Search

AimsStudies have indicated inconsistent results regarding the association between plasma levels of Lipoprotein(a) [Lp(a)] and coronary artery calcification (CAC). We performed a systematic review and meta-analysis to investigate the association between elevated levels of Lp(a) and risk of CAC in populations free of cardiovascular disease (CVD) symptoms.Data synthesisPubMed, Web of Science, Embase, and Scopus were searched up to July 2022 and the methodological quality was assessed using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratio (OR) and 95% confidence interval. Out of 298 studies, data from 8 cross-sectional (n = 18,668) and 4 cohort (n = 15,355) studies were used in meta-analysis. Cohort studies demonstrated a positive significant association between Lp(a) and CAC, so that individuals with Lp(a)≥30-50 exposed to about 60% risk of CAC incidence compared to those with lower Lp(a) concentrations in asymptomatic CVD subjects (OR, 1.58; 95% CI, 1.38-1.80; l2, 0.0%; P, 0.483); Subgroup analysis showed that a cut-off level for Lp(a) measurement could not statistically affect the association, but race significantly affected the relationship between Lp(a) and CAC (OR,1.60; 95% CI, 1.41-1.81). Analyses also revealed that both men and women with higher Lp(a) concentrations are at the same risk for increased CAC.ConclusionsBlood Lp(a) level was significantly associated with CAC incidence in asymptomatic populations with CVD, indicating that measuring Lp(a) may be a useful biomarker for diagnosing subclinical atherosclerosis in individuals at higher risk of CAC score.Prospero registration numberCRD42022350297.

Aim: The association of overweight/obesity and metabolic dysfunction‐associated steatotic liver disease (MASLD) in young adulthood with subclinical atherosclerosis [coronary artery calcification (CAC) and abdominal aortic calcification (AAC)] by middle age is unknown. Method: In total, 2274 participants aged 28‐39 years from the coronary artery risk development in young adults study at year 10 (1995‐1996) who were re‐examined 15 years later were included. CAC and AAC were measured at year 25 using computed tomography. We examined the utility of three young adult phenotypes (lean group; overweight/obese group; overweight/obese MASLD group) at year 10 in predicting CAC or AAC by middle age. Modified Poisson regression was used to estimate the association between groups and CAC, and AAC. Independent determinates of CAC and AAC were determined with linear regression models. Results: Compared with individuals categorized as lean in young adulthood, the relative risk for CAC by middle age was 1.09 (95% confidence interval: 0.93‐1.28) for those with overweight/obesity and 1.32 (95% confidence interval: 1.08‐1.61) for those with overweight/obesity‐related MASLD. For AAC, no difference was observed between these three groups. Group, systolic blood pressure and group × systolic blood pressure interaction were all the independent determinates for CAC. Conclusion: In this study, young adults with overweight/obesity‐related MASLD have a higher risk of developing CAC by middle age. These abnormalities are only partially explained by traditional cardiovascular risk factors, and overweight/obesity‐related MASLD has an independent impact on CAC. Our study provides evidence for identifying young adults at higher risk of developing subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]

The mucosal barrier is crucial for intestinal homeostasis, and goblet cells are essential for maintaining the mucosal barrier integrity. The proviral integration site for Moloney murine leukemia virus-1 (PIM1) kinase regulates multiple cellular functions, but its role in intestinal homeostasis during colitis is unknown. Here, we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models, in the presence of intestinal microbiota. Epithelial PIM1 leads to decreased goblet cells, thus impairing resistance to colitis and colitis-associated colorectal cancer (CAC) in mice. Mechanistically, PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling pathways. Interestingly, PIM1 interacts with histone deacetylase 2 (HDAC2) and downregulates its level via phosphorylation, thereby altering the epigenetic profiles of Wnt signaling pathway genes. Collectively, these findings investigate the unknown function of the PIM1–HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis, which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC. PIM1 is upregulated in colonic epithelia during colitis. PIM1 modulates intestinal homeostasis through Wnt and Notch signaling pathways, partially mediated by its binding, phosphorylating, and downregulating of HDAC2. [Display omitted] [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-associated cachexia (CAC) is a serious condition wherein people with cancer lose muscle and fat, even with proper nutrition. It leads to weakness and can make treatment less effective. This review looks at how the body's immune system and certain proteins affect CAC. Studies show that specific proteins, like IL-6 and TNF-α, play a crucial role in causing muscle and fat loss. Other cells in the immune system, called MDSCs, make CAC worse by causing inflammation. Clinical studies also found high levels of certain proteins in people with CAC. Understanding these processes might improve treatments, especially for those undergoing immunotherapy. A new drug called R-ketorolac has shown promise in reversing weight loss in animals. Combining drugs like this with immunotherapy could help patients with cancer suffering from CAC. However, more research is needed to fully understand how immune problems and CAC interact during treatment. Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, that is unresponsive to nutritional support and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like the neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed the weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy. [ABSTRACT FROM AUTHOR]

Personalizing risk assessment and treatment decisions for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) rely on pooled cohort equations and increasingly coronary artery calcium (CAC) score. A growing body of evidence supports that elevated CAC scores correspond to progressively elevated ASCVD risk, and that scores of ≥100, ≥300, and ≥1000 denote risk that is equivalent to certain secondary prevention populations. This has led consensus guidelines to incorporate CAC score thresholds for guiding escalation of preventive therapy for lowering low-density lipoprotein cholesterol goals, initiation of non-statin lipid lowering medications, and use of low-dose daily aspirin. As data on CAC continues to grow, more decision pathways will incorporate CAC score cutoffs to guide management of blood pressure and cardiometabolic medications. CAC score is also being used to enrich clinical trial study populations for elevated ASCVD risk, and to screen for subclinical coronary atherosclerosis in patients who received chest imaging for other diagnostic purposes. [ABSTRACT FROM AUTHOR]

