconceptions probably did not interfere with the outcome of the treatment (e.g. not closing the device at the end of the demonstration). The technique was considered incorrect when one or more errors were observed in any of the following steps: preparation of the inhalation device for use, expiration, aspiration or apnea, regardless of the severity of the error. Whenever there were misconceptions relating to the inhalation technique, the patient received instructions on the correct use of the inhalation device.The data obtained were digitized in a Microsoft Excel 2010 worksheet and were exported, for statistical analysis, into the Epi Info 7.2 data analysis software. Central trend measurements (average and median) and dispersion measurements were used for descriptive analysis on the numerical data. Simple and relative frequency calculations were used for questions with categorical variables. The chi-square test or Fisher’s exact test was used to verify associations between the quality of the inhalation technique and patient characteristics, asthma control, severity of obstruction, number of evaluations of inhalation technique that had been made and duration of treatment. P-values (descriptive levels) lower than 0.05 were taken to indicate significant associations. A binary logistic regression model was used to identify characteristics that were predictive of incorrect technique. Variables with a significance level of less than 0.1 in univariate analysis, after adjustment for gender and age, were included in a logistic regression model.Between August 2, 2016, and March 10, 2017, 75 patients were enrolled. However, four were excluded: one had an immobilized arm, which prevented unaided demonstration of the inhalation technique; one was subsequently confirmed to have a diagnosis of chronic obstructive pulmonary disease (instead of asthma); and two used the Aerocaps device when they should have been using Aerolizer to administer their medications .The final sample was thus composed of 71 participants between 19 and 81 years old, with a mean age of 57.7 ± 13.9 years, of whom 61 (85.9%) were female. Fourteen (19.7%) were single, 31 (43.7%) were married and 26 (36.6%) were separated, divorced or widowed. Thirty-seven (52.1%) had at most completed elementary education (9 years of schooling), 29 (40.8%) had at most obtained a high school diploma and five (7.1%) had obtained a university degree at bachelor or higher level. Regarding personal income, 49 (70%) received a maximum of one Brazilian minimum salary per month , whereas 20 (28.6%) received between one and three minimum salaries and one (1.4%) earned between three and ten minimum salaries. Regarding family income, 28 (40%) received up to one minimum salary, 38 (54.3%) one to three minimum salaries and four (5.7%) between three and ten minimum salaries.According to the GINA document, two participants (2.8%) were in stage 1 of the treatment of bronchial asthma (as needed short-acting beta2-agonist), 14 (19.7%) in stage 2 , 11 (15.5%) in stage 3 , 43 (60.6%) in stage 4  and one (1.4%) in stage 5 . With regard to the asthma control level, only 18 patients (25.35%) presented controlled asthma, while 20 (28.15%) exhibited partial control over the disease and 33 (46.5%) had uncontrolled asthma. Concerning the severity of the obstructive disorder, 50 (70.42%) had spirometry findings that were considered normal or presented mild obstruction, 13 (18.31%) presented moderate disorder and six (8.45%) had severe obstruction. Two patients (2.82%) were not able to perform the test reliably. Fifty-six patients (78.9%) reported using the prescribed medication in accordance with the physician’s recommendation and nine (12.7%) only rarely failed to use the drugs.Regarding the inhaler devices, 10 patients (14.1%) used Aerolizer, 36 (50.7%) Aerocaps, 6 (8.5%) Diskus and 19 (26.7%) MDI. Fifty-three patients (74.7%) had been using the same device for at least two years and forty-one (57.8%) had been undergoing treatment at the outpatient clinic for two years or more, always coordinated by the same pulmonology specialist.Only one participant (1.4%) reported not receiving any guidance at any time regarding use of the inhalation device, while 13 (18.3%) were never reassessed after their first instruction, 25 (80.3%) were reassessed once at an appointment subsequent to their first instruction and 32 (45.1%) were reassessed at least twice at medical appointments subsequent to their first instruction. This last group was therefore instructed at least three times.Concerning the quality of the inhalation technique, 28 (39.5%) performed it correctly. In the few cases in which there was initial disagreement among the evaluators, the video review always unified opinions