To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, ...we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions.
In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance.
Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40–64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt.
We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide.
World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research.
Nonalcoholic steatohepatitis (NASH) is an advanced nonalcoholic fatty liver disease characterized by chronic inflammation and fibrosis. A dysbiosis of the gut microbiota has been associated with the ...pathophysiology of NASH, and probiotics have proven helpful in its treatment and prevention. Although both traditional and next-generation probiotics have the potential to alleviate various diseases, studies that observe the therapeutic effect of next-generation probiotics on NASH are lacking. Therefore, we investigated whether a next-generation probiotic candidate,
, contributed to the mitigation of NASH.
In this study, we conducted 16S rRNA sequencing analyses in patients with NASH and healthy controls. To test
could alleviate NASH symptoms, we isolated four
strains (EB-FPDK3, EB-FPDK9, EB-FPDK11, and EB-FPYYK1) from fecal samples collected from four healthy individuals. Mice were maintained on a high-fructose high-fat diet for 16 weeks to induce a NASH model and received oral administration of the bacterial strains. Changes in characteristic NASH phenotypes were assessed via oral glucose tolerance tests, biochemical assays, and histological analyses.
16S rRNA sequencing analyses confirmed that the relative abundance of
reduced significantly in patients with NASH compared to healthy controls (
< 0.05). In the NASH mice,
supplementation improved glucose homeostasis, prevented hepatic lipid accumulation, curbed liver damage and fibrosis, restored damaged gut barrier functions, and alleviated hepatic steatosis and liver inflammation. Furthermore, real-time PCR assays documented that the four
strains regulated the expression of genes related to hepatic steatosis in these mice.
Our study, therefore, confirms that the administration of
bacteria can alleviate NASH symptoms. We propose that
has the potential to contribute to the next-generation probiotic treatment of NASH.
We synthetized and investigated the anti-leukemic potential of the novel cytostatic bis(4-hydroxycoumarin) derivative OT-55 which complied with the Lipinski's rule of 5 and induced differential ...toxicity in various chronic myeloid leukemia (CML) cell models. OT-55 triggered ER stress leading to canonical, caspase-dependent apoptosis and release of danger associated molecular patterns. Consequently, OT-55 promoted phagocytosis of OT-55-treated CML cells by both murine and human monocyte-derived macrophages. Moreover, OT-55 inhibited tumor necrosis factor α-induced activation of nuclear factor-кB and produced synergistic effects when used in combination with imatinib to inhibit colony formation in vitro and Bcr-Abl+ patient blast xenograft growth in zebrafish. Furthermore, OT-55 synergized with omacetaxine in imatinib-resistant KBM-5 R cells to inhibit the expression of Mcl-1, triggering apoptosis. In imatinib-resistant K562 R cells, OT-55 triggered necrosis and blocked tumor formation in zebrafish in combination with omacetaxine.
•OT-55 inhibits cell proliferation and viability in CML.•OT-55 induces ER stress, ecto-CRT, ecto-ERp57, ATP and HMGB1 elease leading to immunogenic cell death.•OT-55-treated CML cells are phagocytosed by macrophages.•OT-55 synergizes with imatinib in CML.•OT-55 synergizes with Synribo in Bcr-Abl mutated CML.
Abstract
Background
Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is ...lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery.
Methods
This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery.
Discussion
This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs.
Trial registration
The Clinical Research Information Service
KCT0006279
for RCT and
KCT0006280
for prospective cohort study. Registered on June 21, 2021.
The lithium-air battery is a new type of secondary battery technology that is currently receiving a lot of attention in the field of power storage technology. These batteries are known to offer high ...energy densities and potentially longer driving ranges. In this study, NiCo2O4 and CNTs were used to create a composite for use as the cathode of a Li-air battery. Improving the 3D needl-like structure that provides extensive transport channels for electrolyte infiltration and numerous sites facilitated charge transfer reactions and the synergistic effect of highly electrocatalytic NiCo2O4 with pronounced activity and high conductive CNTs, with the synthesized NiCo2O4@CNTs composites exhibiting active catalytic performance for both OER and ORR reactions. It also showed improved cycle performance at high current densities. NiCo2O4@CNTs composites were successfully fabricated using a hydrothermal method together with a sequential annealing treatment. The components of the completed composite were confirmed using TGA, XRD, and SEM, and the specific surface area was analyzed using BET. The composite was performed for over 120 cycles at a current density of 200 mA∙g−1, and 500 mA∙g−1 was achieved under the capacity limiting condition of 500 mAh∙g−1. The charging/discharging characteristics were compared under various current densities, exhibiting stable cyclability. The high catalytic activity of NiCo2O4 oxide supports its potential use as a cathode in Li-air batteries.