• Among 762 patients with LDL-C≥190 mg/dL without a history of ASCVD or heart failure, coronary artery calcification (CAC), and thoracic aortic calcification (TAC) scores were associated with increased rates of HF hospitalizations. However, only CAC demonstrated an independent association with HF hospitalizations. • EAT, and NAFLD are known cardiometabolic risk factors but were not associated with increased HF hospitalizations in this cohort. • Adding ordinal CAC score to traditional risk factors improved risk stratification for HF hospitalizations. • Given the number of non-cardiac chest CT scans performed in clinical practice, this could represent an opportunity to capitalize on risk information. Coronary artery calcium (CAC), thoracic aorta calcification (TAC), non-alcoholic fatty liver disease (NAFLD), and epicardial adipose tissue (EAT) are associated with atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). We aimed to determine whether these cardiometabolic and atherosclerotic risk factors identified by non-contrast chest computed tomography (CT) are associated with HF hospitalizations in patients with LDL-C≥ 190 mg/dL. We conducted a retrospective cohort analysis of patients with LDL-C ≥190 mg/dL, aged ≥40 years without established ASCVD or HF, who had a non-contrast chest CT within 3 years of LDL-C measurement. Ordinal CAC, ordinal TAC, EAT, and NAFLD were measured. Kaplan-Meier curves and multivariable Cox regression models were built to ascertain the association with HF hospitalization. We included 762 patients with median age 60 (53–68) years, 68% (n=520) female, and median LDL-C level of 203 (194–216) mg/dL. Patients were followed for 4.7 (interquartile range 2.75–6.16) years, and 107 (14%) had a HF hospitalization. Overall, 355 (47%) patients had CAC=0, 210 (28%) had TAC=0, 116 (15%) had NAFLD, and median EAT was 79 mL (49-114). Moderate-Severe CAC (log-rank p <0.001) and TAC (log-rank p=0.006) groups were associated with increased HF hospitalizations. This association persisted when considering myocardial infarction (MI) as a competing risk. NAFLD and EAT volume were not associated with HF. In patients without established ASCVD and LDL-C≥190 mg/dL, CAC was independently associated with increased HF hospitalizations while TAC, NAFLD, and EAT were not. Association of cardiometabolic and atherosclerotic markers on non-contrast Chest CT with Heart Failure Hospitalization in Patients with Severe Hypercholesterolemia. * Unadjusted Hazard Ratio for the moderate-to-severe category. ASCVD: atherosclerotic cardiovascular disease, CAC: coronary artery calcification. HF: heart failure, LDL-C: low-density lipoprotein cholesterol, NAFLD: non-alcoholic fatty liver disease, TAC: thoracic aorta calcification. [Display omitted] [ABSTRACT FROM AUTHOR]

BackgroundCoronary artery calcification (CAC) is a potential risk marker of coronary atherosclerosis that has high specificity and sensitivity. However, the association between high-density lipoprotein cholesterol (HDL-C) concentration and CAC incidence and progression is controversial.MethodsPubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies up to March 2023 and assessed the methodological quality using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratios (OR) and 95% confidence interval considering heterogeneity across studies.ResultsOf the 2,411 records, 25 cross-sectional (n = 71,190) and 13 cohort (n = 25,442) studies were included in the systematic review. Ten cross-sectional and eight cohort studies were not eligible and were omitted from the meta-analysis. A total of 15 eligible cross-sectional studies (n = 33,913) were included in the meta-analysis and pooled results revealed no significant association between HDL-C and CAC > 0, CAC > 10, or CAC > 100 [pooled OR: 0.99 (0.97, 1.01)]. Meta-analysis of the 5 eligible prospective cohort studies (n = 10,721) revealed no significant protective effect of high HDL-C against CAC > 0 [pooled OR: 1.02 (0.93, 1.13)].ConclusionsAccording to this analysis of observational studies, high HDL-C levels were not found to predict protection against CAC. These results suggest HDL quality rather than HDL quantity is important for certain aspects of atherogenesis and CAC.Registration numberCRD42021292077.

Abstract Background While coronary artery calcification (CAC) is recognized as a reliable marker for coronary atherosclerosis, the relationship between the concentration of C-reactive protein (CRP) and the incidence and progression of CAC remains controversial. Method PubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies until October 2023. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was employed to calculate pooled odd ratios (OR) and corresponding 95% confidence intervals, considering heterogeneity among the studies. Results Out of the 2545 records, 42 cross-sectional and 9 cohort studies were included in the systematic review. The meta-analysis on 12 eligible cross-sectional studies revealed no significant association between CAC and CRP [pooled OR: 1.03 (1.00, 1.06)]. Additionally, an insignificant association was found between CAC and CRP through meta-analysis on three eligible cohort studies [pooled OR: 1.05 (0.95, 1.15)] with no considerable heterogeneity across studies. Sensitivity analyses indicated that the meta-analysis models were robust. There was no evidence of publication bias. Conclusion Based on the meta-analysis findings, elevated levels of CRP did not emerge as a valuable prognostic maker for CAC incidence and progression prediction.

Abstract An early diagnosis of atherosclerosis, particularly in subclinical status, can play a remarkable role in reducing mortality and morbidity. Because of coronary artery calcification (CAC) nature in radiation exposure, finding biomarkers associated with CAC could be useful in identifying individuals at high risk of CAC score. In this review, we focused on the association of cardiac troponins (hs-cTns) and CAC to achieve insight into the pathophysiology of CAC. In October 2022, we systematically searched Web of Science, Scopus, PubMed, and Embase databases to find human observational studies which have investigated the association of CAC with cardiac troponins. To appraise the included articles, we used the Newcastle Ottawa scale (NOS). Out of 520 records, 10 eligible studies were included. Based on findings from longitudinal studies and cross-sectional analyses, troponin T and I were correlated with occurrence of CAC and its severity. Two of the most important risk factors that affect the correlation between hs-cTns serum levels and CAC were age and gender. The elevation of cardiac troponins may affect the progression of CAC and future cardiovascular diseases. Verifying the association between cardiac troponins and CAC may lead to identify individuals exposed to enhanced risk of cardiovascular disease (CVD) complications and could establish innovative targets for pharmacological therapy.

Background and aimsWe aimed to determine the utility of coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk stratification in women with and without early menopause (EM).MethodsTo examine the association between CAC and incident ASCVD, we performed Kaplan-Meier survival analysis and multivariable Cox proportional hazards modeling using data from 2,456 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA) with or without EM, defined as occurring at 50% of middle-aged postmenopausal women with EM had CAC = 0, similar to those without EM. Among women with CAC = 0, those with EM had a low to borderline 10-year risk of ASCVD, but the 15-year risk was significantly higher for women with EM versus those without EM. When CAC ≥ 1, the incidence of ASCVD was similar for women with and without EM. These findings support the use of CAC to help improve ASCVD risk stratification in women with EM.Condensed abstractThis study investigated the association between coronary artery calcium (CAC) and incident atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women with and without early menopause (EM). We found that >50% of women had CAC = 0 and an associated low-to-borderline 10-year cumulative incidence of ASCVD. However, the risk for ASCVD was significantly higher for women with EM after 15-years follow-up. Additional research is needed to better understand the differences in long-term ASCVD risk between women with and without EM who have CAC = 0.

