Chinese Adult Patients Research Articles

Guidelines for clinical application of micronutrients in Chinese adult patients (2024 edition)

Micronutrients, including trace elements and vitamins, are essential nutrients in human metabolism. The majority of patients who need nutritional therapy have different levels of micronutrient deficiency for various reasons, which can lead to disease progression and affect clinical outcomes. In order to further standardize the application of micronutrients in medical nutrition therapy, nearly 100 experts in related fields were organized by the Chinese Society of Parenteral and Enteral Nutrition (CSPEN) to elaborate on the role and dosage of micronutrients based on the existing evidence-based medical evidence in common clinical conditions such as severe illness, surgery, burns, inflammatory bowel disease, short bowel disease, malignant tumors, chronic liver and kidney disease, elderly comorbidity, weight loss and chronic infection. Finally, 13 questions and 30 recommendations were put forward to provide reference for clinical standard application of parenteral and enteral nutrition in adult patients.

Application of machine learning combined with population pharmacokinetics to improve individual prediction of vancomycin clearance in simulated adult patients.

Vancomycin, a glycopeptide antimicrobial drug. PPK has problems such as difficulty in accurately reflecting inter-individual differences, and the PPK model may not be accurate enough to predict individual pharmacokinetic parameters. Therefore, the aim of this study is to investigate whether the application of machine learning combined with the PPK method can improve the prediction of vancomycin CL in adult Chinese patients. In the first step, a vancomycin CL prediction model for Chinese adult patients is given by PPK and Hamilton Monte Carlo sampling is used to obtain the reference CL of 1,000 patients; the second step is to obtain the final prediction model by machine learning using an appropriate model for the predictive factor and the reference CL; and the third step is to randomly select, in the simulated data, a total of 250 patients for prediction effect evaluation. XGBoost model is selected as final machine learning model. More than four-fifths of the subjects' predictive values regarding vancomycin CL are improved by machine learning combined with PPK. Machine learning combined with PPK models is more stable in performance than the PPK method alone for predicting models. The first combination of PPK and machine learning for predictive modeling of vancomycin clearance in adult patients. It provides a reference for clinical pharmacists or clinicians to optimize the initial dosage given to ensure the effectiveness and safety of drug therapy for each patient.

NT-proBNP ratio is a potential predictor for COVID-19 outcomes in adult Chinese patients: a retrospective study

Despite the progressive decline in the virulence of the novel coronavirus, there has been no corresponding reduction in its associated hospital mortality. Our aim was to redefine an accurate predictor of mortality risk in COVID-19 patients, enabling effective management and resource allocation. We conducted a retrospective analysis of 2917 adult Chinese patients diagnosed with COVID-19 who were admitted to our hospital during two waves of epidemics, involving the Beta and Omicron variants. Upon admission, NT-proBNP levels were measured, and we collected demographic, clinical, and laboratory data. We introduced a new concept called the NT-proBNP ratio, which measures the NT-proBNP level relative to age-specific maximum normal values. The primary outcome was all-cause in-hospital mortality. Our analysis revealed a higher in-hospital mortality rate in 2022, as shown by the Kaplan–Meier Survival Curve. To assess the predictive value of the NT-proBNP ratio, we employed the time-dependent receiver operating characteristic (ROC) curve. Notably, the NT-proBNP ratio emerged as the strongest predictor of mortality in adult Chinese hospitalized COVID-19 patients (area under the curve, AUC = 0.826; adjusted hazard ratio [HR], 3.959; 95% confidence interval [CI] 3.001–5.221; P < 0.001). This finding consistently held true for both the 2020 and 2022 subgroups. The NT-proBNP ratio demonstrates potential predictive capability compared to several established risk factors, including NT-proBNP, hsCRP, and neutrophil-to-lymphocyte ratio, when it comes to forecasting in-hospital mortality among adult Chinese patients with COVID-19.Trial registration Clinical Trial Registration: www.clinicaltrials.gov NCT05615792.

