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Context Conflicting predictions of malnutrition for the long-term prognosis of coronary artery disease (CAD) exist. Objective This study aimed to investigate the relationship between malnutrition and long-term prognosis of patients with CAD. Data Sources Four databases were searched for articles from February 11, 1936, to September 10, 2022. Data Extraction Cohort studies adjusting for multiple cardiovascular risk factors with data on CAD and malnutrition were included. Malnutrition was measured and defined by different nutritional evaluation tools. The hazard ratios (HRs) and confidence intervals (CIs) for all-cause mortality and major adverse cardiovascular events (MACEs) were synthesized. Subgroup analyses were performed based on study design, assessment tools, ethnicity/race, follow-up, sample size, and types of CAD. Meta-regression was used to compare whether the effect sizes of the 2 subgroups were statistically significant. Data Analysis A total of 30 cohort studies were included, totaling 81 361 participants with CAD. Nutritional evaluation tools, including the Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status (CONUT), Nutritional Risk Screening 2002, Mini-Nutritional Assessment, and Prognostic Nutritional Index, were used. Malnutrition increased all-cause mortality (HR = 1.72; 95% CI: 1.53, 1.93) and MACEs (HR = 1.47; 95% CI: 1.35, 1.60) in patients with CAD. Subgroup analysis revealed the results were consistent across study design, ethnicity/race, follow-up, sample size, and types of CAD. Subgroup analyses and meta-regression revealed that malnutrition was associated with a higher risk of all-cause mortality (HR = 2.26; 95% CI: 1.91, 2.68) and MACEs (HR = 2.28; 95% CI: 1.69, 3.08) in patients with stable CAD than those with other types of CAD. Meta-regression revealed that the GNRI (HR = 2.20; 95% CI: 1.65, 2.93) was more effective than CONUT (HR = 1.47; 95% CI: 1.21, 1.78) in predicting all-cause mortality. Conclusion Malnutrition independently increased all-cause mortality by 72% and MACEs by 47% in patients with CAD, especially with stable CAD. The GNRI is a more effective nutritional evaluation tool than CONUT in predicting all-cause mortality. [ABSTRACT FROM AUTHOR]

Aims: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short‐term intensive insulin therapy (SIIT) during study run‐in (prior to randomization) using a basal‐first insulin titration method. Materials and methods: This was exclusively an exploratory analysis of the 7‐ to 10‐day run‐in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once‐daily insulin glargine and three‐times‐daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre‐meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2‐hour postprandial blood glucose (PBG) targets. Results: Overall, 397 entered the run‐in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2‐hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2‐hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2‐hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. Conclusions: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2‐3 oral antihyperglycaemic drugs (OADs) with twice‐daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short‐term intensive insulin therapy in adults with type 2 diabetes in China. Materials and Methods: This open‐label trial enrolled insulin‐naïve adults with type 2 diabetes and an HbA1c of 7.5%‐11.0% (58‐97 mmol/mol) despite treatment with 2‐3 OADs. All participants stopped previous OADs except MET, then received short‐term intensive insulin therapy during the run‐in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2‐hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase‐4 inhibitor or twice‐daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint). Results: There were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non‐inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of –1.72% and –1.70% (–42.2 and –42.1 mmol/mol), respectively (estimated difference –0.01%; 95% CI –0.20%, 0.17% [–0.1 mmol/mol; 95% CI –2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P =.003), symptomatic (19% vs. 31%; P =.007) or confirmed hypoglycaemia (18% vs. 33%; P <.001) was lower in the Gla + OADs group. Conclusions: Compared with Asp30 + MET, Gla + 2‐3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short‐term intensive insulin therapy. [ABSTRACT FROM AUTHOR]

