-
1.
Short-term exposure to ambient fine particulate pollution aggravates ventilator-associated pneumonia in pediatric intensive care patients undergoing cardiovascular surgeries.
Cui, Z, Ma, Y, Yu, Y, Li, N, Wang, J, Wang, A, Tan, Q
Environmental health : a global access science source. 2023;(1):39
Abstract
BACKGROUND Ambient air pollutants can be hazardous to human health, especially for vulnerable children. The impact of ambient air pollutant exposure before and during intensive care unit (ICU) stays on the development of ventilator-associated pneumonia (VAP) in critically ill children has not been established. We aimed to determine the correlations between short-term exposures to ambient fine particulate matter (PM2.5) and VAP in pediatric cardiac surgery patients in the ICU, and explore the effect of delayed exposure. METHODS The medical record of 1755 child patients requiring artificial ventilation in the ICU between December 2013 to December 2020, were analyzed. The daily average concentrations of particulate matters (PM2.5 and PM10), sulfur dioxide (SO2), and ozone (O3) were calculated from public data. Interactions between these pollutants and VAP were simulated with the distributed lag non-linear model. RESULTS Three hundred forty-eight cases (19.829%) of VAP were identified in this study, while the average concentrations of PM2.5, PM10, O3 and SO2 were 58, 118, 98 and 26 μg/m3, respectively. Exposure to increased levels of PM2.5 two days prior (lag 2-day) to VAP diagnosis is significantly correlated with an enhanced risk for VAP development. Even a slight increase of 10 μg/m3 in PM2.5 can translate to a 5.4% increase in VAP incidence (95% CI: 1.4%-9.5%) while the VAP incidence increased to 11.1% (95%CI: 4.5-19.5%) when PM2.5 concentration is well below the National Ambient Air Quality standard (NAAQS) of 50 μg/m3. The association was more pronounced in those aged below 3-months, with low body mass index or suffered from pulmonary arterial hypertension. CONCLUSION Short-term PM2.5 exposure is a significant risk for development of VAP in pediatric patients. This risk is present even with PM2.5 levels below the NAAQS. Ambient PM2.5 may represent a previously unrecognized risk factor for pneumonia and the current environmental pollution standards need to be reevaluated to consider susceptible populations. TRIAL REGISTRATION The trial was registered with the National Clinical Trial Center: The correlation between ambient air pollution and the complications in ICU underwent cardiac surgery. TRIAL REGISTRATION NUMBER ChiCTR2000030507. Date of registration: March 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx .
-
2.
Pharmacokinetic Evaluation of Intravenous Vitamin C: A Classic Pharmacokinetic Study.
Chen, P, Reed, G, Jiang, J, Wang, Y, Sunega, J, Dong, R, Ma, Y, Esparham, A, Ferrell, R, Levine, M, et al
Clinical pharmacokinetics. 2022;(9):1237-1249
-
-
Free full text
-
Abstract
PURPOSE Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1-100 g. METHODS A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. Healthy participants received IVC infusions of 1-100 g; oncology participants received IVC infusions of 25-100 g. Serial blood and complete urine samples were collected pre-infusion and for 24 h post-infusion. Pharmacokinetic parameters were computed using noncompartmental methods. Adverse events were monitored during the study. RESULTS In both cohorts, IVC exhibited first-order kinetics at doses up to 75 g. At 100 g, maximum concentration (Cmax) plateaued in both groups, whereas area under the concentration-time curve (AUC) only plateaued in the healthy group. IVC was primarily excreted through urine. No saturation of clearance was observed; however, the mean 24-h total IVC excretion in urine for all doses was lower in oncology participants (89% of dose) than in healthy participants at 100 g (99%). No significant adverse events were observed; thus, maximum tolerated dose (MTD) was not reached. CONCLUSION IVC followed first-order pharmacokinetics up to 75 g and at up to 100 g had complete renal clearance in 24 h. IVC up to 100 g elicited no adverse effects or significant physiological/biochemical changes and appears to be safe. These data can be used to rectify existing misinformation and to guide future clinical trials. REGISTRATION ClinicalTrials.gov identifier number NCT01833351.
-
3.
Effect of a Novel Macrophage-Regulating Drug on Wound Healing in Patients With Diabetic Foot Ulcers: A Randomized Clinical Trial.
