Biological effects of diesel exhaust inhalation. III cardiovascular function.

OBJECTIVE: Inhalation of diesel exhaust (DE) has been shown to be an occupational hazard in the transportation, mining, and gas and oil industries. DE also contributes to air pollution, and therefore, is a health hazard to the general public. Because of its effects on human health, changes have been made to diesel engines to reduce both the amounts of particulate matter and volatile fumes they generate. The goal of the current study was to examine the effects of inhalation of diesel exhaust. MATERIALS AND METHODS: The study presented here specifically examines the effects of exposure to 0.2 and 1.0 mg/m3 DE or filtered air (6h/d for 4 d) on measures of peripheral and cardio-vascular function, and biomarkers of heart and kidney dysfunction in male rats. A Tier 2 engine used in oil and gas fracking operations was used to generate the diesel exhaust. RESULTS: Exposure to 0.2 mg/m3 DE resulted in an increase in blood pressure 1d following the last exposure, and increases in dobutamine-induced cardiac output and stroke volume 1 and 27d after exposure. Changes in peripheral vascular responses to norepinephrine and acetylcholine were minimal as were changes in transcript expression in the heart and kidney. Exposure to 1.0 mg/m3 DE did not result in major changes in blood pressure, measures of cardiac function, peripheral vascular function or transcript expression. DISCUSSION AND CONCLUSIONS: Based on the results of this study, we suggest that exposure to DE generated by a Tier 2 compliant diesel engine generates acute effects on biomarkers indicative of cardiovascular dysfunction. Recovery occurs quickly with most measures of vascular/cardiovascular function returning to baseline levels by 7d following exposure.

Application of three-dimensional material CZIF-8/CS-MS as adsorbents for the determination of plant growth regulators in Schisandra chinensis.

In this study, we employed a melamine sponge (MS) as the skeleton material and utilized carbonized ZIF-8 (CZIF-8) and chitosan (CS) as the raw materials to prepare CZIF-8/CS-MS, a novel material featuring a three-dimensional interconnected porous network. The resulting CZIF-8/CS-MS material possesses a unique porous structure, significant specific surface area and abundant active sites. These characteristics make CZIF-8/CS-MS a promising absorbent for selective purification of plant growth regulators (PGRs) including 1-naphthlcetic acid (NAA), naphthoxyacetic acid (NOA), 4-chlorophenoxyacetic acid (4-CPA), 2,4-dichlorophenoxyacetic acid (2,4-D). After optimizing the extraction conditions, excellent linearity (r > 0.9994) was observed within a wide linear range of 1-100 ng/mL using ultra high performance liquid chromatography-tandem quadrupole mass spectrometry. The detection limits (LODs) and limits of quantification (LOQs) were found to be in the range of 0.013-0.154 ng/mL and 0.044-0.515 ng/mL, respectively. Additionally, the relative recovery of Schisandra chinensis fruit samples was determined to be 89.7-99.4 %, with a relative standard deviation (RSDs) of ≤ 8.4 % (n = 3). Compared to other methods, this approach offers a multitude of benefits, which include but are not limited to exceptional sensitivity, reduced sample volume requirements, low LODs, a comparable linear range, and high reproducibility. The findings of this study pave the way for exploring novel functionalized sponge columns, which leverage the integration of nano-sorbent materials and coating agents, for the purpose of analyzing PGRs within intricate matrix samples.

Toxicological Effects of Inhaled Crude Oil Vapor.

PURPOSE OF REVIEW: The purpose of this review is to assess the toxicological consequences of crude oil vapor (COV) exposure in the workplace through evaluation of the most current epidemiologic and laboratory-based studies in the literature. RECENT FINDINGS: Crude oil is a naturally occuring mixture of hydrocarbon deposits, inorganic and organic chemical compounds. Workers engaged in upstream processes of oil extraction are exposed to a number of risks and hazards, including getting crude oil on their skin or inhaling crude oil vapor. There have been several reports of workers who died as a result of inhalation of high levels of COV released upon opening thief hatches atop oil storage tanks. Although many investigations into the toxicity of specific hydrocarbons following inhalation during downstream oil processing have been conducted, there is a paucity of information on the potential toxicity of COV exposure itself. This review assesses current knowledge of the toxicological consequences of exposures to COV in the workplace.

