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Computed tomography-based radiomics improves non-invasive diagnosis of Pneumocystis jirovecii pneumonia in non-HIV patients: a retrospective study.
Yu, H, Yang, Z, Wei, Y, Shi, W, Zhu, M, Liu, L, Wang, M, Wang, Y, Zhu, Q, Liang, Z, et al
BMC pulmonary medicine. 2024;(1):11
Abstract
BACKGROUND Pneumocystis jirovecii pneumonia (PCP) could be fatal to patients without human immunodeficiency virus (HIV) infection. Current diagnostic methods are either invasive or inaccurate. We aimed to establish an accurate and non-invasive radiomics-based way to identify the risk of PCP infection in non-HIV patients with computed tomography (CT) manifestation of pneumonia. METHODS This is a retrospective study including non-HIV patients hospitalized for suspected PCP from January 2010 to December 2022 in one hospital. The patients were randomized in a 7:3 ratio into training and validation cohorts. Computed tomography (CT)-based radiomics features were extracted automatically and used to construct a radiomics model. A diagnostic model with traditional clinical and CT features was also built. The area under the curve (AUC) were calculated and used to evaluate the diagnostic performance of the models. The combination of the radiomics features and serum β-D-glucan levels was also evaluated for PCP diagnosis. RESULTS A total of 140 patients (PCP: N = 61, non-PCP: N = 79) were randomized into training (N = 97) and validation (N = 43) cohorts. The radiomics model consisting of nine radiomic features performed significantly better (AUC = 0.954; 95% CI: 0.898-1.000) than the traditional model consisting of serum β-D-glucan levels (AUC = 0.752; 95% CI: 0.597-0.908) in identifying PCP (P = 0.002). The combination of radiomics features and serum β-D-glucan levels showed an accuracy of 95.8% for identifying PCP infection (positive predictive value: 95.7%, negative predictive value: 95.8%). CONCLUSIONS Radiomics showed good diagnostic performance in differentiating PCP from other types of pneumonia in non-HIV patients. A combined diagnostic method including radiomics and serum β-D-glucan has the potential to provide an accurate and non-invasive way to identify the risk of PCP infection in non-HIV patients with CT manifestation of pneumonia. TRIAL REGISTRATION ClinicalTrials.gov (NCT05701631).
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Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study.
Li, J, Gao, J, Liu, A, Liu, W, Xiong, H, Liang, C, Fang, Y, Dai, Y, Shao, J, Yu, H, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023;(31):4881-4892
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PURPOSE Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. PATIENTS AND METHODS This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. RESULTS We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm (P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm (P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). CONCLUSION HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.
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Lactobacillus paracasei ET-22 and derived postbiotics reduce halitosis and modulate oral microbiome dysregulation - a randomized, double-blind placebo-controlled clinical trial.
Wuri, G, Liu, F, Sun, Z, Fang, B, Zhao, W, Hung, WL, Liu, WH, Zhang, X, Wang, R, Wu, F, et al
Food & function. 2023;(16):7335-7346
Abstract
Oral microbial dysbiosis is the primary etiologic factor for halitosis and may be the critical preventive target for halitosis. This study included randomized controlled trials (RCTs) assessing the effects of Lactobacillus paracasei ET-22 live and heat-killed bacteria on halitosis and the related oral microbiome. 68 halitosis subjects were divided into placebo, ET-22 live (ET-22.L) and ET-22 heat-killed (ET-22.HK) groups. Subjects took different lozenges three times a day for 4 weeks and underwent saliva collection and assessment of breath volatile sulfur compound (VSC) levels at the beginning and end of the intervention. Salivary volatile organic compounds were measured using HS-SPME-GC/MS, and the microbiome profile was determined by 16S rRNA gene amplicon sequencing. A positive decrease in breath volatile sulfur compound (VSC) levels was observed in the means of both ET-22.L and ET-22.HK groups after 4 weeks of intervention, being more marked in the ET-22.L group (p = 0.0148). Moreover, ET-22.L and ET-22.HK intervention remarkably changed the composition of total salivary volatile organic compounds (VOCs) and aroma-active VOCs. Key undesirable VOCs, such as indole, pyridine, nonanoic acid, benzothiazole, and valeric acid, were significantly reduced. Meanwhile, ET-22.L or ET-22.HK also altered the taxonomic composition of the salivary microbiome. The halitosis pathogens Rothia and Streptococcus were significantly reduced in the ET-22.HK group and the pathogenic Solobacterium and Peptostreptococcus were significantly inhibited in the ET-22.L group. Collectively, our study suggests that both ET-22.L and ET-22.HK can significantly inhibit the production of undesirable odor compounds in subjects with halitosis, which may be related to the changes of the oral microbiome.