about the assessment of the inhalation technique. Incorrect inhalation technique showed associations with the asthma control level (P = 0.01) and the number of instructions (P = 0.04). However, there were no associations between incorrect inhalation technique and gender, age, marital status, personal and family income, level of education, duration of treatment orseverity of obstructive disturbance . After c,,,,,,,Lack of information is the main cause of improper use of inhalers,,,,,,Unlike several previous studies,,The length of time for which the treatment had been used did not interfere with the quality of the inhalation technique, as already reported.Regarding the limitations of our study, besides its cross-sectional design and the sample size, the presence of comorbidities was not considered in this investigation. The evaluations were not performed under blinded conditions, and the investigators always analyzed the quality of the inhalation technique together. Adherence to treatment was investigated only through basic questions, and non-adherence might be a confounding factor that, in addition to inadequate technique, may have contributed to the causes of uncontrolled asthma. However, if it is assumed that the patients answered honestly regarding their adherence to treatment, more than 90% were performing the treatment properly. This is an excellent result and therefore would not be a reason for asthma control not to be obtained. The logistic regression model used did not change the results previously obtained, perhaps because of the sample size. Finally, our study was based on a convenience sample in a hospital that is equipped to deal with cases of high complexity, i.e. cases that are more difficult to control are commonly treated there. Thus, the results from this study may not represent the situations for other hospitals, and the ability to generalize from these results is limited.This study did not show any association between the inhalation technique and any of the socioeconomic characteristics, the severity of obstruction, or even the duration of the treatment. One of the only relationships observed was between inadequate technique and uncontrolled asthma. Patients who received a greater number of orientations were also observed to be better at the inhalation technique. There seems to be a single simple conclusion: if patients adhere to the treatment using the correct inhalation technique, their asthma will be controlled. For this to occur, caregivers must insist on teaching the technique regardless of the patient’s profile. This seems to be the only way to achieve the main goal of treating asthma, namely, achievement of control.The inhalation technique was correctly performed by 39.5% of the participants. Uncontrolled asthma was significantly associated with incorrect inhalation technique. The incorrect inhalation technique was observed frequently and had no relationship with age, gender, marital status, educational level, personal and family income, duration of use of the inhalation device or the severity of obstruction. This study emphasizes the need for quality supervision of the inhalation technique and suggests that the larger the number of reevaluations is, the closer it will be possible to come to proper execution of the technique and asthma control. Inhalation technique should be supervised for all patients, especially those who received fewer instructions and those with uncontrolled asthma.


The growing availability of biologics, which until now have only been available for T2-high asthma, has been further enriched by the arrival of tezepelumab. (2) Methods: This review aims to evaluate the baseline characteristics of patients enrolled in RCTs of biologics for severe asthma to understand how they could potentially predict outcomes and how they can help differentiate between available options. (3) Results: The studies reviewed demonstrated that all biologic agents are effective in improving asthma control, especially with regard to reducing exacerbation rates and OCS use. As we have seen, in this regard, there are few data on omalizumab and none yet on tezepelumab. In analysing exacerbations and average doses of OCSs, pivotal studies on benralizumab have enrolled more seriously ill patients. Secondary outcomes, such as improvement in lung function and quality of life, showed better results—especially for dupilumab and tezepelumab. (4) Conclusion: Biologics are all effective, albeit with important differences. What fundamentally guides the choice is the patient’s clinical history, the endotype represented by biomarkers , and comorbidities . Asthma is a disease characterised by a great heterogeneity of immunological pathways and clinical manifestations, and it