Clinical, economic, and health-related quality of life outcomes in patients with overweight or obesity in the United States: 2016-2018.

Objectives: This study aimed to estimate clinical, economic (including productivity), and health-related quality of life (HRQoL) outcomes and associated individual characteristics among adults with overweight (OW) or obesity in the United States. Methods: This study included adult respondents with body mass index (BMI) ≥18.5 kg/m2 in the 2017-2018 National Health and Nutrition Examination Survey (NHANES) and 2016 Medical Expenditure Panel Survey. Respondents were classified according to BMI. Individual characteristics were described by BMI categories. Multivariable regression models estimated the association between BMI categories and outcomes, adjusting for individual characteristics. Results: Nearly three-quarters (73.7%) of NHANES participants were OW or obese. Relative to Normal weight (NW), respondents with Class 3 obesity had more obesity-related complications (2.07 vs. 4.62, p < 0.001). Higher BMI was associated with significantly lower HRQoL, lower productivity, and higher healthcare expenditures as well as more frequent weight loss attempts in the previous 12 months. Weight loss surgery and prescription anti-obesity medications (AOMs) were used only by a very small proportion of individuals. Despite frequent weight loss attempts, most respondents did not achieve clinically meaningful weight loss. Conclusions: Adults with OW or obesity experienced worse clinical, economic and HRQoL outcomes than those with NW. Better use of evidence-based obesity treatments, including prescription AOMs, should be considered to achieve more clinically meaningful weight reduction and improved outcomes in individuals with OW or obesity.

EXIST: EXamining rIsk of excesS adiposiTy-Machine learning to predict obesity-related complications.

Background: Obesity is associated with an increased risk of multiple conditions, ranging from heart disease to cancer. However, there are few predictive models for these outcomes that have been developed specifically for people with overweight/obesity. Objective: To develop predictive models for obesity-related complications in patients with overweight and obesity. Methods: Electronic health record data of adults with body mass index 25-80 kg/m2 treated in primary care practices between 2000 and 2019 were utilized to develop and evaluate predictive models for nine long-term clinical outcomes using a) Lasso-Cox models and b) a machine-learning method random survival forests (RSF). Models were trained on a training dataset and evaluated on a test dataset over 100 replicates. Parsimonious models of <10 variables were also developed using Lasso-Cox. Results: Over a median follow-up of 5.6 years, study outcome incidence in the cohort of 433,272 patients ranged from 1.8% for knee replacement to 11.7% for atherosclerotic cardiovascular disease. Harrell C-index averaged over replicates ranged from 0.702 for liver outcomes to 0.896 for death for RSF, and from 0.694 for liver outcomes to 0.891 for death for Lasso-Cox. The Harrell C-index for parsimonious models ranged from 0.675 for liver outcomes to 0.850 for knee replacement. Conclusions: Predictive modeling can identify patients at high risk of obesity-related complications. Interpretable Cox models achieve results close to those of machine learning methods and could be helpful for population health management and clinical treatment decisions.

Metabolomics and pharmacodynamic analysis unveil the therapeutic role of icaritin on osteoporosis rats.