The quality of teamwork in Child Advocacy Center (CAC) multidisciplinary teams is likely to affect the extent to which the CAC model improves outcomes for children and families. This study examines associations between team functioning and performance in a statewide sample of CAC teams. Multidisciplinary team members (N = 433) from 21 CACs completed measures of affective, behavioral, and cognitive team functioning. Team performance was assessed with three measures: team member ratings of overall performance, ratings of mental health screening/referral frequency, and caregiver satisfaction surveys. Linear mixed models and regression analyses tested associations between team functioning and performance. Affective team functioning (i.e., liking, trust, and respect; psychological safety) and cognitive team functioning (i.e., clear direction) were significantly associated with team members' ratings of overall performance. Behavioral team functioning (i.e., coordination) and cognitive team functioning were significantly associated with mental health screening/referral frequency. Team functioning was not associated with caregiver satisfaction with CAC services. Aspects of team functioning were associated with team members' perceptions of overall performance and mental health screening/referral frequency, but not caregiver satisfaction. Understanding associations between team functioning and performance in multidisciplinary teams can inform efforts to improve service quality in CACs and other team-based service settings. [ABSTRACT FROM AUTHOR]

A sufficient green strength of refractory castables is necessary to avoid damage during demoulding and heating up of refractory linings and prefabricated parts. However, there is a lack of knowledge on the mechanisms underlying the build-up of green strength in refractory castables. This work focuses on how green strength is formed within the matrix of PCE-dispersed and CA cement bonded refractory castables during their setting.Setting was monitored using several measuring methods, such as sonic velocity, amount of hydrate phases formed from CA cement, ζ-potential (stability resp. coagulation of the matrix suspension), porosity, and specific surface area and was linked to the corresponding increase of green strength of refractory castables during setting.Considered by time after adding water, the first stiffening of the refractory castables is related to the collapse of the rheological system of their matrix suspension (coagulation), resulting in a very low increase in green strength (apparent hardening). This stiffening occurs early if Ca-precipitates are formed together with molecules of the dispersing agent (Ca-PCE, PCE with short side chains) or if the amount of pore water is being reduced below a critical value (rheologically stable matrix due to dispersion of hydrate phases by PCE with long side chains). The major increase in green strength occurs when a significant amount of CA cement reacts to hydrate phases and, correspondingly, water is being bonded. This main increase in green strength may occur directly after stiffening (if CA cement is being hydrated quickly) or several hours after stiffening (if the hydration of CA cement is retarded).Regarding the green strength, the predominant factor influencing the build-up of green strength in refractory castables is the reduction of free water in the pores due to its bond in hydrate phases (reduction of a lubricating, interparticle water film). Minor influences are the reduction in porosity (volume expansion by hydration of CA cement), the increase in the specific surface area (hydrate phases are finer than the initial CA cement particles), and the entanglement of plate-like hydrate phases.

Risk for atherosclerotic cardiovascular disease (ASCVD) shows considerable heterogeneity both in generally healthy persons and in those with known ASCVD. The foundation of preventive cardiology begins with assessing baseline ASCVD risk using global risk scores based on standard office-based measures. Persons at low risk are generally recommended for lifestyle management only and those at highest risk are recommended for both lifestyle and pharmacologic therapy. Additional "risk enhancing" factors, including both traditional risk factors and novel biomarkers and inflammatory factors can be used to further assess ASCVD risk, especially in those at borderline or intermediate risk. There are also female-specific risk enhancers, social determinants of health, and considerations for high-risk ethnic groups. Screening for subclinical atherosclerosis, especially with the use of coronary calcium screening, can further inform the treatment decision if uncertain based on the above strategies. Persons with pre-existing ASCVD also have variable risk, affected by the number of major ASCVD events, whether recurrent events have occurred recently, and the presence of other major risk factors or high-risk conditions. Current guidelines define high to very high risk ASCVD accordingly. Accurate ASCVD risk assessment is crucial for the appropriate targeting of preventive therapies to reduce ASCVD risk. Finally, the clinician-patient risk discussion focusing on lifestyle management and the risks and benefits of evidence-based pharmacologic therapies to best lower ASCVD risk is central to this process. This clinical practice statement provides the preventive cardiology specialist with guidance and tools for assessment of ASCVD risk with the goal of appropriately targeting treatment approaches for prevention of ASCVD events.

Coronary computed tomography angiography (CCTA) is a noninvasive imaging modality of cardiac structures and vasculature considered comparable to invasive coronary angiography for the evaluation of coronary artery disease (CAD) in several major cardiovascular guidelines. Conventional image acquisition, processing, and analysis of CCTA imaging have progressed significantly in the past decade through advances in technology, computation, and engineering. However, the advent of artificial intelligence (AI)-driven analysis of CCTA further drives past the limitations of conventional CCTA, allowing for greater achievements in speed, consistency, accuracy, and safety. AI-driven CCTA (AI-CCTA) has achieved a significant reduction in radiation exposure for patients, allowing for high-quality scans with sub-millisievert radiation doses. AI-CCTA has demonstrated comparable accuracy and consistency in manual coronary artery calcium scoring against expert human readers. An advantage over invasive coronary angiography, which provides luminal information only, CCTA allows for plaque characterization, providing detailed information on the quality of plaque and offering further prognosticative value for the management of CAD. Combined with AI, many recent studies demonstrate the efficacy, accuracy, efficiency, and precision of AI-driven analysis of CCTA imaging for the evaluation of CAD, including assessing degree stenosis, adverse plaque characteristics, and CT fractional flow reserve. The limitations of AI-CCTA include its early phase in investigation, the need for further improvements in AI modeling, possible medicolegal implications, and the need for further large-scale validation studies. Despite these limitations, AI-CCTA represents an important opportunity for improving cardiovascular care in an increasingly advanced and data-driven world of modern medicine. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common forms of cancer worldwide and treatment options for advanced CRC, which has a low 5-year survival rate, remain limited. Integrin-linked kinase (ILK), a multifunctional, scaffolding, pseudo-kinase regulating many integrin-mediated cellular processes, is highly expressed in many cancers. However, the role of ILK in cancer progression is yet to be fully understood. We have previously uncovered a pro-inflammatory role for myeloid-specific ILK in dextran sodium sulfate (DSS)-induced colitis. To establish a correlation between chronic intestinal inflammation and colorectal cancer (CRC), we investigated the role of myeloid-ILK in mouse models of CRC. When myeloid-ILK deficient mice along with the WT control mice were subjected to colitis-associated and APCmin/+-driven CRC, tumour burden was reduced by myeloid-ILK deficiency in both models. The tumour-promoting phenotype of macrophages, M2 polarization, in vitro was impaired by the ILK deficiency and the number of M2-specific marker CD206-expressing tumour-associated macrophages (TAMs) in vivo were significantly diminished in myeloid-ILK deficient mice. Myeloid-ILK deficient mice showed enhanced tumour infiltration of CD8+ T cells and reduced tumour infiltration of FOXP3+ T cells in colitis-associated and APCmin/+-driven CRC, respectively, with an overall elevated CD8+/FOXP3+ ratio suggesting an anti-tumour immune phenotypes. In patient CRC tissue microarrays we observed elevated ILK+ myeloid (ILK+ CD11b+) cells in tumour sections compared to adjacent normal tissues, suggesting a conserved role for myeloid-ILK in CRC development in both human and animal models. This study identifies myeloid-specific ILK expression as novel driver of CRC, which could be targeted as a potential therapeutic option for advanced disease. [ABSTRACT FROM AUTHOR]