requires an approach based on personalised medicine and the study of phenotypes and endotypes ,2. Over This review aims to evaluate the baseline characteristics of the patients enrolled in RCTs of biologics for severe asthma, to better define the current landscape and understand how they could potentially predict outcomes, how they can help differentiate between available options, and to give useful insights to clinicians for a more appropriate choice.1), exacerbations, OCSs, and symptoms, which can quantify the response to biologics [The choice of biologics is crucial in the management of patients with severe uncontrolled asthma. In the literature, the presence of a mixed phenotype varies by 37–47%, depending on the case ,9. This iologics . These pFive biologics are currently available for the treatment of severe allergic , eosinophilic , and mixed asthma with atopic–eosinophilic phenotype (dupilumab), along with tezepelumab . In the 1 of 40–80%), and a recent clinically significant history of exacerbations despite high doses of ICSs, long-acting beta-agonists (LABAs), and other control agents. The patients had received either omalizumab or a placebo for 28 weeks. During this treatment period, the rate of clinically significant exacerbations was 26% less in the active treatment arm compared with the placebo group (p = 0.0002). Severe asthma exacerbations and emergency department visits were significantly reduced, and asthma symptoms and morning peak expiratory flow were significantly improved. EXCELS was a post-marketing observational cohort study undertaken by the Food and Drug Administration (FDA) to evaluate the long-term safety of omalizumab [p < 0.001), severe exacerbations (p = 0.023), hospitalisations (p = 0.003), and overall scores on the asthma control questionnaire (ACQ) (p < 0.001). Finally, 62.7% of patients in the active treatment group had reduced or stopped using OCSs, compared with 30.4% in the control arm. The role of combined biomarkers as possible predictors of treatment response was explored in the EXTRA study, which included 850 patients with severe allergic asthma [Omalizumab is a recombinant humanised mAb IgG1 anti-IgE that binds to circulating IgE, preventing its binding to the receptors of mast cells and basophils, and blocking the release of histamine and other mediators ,16 Figu. It is ualizumab . This stalizumab . Patientc asthma . OutcomeMepolizumab is an anti-IL-5 IgG1k mAb approved for severe eosinophilic asthma (SEA) . Numeroup = 0.003), and benralizumab Q8W resulted in a 70% lower annual exacerbation rate than placebo (p < 0.001). At the end of the study, no significant effect on FEV1 was found. A post hoc analysis evaluated the rate of patients in clinical remission among pooled patients in the SIROCCO/CALIMA or ZONDA trials [Benralizumab is an IgG1 mAb targeting the α subunit of the IL-5 receptor. It activates an antibody-mediated cellular cytotoxicity mechanism, leading to a profound depletion of eosinophils and their precursors in the blood and tissues  Figure . In the A trials . In the A trials . MoreoveA trials .1 and asthma control, especially in patients with higher T2 biomarkers (BEC ≥ 300 cells/µL and FeNO ≥ 25 ppb) [1. Specifically, the mean daily dose of prednisone was reduced by 70%, compared with 42% in the placebo group [1, asthma control, and HRQoL, regardless of the presence or absence of atopy [Dupilumab is a fully human IgG4 mAb directed to the alpha subunit of the shared receptors of IL-4 and IL-13 (IL-4/13Rα), simultaneously blocking the IL-4/IL-13 signalling pathway ,46 Figu. The saf 25 ppb)  . Among the patients without type 2 inflammation (baseline BEC < 150 cells/μL and baseline FeNO < 25 ppb) enrolled in the NAVIGATOR study, the therapeutic effect of tezepelumab was positive, albeit with values generally lower than those in patients with type 2 biomarkers. However, the effect was considered clinically significant. Unfortunately, in the phase 3 RCT SOURCE, with 150 patients randomised into 210 mg tezepelumab Q4W or placebo for 48 weeks of treatment, the primary endpoint of the OCS-sparing effect compared with the control group was not met [1 provocative dosage (PD15) with tezepelumab was 1.9 (95% CI 1.2–2.5) versus 1.0 (95% CI 0.3–1.6) by doubling the doses with placebo (p = 0.06). Nine (45%) subjects in the tezepelumab group and three (16%) in the placebo group had a negative PD15 test at week 12 (p = 0.04). The airway tissue eosinophil and bronchoalveolar lavage levels decreased by 74% and 75%, respectively, in the tezepelumab arm, compared with a 28% increase and 7% decrease in the placebo arm (p = 0.004 and p = 0.01), respectively. This study led to an editorial in which it was noted that an even greater effect could have been achieved if only patients with severe mannitol AHR were recruited [1 and patient-reported outcomes (PROs) and reduced type 2 biomarkers compared with placebo in all patients, as well as in those with severe allergic asthma. DESTINATION is an ongoing phase 3 RCT involving patients who completed the NAVIGATOR and SOURCE studies [The phase 3 programme called PATHFINDER brought interesting results, but also some queries. The NAVIGATOR trial randomised 1061 patients  Table 3Table 3.  