Osteoporosis is a systemic metabolic bone disease characterized by a reduction in bone mass resulting from multifactorial causes. Icaritin (ICT), a flavonoid glycoside, exhibits a multitude of effects on bone tissue. To examine the influence of ICT on bone trabecular loss in vivo, ovariectomized (OVX) rats were utilized. The ability of ICT to mitigate bone trabecular loss and the underlying anti-osteoporotic pathways were assessed using ovariectomy-induced osteoporosis rats. Furthermore, we gain insights into the osteoprotective mechanisms of ICT on osteoporosis by conducting UPLC-Orbitrap-MS-based metabolomics of rat urine. The results of experiments demonstrated a significant attenuation of bone trabecular loss, as well as improvements in biochemical indices, biomechanical parameters, and microstructure in the ICT administered group compared to the OVX group. Moreover, metabolomics results suggested that the ICT treatment adjusted 33 different metabolites, which associated with the metabolism of amino acids, lipids, and energy. The findings suggest that the anti-osteoporosis effect of ICT may be related to the activation of PI3K/AKT signal and the inhibition of TLR4 pathway regulated by metabonomics. These results contribute to a better understanding of the therapeutic potential of ICT in the treatment of osteoporosis.

Metabolomics-derived biomarkers for biosafety assessment of Gd-based nanoparticle magnetic resonance imaging contrast agents.

With the rapid development of nanotechnology and biomedicine, numerous gadolinium (Gd)-based nanoparticle MRI contrast agents have been widely investigated. Due to the unique physicochemical properties of nanoparticles and the complexity of biological systems, the biosafety of Gd-based nanoparticle MRI contrast agents has been paid more and more attention. Herein, for the first time, we employed an ultra-high performance liquid chromatography-electrospray ionization quadrupole time-of-flight/mass spectrometry (UPLC-ESI-QTOF/MS)-based metabolomics approach to investigate the potential toxicity of Gd-based nanoparticle MRI contrast agents. In this work, NaGdF4 and PEG-NaGdF4 nanoparticles were successfully constructed and selected as the representative Gd-based nanoparticle MRI contrast agents for the metabolomics analysis. Based on the results of metabolomics, more metabolic biomarkers and pathways were identified in the NaGdF4 group than those in the PEG-NaGdF4 group. Careful analysis of these metabolic biomarkers and pathways suggested that NaGdF4 nanoparticles induced disturbance of pyrimidine and purine metabolism, inflammatory response, and kidney injury to a certain extent compared with PEG-NaGdF4 nanoparticles. These results indicated that Gd-based nanoparticle contrast agents modified with PEG had better biosafety. Additionally, it was demonstrated that the discovery of characteristic metabolomics biomarkers induced by nanoparticles would provide a new approach for biosafety assessment and stimulate the development of nanomedicine.

Near-infrared light-actuated on-demand botanicals release and hyperthermia by an antibiotic-free polysaccharide-based hydrogel dressing for the synergistic treatment of wound infections.

Bacterial infection is a key factor affecting wound healing. Conventional treatments might lead to the widespread emergence of drug-resistant bacteria due to the long-term and excessive use of antibiotics. It is necessary to develop an antibiotic-free method for effective treatment of bacterial wound infections. In this work, we constructed an antibiotic-free polysaccharide-based hydrogel dressing (ATB) with near-infrared light-actuated on-demand botanicals release and hyperthermia for the synergistic treatment of wound infections. The ATB hydrogel dressing was made up of agarose as a support matrix, berberine hydrochloride as the active botanicals and TA-Fe(III) nanoparticles as NIR laser-activated photothermal reagents. The ATB hydrogel dressing showed spatiotemporal botanicals release and excellent photothermal properties with NIR irradiation. With the results of in vitro and in vivo antibacterial experiments, the antibiotic-free ATB hydrogel could synergistically eliminate bacteria and accelerate wound healing. Overall, the near-infrared light-responsive ATB hydrogel could provide a promising antibiotic-free strategy for the treatment of bacterial wound infections.

Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis.