Purpose of Review: To discuss and review the technical considerations, fundamentals, and guideline-based indications for coronary artery calcium scoring, and the use of other non-invasive imaging modalities, such as extra-coronary calcification in cardiovascular risk prediction. Recent Findings: The most robust evidence for the use of CAC scoring is in select individuals, 40–75 years of age, at borderline to intermediate 10-year ASCVD risk. Recent US recommendations support the use of CAC scoring in varying clinical scenarios. First, in adults with very high CAC scores (CAC ≥ 1000), the use of high-intensity statin therapy and, if necessary, guideline-based add-on LDL-C lowering therapies (ezetimibe, PCSK9-inhibitors) to achieve a ≥ 50% reduction in LDL-C and optimally an LDL-C < 70 mg/dL is recommended. In patients with a CAC score ≥ 100 at low risk of bleeding, the benefits of aspirin use may outweigh the risk of bleeding. Other applications of CAC scoring include risk estimation on non-contrast CT scans of the chest, risk prediction in younger patients (< 40 years of age), its value as a gatekeeper for the decision to perform nuclear stress testing, and to aid in risk stratification in patients presenting with low-risk chest pain. There is a correlation between extra-coronary calcification (e.g., breast arterial calcification, aortic calcification, and aortic valve calcification) and incident ASCVD events. However, its role in informing lipid management remains unclear. Summary: Identification of coronary calcium in selected patients is the single best non-invasive imaging modality to identify future ASCVD risk and inform lipid-lowering therapy decision-making. [ABSTRACT FROM AUTHOR]

ObjectiveThe Miami Heart Study (MiHeart) at Baptist Health South Florida is an ongoing, community-based, prospective cohort study aimed at characterizing the prevalence, characteristics, and prognostic value of diverse markers of early subclinical coronary atherosclerosis and of various potential demographic, psychosocial, and metabolic risk factors. We present the study objectives, detailed research methods, and preliminary baseline results of MiHeart.MethodsMiHeart enrolled 2,459 middle-aged male and female participants from the general population of the Greater Miami Area. Enrollment occurred between May 2015 and September 2018 and was restricted to participants aged 40-65 years free of clinical cardiovascular disease (CVD). The baseline examination included assessment of demographics, lifestyles, medical history, and a detailed evaluation of psychosocial characteristics; a comprehensive physical exam; measurement of multiple blood biomarkers including measures of inflammation, advanced lipid testing, and genomics; assessment of subclinical coronary atherosclerotic plaque and vascular function using coronary computed tomography angiography, the coronary artery calcium score, carotid intima-media thickness, pulse wave velocity, and peripheral arterial tonometry; and other tests including 12-lead electrocardiography and assessment of pulmonary function. Blood samples were biobanked to facilitate future ancillary research.ResultsMiHeart enrolled 1,261 men (51.3%) and 1,198 women (48.7%). Mean age was 53 years, 85.6% participants were White and 47.4% were of Hispanic/Latino ethnicity. The study included 7% individuals with diabetes, 33% with hypertension, and 15% used statin therapy at baseline. Overweight or obese participants comprised 72% of the population and 3% were smokers. Median 10-year estimated atherosclerotic CVD risk using the Pooled Cohort Equations was 4%.ConclusionMiHeart will provide important, novel insights into the pathophysiology of early subclinical atherosclerosis and further our understanding of its role in the genesis of clinical CVD. The study findings will have important implications, further refining current cardiovascular prevention paradigms and risk assessment and management approaches moving forward.

The article discusses a rare complication following treatment for chronic venous insufficiency, where a 52-year-old male developed extruding pellets in a sporotrichoid pattern due to a foreign body reaction to cyanoacrylate glue six months after a VenaSeal procedure. The patient required surgical removal of the pellets due to continued foreign body reaction. The article highlights the importance of recognizing potential complications, such as hypersensitivity reactions, after VenaSeal treatment for varicose veins, to ensure timely diagnosis and appropriate management. [Extracted from the article]

Colorectal cancer (CRC) is one of the most common forms of cancer worldwide and treatment options for advanced CRC, which has a low 5-year survival rate, remain limited. Integrin-linked kinase (ILK), a multifunctional, scaffolding, pseudo-kinase regulating many integrin-mediated cellular processes, is highly expressed in many cancers. However, the role of ILK in cancer progression is yet to be fully understood. We have previously uncovered a pro-inflammatory role for myeloid-specific ILK in dextran sodium sulfate (DSS)-induced colitis. To establish a correlation between chronic intestinal inflammation and colorectal cancer (CRC), we investigated the role of myeloid-ILK in mouse models of CRC. When myeloid-ILK deficient mice along with the WT control mice were subjected to colitis-associated and APCmin/+-driven CRC, tumour burden was reduced by myeloid-ILK deficiency in both models. The tumour-promoting phenotype of macrophages, M2 polarization, in vitro was impaired by the ILK deficiency and the number of M2-specific marker CD206-expressing tumour-associated macrophages (TAMs) in vivo were significantly diminished in myeloid-ILK deficient mice. Myeloid-ILK deficient mice showed enhanced tumour infiltration of CD8+ T cells and reduced tumour infiltration of FOXP3+ T cells in colitis-associated and APCmin/+-driven CRC, respectively, with an overall elevated CD8+/FOXP3+ ratio suggesting an anti-tumour immune phenotypes. In patient CRC tissue microarrays we observed elevated ILK+ myeloid (ILK+ CD11b+) cells in tumour sections compared to adjacent normal tissues, suggesting a conserved role for myeloid-ILK in CRC development in both human and animal models. This study identifies myeloid-specific ILK expression as novel driver of CRC, which could be targeted as a potential therapeutic option for advanced disease.

