BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective·To investigate the current situation and distribution characteristics of chronic comorbidities,and to provide reference for further improving the self-management of comorbidities and implementing the whole course and all-round management of comorbidity.Methods·Two thousand and forty-five inpatients in the Department of Geriatrics,Renji Hospital,Shanghai Jiao Tong University School of Medicine were enrolled in this study from December 2020 to February 2023.The general vital signs,routine laboratory examination and disease status were collected.The epidemiological distribution characteristics of chronic diseases and comorbidities were analyzed.Results·The incidence of chronic diseases in the surveyed population was 99.6％,and the incidence of comorbidities was 94.2％.The top 5 chronic diseases were hypertension(43.68％),diabetes mellitus(24.81％),malignant tumor(21.48％),hyperlipidemia(18.38％)and coronary heart disease(11.99％).The detection rates of hypertension,diabetes mellitus,coronary heart disease,chronic obstructive pulmonary disease,stoke and chronic kidney disease in males were significantly higher than those in females(P＜0.05).The proportion of patients with 5 chronic diseases was the highest(11.99％),followed by 7 chronic diseases(10.26％)and 6 chronic diseases(10.04％).Among the patients of different ages,the comorbidity rate was the highest in the patients aged 50-59 years(27.78％).In different age groups,patients aged 50 to 59 with 2 chronic diseases had the highest incidence of comorbidity,which was as high as 40.82％.Although the overall proportion of comorbidities among male patients(95.37％)was higher than that among females(93.77％),there was no statistically significant difference(P=0.125).However,the proportions of male patients with 2 and 5 chronic diseases were 70.41％and 60.63％,respectively,which were significantly higher than those of female patients(29.59％and 39.37％).The correlations between coronary heart disease and diabetes mellitus,hypertension and coronary heart disease,hypertension and diabetes mellitus were higher(r=0.24,r=0.27,r=0.35,all P＜0.05).Conclusion·The prevalence of chronic diseases and comorbidities is high in the middle-aged and elderly population,and the number of comorbidities increases significantly with the increase of age.

Objective·To explore the correlation between comorbidities of chronic non-communicable diseases(chronic diseases),phase angle(PhA),and muscle mass decline associated with sarcopenia in the elderly,and the predictive value of chronic disease comorbidities and PhA in muscle mass decline in the elderly.Methods·By retrospectively screening inpatients aged≥60 years who were admitted to the Department of Geriatrics,Renji Hospital,Shanghai Jiao Tong University School of Medicine from August 1,2018 to July 31,2019,basic information and medical history of the patients(gender,age,number of medications used,number of comorbidities,presence of osteoporosis,smoking history,etc.)were collected,as well as laboratory examination indicators(hemoglobin,albumin,serum creatinine,serum uric acid,ferritin,vitamin D,triacylglycerol,total cholesterol,high-density lipoprotein,low-density lipoprotein,etc.).The age-adjusted Charlson comorbidity index(aCCI)was calculated.The InBody S10 bioelectrical impedance body composition detector was used to test the body composition.Body mass index(BMI),skeletal muscle mass index(SMI),and PhA were collected.Some patients underwent measurement of grip strength.Muscle mass decline was diagnosed by using the SMI values recommended by the 2019 Asian Working Group for Sarcopenia(AWGS)(≤7.0 kg/m2 for males and≤5.7 kg/m2 for females).According to the measured SMI values,patients were divided into a group with normal muscle mass and a group with muscle mass decline.Univariate and multivariate Logistic analyses were employed to investigate the risk factors associated with muscle mass decline related to sarcopenia in the elderly.Additionally,the receiver operator characteristic(ROC)curve and the area under the curve were utilized to predict the significance of these factors in muscle mass decline.Results·A total of 359 chronic disease patients were enrolled,including 226 males and 133 females.There were 241 cases in the normal muscle mass group and 118 cases in the muscle mass decline group.The incidence of muscle mass decline related to sarcopenia in the elderly was 32.9%.The univariate Logistic regression analysis showed that age(OR=1.036,95%CI 1.013?1.060),comorbidities(OR=1.117,95%CI 1.025?1.217),aCCI(OR=1.123,95%CI 