AIM: To assess the effect of tirzepatide on long-term risk of atherosclerotic cardiovascular disease (ASCVD) among people with obesity or overweight without diabetes from SURMOUNT-1. MATERIALS AND METHODS: SURMOUNT-1, a phase 3 trial, evaluated the efficacy and safety of tirzepatide in adults with body mass index ≥30 or ≥27 kg/m2 and at least one weight-related complication, excluding diabetes. Participants were randomly assigned to tirzepatide (5/10/15 mg) or placebo. Changes from baseline in cardiometabolic variables were assessed. The predicted 10-year ASCVD risk scores were calculated (American College of Cardiology/American Heart Association risk engine) at baseline, week 24, and week 72 in SURMOUNT-1 participants without a history of ASCVD. Percent change in risk scores from baseline to weeks 24 and 72 was compared between tirzepatide and placebo using mixed model for repeated measures analysis. Analyses were also conducted in participants with intermediate to high risk at baseline. RESULTS: Tirzepatide-treated groups demonstrated reductions in cardiometabolic variables over 72 weeks. In participants without a history of ASCVD (N = 2461), the baseline median risk score was low and did not differ across groups (1.5%-1.6%). Relative change in risk from baseline to week 72 was greater for tirzepatide (-23.5% to -16.4%) than placebo (12.7%; P < 0.001). Relative change among participants with intermediate-to-high baseline risk was significantly greater for tirzepatide (P < 0.05). Intermediate-to-high-risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population. CONCLUSION: Tirzepatide treatment significantly reduced the 10-year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes.

Weight management treatment modalities in patients with overweight or obesity: A retrospective cohort study of administrative claims data.

Background: The purpose of this study was to describe demographic and clinical characteristics among patients who have medical encounters for weight management treatments and to investigate the association of those characteristics with treatment modality. Methods: This was a retrospective database study using medical claims, pharmacy claims, and enrollment information from commercial and Medicare Advantage with Part D members in the Optum Research Database from 01/01/2011-2/29/2020. Adult patients with a claim for a weight management treatment from 01/01/2012-2/28/2019 were categorized into cohorts according to the highest intensity intervention received. To examine the association between patient characteristics and treatment modality received, a multinomial logit model was performed. Results: Cohorts by increasing intensity included lifestyle intervention (LSI, n = 67,679), weight reduction pharmacotherapy (WRRx) with an anti-obesity medication (AOM, n = 6,905), weight reduction procedure (WRP, n = 1,172), and weight reduction surgery (WRS, n = 18,036). Approximately 32.1% and 16.6% of patients who received WRS or WRP had an LSI during the 12-month baseline, and only 0.6% and 0.4% had treatment with long-term AOMs. In a multinomial logit model, patients with type 2 diabetes (not including WRRx cohort), respiratory disorders, cardiovascular risk factors, pain disorders, and mental health conditions had increased odds of treatment with higher intensity intervention versus LSI. Patients who were male, received an intervention more recently (2016-2019), or had a Charlson comorbidity score of 1 (compared to 0) had decreased odds of treatment with higher intensity interventions. Conclusion: In this study, age, sex, body mass index, obesity-related complications, and Charlson comorbidity score appeared to influence the type of weight management treatment modality received. This study improves understanding of weight management treatment utilization and identifies gaps and opportunities to improve obesity care with the appropriate use of different treatment modalities.

Application of a three dimensional polyethyleneimine functionalized graphene oxide aerogel as an adsorbent for the determination of phytohormones in ginseng.

Aerogels have attracted considerable attention in sample pretreatment for their outstanding properties, such as the unique porous structure, large surface area and abundant modifiable active sites. The present research reports a three-dimensional interconnected porous network aerogel (PEI-AGO) manufactured based on graphene oxide (GO), polyethyleneimine (PEI) and agar as basic materials through a vacuum freeze-drying treatment. The PEI-AGO aerogel exhibits great potential as a solid phase extraction adsorbent for the selective purification of six endogenous plant hormones in conjunction with high performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS). Several factors affecting the extraction efficiency were investigated. Under the optimized extraction conditions, a wide linear range of 0.5-100 ng mL-1 with a good linearity (r > 0.9934) was observed. Low limits of detection (LODs) and limits of quantification (LOQs) were obtained in the range of 0.032-0.155 ng mL-1 and 0.107-0.518 ng mL-1, respectively. Furthermore, the relative recoveries for spiked ginseng samples exhibited remarkable consistency, ranging from 90.2% to 117.6%, with a relative standard deviation (RSD) of ≤9.4% (n = 3). In summary, PEI-AGO has proven to be an effective adsorbent for the pretreatment and enrichment of phytohormones which can be used for the determination of trace endogenous acidic plant hormones in ginseng leaves.