Aim: To determine the safety of a higher starting dose of basal insulin in overweight/obese patients with type 2 diabetes (T2D). Materials and methods: This 16‐week, randomized, multicentre, open‐label trial enrolled adults with T2D (body mass index 25–40 kg/m2) and suboptimal glycaemic control (glycated haemoglobin [HbA1c] 7.5–11.0% [58–97 mmol/mol] and fasting plasma glucose [FPG] >9.0 mmol/L) with two to three oral anti‐hyperglycaemic drugs at 51 centres in China. Patients were randomized (1:1) to a higher (0.3 U/kg) or standard (0.2 U/kg) starting dose of insulin glargine 100 U/mL, which was then titrated to achieve a self‐monitored fasting blood glucose (FBG) of 4.4 to 5.6 mmol/L. The primary endpoint was the percentage of patients with ≥1 episode of overall confirmed hypoglycaemia (≤3.9 mmol/L or severe). Results: At the end of study (n = 866), 11.0% patients treated with the 0.3 U/kg starting insulin dose experienced overall confirmed hypoglycaemia versus 8.6% of patients treated with 0.2 U/kg (estimated difference 2.1%, 95% confidence interval − 1.68, 5.89). The proportions of patients with symptomatic (9.8% vs 7.0%; P = 0.128) and nocturnal hypoglycaemia (2.7% vs 1.2%; P = 0.102) were similar in the two groups. There were no events of severe hypoglycaemia or FBG <3.0 mmol/L during the 16‐week treatment, and achievement of HbA1c <7.0% (53 mmol/mol) (37.1% vs 37.1%) or FPG <5.6 mmol/L (15.9% vs 16.3%), <6.1 mmol/L (27.6% vs 26.1%), or < 7.0 mmol/L (48.8% vs 48.3%) without hypoglycaemia were comparable in the two groups. Moreover, the mean time was shorter (4.53, 3.95 and 2.74 weeks vs 5.51, 5.21 and 3.64 weeks) and number of titrations was lower (3.5, 3.0 and 2.0 vs 4.3, 4.0 and 2.8) to achieve self‐monitored FBG targets of <5.6, <6.1 and <7.0 mmol/L in the higher versus the standard insulin dose group (all P < 0.01). Conclusions: Among overweight/obese patients with T2D, a higher insulin starting dose was as safe as the standard starting dose, and self‐monitored FBG targets were achieved earlier with the higher versus the standard dose. [ABSTRACT FROM AUTHOR]

Premixed insulin is the most commonly used insulin in China. This trial compared the efficacy and safety of once-daily insulin glargine 100 U/mL (Gla-100) + oral antihyperglycemic drugs (OADs) and twice-daily insulin aspart 70/30 (Asp 30) + OAD in T2D patients. Chinese adults with T2D receiving stable doses of metformin and 1-2 OADs with HbA1c 7.5%-11.0% were enrolled and entered a 7-10 day SIT period in which they were treated with basal-bolus to achieve a fasting blood glucose (FBG) <7 mmol/L and 2-hour postprandial glucose (2hPG) <10 mmol/L. Patients were then randomized 1:1 to receive Gla-100 + OADs (n=192) or Asp 30 + OAD (n=192) for 24 weeks. Baseline characteristics were balanced across groups. Mean (SD) age was 54.2 (8.8) years, BMI was 26.0 (3.1) kg/m2, and duration of diabetes was 6.8 (3.0) years. At week 24, the least square mean (SE) change from baseline in HbA1c was -1.72% (0.07) and -1.70% (0.07) in the Gla-100 and Asp 30 groups, respectively (Table); group difference (-0.01%; 95% CI -0.20, 0.17) met the pre-specified non-inferiority criteria (upper bound 95% CI <0.4%). All hypoglycemia events were significantly lower in the Gla-100 group. In conclusion, compared with Asp 30 + OAD, Gla-100 + OAD showed similar efficacy but lower hypoglycemia risk in Chinese T2D patients. Disclosure: Y. Mu: Speaker's Bureau; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi-Aventis. J. Liu: Employee; Self; Sanofi China. X. Zhang: None. N. Cui: Employee; Self; Sanofi China. H. Yin: None. L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China. H. Wan: None. J. Wang: None. B. Xu: None. G. Wang: None. C. Jiang: None. L. Liang: None. W. Feng: Employee; Self; Sanofi China. Funding: Sanofi China (NCT03359837) [ABSTRACT FROM AUTHOR]