Huang, YY, Lin, CW, Cheng, NC, Cazzell, SM, Chen, HH, Huang, KF, Tung, KY, Huang, HL, Lin, PY, Perng, CK, et al
JAMA network open. 2021;(9):e2122607
-
-
Free full text
-
Abstract
IMPORTANCE Delayed healing of diabetic foot ulcers (DFUs) is known to be caused by dysregulated M1/M2-type macrophages, and restoring the balance between these macrophage types plays a critical role in healing. However, drugs used to regulate M1/M2 macrophages have not yet been studied in large randomized clinical trials. OBJECTIVE To compare the topical application of ON101 cream with use of an absorbent dressing (Hydrofiber; ConvaTec Ltd) when treating DFUs. DESIGN, SETTING, AND PARTICIPANTS This multicenter, evaluator-blinded, phase 3 randomized clinical trial was performed in 21 clinical and medical centers across the US, China, and Taiwan from November 23, 2012, to May 11, 2020. Eligible patients with debrided DFUs of 1 to 25 cm2 present for at least 4 weeks and with Wagner grade 1 or 2 were randomized 1:1 to receive ON101 or control absorbent dressings. INTERVENTIONS Twice-daily applications of ON101 or a absorbent dressing changed once daily or 2 to 3 times a week for 16 weeks, with a 12-week follow-up. MAIN OUTCOMES AND MEASURES The primary outcome was the incidence of complete healing, defined as complete re-epithelialization at 2 consecutive visits during the treatment period assessed on the full-analysis set (FAS) of all participants with postrandomization data collected. Safety outcomes included assessment of the incidences of adverse events, clinical laboratory values, and vital signs. RESULTS In the FAS, 236 eligible patients (175 men [74.2%]; mean [SD] age, 57.0 [10.9] years; mean [SD] glycated hemoglobin level, 8.1% [1.6%]) with DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 4.8 [4.4] cm2) were randomized to receive either the ON101 cream (n = 122) or the absorbent dressing (n = 114) for as long as 16 weeks. The incidence of complete healing in the FAS included 74 patients (60.7%) in the ON101 group and 40 (35.1%) in the comparator group during the 16-week treatment period (difference, 25.6 percentage points; odds ratio, 2.84; 95% CI, 1.66-4.84; P < .001). A total of 7 (5.7%) treatment-emergent adverse events occurred in the ON101 group vs 5 (4.4%) in the comparator group. No treatment-related serious adverse events occurred in the ON101 group vs 1 (0.9%) in the comparator group. CONCLUSIONS AND RELEVANCE In this multicenter randomized clinical trial, ON101 exhibited better healing efficacy than absorbent dressing alone in the treatment of DFUs and showed consistent efficacy among all patients, including those with DFU-related risk factors (glycated hemoglobin level, ≥9%; ulcer area, >5 cm2; and DFU duration, ≥6 months). TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01898923.
-
4.
Bazedoxifene effects on osteoprotegerin, insulin-like growth factor, tumor necrosis factor and bone mineral density.
Ma, Y, Chai, Z, Ren, L, Hu, Q
Cellular and molecular biology (Noisy-le-Grand, France). 2020;(3):109-112
Abstract
UNLABELLED To observe the clinical effect of estrogenic drugs (Bazedoxifene) on bone targeting in the treatment of osteoporosis and explore its mechanism. METHODS 112 patients with postmenopausal osteoporosis who received Bazedoxifene drugs in our hospital from January to December 2018 were collected as a study group, and 56 patients treated with calcium alone were collected as a control group. the risk of adverse events such as bone mineral density, osteoprotegerin (OPG), insulin-like growth factor (IGF), tumor necrosis factor (TNF-α), and fracture after treatment were analyzed before and after treatment. RESULTS There was no significant difference in the mean lumbar positive position (L2-4) and right femoral neck bone density and OPG, IGF, TNF-α level between the two groups before treatment (P>0.05). The total effective rate of clinical treatment in the study group was 88.39%, the control group was 23.21%, the difference between the two groups was statistically significant (P˂0.05). After treatment, the mean lumbar positive position (L2-4) and the right femoral neck bone density and OPG, IGF in the study group were higher than those in the control group, lower than those in the control group (P<0.05). the occurrence of adverse events such as fracture, spinal deformation and fatigue in the study group after 12 months of treatment was significantly lower than that in the control group (P<0.05), but there was no significant difference in the occurrence of hot flashes and venous thromboembolism between the two groups (P>0.05). CONCLUSION Bazedoxifene is an effective drug for the treatment of postmenopausal osteoporosis. It can not only prevent the rapid loss of bone mass, effectively relieve the symptoms of menopause, but also improve bone density and reduce the risk of fracture.
-
5.
PML-RARA monitoring in newly diagnosed acute promyelocytic leukemia treated with an entirely oral chemotherapy-free postremission approach: A multiple institution experience.
Lou, Y, Lu, Y, Ye, X, Wang, Y, Ma, Y, Fan, C, Jiang, H, Jin, J
Hematological oncology. 2020;(4):618-621
-
6.
Pharmacokinetics, Safety, and Tolerability of Orally Administered Ursodeoxycholic Acid in Patients With Parkinson's Disease-A Pilot Study.