Tirzepatide reduces the predicted risk of developing type 2 diabetes in people with obesity or overweight: Post hoc analysis of the SURMOUNT-1 trial.

AIM: We assessed the impact of tirzepatide on 10-year predicted risk of developing type 2 diabetes (T2D) among participants in the SURMOUNT-1 trial. MATERIALS AND METHODS: In this post hoc analysis of SURMOUNT-1, the Cardiometabolic Disease Staging risk engine was used to calculate the 10-year predicted risk of T2D at baseline, week 24 and week 72 among participants randomized to receive 5, 10, or 15 mg tirzepatide or placebo. Mean changes in risk scores from baseline to weeks 24 and 72 were compared between tirzepatide and placebo groups. Subgroup analyses were conducted based on participants' glycaemic status and body mass index at baseline. RESULTS: Mean baseline T2D predicted risk scores did not differ between tirzepatide and placebo groups (range: 22.9%-24.3%). At week 72, mean absolute T2D predicted risk score reductions were significantly greater in tirzepatide groups (5 mg, 12.4%; 10 mg, 14.4%; 15 mg, 14.7%) versus placebo (0.7%). At week 72, median relative predicted risk reductions following tirzepatide treatment ranged from 60.3% to 69.0%. For participants with and without prediabetes, risk reductions were significantly greater in tirzepatide groups versus placebo. At week 72, participants with prediabetes (range: 16.0%-20.3%) had greater mean risk score reductions from baseline versus those without prediabetes (range: 10.1%-11.3%). Across body mass index subgroups, mean reductions from baseline were significantly greater in tirzepatide groups versus placebo. CONCLUSION: Tirzepatide treatment significantly reduced the 10-year predicted risk of developing T2D compared with placebo in participants with obesity or overweight, regardless of baseline glycaemic status.

Role of comprehensive geriatric assessment in screening for mild cognitive disorders.

BACKGROUND: The role of comprehensive geriatric assessment (CGA) in screening for mild cognitive disorders was not known. AIM: To evaluate the role of CGA in screening for mild cognitive disorders. METHODS: A total of 100 elderly people who underwent health examinations in our hospital and community between January 2020 and December 2021 were included for analysis. Using Petersen as the diagnostic gold standard, healthy individuals were included in the control group and patients with mild cognitive impairment were assigned to the study group. The correlation between the cognitive function of the patients and their baseline clinical profiles was analyzed. Patients' Montreal Cognitive Assessment (MoCA) and CGA screening results were compared, and the sensitivity and specificity were calculated to assess the screening role of CGA. RESULTS: CGA assessment yielded higher diagnostic accuracy than MoCA. The results of the multivariate regression analysis showed no correlation of gender, age, body mass index and literacy with cognitive function. Patients with mild cognitive impairment obtained significantly lower MoCA scores than healthy individuals (P < 0.05). In the CGA scale, patients with mild cognitive impairment showed significantly lower Mini-mental State Examination, Miniature Nutritional Assessment and Berg Balance Scale scores, and higher Activity of Daily Living, Instrumental Activities of Daily Living Scale and Frailty Screening Inventory scores than healthy individuals (P < 0.05), whereas the other assessment scales showed no significant differences (P > 0.05). The CGA provides higher diagnostic sensitivity and specificity than the MoCA (P < 0.05). CONCLUSION: CGA allows accurate identification of mild cognitive impairment with high sensitivity and specificity, facilitating timely and effective intervention, and is thus recommended for clinical use.

Real-world primary nonadherence to antiobesity medications.