The association between hemoglobin level and sarcopenia in Chinese patients with Crohn’s disease

Sarcopenia and anemia are common complications in patients with Crohn’s Disease (CD). However, few studies have shown the association between sarcopenia and hemoglobin levels in CD patients. This retrospective study aimed to explore such association in Chinese patients with CD. Two hundred and twelve adult CD inpatients who underwent computed tomography (CT) or magnetic resonance imaging (MRI) examinations from July 2019 to December 2021 were included in the study. Sarcopenia was defined according to the cutoff value of skeletal muscle index of lumbar spine 3 (SMI-L3) (< 44.77cm2/m2 for males and < 32.5cm2/m2 for females). The CD patients were divided into two groups based on the presence or absence of sarcopenia. Clinical data, hemoglobin levels, and other laboratory data were retrospectively collected. The association between hemoglobin levels and sarcopenia was analyzed by univariable and multivariable logistic regression analysis. Sarcopenia occurred in 114 CD patients (53.8%). Compared to patients without sarcopenia, patients with sarcopenia had a lower proportion of L1 (30.7% vs. 45.8%, p = 0.032) and B1 classification (58.8% vs. 72.4%, p = 0.037). Patients with sarcopenia had significantly lower levels of hemoglobin (Hb) (116.5 ± 22.8 vs. 128.1 ± 21.0, p < 0.001). The prevalence of sarcopenia increased with the decrease in hemoglobin level (p for trend < 0.05). Linear regression analysis showed that hemoglobin levels were associated with SMI-L3 (β = 0.091, p = 0.001). Multivariable logistic regression analysis found that higher hemoglobin levels (OR:0.944; 95% CI: 0.947,0.998; p = 0.036) were independent protective factors for sarcopenia. Lower hemoglobin levels are independently associated factors of sarcopenia in adult Chinese patients with CD.

GATA2 mutant variant allele frequency may reflect prognosis in Chinese adult patients with de novo cytogenetically normal acute myeloid leukemia.

Exploration of variant allele frequency (VAF) of GATA2 mutations (GATA2mut) provides insights into acute myeloid leukemia (AML) prognosis. In this study, we analyzed GATA2mut and co-mutations in 166 Chinese patients with cytogenetically normal AML. This was done through targeted next-generation sequencing of 34 genes associated with myeloid leukemia. GATA2mut was identified in 17 (10%) patients being significantly correlated with co-mutations in CCAAT/enhancer-binding protein alpha (CEBPA) double mutation (P = 0.001). We observed that the N-terminal zinc finger domain (ZF1) was linked to CEBPA mutations, while the C-terminal zinc finger domain (ZF2) was associated with Wilms' tumor 1 (WT1) mutations. It was also noted that patients with GATA2mut had lower platelet counts at diagnosis (P = 0.032). In the entire cohort, GATA2mut had no significant prognostic impact on overall survival (OS) (P = 0.762) and relapse-free survival (RFS) (P = 0.369) compared to patients with GATA2wt. The OS (P = 0.737) and RFS (P = 0.894) of the ZF1 mutation were similar to those of the ZF2 mutation. Most patients with GATA2 mutations were classified in the ELN2022 favorable- and intermediate-risk groups. GATA2mut patients in the favorable-risk group were divided into GATA2High and GATA2Low groups using a median cutoff variant allele frequency (VAF) of 40.13%. GATA2High patients were associated with worse OS (P = 0.031) and RFS (P = 0.021) than GATA2Low patients. In the intermediate-riskgroup, the high median VAF ofGATA2 (≥38.51%) had no significant effect in OS and RFS compared with the low median VAF (<38.51%). This study offers new insights on the prognosis of GATA2mut in the favorable-risk group, where VAF can be used as a guide.

Safety of teriflunomide in Chinese adult patients with relapsing multiple sclerosis: A phase IV, 24-week multicenter study.

Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. Eighty-two patients were assigned to variant (n = 42) and wild type groups (n = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUCtau) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. NCT04410965, https://clinicaltrials.gov.