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Effects of blood pressure and antihypertensive drugs on osteoarthritis: a mendelian randomized study.
Zhang, Y, Wang, Y, Zhao, C, Cai, W, Wang, Z, Zhao, W
Aging clinical and experimental research. 2023;(11):2437-2444
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BACKGROUND Previous studies have suggested that antihypertensive drugs may play a role in the treatment of osteoarthritis, but these studies may be limited by confounding factors and lead to biased results. Therefore, we conducted a Mendelian randomization study to investigate the effects of blood pressure and antihypertensive drugs on osteoarthritis. METHODS We used published large-scale genome-wide association data and applied univariate and multivariate Mendelian randomization methods. The main analysis model was inverse variance weighting, and the reliability of the results was tested using MR-Egger intercept analysis, Cochran's Q test, and leave-one-out analysis. We comprehensively evaluated the relationship between systolic blood pressure, diastolic blood pressure, 12 antihypertensive drugs, and osteoarthritis. We also conducted verification in the independent queue of UK Biobank and built a simple linear regression model to obtain an independent comparison. RESULTS We found no evidence that systolic and diastolic blood pressure significantly affected osteoarthritis. However, among antihypertensive drugs, we observed a significant positive correlation between potassium-preserving diuretics and aldosterone antagonists and all osteoarthritis (OR: 0.560, 95% CI 0.406-0.772, P = 0.0004). Sensitivity analysis showed no horizontal pleiotropy or heterogeneity, and the leave-one-out analysis demonstrated the reliability of the results. This result was replicated with nominally statistical significance in the validation cohort and exhibited significant correlation in the linear regression analysis. CONCLUSIONS Our study suggested that controlling the protein targets of potassium-sparing diuretics and aldosterone antagonists may have beneficial results for osteoarthritis. These findings provide valuable medication strategies for the control of hypertension in patients with osteoarthritis.
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Efficacy and safety of cetagliptin as monotherapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial.
Ji, L, Lu, J, Gao, L, Ying, C, Sun, J, Han, J, Zhao, W, Gao, Y, Wang, K, Zheng, X, et al
Diabetes, obesity & metabolism. 2023;(12):3671-3681
Abstract
AIM: To assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor, cetagliptin, as monotherapy in Chinese patients with type 2 diabetes (T2D) and inadequate glycaemic control. MATERIALS AND METHODS In total, 504 eligible patients with T2D were enrolled and randomized to cetagliptin 50 mg once daily, cetagliptin 100 mg once daily or placebo at a ratio of 2:2:1 for 24 weeks of double-blind treatment, then all patients received cetagliptin 100 mg once daily for 28 weeks of open-label treatment. The primary efficacy endpoint was the change in HbA1c level from baseline at week 24. RESULTS After 24 weeks, HbA1c from baseline was significantly reduced with cetagliptin 50 mg (-1.08%) and cetagliptin 100 mg (-1.07%) compared with placebo (-0.35%). The placebo-subtracted HbA1c reduction was -0.72% with cetagliptin 50 mg and 100 mg. Patients with a baseline HbA1c of 8.5% or higher had a greater HbA1c reduction with cetagliptin than those patients with a baseline HbA1c of less than 8.5%. Both doses studied led to a significantly higher proportion of patients (42.3% with 100 mg and 45.0% with 50 mg) achieving an HbA1c of less than 7.0% compared with placebo (12.9%). Cetagliptin also significantly lowered fasting plasma glucose and 2-hour postmeal plasma glucose relative to placebo. The incidence of adverse experiences was similar between cetagliptin and placebo. No drug-related hypoglycaemia was reported. CONCLUSIONS Cetagliptin monotherapy was effective and well tolerated in Chinese patients with T2D who had inadequate glycaemic control on exercise and diet.
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Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2).