BACKGROUND: Primary nonadherence (PNA), when a medication is newly prescribed but not filled, has been identified as a major research gap potentially impacting the optimal treatment of patients with overweight and obesity who are newly prescribed antiobesity medications (AOMs). OBJECTIVES: To assess PNA among patients with newly prescribed AOMs and to examine factors associated with PNA to AOMs. METHODS: This was a retrospective study that used the Optum Integrated Clinical plus Claims database to identify individuals who had at least 1 prescription order for an AOM the US Food and Drug Administration approved for long-term use. Individuals with prescription orders between January 1, 2012, and February 28, 2019, were identified, and patient demographics, clinical characteristics, medication prescribed, baseline health care utilization, and obesity-related complications were described by PNA status. PNA was defined as no pharmacy claim for the AOM within 60 days of the date of the new prescription order as identified in electronic health record data. A multivariable logistic regression model was used to examine factors associated with PNA. RESULTS: The study sample included a total of 1,563 patients. The mean body mass index was 38.4 kg/m2; 10.7% were prescribed liraglutide 3.0 mg, 26.0% were prescribed lorcaserin, 36.3% of patients were prescribed naltrexone-bupropion, 5.4% were prescribed orlistat, and 21.6% were prescribed phentermine-topiramate. Most patients (91.1%) exhibited PNA, with only 8.9% filling their newly prescribed AOM within 60 days. Both the adherent and nonadherent groups were predominately female sex, White, and covered by commercial insurance. The mean age was similar between the 2 groups. Most obesity-related complications were less prevalent in the adherent group, although the Charlson comorbidity index score was similar between the 2 groups. After adjustment for patient demographics and clinical characteristics, there was not a statistically significant association between the specific AOM and PNA (P = 0.299). Patients with depression or living in the Midwest or South regions were at significantly increased risk of PNA. CONCLUSIONS: The rate of PNA to AOMs was very high, suggesting barriers in effective medical management of patients with overweight and obesity. Future research is warranted to understand reasons for PNA to AOMs and how to address these barriers. DISCLOSURES: Dr Kan, Dr Bae, Dr Dunn, and Dr Ahmad are employees of Eli Lilly and Company. Ms Buysman and Dr Gronroos are employees of Optum. Dr Swindle was an employee of Optum at the time the study was conducted and is currently employed at Evidera. Dr Bengtson is employed at Boehringer Ingelheim Pharmaceuticals, Inc. (Boehringer Ingelheim has no connection to this study), and during the conduct of this study was employed at Optum.

Recent advances in emerging application of functional materials in sample pretreatment methods for liquid chromatography-mass spectrometry analysis of plant growth regulators: A mini-review.

Plant growth regulators (PGRs) are a class of small molecular compounds, which can remarkably affect the physiological process of plants. The complex plant matrix along with a wide polarity range and unstable chemical properties of PGRs hinder their trace analysis. In order to obtain a reliable and accurate result, a sample pretreatment process must be carried out, including eliminating the interference of the matrix effect and pre-concentrating the analytes. In recent years, the research of functional materials in sample pretreatment has experienced rapid growth. This review comprehensively overviews recent development in functional materials covering one-dimensional materials, two-dimensional materials, and three-dimensional materials applied in the pretreatment of PGRs before liquid chromatography-mass spectrometry (LC-MS) analysis. Besides, the advantages and limitations of the above functionalized enrichment materials are discussed, and their future trends have been prospected. The work could be helpful to bring new insights for researchers engaged in functional materials in sample pretreatment of PGRs based on LC-MS.

Neuroprotective effect of total flavonoids in stems and leaves of Glycyrrhiza uralensis Fisch. on oxidative stress in HT-22 cells and Caenorhabditis elegans.