Rs1800629 polymorphism in TNF-alpha is associated with the susceptibility and initial short-term glucocorticoids efficacy in myasthenia gravis patients

Tumor necrosis factor-alpha (TNF-α) is a potent pro-inflammatory agent involved in various autoimmune and inflammatory diseases including myasthenia gravis (MG). In this study, we enrolled 409 adult MG patients and 487 healthy individuals to investigate the association between TNF-α polymorphism and MG. We found the rs1800629 A allele frequency was significantly higher in the MG group than in the control group. Subgroup analysis revealed that the A allele frequencies were significantly higher in the early-onset subgroup, non-thymoma subgroup, ocular-onset subgroup, and mild severity subgroup than in the control group. To minimize the interactions between clinical features, we used a comprehensive classification and found that the rs1800629 A allele frequency was significantly higher in the non-thymoma AChR-Ab negative subgroup than in the control group. In the analysis of initial short-term glucocorticoids (GC) efficacy in the treatment-naive patients, the rs1800629 A allele frequency was significantly higher in the unresponsive subgroup than in the responsive group and the control group. Logistic regression demonstrated the rs1800629 genotypes in the dominant model and disease duration prior to GC treatment independently contributed to initial short-term GC efficacy. In conclusion, our study revealed that in Chinese adult MG patients, rs1800629 polymorphism in TNF-α was associated with the susceptibility of MG and might indicate the initial short-term GC efficacy.

Pharmacokinetics, pharmacodynamics and safety of 15mg-tolvaptan administered orally for 7 consecutive days to Chinese patients with child-Pugh B cirrhosis.

Background: Tolvaptan, a selective vasopressin V2-receptor antagonist, can elicit a diuretic effect without significant electrolyte loss. The aims were to evaluate multiple-dose pharmacokinetics, pharmacodynamics and safety of daily administration of 15mg tolvaptan in Chinese adult patients with confirmed Child-Pugh Class B cirrhosis accompanied by ascites. Methods: This was an open-label, single-center, single- and multiple-dose study. All patients received a daily 15mg dose of tolvaptan for 7 consecutive days. The plasma concentrations of tolvaptan and its two metabolites (DM-4103, DM-4107) were measured using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). In addition, various pharmacokinetics parameters were calculated. The pharmacodynamic outcomes evaluated changes in serum sodium and potassium concentrations, daily urine volume, daily water consumption, fluid balance and body weight. Safety profiles, including the incidence of treatment-emergent adverse events (TEAEs), were carefully recorded. Results: Eleven patients with Child-Pugh B cirrhosis were eventually enrolled in the study. Plasma concentrations of tolvaptan and DM-4107 reached steady-states after 7 days of consecutive oral administration. No accumulation of tolvaptan or DM-4107 was found, but DM-4103 accumulated 18.2-fold after multiple-dosing. The daily urine volume and daily water consumption were statistically significantly increased after administration of tolvaptan from Day 1 to Day 7 (all p < 0.05), accompanied by an increased serum sodium concentration. Of 11 patients, 9 (81.8%) reported 20 TEAEs, with the majority being mild to moderate in severity. The most commonly occurring TEAEs were thirst (45.5%), pollakiuria (36.4%) and dry mouth (27.3%). Conclusion: Tolvaptan at a daily dose of 15mg had a diuretic effect but did not increase serum sodium excretion or lead to tolvaptan accumulation. It is therefore can be safely used for short-term treatment of Chinese adult patients with confirmed Child-Pugh B cirrhosis. Clinical Trial Registration: https://clinicaltrials.gov/search?term=NCT01359462, identifier NCT01359462.

P776 A Prospective, Multicenter, Single-arm, Observational Study to Evaluate the Safety and Effectiveness of Vedolizumab in Real-world Clinical Practice in China: Interim Analysis of Safety results