Sathe, AG, Tuite, P, Chen, C, Ma, Y, Chen, W, Cloyd, J, Low, WC, Steer, CJ, Lee, BY, Zhu, XH, et al
Journal of clinical pharmacology. 2020;(6):744-750
-
-
Free full text
-
Abstract
Mitochondrial dysfunction is implicated in the pathogenesis of Parkinson's disease. Preliminary data have shown lower brain adenosine triphosphate (ATP) levels in Parkinson's disease versus age-matched healthy controls. Ursodeoxycholic acid (UDCA) may improve impaired mitochondrial function. Our objective was to evaluate UDCA tolerability, pharmacokinetics, and its effect on brain bioenergetics in individuals with Parkinson's disease. An open-label, prospective, multiple-ascending-dose study of oral UDCA in 5 individuals with Parkinson's disease was completed. A blood safety panel, plasma concentrations of UDCA and UDCA conjugates, and brain ATP levels were measured before and after therapy (week 1: 15 mg/kg/day; week 2: 30 mg/kg/day; and weeks 3-6: 50 mg/kg/day). UDCA and conjugates were measured using liquid chromatography-mass spectrometry. ATP levels and ATPase activity were measured using 7-Tesla 31 P magnetic resonance spectroscopy. Secondary measures included the Unified Parkinson's Disease Rating Scale and Montreal Cognitive Assessment. UDCA was generally well tolerated. The most frequent adverse event was gastrointestinal discomfort, rated by subjects as mild to moderate. Noncompartmental pharmacokinetic analysis resulted in (mean ± standard deviation) a maximum concentration of 8749 ± 2840 ng/mL and half-life of 2.1 ± 0.71 hr. Magnetic resonance spectroscopy data were obtained in 3 individuals with Parkinson's disease and showed modest increases in ATP and decreases in ATPase activity. Changes in Unified Parkinson's Disease Rating Scale (parts I-IV) and Montreal Cognitive Assessment scores (mean ± standard deviation) were -4.6 ± 6.4 and 2 ± 1.7, respectively. This is the first report of UDCA use in individuals with Parkinson's disease. Its pharmacokinetics are variable, and at high doses it appears reasonably well tolerated. Our findings warrant additional studies of its effect on brain bioenergetics.
-
7.
Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma.
Shimagaki, T, Yoshio, S, Kawai, H, Sakamoto, Y, Doi, H, Matsuda, M, Mori, T, Osawa, Y, Fukai, M, Yoshida, T, et al
Scientific reports. 2019;(1):15788
Abstract
Current serum hepatocellular carcinoma (HCC) biomarkers are insufficient for early diagnosis. We aimed to clarify whether serum MFG-E8 can serve as a diagnostic or prognostic biomarker of HCC. Serum MFG-E8 levels of 282 HCC patients, who underwent primary hepatectomy, were examined by ELISA. We also quantified serum MFG-E8 levels in patients with chronic hepatitis (CH), liver cirrhosis (LC), as well as in healthy volunteers (HVs). Serum MFG-E8 levels were significantly lower in HCC patients than in HVs regardless of the etiology of liver disease (3.6 ± 0.1 vs 5.8 ± 0.2 ng/mL, p < 0.0001), and recovered after treatment of HCC. Serum MFG-E8 levels in CH and LC patients were comparable to those in HVs. Serum MFG-E8 could detect HCCs, even α-fetoprotein (AFP)-negative or des-γ-carboxy prothrombin (DCP)-negative HCCs, in CH and LC patients. Our new HCC prediction model using MFG-E8 and DCP (Logit(p) = 2.619 - 0.809 × serum MFG-E8 + 0.0226 × serum DCP) distinguished HCC patients from CH and LC patients with an area under the curve of 0.923, a sensitivity of 81.1%, and a specificity of 89.8%. Futhermore, low preoperative serum MFG-E8 was an independent predictor of poor overall survival. Thus, serum MFG-E8 could serve as a feasible diagnostic and prognostic biomarker for HCC.
-
8.
A nonrestrictive, weight loss diet focused on fiber and lean protein increase.