Depression is common after acute coronary syndrome (ACS) and has adverse effects on prognosis. There are few evidence-based interventions for treating depression in ACS. This study investigated the ...efficacy and safety of escitalopram in treating depressive disorders identified 2-14 weeks after a confirmed ACS episode.
A total of 217 patients with DSM-IV depressive disorders (121 major and 96 minor) and ACS were randomly assigned to receive escitalopram in flexible doses of 5-20 mg/d (n = 108) or placebo (n = 109) for 24 weeks. The study was conducted from 2007 to 2013. The primary outcome measure was the Hamilton Depression Rating Scale (HDRS). Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), Clinical Global Impressions-Severity of Illness scale (CGI-S), Social and Occupational Functioning Assessment Scale (SOFAS), and World Health Organization Disability Assessment Schedule-12. Cardiovascular safety outcomes included echocardiography, electrocardiography, laboratory test, body weight, and blood pressure results.
Escitalopram was superior to placebo in reducing HDRS scores (mean difference = 2.3, P = .016, effect size = 0.38). Escitalopram was also superior to placebo in decreasing depressive symptoms evaluated by the MADRS, BDI, and CGI-S and in improving SOFAS functioning level. Escitalopram was not associated with any harmful changes in cardiovascular safety measures. Dizziness was significantly more frequently reported in the escitalopram group (P = .018), but there were no significant differences in any other adverse events.
These results indicate that escitalopram has clinically meaningful antidepressant effects with no evidence of reduced cardiovascular safety in depressive disorder following ACS.
ClinicalTrials.gov identifier: NCT00419471.
Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, ...UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.
Advanced esophageal cancer is known to have a poor prognosis. The early detection of esophageal neoplasms, including esophageal dysplasia and early esophageal cancer, is highly important for the ...accurate treatment of the disease. However, esophageal dysplasia and early esophageal cancer are usually subtle and can be easily missed. In addition to the early detection, proper pretreatment evaluation of the depth of invasion of esophageal cancer is very important for curative treatment. The progression of non-invasive diagnosis via image-enhanced endoscopy techniques has been shown to aid the early detection and estimate the depth of invasion of early esophageal cancer and, as a result, may provide additional opportunities for curative treatment. Here, we review the advancement of image-enhanced endoscopy-related technologies and their role in the early identification of esophageal neoplasms.
The aim of this study was to evaluate the safety and efficacy of combination treatment of rosuvastatin with ezetimibe in patients with primary hypercholesterolemia.
This multicenter, randomized, ...double-blind study comprised a main study and an extension study. In the main study, the efficacy and safety of a combination of rosuvastatin (5, 10, and 20 mg) with ezetimibe (10 mg) were compared with those of rosuvastatin (5, 10, and 20 mg) alone. The subjects who achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the main study and agreed to a further study were enrolled for the extension study. In the extension study, ezetimibe 10 mg was also administered to subjects who had received rosuvastatin (5, 10, and 20 mg) alone in the main study, and the same treatment was continued for subjects who had received a combination of rosuvastatin with ezetimibe in the main study.
At the end of the main study (week 8), LDL-C levels were significantly lower in subjects receiving combination therapy than in those receiving rosuvastatin monotherapy. Other lipid profiles also significantly improved in the combination therapy group. These improvements continued in the extension study. The combination therapy of rosuvastatin and ezetimibe was generally well tolerated. At the end of the main study, more subjects achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the combination therapy group than in the monotherapy group. The increased dosage of rosuvastatin was also well tolerated in the combination treatment.
Combination therapy of ezetimibe 10 mg with varying doses of rosuvastatin that are commonly used in the clinical field improved the lipid profile and allowed more subjects to reach the LDL-C goal in primary hypercholesterolemia compared with rosuvastatin monotherapy. In addition, the efficacy of the combination therapy was maintained for the extended period. Additional beneficial changes were also achieved with combination therapy even in patients who responded well to rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT03288038.
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