not met . A stati not met . We can  not met . In thisecruited . In addi studies . The priThe almost absolute majority of patients enrolled in severe asthma RTCs are primarily classified as having T2-high endotypes . At the With regard to blood eosinophilia, it is interesting to note how the baseline values differed between pivotal studies, due to the selection of patients based on partially different characteristics and who were at least theoretically more suited to the mechanism of action of the various biological agents . The eosIt should be noted that the baseline level of BEC affects important outcomes, such as exacerbation for all mAbs examined, even in anti-IgE, which does not target these cells but can also have indirect effects on eosinophils ,26,64 T. Higher Regarding atopy, all patients had this characteristic in the case of anti-IgE , along w1 improved with higher baseline FeNO values and increased with higher baseline FeNO . These results were independent of BEC, confirming that FeNO was the main biomarker for the management of patients treated with dupilumab [FeNO is a useful biomarker for T2-high asthma phenotyping and a predictor of the response to some biologics. Its production is induced by pro-inflammatory cytokines, including tumour necrosis factor-α, IL-1b, IL-4, and IL-13 . The omaupilumab . Concernupilumab . Therefoupilumab .1 and ICS/LABA doses were similar [Examining the baseline patient characteristics of patients enrolled in clinical trials, they differed—at least in part—not only with regard to biomarkers, but also in the level of disease severity. This resulted in different exacerbation rates and prednisone doses, while FEV similar . Focusin similar , at base similar , 3.8 in  similar , 2.0 in  similar , and an  similar . Thus, tp = 0.002), in which 62.7% reduced or were weaned off OCSs. In the MENSA study, the mean dose of OCSs was 12.6 mg, while the mean dose of patients enrolled in SIROCCO was higher (15.2 mg). No data were available for the LIBERTY ASTHMA QUEST and NAVIGATOR studies because their endpoints were completely delegated to OCS-sparing RCTs. In the dupilumab LIBERTY ASTHMA VENTURE and tezepelumab SOURCE studies, the mean baseline doses were 11 mg and 11.8 mg, respectively [In analysing steroid use, as pivotal omalizumab clinical trials were conducted many years ago, no specific OCS assessment was performed. For this reason, an average baseline dose of prednisone was not reported in INNOVATE. An OCS-sparing study (EXALT) was subsequently conducted . Eighty-ectively ,57. Whenectively ,41, althectively . The mea1 reported in the INNOVATE study was predicted to be 61% . At the end of the treatment period, an improvement of 190 mL was obtained. In the MENSA study, the baseline FEV1 value was 1.73 L, and an improvement of 98 mL was reported at the end of the study. The SIROCCO study had a baseline value of 1.65 L, with an improvement of 159 mL. The QUEST trial reported an FEV1 value of 1.70 L, with an improvement of 340 mL after treatment. The NAVIGATOR study had a baseline FEV1 of 1.8 L, with an improvement of 230 mL.In all investigations, respiratory function was considered as a secondary outcome. Nevertheless, it was still interesting to evaluate the overall behaviour of the biologics analysed. The baseline FEV1, confirming the effectiveness of these agents in this respect.These results show that the efficacy of mAbs differs in the improvement of respiratory function. Dupilumab was the biologic that obtained the best data, followed by tezepelumab  . In genep < 0.001 vs. placebo). In addition, dupilumab improved lung function, asthma control, and HRQoL by suppressing type 2 biomarkers compared with placebo in both subgroups. Benralizumab did not satisfy the outcomes in the pivotal phase 3 OSTRO study in patients with CRSwNP, because it failed to improve the score of the Sinonasal-22 (SNOT-22) outcome test during the first surgery, and the use of OCSs was not statistically significant among the treatment groups [1 + 320 mL in the NP group and + 160 mL in the overall population). This study confirmed the efficacy of anti-IL-5Rα in patients with NP but, as there were no statistically significant improvements in the SNOT-22 scores and the other outcomes described, the