1.031?1.222),and high-density lipoprotein(OR=3.688,95%CI 2.065?6.622)were positively correlated with the risk of muscle mass decline in the elderly.BMI(OR=0.514,95%CI 0.443?0.597),PhA(OR=0.195,95%CI 0.126?0.303),hemoglobin(OR=0.984,95%CI 0.972?0.996)and triacylglycerol(OR=0.606,95%CI 0.424?0.866)were negatively correlated with the risk of muscle mass decline in the elderly.Multivariate Logistic regression model indicated that PhA(OR=0.338,95%CI 0.119?0.959)and BMI(OR=0.634,95%CI 0.476?0.844)were negatively correlated with the risk of muscle mass decline in elderly.The area under the ROC curve for predicting muscle mass decline related to sarcopenia in elderly by using BMI and PhA was 0.893(95%CI 0.855?0.931)and 0.786(95%CI 0.736?0.837),respectively.The sensitivity was 0.724 and 0.676,respectively.The specificity was 0.916 and 0.762,respectively.When BMI combined with PhA predicted muscle mass decline in the elderly,the area under the ROC curve was 0.917(95%CI 0.883?0.951).The sensitivity was 0.867,and the specificity was 0.860.Conclusion·aCCI is correlated with muscle mass decline associated with sarcopenia in the elderly.As BMI and PhA decrease,the risk of muscle mass decline in the elderly increases.The combination of BMI and PhA has a high predictive value in muscle mass decline in the elderly.No predictive value of chronic diseases comorbidities in muscle mass decline related to sarcopenia in the elderly is found.

Objective:To analyze the efficacy and safety of daratumumab plus dexamethasone in the treatment of renal injury patients with light chain amyloidosis, and to provide clinical reference.Methods:It was a single center retrospective observational study. The clinical data before and after daratumumab treatment of renal injury patients with light chain amyloidosis treated with daratumumab plus dexamethasone from December 2021 to August 2022 were retrospectively collected. The hematologic response, kidney response, prognosis, and adverse events were analyzed. The treatment regimen was 16 mg/kg intravenous infusion of daratumumab on day 1 + 20 mg intravenous push of dexamethasone on day 1-2, once every 2 weeks. The follow-up was up to February 28, 2023.Results:The study included 18 patients, with age of (58.4±7.7) years old, and a male to female ratio of 11∶7. Eleven patients were newly diagnosed and 7 patients were retreated. There were 7, 5, 5 and 1 patients, respectively at the stage Ⅰ, Ⅱ, Ⅲ and Ⅳ of light chain amyloidosis according to 2012 Mayo stage criteria. The median course of disease before onset was 2.5 (1.0, 8.0) months and the follow-up time was (8.7±2.8) months. The patients received (10±3) times of treatment. The overall hematologic response rates were 9/13, 11/13 and 13/13 at 1 month, 3 months, and 6 months respectively after treatment, meanwhile 8/13, 10/13 and 12/13 achieved at least very good partial response at 1 month, 3 months, and 6 months respectively (the other 5 patients did not undergo detailed evaluation due to baseline difference of serum free κ and λ light chain <20 mg/L). The median duration of hematologic response was 16 (13, 40) days. At 3 months, 6 months and the end of follow-up, 10, 13 and 13 of 18 patients respectively achieved renal response, and the median duration of response was 66 (26, 182) days. During follow-up, the median difference of serum free κ and λ light chain decreased by 93% (72%, 97%). Until the last follow-up, one patient died of organ hemorrhage. Other infusion reactions, leukopenia, neutropenia and infection all improved after symptomatic treatments.Conclusion:Daratumumab plus dexamethasone treatment is effective for light chain amyloidosis nephropathy in inducing hematologic remission and kidney remission, with good safety.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Hepatitis B virus (HBV) infection is a common cause of liver disease in China, and with the continuous progress in the research on antiviral therapy for chronic hepatitis B, the indications for antiviral therapy are constantly expanding. However, there are still controversies over the indications for antiviral therapy in patients with chronic hepatitis B (CHB), especially those with negative HBV. By analyzing the limitations of HBV DNA detection, the risk of HBV reactivation in HBV-negative CHB patients, the risk of disease progression in the DNA-negative population with compensated hepatitis B cirrhosis, antiviral response, and the economic benefits of antiviral therapy, this article proposes the necessity of antiviral therapy for HBV-negative HBsAg-positive patients with compensated hepatitis B cirrhosis.