Chai, M, He, Y, Zhao, W, Han, X, Zhao, G, Ma, X, Qiao, P, Shi, D, Liu, Y, Han, W, et al
BMC medicine. 2023;(1):77
Abstract
BACKGROUND Heterozygous familial hypercholesterolemia (HeFH) is largely underdiagnosed and undertreated in China where few patients achieved recommended target levels of low density lipoprotein cholesterol (LDL-C). We conducted the first randomized, placebo-controlled clinical trial in Chinese patients with HeFH to assess the efficacy and safety of tafolecimab, a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody. METHODS Patients diagnosed with HeFH by Simon Broome criteria and on a stable lipid-lowering therapy for at least 4 weeks were randomized 2:2:1:1 to receive subcutaneous tafolecimab 150 mg every 2 weeks (Q2W), tafolecimab 450 mg every 4 weeks (Q4W), placebo Q2W or placebo Q4W in the 12-week double-blind treatment period. After that, participants received open-label tafolecimab 150 mg Q2W or 450 mg Q4W for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Secondary endpoints included proportion of participants achieving ≥50% LDL-C reductions and proportion of participants with LDL-C <1.8 mmol/L at week 12 and 24, the change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and lipoprotein(a) levels, as well as the change from baseline to week 24 in lipid levels. RESULTS In total, 149 participants were randomized and 148 received at least one dose of the study treatment. At week 12, tafolecimab treatment induced significant reductions in LDL-C levels (treatment difference versus placebo [on-treatment estimand]: -57.4% [97.5% CI, -69.2 to -45.5] for 150 mg Q2W; -61.9% [-73.4 to -50.4] for 450 mg Q4W; both P <0.0001). At both dose regimens, significantly more participants treated with tafolecimab achieved ≥50% LDL-C reductions or LDL-C <1.8 mmol/L at week 12 as compared with corresponding placebo groups (all P <0.0001). Meanwhile, non-HDL-C, apolipoprotein B and lipoprotein(a) levels were significantly reduced in the tafolecimab groups at week 12. The lipid-lowering effects of tafolecimab were maintained till week 24. During the double-blind treatment period, the most commonly-reported adverse events in the tafolecimab groups included upper respiratory tract infection, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase and hypertension. CONCLUSIONS Tafolecimab administered either 150 mg Q2W or 450 mg Q4W yielded significant and persistent reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with HeFH. TRIAL REGISTRATION ClinicalTrials.gov, NCT04179669.
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Effect and mechanism of tai chi on blood pressure of patients with essential hypertension: a randomized controlled study.
Lin, B, Jin, Q, Liu, C, Zhao, W, Ji, R
The Journal of sports medicine and physical fitness. 2022;(9):1272-1277
Abstract
BACKGROUND Tai chi is a traditional Chinese martial art that is increasingly popular in the world for positive health benefits. The influence and mechanism of tai chi on blood pressure in patients with essential hypertension still have high value for research. METHODS A total of 99 patients with hypertension were randomly divided into control group and tai chi group. Tai chi intervention lasted for 12 weeks, and the control group maintained normal dietary and exercise habits. The changes of systolic and diastolic blood pressures in patients before and after the intervention were monitored. The serum concentrations of angiotensin II (Ang II) and nitric oxide (NO) were detected. RESULTS There was no significant difference in baseline parameters between the two groups (P>0.05). Compared with the control group, the decreased systolic and diastolic blood pressure in tai chi group was higher after 12 weeks (P<0.001). At the 12th week, the decreased level of Ang II and the increased level of NO in tai chi group were higher than those in the control group (P<0.001). CONCLUSIONS Tai chi can improve the blood pressure of patients with hypertension by decreasing the serum Ang II level and increasing the serum NO level.
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Rationale and Design of the ADIDAS Study: Association Between Dapagliflozin-Induced Improvement and Anemia in Heart Failure Patients.