Zhang, L, Pagoto, S, Olendzki, B, Persuitte, G, Churchill, L, Oleski, J, Ma, Y
Nutrition (Burbank, Los Angeles County, Calif.). 2018;:12-18
Abstract
OBJECTIVE We examined the feasibility and acceptability of a non-restrictive diet that was focused on increasing dietary fiber and lean protein intake for weight loss. METHODS Dietary intake was assessed using three randomly selected 24-h dietary recalls. Fifteen obese adults enrolled in a 12-wk study that included six biweekly individual dietary counseling sessions to attain a daily goal of higher fiber (35 g/d) and lean protein (0.8 g/kg/d of individual's ideal body weight) intake. Feasibility was determined by retention and attendance and dietary adherence was measured. RESULTS One participant dropped out of the study before the 12-wk assessment visit. Fourteen participants completed all six counseling sessions and one participant completed five sessions. At week 12, 93% of participants approved of the diet and 92% of participants did not feel hungry while on the diet. Mean fiber intake increased by 6.8 g/d (95% confidence interval [CI], 3.2 to 10.5 g/d) and total protein intake increased by 5.7 g/d (95% CI, -3.7 to 15.0 g/d). The mean change in energy intake was -265.5 kcal/d (95% CI, -454.8 to -76.2 kcal/d). The dietary quality score as measured by the Alternative Healthy Eating Index increased by 6.1 (95% CI, 1.5 to 10.7). The mean change in weight was -2.2% (95% CI, -3.6 to -0.7%). CONCLUSIONS A diet that promotes increased fiber and lean protein intake demonstrates feasibility and high acceptability ratings, which resulted in calorie and weight reductions and an improvement of the dietary quality.
-
9.
Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies.
Stroes, E, Robinson, JG, Raal, FJ, Dufour, R, Sullivan, D, Kassahun, H, Ma, Y, Wasserman, SM, Koren, MJ
Clinical cardiology. 2018;(10):1328-1335
Abstract
BACKGROUND Evolocumab significantly lowers low-density lipoprotein cholesterol (LDL-C) when dosed 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) subcutaneously. HYPOTHESIS LDL-C changes are comparable among different patient subgroups in a pooled analysis of data from phase 3 trials. METHODS A total of 3146 patients received ≥1 dose of evolocumab or control in four 12-week phase 3 studies. Percent change from baseline in LDL-C for evolocumab 140 mg Q2W or 420 mg QM vs control was reported as the average of week 10 and 12 values. Quantitative and qualitative interactions between treatment group and subgroup by dose regimen were tested. RESULTS In the pooled analysis, treatment differences vs placebo or ezetimibe were similar for both 140 mg Q2W and 420 mg QM doses across ages (<65 years, ≥65 years); gender; race (Asian, black, white, other); ethnicity (Hispanic, non-Hispanic); region (Europe, North America, Asia Pacific); glucose tolerance status (type 2 diabetes mellitus, metabolic syndrome, neither); National Cholesterol Education Program risk categories (high, moderately high, moderate, low); and European Society of Cardiology/European Atherosclerosis Society risk categories (very high, high, moderate, or low). Certain low-magnitude variations in LDL-C lowering among subgroups led to significant quantitative interaction P values that, when tested by qualitative interaction, were not significant. The incidences of adverse events were similar across groups treated with each evolocumab dosing regimen or control. CONCLUSIONS Consistent reductions in LDL-C were observed in the evolocumab group regardless of demographic and disease characteristics.
-
10.
Incorporation of high-dose 131I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study.
Lee, JW, Lee, S, Cho, HW, Ma, Y, Yoo, KH, Sung, KW, Koo, HH, Cho, EJ, Lee, SK, Lim, DH
Journal of hematology & oncology. 2017;(1):108
Abstract
BACKGROUND In our previous SMC NB-2004 study of patients with high-risk neuroblastomas, which incorporated total-body irradiation (TBI) with second high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the survival rate was encouraging; however, short- and long-term toxicities were significant. In the present SMC NB-2009 study, only TBI was replaced with 131I-meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities. METHODS From January 2009 to December 2013, 54 consecutive patients were assigned to receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy. The CEC (carboplatin + etoposide + cyclophosphamide) regimen and the TM (thiotepa + melphalan) regimen with (for metastatic MIBG avid tumors) or without (for localized or MIBG non-avid tumors) 131I-MIBG treatment (18 or 12 mCi/kg) were used for tandem HDCT/auto-SCT. Local radiotherapy, differentiation therapy with 13-cis-retinoic acid, and immunotherapy with interleukin-2 were administered after tandem HDCT/auto-SCT. RESULTS Fifty-two patients underwent the first HDCT/auto-SCT and 47 patients completed tandem HDCT/auto-SCT. There was no significant immediate toxicity during the 131I-MIBG infusion. Acute toxicities during the tandem HDCT/auto-SCT were less severe in the NB-2009 study than in the NB-2004 study. Late effects such as growth hormone deficiency, cataracts, and glomerulopathy evaluated at 3 years after the second HDCT/auto-SCT were also less significant in the NB-2009 study than in NB-2004 study. There was no difference in the 5-year event-free survival (EFS) between the two studies (67.5 ± 6.7% versus 58.3 ± 6.9%, P = 0.340). CONCLUSIONS Incorporation of high-dose 131I-MIBG treatment into tandem HDCT/auto-SCT could reduce short- and long-term toxicities associated with TBI, without jeopardizing the survival rate. TRIAL REGISTRATION ClinicalTrials.gov NCT03061656.