Objective:To investigate the risk factors of non-alcoholic fatty liver disease (NAFLD) in patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer (HR+/HER2-BC) and the impact of NAFLD on the survival of patients.Methods:54 HR+BC patients were enrolled in this study. The liver fat accumulation was examined by magnetic resonance imaging (MRI). The patients were divided into two groups: non-NAFLD and NAFLD. Student's t test or Fisher's test was used to analyze the clinical indicators of the two groups. Logistic univariate and multivariate tests were used to analyze the clinical risk factors related to NAFLD. Receiver operating characteristic curve (ROC curve) was used to further analyze the sensitivity of clinical risk factors to predict the diagnosis of NAFLD. The Disease-free survival (DFS) and Overall survival (OS) of the two groups were analyzed by Log-rank (Mantel-Cox) test. Results:There were 22 NAFLD patients and 32 non-NAFLD patients diagnosed by MRI. Student's t test or Fisher's test showed that BMI, waist circumference, AST, ALT, GGT, TG, LDL and HDL were statistically different between the two groups (all P<0.05). Logistic univariate and multivariate analysis showed that AST ( OR=1.05, 95% CI: 1.02-1.10, P=0.007), GGT ( OR=1.04, 95% CI: 1.01-1.09, P=0.038), TG ( OR=1.03, 95% CI: 1.01-1.06, P=0.011) and HDL ( OR=1.06, 95% CI: 1.01-1.12, P=0.037) were the risk factors associated with NAFLD. ROC curve analysis showed that the combination of AST, GGT, TG and HDL had high sensitivity in predicting NAFLD (AUC=0.869, P<0.05). There was no difference in DFS ( HR=1.830, 95% CI: 0.983-3.409, P=0.057) or OS ( HR=2.482, 95% CI: 0.761-8.093, P=0.132) between the two groups. Conclusion:AST, GGT, TG and HDL are the independent risk factors for NAFLD in HR+BC patients during treatment, but concurrent NAFLD has no significant effect on DFS or OS.

Objective:To investigate the correlation between serum miR-122-5p and FOXO3 levels and osteoporosis (OP) in postmenopausal women with non-alcoholic fatty liver disease (NAFLD) .Methods:The clinical data and serum of 30 postmenopausal women with NAFLD and 48 postmenopausal women with no-NAFLD were collected. The levels of miR-122-5p and FOXO3 in serum were detected by qRT-PCR. Triglycerides, high-density lipoproteins, and low-density lipoproteins were detected by biochemical autoanalyzer. The bone mineral density of lumbar vertebrae 1-4, Wards triangular bone, femoral neck, greater trochanter and total hip was detected by bone mineral density analyzer. The correlation between the above clinical indicators and OP was analyzed.Results:The expression of miR-122-5p in postmenopausal female NAFLD patients (0.76±0.28) was lower than that in non-NAFLD patients (1±0.31) ( t=3.43, P=0.001) . The downstream target gene FOXO3 of miR-122-5p was identified by bioinformatics website analysis. The expression of FOXO3 in postmenopausal female NAFLD patients (1.31±0.30) was higher than that in non-NAFLD patients (1±0.27) ( t=4.73, P<0.001) . Student’ s t test and Logistic regression analysis showed that triglyceride, miR-122-5p and FOXO3 levels were risk factors for NAFLD (all P<0.05) . Pearson correlation coefficient showed that miR-122-5p level was significantly positively correlated with BMD of femoral neck ( r=0.488, P=0.006) , greater trochanter ( r=0.367, P=0.046) and whole hip ( r=0.404, P=0.027) . FOXO3 level was negatively correlated with bone mineral density of femoral neck ( r=-0.445, P=0.014) and whole hip ( r=-0.507, P=0.004) , while other indexes were not significantly correlated (all P>0.05) . Conclusion:Decreased serum miR-122-5p level and increased FOXO3 level in postmenopausal women with NAFLD may increase the risk of OP.