BackgroundInsulin resistance (IR), a risk factor for cardiovascular diseases, has garnered significant attention in scientific research. Several studies have investigated the correlation between IR and coronary artery calcification (CAC), yielding varying results. In light of this, we conducted a systematic review to investigate the association between IR as evaluated by the homeostasis model assessment (HOMA-IR) and CAC.MethodsA comprehensive search was conducted to identify relevant studies in PubMed, Embase, Scopus, and Web of Science databases. In addition, preprint servers such as Research Square, BioRxiv, and MedRxiv were manually searched. The collected data were analyzed using either fixed or random effects models, depending on the heterogeneity observed among the studies. The assessment of the body of evidence was performed using the GRADE approach to determine its quality.ResultsThe current research incorporated 15 studies with 60,649 subjects. The analysis revealed that a higher category of HOMA-IR was associated with a greater prevalence of CAC in comparison to the lowest HOMA-IR category, with an OR of 1.13 (95% CI: 1.06–1.20, I2 = 29%, P < 0.001). A similar result was reached when HOMA-IR was analyzed as a continuous variable (OR: 1.27, 95% CI: 1.14–1.41, I2 = 54%, P < 0.001). In terms of CAC progression, a pooled analysis of two cohort studies disclosed a significant association between increased HOMA-IR levels and CAC progression, with an OR of 1.44 (95% CI: 1.04–2.01, I2 = 21%, P < 0.05). It is important to note that the strength of the evidence was rated as low for the prevalence of CAC and very low for the progression of CAC.ConclusionThere is evidence to suggest that a relatively high HOMA-IR may be linked with an increased prevalence and progression of CAC.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Treatment of environmental media contaminated with per- and polyfluoroalkyl substances (PFAS) is crucial to mitigate mounting health risks associated with exposure. Colloidal activated carbon (CAC) has shown promise in treating contaminated soils, but understanding the interaction among PFAS during sorption is necessary for optimal remediation. This study investigated the extent to which PFAS of varying chain lengths and functional groups compete for sorption to CAC. Batch tests were conducted with natural soil and spiked water, using CAC at 0.2% w/w to remove seven PFAS with individual starting concentrations up to 0.05 mmol L−1. PFAS sorption to CAC was evaluated in three systems: a composite mixture of all studied compounds, a binary-solute system, and a single-solute system. The sorption experiments exhibited strong PFAS affinity to CAC, with removal rates between 41% and 100%, and solid/liquid partition coefficients (Kd) between 10 and 104 L kg−1. Differences were noticed among the various spiking mixtures, based on perfluorocarbon chain length, functional group, and the starting PFAS concentrations. Competition effects were detected when PFAS were in a multi-solute system, with an average 10% drop in removal, which can evidently become more relevant at higher concentrations, due to the observed non-linearity of the sorption process. The PFAS most vulnerable to competition effects in multi-solute systems were the short-chain perfluoropentanoic acid (PFPeA) and perfluorobutane sulfonic acid (PFBS), with an up to 25% reduction in removal. In bi-solute systems, perfluorooctane sulfonamide (FOSA) dominated over its ionisable counterparts, i.e. perfluorooctane sulfonic acid (PFOS) and perfluorononanoic acid (PFNA), indicating the importance of hydrophobic effects or layer formation in the sorption process. These results underscore the importance of considering competition in PFAS sorption processes when designing and implementing remediation techniques for PFAS-contaminated media.

BackgroundGenetic risk scores (GRSs) have been associated with CHD events and coronary artery calcium (CAC). We sought to evaluate the ability of a GRS to improve CAC as a screening test.MethodsUsing the results of the most recent genome-wide association studies, we calculated a GRS in 6660 individuals from the Multi-Ethnic Study of Atherosclerosis and used it to determine the optimal age for an individual to undergo CAC screening.ResultsThis 157-SNP GRS was predictive of non-zero CAC in individuals aged 44-54 and improved the positive yield of CAC as a screening test in this age group. The GRS was predictive of CAC in the entire multi-ethnic cohort and in each self-identified ethnic group (European American, Chinese American, African American, and Hispanic American) assessed individually. Given a specified target yield rate of non-zero CAC, an equation was derived to calculate an individual's optimal age to undergo CAC screening. In addition, a "direct-to-consumer" GRS consisting of only risk SNPs or their proxies that are directly genotyped on the 23andMe v5 chip (102-SNP GRS) was assessed in the European American population and was predictive of non-zero CAC in younger individuals.ConclusionA GRS is associated with non-zero CAC in a multi-ethnic cohort and can be used to calculate the age of a person's first calcium scan, given a target threshold for CAC discovery. Furthermore, an inexpensive and widely available "direct-to-consumer" GRS was found to be a viable option to calculate the optimal age for CAC screening.

AimsCoronary artery calcium (CAC) is the strongest predictor of cardiovascular disease (CVD), yet is also associated with chronic non-CVD such as cancer. We performed this analysis in order to describe the association of CAC with CVD vs. cancer mortality.Methods and resultsThe CAC Consortium is comprised of 66 636 scans performed in asymptomatic patients without known CVD. The mean age was 54 ± 11 years and 67% of participants were men. Cause of death was ascertained from death certificates. The association of CAC with cause-specific mortality was calculated using Fine and Gray sub-distribution hazard ratio (SHR) models, which account for competing causes of death. There were 3158 deaths over a median 12 ± 4 years follow-up (37% cancer and 32% CVD). Cancer was the leading cause of death when CAC = 0 (50%) with CVD overtaking cancer when baseline CAC >300. Compared to participants with CAC = 0, the SHR for CVD mortality was 1.44 [95% confidence interval (CI) 1.14-1.81], 2.26 (95% CI 1.76-2.90), and 3.68 (95% CI 2.90-4.67) for patients with CAC 1-99, 100-299, and ≥300, and the SHR for cancer was 1.04 (95% CI 0.88-1.23), 1.19 (95% CI 0.98-1.46), and 1.30 (95% CI 1.07-1.58).ConclusionCancer was the leading cause of death for patients with baseline CAC = 0, whereas CVD overtook cancer above a threshold of CAC >300. These results argue for a focused approach for patients at the extremes of CAC scoring while suggesting that combined CVD and cancer primary prevention strategies for patients with intermediate CAC scores may significantly decrease mortality from the two leading causes of death.