Zeng, J, Zhu, Y, Zhao, W, Wu, M, Huang, H, Huang, H, Wu, C, Zhou, X, Zhou, S, Wang, C, et al
Cardiovascular drugs and therapy. 2022;(3):505-509
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BACKGROUND Heart failure (HF) is one of the most serious health concerns worldwide. Anemia is a highly prevalent comorbidity and outcome predictor in HF patients. Sodium glucose co-transport 2 (SGLT2) inhibitors have been demonstrated to reduce the risk of cardiovascular death and HF hospitalization in HF patients. PURPOSE This investigator-initiated, interventional, prospective, double-blind, multicenter study is designed to investigate whether anemia correction is one of the prerequisites and determinants related to the beneficial effects of dapagliflozin in HF patients. METHODS AND RESULTS Up to 2030 HF participants receiving standard care will be randomly assigned to either oral dapagliflozin 10 mg once daily or placebo 10 mg once daily for 12 months. The primary outcome is the composite incidence of hospital admission for HF and all-cause death. Secondary outcomes include change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score and change in 6-min walk distance and hemoglobin level. Patients will be followed for 12 months after randomization. CONCLUSIONS The ADIDAS trial offers an opportunity to assess the hemoglobin change and association between hemoglobin change and readmissions due to heart failure and all-cause death in patients with heart failure treated with dapagliflozin or placebo. This study could highlight if dynamic hemoglobin change is related to the outcome for HF patients. TRIAL REGISTRATION ClinicalTrials.gov ; NCT04707261. Registration date, 2020/12/01, "retrospectively registered".
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Comparison of 3 Paclitaxel-Based Chemoradiotherapy Regimens for Patients With Locally Advanced Esophageal Squamous Cell Cancer: A Randomized Clinical Trial.
Ai, D, Ye, J, Wei, S, Li, Y, Luo, H, Cao, J, Zhu, Z, Zhao, W, Lin, Q, Yang, H, et al
JAMA network open. 2022;(2):e220120
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IMPORTANCE Multiple paclitaxel-based regimens are widely used in chemoradiation therapy against esophageal cancer, including regimens combining paclitaxel with fluorouracil, cisplatin, and carboplatin. However, which among these 3 regimens provides the best prognosis with minimum adverse events is still unknown. OBJECTIVE To compare the efficacy and adverse events of fluorouracil, cisplatin, and carboplatin in definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial of patients with ESCC was conducted in 11 treatment centers in China. Eligible patients were aged 18 to 75 years and had histologically confirmed ESCC stages IIa to IVa with no prior treatment, Eastern Cooperative Oncology Group performance status of 2 or lower, and adequate organ functions. The study was conducted between July 2015 and February 2018, and the cutoff date for data analysis was August 31, 2020. INTERVENTIONS Patients with locally advanced ESCC were randomly assigned (1:1:1) to groups combining paclitaxel treatment with fluorouracil, cisplatin, or carboplatin. Patients in the cisplatin group were treated with 2 cycles of concurrent chemoradiotherapy followed by 2 cycles of consolidation chemotherapy with monthly paclitaxel plus cisplatin. For the fluorouracil group, patients were administered 6 cycles of weekly paclitaxel plus fluorouracil in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus fluorouracil in consolidation chemotherapy. Patients in the carboplatin group were treated with 6 cycles of weekly paclitaxel plus carboplatin in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus carboplatin in consolidation chemotherapy. All patients received radiotherapy of 61.2 Gy delivered in 34 fractions. MAIN OUTCOMES AND MEASURES The primary end point was overall survival (OS). The secondary end points were progression-free survival and adverse events. RESULTS Overall, 321 patients (median [IQR] age, 64 years [59-69 years]; 248 [77.3%] men) with ESCC from 11 centers were randomized into fluorouracil, cisplatin, or carboplatin groups between July 2015 and February 2018. Over a median (IQR) follow-up time of surviving patients of 46.0 months (36.6-53.0 months), the 3-year OS rates were 57.2% in the fluorouracil group, 60.1% in the cisplatin group, and 56.5% in the carboplatin group, respectively (fluorouracil vs cisplatin: HR, 1.06; 95% CI, 0.71-1.60; P = .77; fluorouracil vs carboplatin: HR, 0.94; 95% CI, 0.63-1.40; P = .77). The cisplatin group had significantly higher incidences of acute grade 3 or 4 neutropenia (69 events [60.8%] vs 19 [17.8%] for fluorouracil and 37 [34.6%] carboplatin; P < .001), thrombocytopenia (14 events [13.1%] vs 4 [3.7%] for fluorouracil and 5 [4.7%] for carboplatin; P = .01), anemia (50 events above grade 2 [46.7%] vs 25 [23.4%] for fluorouracil and 37 [34.6%] for carboplatin; P = .35), fatigue (11 events [10.3%] vs 2 [1.9%] for fluorouracil and 1 [0.9%] carboplatin; P = .007), and vomiting (17 events above grade 2 [15.9%] vs 3 [2.8%] for fluorouracil and 5 [4.7%] for carboplatin; P < .001) than the other 2 groups. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, paclitaxel plus fluorouracil did not show OS superiority over paclitaxel plus cisplatin or paclitaxel plus carboplatin regimens in definitive chemoradiation in patients with locally advanced ESCC. Higher rates of hematologic and gastrointestinal toxic effects were reported in the cisplatin group compared with those in the fluorouracil or carboplatin groups. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02459457.