Abstract Background Crohn's disease (CD) and ulcerative colitis (UC) are categorized as inflammatory bowel disease [IBD] usually treated by corticosteroids, immunomodulators and biologics, etc. Vedolizumab, a gut-selective α4β7 integrin antibody, has been approved in China for IBD patients who are intolerant /lost response to conventional therapies or TNF-α inhibitors. Of late, there is a paucity of data on the safety and effectiveness of vedolizumab in real-world clinical practice in China. This study evaluates the safety and effectiveness of vedolizumab in adult patients with UC or CD Here, we present the first interim analysis. Methods In this multicenter, single arm, prospective, observational, real-world study (NCT04872491), adults (aged &amp;gt;18 years) with UC or CD were administered intravenous vedolizumab 300 mg at week 0, 2, 6, and thereafter every 8 weeks. Incidence of adverse events (AEs), serious AEs (SAEs), Treatment-related AEs (TRAEs) and AEs of special interest (AESIs) were the primary endpoints Patients with administration of at least 1 dose of VDZ were included and observed 18 weeks after completion of the study or early termination, up to maximum of 72 weeks. AESIs included infections, malignancies, infusion-related reactions, and hypersensitivity. The secondary endpoints included the effectiveness of vedolizumab in terms of clinical response, clinical remission and endoscopic remission assessed at week 14 and week 54 after vedolizumab initiation. Results A total of 307 patients (UC, n=245; CD, n=62) with a median age of 41 years (range: 18-86) were included in the interim analysis. Median duration was 883 days (UC: 1035 days; CD: 731 days) and 105 days (UC: 107 days; CD: 99 days) for IBD and vedolizumab exposure, respectively. A total of 105 (34.20%) patients (UC: 35.92%; CD: 27.42%) developed 225 AEs and the most frequent AEs were infections and infestations (16.61%) followed by gastrointestinal disorders (GID) (14.66%) and general disorders (GD) (4.56%). Colitis and pyeria were the most common GID and GD, respectively occurred in 7(2.28%) patients each (Table 1). Forty-one TRAEs were observed and ten AEs lead to study discontinuation. Total 13 AESIs and 34 SAEs were reported and at least one AESI was reported in 10 patients. No deaths were reported during the study (Table 2). A total of 79.19% (118/149) and 34.48% (10/29) patients with UC and CD respectively, achieved clinical response at week 14 (±4 weeks). Clinical remission and endoscopic remission was achieved by 2/2 and 1/1 patients with UC, respectively at week 54 (±4 weeks). Conclusion Vedolizumab demonstrated favorable safety profile and treatment effectiveness among Chinese adult patients with UC or CD in real-world clinical practice.

A study of the mediating effect of social support on self-disclosure and demoralization in Chinese older adult homebound breast cancer patients.

Demoralization is common in older adult homebound breast cancer patients, seriously affecting their quality of life. This study aimed to investigate the demoralization of older adult homebound breast cancer patients and to analyse the mediating effects of social support between self-disclosure and demoralization. The study enrolled 368 older adult homebound breast cancer patients reviewed in outpatient clinics of three hospitals from January 2022 to August 2023. A questionnaire survey was conducted using the general information questionnaire, the distress disclosure index (DDI), the social support revalued scale (SSRS), and the demoralization scale (DS). Path analysis was conducted to test the hypothesised serial mediation model. The total scores of self-disclosure, social support, and demoralization were 37 (25-42), 34 (19-48.75), and 46.5 (35-68), respectively. The results indicated a positive correlation between self-disclosure and social support (p < 0.01). In contrast, a statistically significant negative correlation was observed between self-disclosure, social support, and various demoralization dimensions (p < 0.01). Social support played a partial mediation effects between self-disclosure and demoralization, indirect effect =0.6362, SE = -0.591, 95% CI (-0.785 ~ -0.415); Self-disclosure direct effect demoralization, direct effect =0.3638, SE = -0.337, 95% CI (-0.525 ~ -0.144); total effect, SE = -0.929, 95% CI (-0.945 ~ -0.904). Social support a partial mediated between self-disclosure and demoralization in Chinese older adult homebound breast cancer patients. Clinical staff should focus on developing a social support system for Chinese older adult homebound breast cancer patients, encouraging patients to reveal their minds, and providing psychological counselling to enhance self-confidence and rebirth from adversity.

Retrospective Analysis of Risk Factors for Cefoperazone/Sulbactam-Induced Thrombocytopenia in Adult Chinese Patients: A Six-Year Real-World Study.