To titrate basal and bolus insulin sequentially or simultaneously during SIT remains controversial. Here we report an easy titration order verified in a 7-10 day SIT period. Insulin naïve Chinese T2D adults receiving stable doses of metformin and 1-2 oral antihyperglycemic drugs with HbA1c 7.5%-11.0% were treated with once-daily insulin glargine 100 U/mL (Gla-100) and thrice-daily insulin glulisine (Glu) for 7-10 days titrated to achieve a fasting blood glucose (FBG) <7 mmol/L and 2-hour postprandial glucose (2hPG) <10 mmol/L. Gla-100 was titrated first until FBG achieved 4.4-6.1 mmol/L, then Glu was titrated to achieve pre-meal blood glucose 4.4-6.1 mmol/L. Of 466 patients screened, 397 entered the SIT period; 391 (98.5%) completed. Baseline mean (SD) age was 54.2 (8.8) years, duration of disease was 6.8 (3.0) years, BMI was 26.0 (3.2) kg/m2, HbA1c was 9.1% (1.1), and FBG was 10.7 (2.5) mmol/L; 59.2% were male. Overall, 94.4% of patients achieved the predefined target at the end of the SIT period (Table). The mean time to first achieving 2hPG target was less than the time to first achieving FBG target, implying that titrating basal insulin first could minimize Glu dose increases and potential hypoglycemia risk. In conclusion, when starting basal-bolus regimen in SIT, basal-first titration order was effective, fast to target and well tolerated in Chinese T2D patients. Disclosure: L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China. J. Liu: Employee; Self; Sanofi China. X. Zhang: None. N. Cui: Employee; Self; Sanofi China. H. Yin: None. Y. Mu: Speaker's Bureau; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi-Aventis. H. Wan: None. J. Wang: None. B. Xu: None. G. Wang: None. C. Jiang: None. L. Liang: None. W. Feng: Employee; Self; Sanofi China. Funding: Sanofi China (NCT03359837) [ABSTRACT FROM AUTHOR]

With type 2 diabetes (T2D) progression, patients require insulin, but insufficient titration often leads to poor glycemic control. A higher insulin starting dose may reduce the optimal dose deficit, but whether this procedure increases hypoglycemia risk is unknown. This open-label, multicenter trial (NCT02836704) evaluated safety and efficacy of a high (0.3 U/kg) vs. standard (0.2 U/kg) starting dose of glargine 100 U/ml (Gla-100) followed by titration over 16 weeks to achieve self-monitored FBG 4.4-5.6 mmol/L using the same algorithm in each group. Overall, 892 patients with overweight/obesity (BMI 25-40 kg/m2) and uncontrolled T2D (HbA1c 7.5-11.0%; lab FPG >9.0 mmol/L) on stable doses of 2-3 OADs were randomized to receive a high (n=444) or standard (n=448) starting dose of Gla-100. At week 16, 92% of patients completed the study and 866 were analyzed. The primary endpoint (percentage of patients with ≥1 confirmed hypoglycemia, BG <3.9 mmol/L) met the pre-specified threshold (upper bound 95% CI <10%) for non-inferiority of Gla-100 0.3 U/kg vs. 0.2 U/kg with 11.0% and 8.6% in the respective groups (log-binomial regression estimated difference 2.1%; 95% CI: −1.68%, 5.89%). At week 16, symptomatic (9.8% vs. 7.0%, p=0.13) and nocturnal hypoglycemia (2.7% vs. 1.2%, p=0.10), percentage of patients achieving HbA1c <7.0% without hypoglycemia (37.1% vs. 37.1%), and percentage of patients achieving lab FPG targets <5.6 mmol/L (15.9% vs. 16.3%), <6.1 mmol/L (27.6% vs. 26.1%), or <7.0 mmol/L (48.8% vs. 48.3%) were all similar in both groups. However, time to achieve first self-monitored FBG <5.6, <6.1, or <7 mmol/L was 6, 9, and 7 days shorter in the 0.3 U/kg group (all p<0.01). In conclusion, among patients with overweight/obesity and T2D, a higher Gla-100 starting dose was as safe as a standard Gla-100 starting dose and achieved FBG targets earlier during the course of therapy. Disclosure: L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi. H. Wan: None. B. Wen: None. X. Wang: None. J. Wang: Research Support; Self; Sanofi. R. Bian: None. W. Pang: None. W. Feng: Employee; Self; Sanofi. X. Zhang: None. N. Cui: Employee; Self; Sanofi. Funding: Sanofi China [ABSTRACT FROM AUTHOR]