Objective:To explore the effect of three-dimensional(3D) design and printing in the reoperation of asymmetric deformity after orthognathic surgery.Methods:Patients of facial asymmetry after orthognathic surgery were included in the Department of Stomatology, Shenzhen University General Hospital and Department of Oral & Maxillofacial Surgery, Shenzhen Stomatology Hospital Affiliated to Shenzhen University from January 2016 to August 2020. Surgical plans and guide plates (positioning guide plate, bone cutting guide plate, reset guide plate) were made by 3D design and printing. During the operations, guide plates were used to guide osteotomy. The facial shape satisfaction of clinicians/patients/third-party were recorded and analyzed at preoperation and 6-12 months postoperation. These patients’ CT scan data was imported to the digital surgery software. Then the distance of chin-midpoint to mid-sagittal plane and the difference of bilateral protuberant point of mandible body to mid-sagittal plane were measured at preoperation and 6-12 months postoperation to determine whether the asymmetry were corrected and postoperative distance were the same as the preoperative design. Data analysis was conducted using SPSS 17.0 statistical software, and measurement data were expressed as Mean±SD. The preoperative and postoperative satisfaction of patients/clinicians/third-party, digital data of preoperation/postoperation and digital data of design-operations/postoperation were analyzed by paired t-test. Analysis of variance and dunnett- t test were used to compare the satisfaction of the surgeon, the third party and patients before and after operation. Results:There were 16 cases of facial asymmetry after orthognathic surgery, including 3 males and 13 females, aged from 18 to 35 years. In 9 cases, genioplasty were used to correct chin deviation. In the other 4 cases, unilateral buccal cortical bone resection were used to correct mandibular body deviation. In the last 3 cases, genioplasty and unilateral buccal cortical bone resection were both applied. All 16 patients successfully received the operation according to the preoperative digital designed plate. Postoperative follow-up ranged 6 months to 1 year. In the 12 cases of genioplasty, the distance of chin-midpoint to mid-sagittal plane reduced from(4.99±0.83) mm preoperatively to (1.63±0.80) mm postoperatively and the difference significant ( t=9.09, P<0.001). There was no significant difference between the distance of preoperative design [(1.50±0.43) mm] and the postoperative one ( t=-0.83, P=0.423). In the 7 cases of unilateral buccal cortical bone resection, the difference of bilateral protuberant point of mandible body to mid-sagitta plane reduced from (7.26±1.20) mm preoperatively to (2.44±0.56) mm postoperatively and the difference was statistically significant ( t=10.26, P<0.001). There was no significant difference was observed between the distance of preoperative design [(2.39±0.16) mm] and the postoperative one ( t=-0.29, P=0.779). The preoperative satisfaction of patients, clinicians and third-party were 65.94±8.21, 79.69±5.91, 79.38±7.50. The postoperative satisfaction of patients, clinicians and third-party were 90.00±5.48, 90.63±2.50, 90.00±4.08. The postoperative satisfaction of patients, chief surgeon and third party was higher than that preoperative satisfaction and the difference was statistically significant( t=-9.15, P<0.001; t=-7.50, P<0.001; t=-6.04, P<0.001). The difference of preoperation satisfaction was statistically significant( F=18.66, P<0.001). The difference of satisfaction of the clinicians and the patients was statistically significant ( P<0.001). The difference of satisfaction of the third-party and the patients was statistically significant ( P<0.001). The difference of postoperation satisfaction was not statistically significant( F=0.12, P=0.889). Conclusions:3D design and printing can 3D analyze comprehensively, simulate surgery accurately, visualize proposed result and guide 3D printing digital guiding plate to perform surgery accurately. In addition, it can improve postoperative satisfaction. So 3D design and printing had obvious advantages in the secondary surgery of asymmetric deformity correction after orthognathic surgery.