Although there is increasing evidence that oxidative stress and inflammation induced by COVID-19 may contribute to increased risk and severity of thromboses, the underlying mechanism(s) remain to be understood. The purpose of this review is to highlight the role of blood lipids in association with thrombosis events observed in COVID-19 patients. Among different types of phospholipases A2 that target cell membrane phospholipids, there is increasing focus on the inflammatory secretory phospholipase A2 IIA (sPLA2-IIA), which is associated with the severity of COVID-19. Analysis indicates increased sPLA2-IIA levels together with eicosanoids in the sera of COVID patients. sPLA2 could metabolise phospholipids in platelets, erythrocytes, and endothelial cells to produce arachidonic acid (ARA) and lysophospholipids. Arachidonic acid in platelets is metabolised to prostaglandin H2 and thromboxane A2, known for their pro-coagulation and vasoconstrictive properties. Lysophospholipids, such as lysophosphatidylcholine, could be metabolised by autotaxin (ATX) and further converted to lysophosphatidic acid (LPA). Increased ATX has been found in the serum of patients with COVID-19, and LPA has recently been found to induce NETosis, a clotting mechanism triggered by the release of extracellular fibres from neutrophils and a key feature of the COVID-19 hypercoagulable state. PLA2 could also catalyse the formation of platelet activating factor (PAF) from membrane ether phospholipids. Many of the above lipid mediators are increased in the blood of patients with COVID-19. Together, findings from analyses of blood lipids in COVID-19 patients suggest an important role for metabolites of sPLA2-IIA in COVID-19-associated coagulopathy (CAC). [ABSTRACT FROM AUTHOR]

Purpose: Virtual non-contrast (VNC) coronary artery calcium scoring (CAC) may obviate the need for traditional non-contrast (TNC) CAC. There is no data on the influence of body mass index (BMI) on VNC reliability. We aimed to evaluate the influence of BMI on VNC CAC agreement with TNC. Materials and methods: All patients who underwent sequential CAC and coronary CT angiography (CCTA) using spectral CT with TNC CAC > 0 between August 2020 and December 2021 were included. Agatston CAC scores were calculated manually by 2 blinded readers from VNC scans. A correction factor was calculated from the slope of the linear regression using the method of least squares and applied to the VNC scores. Bland-Altman plots and Cohen's weighted Kappa were utilized. Results: We included 174 patients (57.5% female). Mean BMI was 32.6 ± 7.02 kg/m2 [BMI < 30 (39.7%); BMI 30–40 (45.4%); and BMI > 40 kg/m2 (14.9%)]. Mean TNC CAC was 177.8 ± 316.86 and mean VNC CAC after applying the correction factor 149.34 ± 296.73. The TNC value strongly correlated with VNC (r = 0.94; p < 0.0001). As BMI increased there was a progressive reduction in signal-to-noise ratio, contrast-to-noise ratio and coronary enhancement (p < 0.05). The degree of agreement between VNC and TNC CAC decreased as BMI increased (agreement = 91.79 (weighted Kappa = 0.72), 91.14 (weighted Kappa = 0.58) and 88.46% (weighted Kappa = 0.48) (all P values < 0.001) for BMI < 30; 30–40 and > 40 kg/m2, respectively). Conclusion: BMI has a significant influence on the accuracy of VNC CAC. VNC CAC shows substantial agreement in non-obese patients but performs poorly in BMI > 40 kg/m2. Summary statement: This is the first study to evaluate the influence of body mass index (BMI) on virtual non-contrast (VNC) coronary artery calcium scoring (CAC) as compared to traditional non-contrast (TNC). We retrospectively evaluated 174 patients with TNC CAC and two blinded reviewers manually calculated the VNC CAC. All cases were included without specific selection for quality. The ratio between the two directly proportional values was determined using the slope from the linear regression through the method of least squares. This correction factor of 2.65 was applied to the calcium scores obtained from VNC images. We found that VNC CAC shows substantial risk-class agreement with TNC in non-obese patients (agreement = 91.79 and weighted Kappa = 0.72) but performs poorly in BMI > 40 kg/m2 (agreement: 88.46% and weighted Kappa = 0.48). These findings show the potential use of VNC CAC to avoid additional radiation in non-obese patients. However, further research on potential improvement strategies for VNC CAC in obese patients is needed. [ABSTRACT FROM AUTHOR]

Purpose of Review: Imaging of adverse coronary plaque features by coronary computed tomography angiography (CCTA) has advanced greatly and at a fast pace. We aim to describe the evolution, present and future in plaque analysis, and its value in comparison to plaque burden. Recent Findings: Recently, it has been demonstrated that in addition to plaque burden, quantitative and qualitative assessment of coronary plaque by CCTA can improve the prediction of future major adverse cardiovascular events in diverse coronary artery disease scenarios. The detection of high-risk non-obstructive coronary plaque can lead to higher use of preventive medical therapies such as statins and aspirin, help identify culprit plaque, and differentiate between myocardial infarction types. Even more, over traditional plaque burden, plaque analysis including pericoronary inflammation can potentially be useful tools for tracking disease progression and response to medical therapy. Summary: The identification of the higher risk phenotypes with plaque burden, plaque characteristics, or ideally both can allow the allocation of targeted therapies and potentially monitor response. Further observational data are now required to investigate these key issues in diverse populations, followed by rigorous randomized controlled trials. [ABSTRACT FROM AUTHOR]

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DNA methylation (DNAm) in mammals is mostly examined within the context of CpG dinucleotides. Non-CpG DNAm is also widespread across the human genome, but the functional relevance, tissue-specific disposition, and inter-individual variability has not been widely studied. Our aim was to examine non-CpG DNAm in the wider methylome across multiple tissues from the same individuals to better understand non-CpG DNAm distribution within different tissues and individuals and in relation to known genomic regulatory features. DNA methylation in umbilical cord and cord blood at birth, and peripheral venous blood at age 12–13 y from 20 individuals from the Southampton Women’s Survey cohort was assessed by Agilent SureSelect methyl-seq. Hierarchical cluster analysis (HCA) was performed on CpG and non-CpG sites and stratified by specific cytosine environment. Analysis of tissue and inter-individual variation was then conducted in a second dataset of 12 samples: eight muscle tissues, and four aliquots of cord blood pooled from two individuals. HCA using methylated non-CpG sites showed different clustering patterns specific to the three base-pair triplicate (CNN) sequence. Analysis of CAC sites with non-zero methylation showed that samples clustered first by tissue type, then by individual (as observed for CpG methylation), while analysis using non-zero methylation at CAT sites showed samples grouped predominantly by individual. These clustering patterns were validated in an independent dataset using cord blood and muscle tissue. This research suggests that CAC methylation can have tissue-specific patterns, and that individual effects, either genetic or unmeasured environmental factors, can influence CAT methylation.