FDA requested additional data. For this purpose, a second phase 3 trial called ORCHID  is underway, the main endpoints of which are nasal polyp burden and patient-reported nasal blockage [Comorbid conditions in severe asthma are common. They complicate management and may affect patient outcomes by contributing to poor disease control. For this reason, identifying comorbidities is important. Comorbidities are numerous, can be pulmonary or extrapulmonary, and are more or less frequently associated with asthma. Among the most common are gastroesophageal reflux disease, bronchiectasis, obesity, allergic rhinitis, depression, diabetes mellitus, and cardiovascular diseases. The most evaluated comorbidity in clinical trials was chronic rhinosinusitis with CRSwNP . All of t groups . Howevert groups . The rect groups . The subblockage . Prelimiblockage . A subseblockage . To confblockage . Currentblockage —a phase 1. Carefully defining the real efficacy of the different drugs and their correct positioning can also be very useful in the case of overlaps, which can potentially make a patient eligible to receive more than one mAb. In this regard, identifying the predominant mechanism, key biomarkers, and comorbidities is the winning strategy. A history of atopy with sensitisation to perennial aeroallergens and early-onset asthma may predict response to omalizumab. For this purpose, the total IgE level is a biomarker that is useful only for calculating the personalised dose, but not for predicting the response [Over the last 15 years, we have seen a radical change in the management of severe asthma due to the arrival of more options represented by biologics. These biologics have all been focused on the treatment of the T2-high endotype until the advent of tezepelumab, which addresses a large unmet need in patients with T2-low asthma. Fortunately, all randomised controlled trials demonstrated that all mAbs are effective in improving asthma control, especially with regard to reducing the exacerbation rate and the use of OCSs. As we have seen, in this regard, for various reasons, there are few data on omalizumab—and none yet on tezepelumab, as the SOURCE study missed its primary endpoint. Fortunately, a new trial is ongoing that could resolve this important shortcoming . Howeverresponse . With reresponse ,65. The response ,40,88. Fresponse ,48. Thisresponse . This coresponse .1 compared to omalizumab and mepolizumab. Not only is it difficult to compare the efficacy of mAbs, the very development of these agents has also always been very complex, as demonstrated by the numerous biologics that have failed during RCTs [Due to the lack of head-to-head studies, a few meta-analyses have been conducted in recent years to compare the efficacy of biologics. Without forgetting the limitations of this type of study, generally only slight differences in efficacy and safety have emerged between the various agents ,96. A veing RCTs .A fundamental aspect in considering the process of choosing the correct therapeutic option is the type of comorbidity present, which is closely associated with the type of inflammatory process. Atopy and allergic rhinitis guide the choice and efficacy of omalizumab . ConversDespite the great advances that have been made in the knowledge of molecular mechanisms, many questions about severe asthma remain open and unanswered, especially regarding the profound understanding of the inflammatory microenvironment and its contributions to clinical expression. Asthma is an increasingly common disease, and severe refractory asthma in particular has a high impact worldwide. For this reason it is necessary to further improve its management . In the


To explore the application value of N-terminal pro-B type natriuretic peptide (NT-proBNP) combined with neutrophil-to-lymphocyte ratio (NLR) in evaluation of major adverse cardiac events (MACEs) in elderly patients with chronic heart failure (CHF).  50 CHF patients admitted to the Department of Cardiovascular Medicine of our hospital from January 2021 to December 2021 were selected as the observation group. Another 50 non-CHF patients of our hospital were selected as the control group. Clinical data were collected from subjects who met the inclusion criteria, including general information, personal disease history, and laboratory test indicators. Patients with CHF were followed up for 6 months. Patients with CHF were divided into two groups, MACE group and non-MACE group. P < 0.05). The age, WBC, NEU, LYM, PLT, blood glucose, NLR, and NT-proBNP of MACE group and non-MACE group were significantly different (P < 0.05). The increased levels of NEU, NLR, NT-proBNP and the decreased levels of LYM and PLT are all independent risk factors for MACE in elderly patients with CHF (P < 0.05). The AUC of NLR in evaluating the occurrence of MACE in elderly CHF patients was 0.841. When the Youden index was 0.7692, the sensitivity was 76.92% and the specificity was 100.00%. The AUC of NT-proBNP in evaluating the occurrence of MACE in elderly CHF patients was 0.705. When the Youden index was 0.5260, the sensitivity was 76.92% and the specificity was 75.68%. The AUC of NT-proBNP combined with NLR in evaluating the occurrence of MACE in elderly CHF patients was 0.954. When the Youden index was 0.8420, the sensitivity was 92.31% and the specificity was 91.89%.  