Drug-induced thrombocytopenia is a rare adverse reaction of drug therapy and usually underdiagnosed. Cefoperazone/sulbactam is a compound preparation composed of the third generation of cephalosporin and β-lactamase inhibitor, of which thrombocytopenia is an uncommon but serious adverse reaction. However, the existing literature on cefoperazone/sulbactam-induced thrombocytopenia remains limited, and the specific risk factors associated with this adverse effect have not been thoroughly elucidated. Consequently, this study aims to investigate the clinical characteristics and identify the risk factors for thrombocytopenia in adult patients undergoing cefoperazone/sulbactam therapy. In this retrospective study, we reviewed patients treated with cefoperazone/sulbactam at Beijing Hospital between January 2017 and June 2023. Patients were categorized into two groups based on the presence or absence of thrombocytopenia: the thrombocytopenia group and the non-thrombocytopenia group. We collected data on demographic features, clinical characteristics, laboratory parameters, treatments, and outcomes. Subsequently, univariate and multivariate logistic regression analyses were performed to identify potential risk factors for cefoperazone/sulbactam-induced thrombocytopenia. In total, 6489 patients were included in this study, and 2.4% (155/6489) developed thrombocytopenia. The results of multivariate analysis showed that cefoperazone/sulbactam therapy duration (d) >14, PLT (109/L) <200, daily dose of cefoperazone/sulbactam (g) ≥6, TBil (μmoL/L) >21, AST (U/L) >35, and use of non-invasive ventilator were risk factors for cefoperazone/sulbactam-induced thrombocytopenia. Despite the low incidence (2.4%), cefoperazone/sulbactam could cause serious thrombocytopenia sometimes accompanied with hemorrhage. In clinical therapy, clinicians should be vigilant in monitoring platelet count, especially for patients with risk factors of cefoperazone/sulbactam-induced thrombocytopenia.

Comparison of the therapeutic effects of 15 mg and 30 mg initial daily prednisolone doses in patients with subacute thyroiditis: a multicenter, randomized, open-label, parallel-controlled trial

Introduction Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We designed a randomized controlled trial (RCT) to compare the efficacy and safety of using a low initial dose of PSL with a standard initial dose of PSL in SAT patients. Patients and methods This open-label RCT was conducted at five hospitals in China from June 2019 to January 2022. SAT patients with moderate-to-severe pain or a poor response to non-steroidal anti-inflammatory drugs (NSAIDs) were randomly assigned in a 1:1 ratio to the experimental and control groups. The initial dose of PSL was 15 mg/d in the experimental group and 30 mg/d in the control group. The primary outcome was the total duration of PSL treatment, with non-inferiority prespecified with a margin of 7 days. Clinical trial registration number: ChiCTR1900023884. Results The full analysis set included 60 patients (30 in each group). The mean duration of PSL treatment in the experimental and control group was 34.62 ± 14.12 and 41.18 ± 16.89 days, respectively, meeting the non-inferiority criterion (pnon-inferiority = 0.0006). The total dose of PSL used in the experimental group was lower than in the control groups (330 vs 595 mg, p < 0.0001). There were no differences in the mean time to pain relief and complete resolution, the occurrence of recurrence, hypothyroidism, or adverse events between the groups. Conclusions The initial dose of 15 mg/d of PSL was not inferior to the dose of 30 mg/d in terms of efficacy and showed a similar safety profile. A low initial dose of PSL could be recommended for Chinese adult SAT patients who have a suboptimal response using NSAIDs or experience moderate-to-severe pain. KEY MESSAGES Low initial dose (15 mg/d) of prednisolone was non-inferior to the standard initial dose of prednisolone (30 mg/d) in treatment duration, time to pain relief, or the prevalence of hypothyroidism, recurrence, and adverse reactions in the treatment of subacute thyroiditis. Patients with subacute thyroiditis administered a low initial dose of prednisolone had a lower total dose of prednisolone compared to those receiving the standard dose of prednisolone.

NLRP12-associated autoinflammatory disease in Chinese adult patients: a single-centre study

BackgroundNLRP12-associated autoinflammatory disease (NLRP12-AID) is an autosomal dominant autoinflammatory disorder caused by variants of NLRP12 gene. We aimed to report a cohort of Chinese adult patients with NLRP12-AID and summarised...

Prevalence and clinical profile of comorbid anxiety in young adult patients with first-episode and drug-naive major depressive disorder.