Objective:To explore the effect of three-dimensional(3D) design and printing in the reoperation of asymmetric deformity after orthognathic surgery.Methods:Patients of facial asymmetry after orthognathic surgery were included in the Department of Stomatology, Shenzhen University General Hospital and Department of Oral & Maxillofacial Surgery, Shenzhen Stomatology Hospital Affiliated to Shenzhen University from January 2016 to August 2020. Surgical plans and guide plates (positioning guide plate, bone cutting guide plate, reset guide plate) were made by 3D design and printing. During the operations, guide plates were used to guide osteotomy. The facial shape satisfaction of clinicians/patients/third-party were recorded and analyzed at preoperation and 6-12 months postoperation. These patients’ CT scan data was imported to the digital surgery software. Then the distance of chin-midpoint to mid-sagittal plane and the difference of bilateral protuberant point of mandible body to mid-sagittal plane were measured at preoperation and 6-12 months postoperation to determine whether the asymmetry were corrected and postoperative distance were the same as the preoperative design. Data analysis was conducted using SPSS 17.0 statistical software, and measurement data were expressed as Mean±SD. The preoperative and postoperative satisfaction of patients/clinicians/third-party, digital data of preoperation/postoperation and digital data of design-operations/postoperation were analyzed by paired t-test. Analysis of variance and dunnett- t test were used to compare the satisfaction of the surgeon, the third party and patients before and after operation. Results:There were 16 cases of facial asymmetry after orthognathic surgery, including 3 males and 13 females, aged from 18 to 35 years. In 9 cases, genioplasty were used to correct chin deviation. In the other 4 cases, unilateral buccal cortical bone resection were used to correct mandibular body deviation. In the last 3 cases, genioplasty and unilateral buccal cortical bone resection were both applied. All 16 patients successfully received the operation according to the preoperative digital designed plate. Postoperative follow-up ranged 6 months to 1 year. In the 12 cases of genioplasty, the distance of chin-midpoint to mid-sagittal plane reduced from(4.99±0.83) mm preoperatively to (1.63±0.80) mm postoperatively and the difference significant ( t=9.09, P<0.001). There was no significant difference between the distance of preoperative design [(1.50±0.43) mm] and the postoperative one ( t=-0.83, P=0.423). In the 7 cases of unilateral buccal cortical bone resection, the difference of bilateral protuberant point of mandible body to mid-sagitta plane reduced from (7.26±1.20) mm preoperatively to (2.44±0.56) mm postoperatively and the difference was statistically significant ( t=10.26, P<0.001). There was no significant difference was observed between the distance of preoperative design [(2.39±0.16) mm] and the postoperative one ( t=-0.29, P=0.779). The preoperative satisfaction of patients, clinicians and third-party were 65.94±8.21, 79.69±5.91, 79.38±7.50. The postoperative satisfaction of patients, clinicians and third-party were 90.00±5.48, 90.63±2.50, 90.00±4.08. The postoperative satisfaction of patients, chief surgeon and third party was higher than that preoperative satisfaction and the difference was statistically significant( t=-9.15, P<0.001; t=-7.50, P<0.001; t=-6.04, P<0.001). The difference of preoperation satisfaction was statistically significant( F=18.66, P<0.001). The difference of satisfaction of the clinicians and the patients was statistically significant ( P<0.001). The difference of satisfaction of the third-party and the patients was statistically significant ( P<0.001). The difference of postoperation satisfaction was not statistically significant( F=0.12, P=0.889). Conclusions:3D design and printing can 3D analyze comprehensively, simulate surgery accurately, visualize proposed result and guide 3D printing digital guiding plate to perform surgery accurately. In addition, it can improve postoperative satisfaction. So 3D design and printing had obvious advantages in the secondary surgery of asymmetric deformity correction after orthognathic surgery.