The levels of WBC, NEU, NLR, and NT-proBNP in observation group were higher than those in control group, but the level of LYM was the opposite ( NT-proBNP combined with NLR has high value in the evaluation of MACE in elderly CHF patients and can be used as an auxiliary predictive index in clinic. Chronic heart failure (CHF) is a serious stage of many cardiovascular diseases, mainly caused by hypertension, coronary heart disease, myocardial ischemia, stress response, cardiac insufficiency, and other inducements . The patN-terminal pro-B type natriuretic peptide (NT-proBNP) is an inactive N-terminal fragment of probrain natriuretic peptide (BNP) hormone after splitting, which has the characteristics of longer half-life and more stability . As a naAt present, there are few reports about the evaluation value of NT-proBNP combined with NLR in elderly CHF patients with MACE. We will analyze this content in order to improve the prognosis of patients.50 CHF patients admitted to the Department of Cardiovascular Medicine of our hospital from January 2021 to December 2021 were selected as the observation group. Inclusion criteria are as follows: the age ranged from 65-82 years, with an average age of (74.16 ± 2.94) years; all patients met the 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure ; NYHA isClinical data were collected from subjects who met the inclusion criteria, including general information (age and sex), personal disease history , and laboratory examination indicators (white blood cell (WBC), NEU, LYM, platelet count (PLT), blood glucose, NLR, and NT-proBNP).Patients with CHF were followed up for 6 months, and the follow-up mode was outpatient follow-up or telephone. The end point of follow-up was MACE or death. MACE includes cardiac death, nonfatal myocardial infarction, and hospitalization for recurrent heart failure. Patients with CHF were divided into MACE group and non-MACE group according to the occurrence of MACE.s), and t-test was used for comparison. The data are expressed as %, and the comparison was made by χ2 test. Logistic regression was used to analyze the influencing factors of MACE. ROC was used to analyze the evaluation value of different indexes on the occurrence of MACE. P < 0.05 was statistically significant.SPSS 22.0 software was used for processing, and the measurement data were expressed as mean ± standard deviation (P < 0.05)  see .P < 0.05)  see .P < 0.05)  see .The AUC of NLR in evaluating the occurrence of MACE in elderly CHF patients was 0.841. When the Youden index was 0.7692, the sensitivity was 76.92% and the specificity was 100.00%. The AUC of NT-proBNP in evaluating the occurrence of MACE in elderly CHF patients was 0.705. When the Youden index was 0.5260, the sensitivity was 76.92% and the specificity was 75.68% see .The AUC of NT-proBNP combined with NLR in evaluating the occurrence of MACE in elderly CHF patients was 0.954. When the Youden index was 0.8420, the sensitivity was 92.31% and the specificity was 91.89% see .In recent years, good clinical progress has been made in the diagnosis and treatment of CHF. However, due to various factors, the prognosis of CHF patients has not been comprehensively improved, and the risk of MACE after the patient is discharged from hospital is still high . EspeciaAs a metabolite of BNP, NT-proBNP has a relatively stable activity in normal people . PatientROC analysis in this study further showed that the AUC of NLR and NT-proBNP in evaluating MACE in elderly CHF patients was 0.841 and 0.705, respectively. The results indicate that NLR and NT-proBNP have certain value in predicting MACE in elderly CHF patients. The detection of NLR has the advantages of simple operation, easy access, low cost, saving detection time, etc., and the variability in the detection process is small . The advTo sum up, NT-proBNP combined with NLR has high value in the evaluation of MACE in elderly CHF patients and can be used as an auxiliary predictive index in clinic. This study only selected elderly patients with CHF, and it was a single-center and small-sample study. We need to further improve the research scheme in the future.