The Glycyrrhiza uralensis Fisch. is a common traditional Chinese medicine. However, its aerial part is currently not widely studied and used. Therefore, we aimed to investigate the neuroprotective effects of total flavonoids in aerial stems and leaves of Glycyrrhiza uralensis Fisch. (GSF) by an in vitro LPS-induced HT-22 cell model and an in vivo Caenorhabditis elegans (C. elegans) model. In this study, cell apoptosis was evaluated by CCK-8 and Hoechst 33258 staining in LPS-induced HT-22 cells. Meanwhile, ROS level, mitochondrial membrane potential (MMP), and Ca2+ level were detected by the flow cytometer. In vivo, C. elegans was also investigated the effect of GSF on lifespan, spawning, and paralysis. Moreover, the survival of C. elegans to oxidative stimuli (juglone and H2O2), and the nuclear translocation of DAF-16 and SKN-1 were evaluated. The results showed that GSF could inhibit LPS-induced HT-22 cell apoptosis. Moreover, GSF decreased the levels of ROS, MMP, Ca2+, and malondialdehyde (MDA) and increased the activities of SOD and CAT in HT-22 cells. Furthermore, GSF did not affect the lifespan and laying of eggs of C. elegans N2. However, it delayed paralysis in C. elegans CL4176 in a dose-dependent manner. Meanwhile, GSF increased the survival rate of C. elegans CL2006 after juglone and H2O2 treatment, increased SOD and CAT, and decreased MDA levels. Importantly, GSF promoted the nuclear translocation of DAF-16 and SKN-1 in C. elegans TG356 and LC333, respectively. Taken together, GSF can play a protective role in neuronal cells by inhibiting oxidative stress.

Tirzepatide 10 and 15 mg compared with semaglutide 2.4 mg for the treatment of obesity: An indirect treatment comparison.

AIM: To compare the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. MATERIALS AND METHODS: Using SURMOUNT-1 and STEP 1 trial data, mean percentage change in body weight from baseline and odds ratio (OR) of achieving 5% or greater weight loss were compared between tirzepatide 10 and 15 mg at week 72 and semaglutide 2.4 mg at week 68 using matching-adjusted indirect comparison of the efficacy estimand. Sensitivity analyses were completed using different methods, including the Bucher method, also using different estimands and/or time points. RESULTS: Greater reductions in percentage change in body weight were observed with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg (tirzepatide 10 mg mean difference: -4.67% [95% CI -5.91%, -3.43%]; tirzepatide 15 mg mean difference: -5.92% [95% CI -7.16%, -4.68%]; both P < .001). Similarly, more participants achieved 5% or greater weight loss with tirzepatide 10 mg (OR 2.61 [95% CI 1.48, 4.57]; P < .001) and 15 mg (OR 2.75 [95% CI 1.57, 4.81]; P < .001) compared with semaglutide 2.4 mg. All sensitivity analyses were consistent, except for an OR of achieving 5% or greater weight loss with tirzepatide 10 mg using the Bucher method to analyse the treatment regimen estimand (P = .074). CONCLUSIONS: Currently there are no direct comparisons of tirzepatide and semaglutide for weight management. Using the matching-adjusted indirect treatment comparison method to compare the efficacy of tirzepatide and semaglutide for chronic weight management, this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.

Identification of anti-inflammatory components in Panax ginseng of Sijunzi Decoction based on spectrum-effect relationship.

Objective: This study aimed to identify the main medicinal active components of Panax ginseng (P. ginseng) in the compatibility environment of clinical application. For this purpose, the anti-inflammatory ingredients of P. ginseng were investigated based on its therapeutic effect in Sijunzi Decoction (SJD) which is a widely used traditional Chinese formula. Methods: The fingerprints of 10 batches of SJD consisting of different sources of P. ginseng were established by UPLC technique to investigate the chemical components. At the same time, the anti-inflammatory effects of these components were evaluated by dextran sulfate sodium-induced ulcerative colitis mouse model. Grey relational analysis was applied to explore the correlation degree between fingerprints and anti-inflammatory effects in SJD. Lipopolysaccharide-stimulated RAW264.7 murine macrophages were established to evaluate the anti-inflammatory action of the screened effective substances of P. ginseng. Results: According to grey relational analysis, notoginsenoside R1, ginsenoside Rg2 and ginsenoside Rb3 of P. ginseng were the major anti-inflammatory contributions in SJD. They had been proven to be closely associated with the anti-inflammatory process of SJD and displayed a close effect compared with SJD by LPS-stimulated RAW264.7 murine macrophages. Conclusion: Our work provides a general strategy for exploring the pharmacological ingredients of P. ginseng in traditional Chinese formulas which is beneficial for establishing the quality standards of traditional herbs in traditional Chinese medicine prescription based on their clinical therapeutic effect.