Patients with major depressive disorder (MDD) frequently have coexisting anxiety disorders. However, few studies have focused on the prevalence and risk factors of comorbid anxiety symptoms in young adult first-episode and drug-naive (FEDN) MDD patients. We recruited 520 FEDN MDD patients and collected their demographic and clinical data. The Hamilton Depression Rating Scale (HAMD), the Hamilton Anxiety Rating Scale (HAMA) and the positive scale of the Positive and Negative Syndrome Scale (PANSS) were used to measure depressive symptoms, anxiety symptoms and psychotic symptoms, respectively. Anxiety symptoms were found in 79.6% of young adult patients. Besides, anxiety group patients had a higher prevalence of psychotic symptoms than the non-anxiety group. Anxiety symptoms were substantially related to suicide attempts in young adult patients. Logistic analysis shows that suicide attempts and total HAMD scores were significantly associated with anxiety symptoms. The findings show that anxiety symptoms are common in Chinese young adult MDD patients. The anxiety group was more likely to have psychotic symptoms, suicide attempts, and more severe depressive symptoms than the non-anxiety group. Suicide attempts were associated with anxiety symptoms in young adult MDD patients, suggesting the importance of reducing anxiety symptoms in this population to prevent suicides.

Good efficacy and safety profile of abrocitinib in Chinese adult patients with atopic dermatitis: A case series study.

Good efficacy and safety profile of abrocitinib in Chinese adult patients with atopic dermatitis: A case series study.

Cognitive impairment in Chinese adult patients with type III spinal muscular atrophy without disease-modifying treatment.

Spinal muscular atrophy (SMA) is a neurodegenerative disorder characterized by the degeneration of motor neurons in the spinal cord. It remains uncertain whether the cognitive performance of adult patients with SMA is impaired. The objective of this study was to assess the cognitive profile of adult Chinese patients with SMA and the association between clinical features and cognitive ability, particularly executive function. This cross-sectional study included 22 untreated adult patients with type III SMA and 20 healthy subjects. The following variables were assessed: general intelligence, memory, attention, language, executive function, depression, anxiety, and other demographic and clinical parameters. In addition, physical function was evaluated using the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), and the 6-Minute Walk Test (6MWT). SMA patients had lower scores than healthy subjects in the Verbal Fluency Test, Stroop effect, Total Errors, Perseverative Responses, Perseverative Errors, and Non-perseverative Errors in the Wisconsin Card Sorting Test, showing impaired abilities of SMA patients in executive function. In the Attention Network Test (ANT), the results indicated that the SMA patients also had selective deficits in their executive control networks. Ambulant patients had better executive function test performance than non-ambulant ones. Compromised executive abilities in patients with SMA were correlated with a younger age at onset, poorer motor function, and higher levels of anxiety and depression. Our study presented the distribution of cognitive impairment in a Chinese cohort with SMA. Patients with type III SMA showed selective deficits in executive function, which may be associated with disease severity, physical impairment, depression and anxiety. Future cognitive studies, accounting for motor and emotional impairment, are needed to evaluate if executive impairment is driven by specific brain changes or by those confounding factors.

Efficacy and safety of eltrombopag in Chinese patients with refractory or relapsed severe aplastic anemia

For patients with severe aplastic anemia (SAA) in China who have had an insufficient response to the first-line treatment with hematopoietic stem cell transplantation or immunosuppressive therapy, there is no established standard of care other than transfusion support and treatment of infections. This non-randomized, open-label, Phase II multicenter trial investigated the efficacy and safety of eltrombopag in 20 adult Chinese patients with refractory or relapsed (r/r) SAA. The primary endpoint of hematologic response rate at Week 26, defined as the proportion of patients who met any of the International Working Group criteria, was observed in 70% (14/20) of patients, with more than 50% of these having at least bi-lineage response. Reduced red blood cell and platelet transfusion at Week 26 were observed in 57% (8/14) and 80% (8/10) of patients, respectively. Safety findings were consistent with the established safety profile of eltrombopag and no new safety signals were reported. None of the patients discontinued eltrombopag because of safety concerns. Although the sample size was small, this is the first prospective study to show that eltrombopag is efficacious and has a favorable safety profile in a Chinese patient population with r/r SAA.Trial registration: This trial is registered on ClinicalTrials.gov (NCT03988608); registered 17 June 2019.

Treatment of functional dyspepsia in Chinese adult patients with domperidone: A multicenter, randomized, double-blind, placebo-controlled pilot study.