Background: Subclinical coronary artery calcification (CAC) is a risk factor for adverse cardiovascular events, but studies investigating its association with outcomes in hospitalized patients with COVID-19 are limited. Methods: This was a retrospective study of 457 patients without history of clinical coronary artery disease (CAD) who underwent chest CT imaging during COVID-19 hospitalization at MCW/Froedtert-affiliated hospitals from July 1, 2020 to July 1, 2021. Visually estimated CAC (yes/no) and CAC burden (none/mild/moderate/severe) were recorded from radiology reports. Unadjusted and adjusted regression models were used to assess associations between CAC and hospital length of stay (LOS), ICU admission, mechanical ventilation, and mortality. Results: The mean age was 63.1 ± 15.3 years. Presence of CAC was associated with mechanical ventilation (p = 0.01), ICU admission (p = 0.02), in-hospital or 30-day mortality (p

Atherosclerotic cardiovascular disease risk (ASCVD) is an ongoing epidemic, and lipid abnormalities are its primordial cause. Most individuals suffering a first ASCVD event are previously asymptomatic and often do not receive preventative therapies. The cornerstone of primary prevention has been the identification of individuals at risk through risk calculators based on clinical and laboratory traditional risk factors plus risk enhancers. However, it is well accepted that a clinical risk calculator misclassifies a significant proportion of individuals leading to the prescription of a lipid-lowering medication with very little yield or a missed opportunity for lipid-lowering agents with a potentially preventable event. The development of coronary artery calcium scoring (CAC) and CT coronary angiography (CCTA) provide complementary tools to directly visualize coronary plaque and other risk-modifying imaging components that can potentially provide individualized lipid management.Understanding patient selection for CAC or potentially CCTA and the risk implications of the different parameters provided, such as CAC score, coronary stenosis, plaque characteristics and burden, epicardial adipose tissue, and pericoronary adipose tissue, have grown more complex as technologies evolve. These parameters directly affect the shared decision with patients to start or withhold lipid-lowering therapies, to adjust statin intensity or LDL cholesterol goals. Emerging lipid lowering studies with non-invasive imaging as a guide to patient selection and treatment efficacy, plus the evolution of lipid lowering therapies from statins to a diverse armament of newer high-cost agents have pushed these two fields forward with a complex interaction. This review will discuss existing risk estimators, and non-invasive imaging techniques for subclinical coronary atherosclerosis, traditionally studied using CAC and more recently CCTA with qualitative and quantitative measurements. We will also explore the current data, gaps of knowledge and future directions on the use of these techniques in the risk-stratification and guidance of lipid management.

Background: Coronary artery calcifications comprise one of the most significant factors interfering with the diagnostic accuracy of Multi-Slice Computed Tomography (MSCT). Despite this fact, measurement of Coronary Artery Calcification (CAC) score using Agatston method is a useful noninvasive test for expecting rare but serious potentially life - threatening Percutaneous Coronary Intervention (PCI) complications, our aim to highlight the role of MSCT in coronary disease severity and CAC score as a predictor tool to determine PCI associated complications. Methods: A prospective study was carried out in the period from January 2022 to May 2022, conducted at the radiology and cardiology departments of Zagzig University Hospitals, and enrolled 60 patients with 78 significant stenotic calcified coronary lesions diagnosed by conventional coronary angiography and MSCT coronary angiography with total, target vessel and significant lesion CAC scores calculation using the Agatston method prior to percutaneous coronary intervention (PCI). Results: Our patients were divided into a lower CAC score cases (CAC score, =300, n=12 cases/12 lesions) and a higher CAC case (CAC score, >300, n=48 cases/66 lesions). The highest vessel CAC score mean is of LAD 100.1± 61.98 followed by RCA then LCX and lastly LM, with only three cases of higher CAC score group developed dissection during PCI. with significant difference between successful and complicated PCI regarding the total, target vessel and significant lesion CAC scores with P value < 0.02 Conclusion: Using MSCT to measure CCS prior to intervention can anticipate PCI problems and improve PCI outcomes. [ABSTRACT FROM AUTHOR]