Introduction: Linear-array endoscopic ultrasound (EUS) and narrow-band imaging (NBI) are both used to estimate the invasion depth of nonpedunculated rectal lesions (NPRLs). However, it is unclear which procedure is more accurate. This randomized controlled trial aimed to compare the diagnostic accuracy of linear EUS and NBI for estimating the invasion depth of NPRLs., Methods: This study is a single-center, randomized, tandem trial. Eligible patients with NPRLs were randomly assigned to A group (assessment with EUS followed by NBI) or B group (assessment with NBI followed by EUS). The invasion depth of each lesion was independently measured by each procedure and categorized as mucosal to slight submucosal (M-SM s , invasion depth <1,000 μm) or deep submucosal (SM d , invasion depth ≥1,000 μm) invasion, with postoperative pathology as the standard of measurement. The primary outcome was diagnostic accuracy, and secondary outcomes included sensitivity, specificity, and procedure time., Results: Eighty-six patients with NPRLs were enrolled, and 79 patients were finally analyzed, including 39 cases in the A group and 40 cases in the B group. Comparable diagnostic accuracies were observed between EUS and NBI (96.2% vs 93.7%, P = 0.625). EUS identified lesions with deep submucosal invasion with 81.8% sensitivity while that of NBI was 63.6% ( P = 0.500). The specificity of both EUS and NBI was 98.5%. The procedure time was also similar between EUS and NBI (5.90 ± 3.44 vs 6.4 ± 3.94 minutes, P = 0.450). Furthermore, the combined use of EUS and NBI did not improve diagnostic accuracy compared with EUS or NBI alone (94.9% vs 96.2% vs 93.7%, P = 0.333)., Discussion: Linear EUS and NBI measure the invasion depth of NPRLs with comparable accuracy. The combination of the 2 methods does not improve the diagnostic accuracy. Single NBI should be preferred, considering its simplicity and convenience in clinical practice., (Copyright © 2024 by The American College of Gastroenterology.)

Molecular imaging of inflammatory mediators in atria may contribute to thrombotic risk assessment of atrial fibrillation (AF). We investigated the feasibility of ultrasound molecular imaging (UMI) targeted to P-selectin to assess thrombotic risk in AF. Rat AF models were established with rapid atrial pacing. Microbubbles targeted to P-selectin were injected into the rats, followed by left atrial (LA) UMI examination. Furthermore, P-selectin, platelets (PLTs), fibrin and tissue factor (TF) of LA were detected by histopathology and scanning electron microscopy. Plasma levels of P-selectin, thrombin-antithrombin complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2) were measured by enzyme-linked immunosorbent assay. The data showed that P-selectin in LA was correlated with PLT, fibrin and TF ( r  = 0.735, p  < 0.05; r  = 0.827, p  < 0.05; r  = 0.785, p  < 0.05, respectively). The plasma level of P-selectin was correlated with the expression of TAT and F1 + 2 ( r  = 0.866, p  < 0.05; r  = 0.916, p  < 0.05, respectively). The contrast video intensity of adhered microbubbles targeted to P-selectin was correlated with the levels of P-selectin, PLT and fibrin in LA ( r  = 0.768, p  < 0.05; r  = 0.798, p  < 0.05; r  = 0.745, p  < 0.05, respectively). In conclusion, P-selectin may serve as a biomarker for thrombotic risk in AF and can be quantified by UMI to assess thrombotic risk., Competing Interests: None., (Schattauer GmbH Stuttgart.)

Objective: Ultrasound molecular imaging (UMI) of glycoprotein (GP) IIb/IIIa receptor on activated platelets offers a unique means of identifying high-risk atherosclerosis. We hypothesized that contrast-enhanced ultrasound with microbubbles (MBs) targeted to GP IIb/IIIa could be used to detect and quantify activated platelets on the surface of advanced plaques., Methods and Results: A mouse model of advanced atherosclerosis was generated by maintaining apolipoprotein E-deficient (ApoE(-/-)) mice on a hypercholesterolemic diet (HCD). The three other experimental groups consisted of ApoE(-/-) and wild-type (C57BL/6) mice fed a normal chow diet and C57BL/6 mice on an HCD diet. Plaque formation was confirmed by histological and immunohistochemical methods using light, fluorescence, and electron microscopy. Mice were injected with a lipid MB-conjugated cyclic Arg-Gly-Asp peptide or nonspecific control peptide, and the abdominal aorta was examined by UMI. The accumulation of GP IIb/IIIa and activated platelets on the surface of atherosclerotic plaques was highest in the ApoE(-/-)+HCD group, followed by ApoE(-/-)+chow, C57BL/6+HCD, and C57BL/6+chow groups (P<0.05). Notably, GP IIb/IIIa expression was associated with the vulnerability index and necrotic center/fiber cap ratio (P<0.05), and contrast video intensity from adhered cyclic Arg-Gly-Asp-modified MBs (MB-cRGDs) was correlated with GP IIb/IIIa expression on the plaque surface (P<0.05)., Conclusion: GP IIb/IIIa of activated platelets on the atherosclerotic endothelium is a biomarker for high-risk plaques that can be quantified by UMI using MB-cRGDs, providing a noninvasive means for detecting high-risk plaques and preventing acute cardiovascular events.