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White common bean extract remodels the gut microbiota and ameliorates type 2 diabetes and its complications: A randomized double-blinded placebo-controlled trial.
Feng, Y, Zhu, J, Wang, Q, Cao, H, He, F, Guan, Y, Li, D, Yan, J, Yang, J, Xia, Y, et al
Frontiers in endocrinology. 2022;13:999715
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Patients with type 2 diabetes (T2D) have a higher risk of macrovascular complications. Intensive glycaemic control reduces microvascular complications and exerts a modest improved effect on macrovascular outcomes. The main aim of this study was to explore the effects of white common bean extract (WCBE) on glucose metabolism and diabetic complications in patients with T2D. This study was a randomised double-blind placebo-controlled trial which enrolled ninety-six patients with T2D aged between 35 and 75 years. Participants were randomly assigned in a 1:2 ratio to the control group and WCBE group. Results showed that WCBE alleviated glucose metabolism dysbiosis and diabetic complication indices. In fact, after 2 months of an intense intervention with a WCBE treatment and in the following two-month maintenance period, the improvements to glycaemic metabolism were preserved. Furthermore, there was notable improvement of the structure of the gut microbiota, especially the enrichment of short-chain fatty acid-producing bacteria and inhibition of opportunistic pathogens. Authors conclude that WCBE may be considered as a novel prebiotic antidiabetic agent for the regulation of glucose metabolism and gut microbiota homeostasis and may slightly ameliorate diabetic complications in patients with T2D.
Abstract
OBJECTIVE Excessive carbohydrate intake is a high risk factor for increased morbidity of type 2 diabetes (T2D). A novel regimen for the dietary care of diabetes that consists of a highly active α-amylase inhibitor derived from white common bean extract (WCBE) and sufficient carbohydrates intake was applied to attenuate T2D and its complications. Furthermore, the role of gut microbiota in this remission was also investigated. METHODS We conducted a 4-month randomized double-blinded placebo-controlled trial. During the intense intervention period, ninety subjects were randomly assigned to the control group (Group C) and WCBE group (Group W). Subjects in Group C were supplemented with 1.5 g of maltodextrin as a placebo. Subjects in Group W took 1.5 g of WCBE half an hour before a meal. Fifty-five participants continued the maintenance intervention receiving the previous dietary intervention whereas less frequent follow-up. The variation in biochemical, vasculopathy and neuropathy indicators and the structure of the fecal microbiota during the intervention was analyzed. RESULT Glucose metabolism and diabetic complications showed superior remission in Group W with a 0.721 ± 0.742% decline of glycosylated hemoglobin after 4 months. The proportion of patients with diabetic peripheral neuropathy (Toronto Clinical Scoring System, TCSS ≥ 6) was significantly lower in Group W than in Group C. Both the left and right sural sensory nerve conduction velocity (SNCV-left sural and SNCV-right sural) slightly decreased in Group C and slightly increased in Group W. Additionally, the abundances of Bifidobacterium, Faecalibacterium and Anaerostipes were higher in Group W, and the abundances of Weissella, Klebsiella, Cronobacter and Enterobacteriaceae_unclassified were lower than those in Group C at month 2. At the end of month 4, Bifidobacterium remained more abundant in Group W. CONCLUSION To our knowledge, this is the first report of improvement to diabetes complications by using a dietary supplement in such a short-term period. The enrichment of SCFA-producing bacteria might be responsible for the attenuation of T2D and its complications. CLINICAL TRIAL REGISTRATION NUMBER http://www.chictr.org.cn/edit.aspx?pid=23309&htm=4, identifier ChiCTR-IOR-17013656.