This pilot study aimed to evaluate the efficacy and safety of domperidone for the treatment of Chinese patients with functional dyspepsia (FD) who were diagnosed according to the Rome IV criteria and to identify the FD subtypes that potentially responded better to domperidone. This multicenter prospective study was conducted in China from August 2018 to July 2020, consisting of a 1-week screening phase and a 2-week double-blind treatment phase. Participants were randomized to receive domperidone 10 mg or matching placebo tablets thrice daily for 14 days. The primary end-point was the overall treatment effect (OTE) response rate after 2-week therapy. Altogether 160 patients were included, with 80 patients in each group. The OTE response rate after 2-week therapy was significantly higher for domperidone compared with placebo (60.7% vs 46.0%; relative risk [RR] 1.318, 95% confidence interval [CI] 0.972-1.787). Moreover, the OTE response rate after 2-week domperidone or placebo treatment was 60.3% versus 54.9% for postprandial distress syndrome (PDS) (RR 1.098, 95% CI 0.750-1.607) and 60.6% versus 35.2% for overlapping PDS-epigastric pain syndrome (EPS) (RR 1.722, 95% CI 0.995-2.980). Adverse events were reported by seven patients in the domperidone group and 12 patients in the placebo group. None of the adverse events in the domperidone group were serious. Domperidone showed a positive pattern regarding OTE response rates after 2-week therapy compared to placebo in patients with FD, as well as in subtypes of PDS and overlapping PDS-EPS. No new safety issue was observed.

Model-based dosing optimization and therapeutic drug monitoring practices of teicoplanin in patients with complicated or non-complicated methicillin-resistant staphylococcus aureusinfection.

This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. Nonlinear mixed-effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non-complicated methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow-up therapeutic drug monitoring of teicoplanin at least once every week.

Sustained Remission and Decreased Severity of CAR T-Cell Related Adverse Events: A Pivotal Study Report of CNCT19 (inaticabtagene autoleucel) Treatment in Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-Cell ALL) in China

CNCT19 (inaticabtagene autoleucel) is an autologous CD19-specific chimeric antigen receptor (CAR) T-cell product. The patent protected CAR structure of CNCT19 contains a unique CD19 scFv, HI19a, which is different from commonly used FMC63. Together with using 4-1BB co-stimulatory domain in the CAR structure, CNCT19 is expected to reduce the severity of treatment-associated cytokine release syndrome (CRS) and neurologic toxicities (NT) while maintaining a stronger and longer durable anti-tumor effect.CNCT19 has been granted Breakthrough Therapy Designation by China National Medical Products Administration and Orphan Drug Designation by the U.S. FDA for the treatment of ALL.The trial of CNCT19 in adult Chinese patients with R/R B-cell ALL (NCT04684147) is a single-arm, open-label pivotal study conducted at 10 centers in China. The primary endpoint was the overall complete response rate (OCR) of complete response (CR) and CR with incomplete hematological recovery (CRi) within 3 months and at the end of Month 3 after CNCT19 infusion by central assessment.All 39 patients diagnosed with B-cell ALL were refractory and relapsed to multiple lines of prior therapy. Among the 39 patients 32 (82.1%) had reached MRD-negative OCR within 3 months after CNCT19 infusion, The median duration of response and OS have not been reached. 25 patients (64.1%) remained on CR (51.3%) or CRi (12.8%). at the end of Month 3 after CNCT19 infusion These patients had sustained long-term remission regardless of whether subsequent allo-HSCT treatment was done or not. The most common CNCT19-related adverse events (AEs) were CRS and NT and there were 4 cases of Grade ≥ 3 CRS (n=4, 10.3%) and 3 cases of Grade ≥ 3 NT (n=3, 7.7%). Following CNCT19 infusion, all the patients recovered. No death cases were reported due to CRS or NT.CNCT19 CAR-T cell therapy achieved a high rate of MRD-negative complete remission in adult patients with R/R B-cell ALL. Thus, with its distinct CAR structure containing a unique CD19 scFv (HI19a), CNCT19 provides effective treatment with potential long-term clinical benefits for adult patients with R/R B-cell ALL.