General versus central adiposity as risk factors for cardiovascular-related outcomes in a high-risk population with type 2 diabetes: a post hoc analysis of the REWIND trial.

BACKGROUND: In clinical practice, anthropometric measures other than BMI are rarely assessed yet may be more predictive of cardiovascular (CV) risk. We analyzed the placebo group of the REWIND CV Outcomes Trial to compare several anthropometric measures as baseline risk factors for cardiovascular disease (CVD)-related outcomes in participants with type 2 diabetes (T2D). METHODS: Data from the REWIND trial placebo group (N = 4952) were analyzed. All participants had T2D, age ≥ 50 years, had either a previous CV event or CV risk factors, and a BMI of ≥ 23 kg/m2. Cox proportional hazard models were used to investigate if BMI, waist-to-hip ratio (WHR), and waist circumference (WC) were significant risk factors for major adverse CV events (MACE)-3, CVD-related mortality, all-cause mortality, and heart failure (HF) requiring hospitalization. Models were adjusted for age, sex, and additional baseline factors selected by LASSO method. Results are presented for one standard deviation increase of the respective anthropometric factor. RESULTS: Participants in the placebo group experienced 663 MACE-3 events, 346 CVD-related deaths, 592 all-cause deaths, and 226 events of HF requiring hospitalization during the median follow-up of 5.4 years. WHR and WC, but not BMI, were identified as independent risk factors of MACE-3 (hazard ratio [HR] for WHR: 1.11 [95% CI 1.03 to 1.21]; p = 0.009; HR for WC: 1.12 [95% CI 1.02 to 1.22]; p = 0.012). WC adjusted for hip circumference (HC) showed the strongest association with MACE-3 compared to WHR, WC, or BMI unadjusted for each other (HR: 1.26 [95% CI 1.09 to 1.46]; p = 0.002). Results for CVD-related mortality and all-cause mortality were similar. WC and BMI were risk factors for HF requiring hospitalization, but not WHR or WC adjusted for HC (HR for WC: 1.34 [95% CI 1.16 to 1.54]; p < 0.001; HR for BMI: 1.33 [95% CI 1.17 to 1.50]; p < 0.001). No significant interaction with sex was observed. CONCLUSIONS: In this post hoc analysis of the REWIND placebo group, WHR, WC and/or WC adjusted for HC were risk factors for MACE-3, CVD-related mortality, and all-cause mortality; while BMI was only a risk factor for HF requiring hospitalization. These findings indicate the need for anthropometric measures that consider body fat distribution when assessing CV risk.

Bilateral common carotid artery mycotic aneurysms in the setting of intravenous drug abuse.

Carotid mycotic aneurysms are rare, and fewer than five case reports have described carotid mycotic aneurysms due to intravenous drug abuse. Rare bilateral intracranial mycotic carotid aneurysms have been reported, although a review of literature revealed no cases of bilateral extracranial carotid aneurysms. We have reported the case of a 41-year-old man who had presented with intermittent fevers, headaches, and myalgias of 2 weeks' duration. He was found to have bilateral carotid artery mycotic aneurysms after intravenous drug abuse with neck injections. We used a management strategy entailing unilateral endovascular balloon control with open surgical resection followed by placement of a saphenous vein graft. The contralateral aneurysm was managed nonoperatively with antibiotics.