Machine learning (ML) models of risk prediction with coronary artery calcium (CAC) and CAC characteristics exhibit high performance, but are not inherently interpretable. To determine the direction and magnitude of impact of CAC characteristics on 10-year all-cause mortality (ACM) with explainable ML. We analyzed asymptomatic subjects in the CAC consortium. We trained ML models on 80% and tested on 20% of the data with XGBoost, using clinical characteristics ​+ ​CAC (ML 1) and additional CAC characteristics of CAC density and number of calcified vessels (ML 2). We applied SHAP, an explainable ML tool, to explore the relationship of CAC and CAC characteristics with 10-year all-cause and CV mortality. 2376 deaths occurred among 63,215 patients [68% male, median age 54 (IQR 47–61), CAC 3 (IQR 0–94.3)]. ML2 was similar to ML1 to predict all-cause mortality (Area Under the Curve (AUC) 0.819 vs 0.821, p ​= ​0.23), but superior for CV mortality (0.847 vs 0.845, p ​= ​0.03). Low CAC density increased mortality impact, particularly ≤0.75. Very low CAC density ≤0.75 was present in only 4.3% of the patients with measurable density, and 75% occurred in CAC1-100. The number of diseased vessels did not increase mortality overall when simultaneously accounting for CAC and CAC density. CAC density contributes to mortality risk primarily when it is very low ≤0.75, which is primarily observed in CAC 1–100. CAC and CAC density are more important for mortality prediction than the number of diseased vessels, and improve prediction of CV but not all-cause mortality. Explainable ML techniques are useful to describe granular relationships in otherwise opaque prediction models. Original TOC summary: We used SHAP, an explainable machine learning (ML) technique, to determine the risk predictive value and age interaction of coronary artery calcium (CAC) characteristics among 63,215 asymptomatic patients in the CAC consortium. The addition of CAC density and number of calcified vessels to an ML model with clinical characteristics ​+ ​CAC did not improve prediction for all-cause mortality (p ​= ​0.23), but did improve for cardiovascular mortality (p ​= ​0.03). Lower CAC density increased mortality, particularly very low CAC density ≤0.75, which occurred predominantly in CAC1-100. Explainable ML should be applied in clinical research for transparent predictive modeling. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the malignant tumors globally, with high morbidity and mortality rates. The mainstay treatment of CRC includes surgery, radiotherapy, and chemotherapy. However, these treatments are associated with a high recurrence rate, poor prognosis, and highly toxic side effects. The probiotics have the potential to prevent CRC, and they display a favorable safety performance. Probiotics could provide a potential strategy to prevent and treat CRC. The impact of LZZAY01 on cancer cell lines CT-26, HCT-116, and SW-620 was evaluated by conducting cytotoxicity and clonogenicity tests. A model of colitis-associated cancer (CAC) was established in C57BL/6j mice following induction with AOM/DSS. The levels of autophagy and apoptosis proteins, tight junction proteins, and inflammatory factors were detected by western blotting, immunofluorescence assay, and enzyme-linked immunosorbent assay. High-throughput sequencing of gut 16S rRNA was performed to analyze the abundance and diversity of the gut microbiome. LZZAY01, a new strain of Ligilactobacillus salivarius , was certified by an evolutionary tree and average nucleotide identity. LZZAY01 enhanced autophagy and apoptosis in CT-26, HCT-116, and SW-620 cell lines. It preserved the integrity of the intestinal barrier by regulating the tight junction protein ZO-1 and claudin-1. The tumor necrosis factor-α and interleukin-6 were reduced by LZZAY01. The abundance and diversity of the intestinal microbiota were enhanced, especially the beneficial bacterial species maintaining the balance of the intestinal flora such as Bifidobacterium and Lactobacillus . L. salivarius LZZAY01 improved CAC via suppressing the growth of colon cancer cells, promoting autophagy and apoptosis, enhancing intestinal tight junctions, reducing intestinal barrier degradation, modifying the gut microbiota abundance, and decreasing inflammatory reactions.IMPORTANCEAlthough similar probiotics have been shown to have anticancer potential in colorectal cancer (CRC), there is a paucity of research related to the preventive function of probiotics against CRC. And there are fewer studies about the mechanism of probiotics' preventive effects on CRC. The regulation of tumor cell proliferation and apoptosis by the active ingredients of probiotics may be one of the mechanisms of their prevention of CRC. In this study, we explored the effects of L. salivarius LZZAY01 on autophagy and apoptosis of colon cancer cells in vitro and in vivo and proposed a possible mechanism for the prevention of CRC by probiotics.

There are significant sex differences in colorectal cancer (CRC), including in incidence, onset, and molecular characteristics. Further, while inflammatory bowel disease (IBD) is a risk factor for CRC in both sexes, men with IBD have a 60% higher risk of developing CRC compared to women. In this study, we investigated sex differences during colitis-associated CRC (CAC) using a chemically induced CAC mouse model. The mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) and followed for 9 and 15 weeks. We performed RNA-sequencing of colon samples from males (n = 15) and females (n = 15) to study different stages of inflammation and identify corresponding transcriptomic sex differences in non-tumor colon tissue. We found a significant transcriptome response to AOM/DSS treatment in both sexes, including in pathways related to inflammation and cell proliferation. Notably, we found a stronger response in males and that male-specific differentially expressed genes were involved in NFκB signaling and circadian rhythm. Further, an overrepresented proportion of male-specific gene regulations were predicted to be targets of Stat3, whereas for females, targets of the glucocorticoid receptor (Gr/Nr3c1) were overrepresented. At 15 weeks, the most apparent sex difference involved genes with functions in T cell proliferation, followed by the regulation of demethylases. The majority of sex differences were thus related to inflammation and the immune system. Our novel data, profiling the transcriptomic response to chemically induced colitis and CAC, indicate clear sex differences in CRC initiation and progression. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) are common diseases of the digestive system. Vitamin deficiencies and gut microbiota dysbiosis have a close relationship with the risk, development, and progression of IBD and CAC. There is a strong link between vitamins and the gut microbiome. Vitamins are extremely crucial for maintaining a healthy gut microbiota, promoting growth and development, metabolism, and innate immunity. Gut microbiota can not only influence the transport process of vitamins, but also produce vitamins to compensate for insufficient food intake. Emerging evidence suggests that oral vitamin supplementation can reduce inflammation levels and improve disease prognosis. In addition, improving the diet structure and consuming foods rich in vitamins not only help to improve the vitamin deficiency, but also help to reduce the risk of IBD. Fecal microbiota transplantation (FMT) and the application of vitamin-producing probiotics can better assist in the treatment of intestinal diseases. In this review, we discuss the interaction and therapeutic roles of vitamins and gut microbiota in IBD and CAC. We also summarize the methods of treating IBD and CAC by modulating vitamins. This may highlight strategies to target gut-microbiota-dependent alterations in vitamin metabolism in the context of IBD and CAC therapy. [ABSTRACT FROM AUTHOR]

Chest CT is valuable to detect alternative diagnoses/complications of COVID-19, while its role for prognostication requires further investigation. Non-pulmonary radiological findings such as cardiovascular calcifications could increase the predictivity of clinical outcomes of COVID-19 patients beyond pulmonary involvement. Several observational studies have reported mixed results on the role of coronary calcifications in COVID-19 patients as a predictor of hospitalization, ventilatory support, and mortality. The purpose of the study is to systematically review the available evidence on the predictive role of cardiovascular calcifications in SARS-CoV2 disease. The meta-analysis confirms the prognostic significance of coronary calcifications on hospital mortality, and coronary calcifications (CAC ≠ 0) were associated with an OR for mortality of 2.19 (95% CI 1.36–3.52). CAC was neutral on respiratory outcomes, but it was associated with an increased trend of cardiovascular events. Coronary calcium appears as a promising biomarker imaging even in short-term outcomes (MACEs, hospital mortality) in a non-cardiovascular disease such as Sars-CoV2 infection. Further large studies are needed to confirm promising results of this imaging biomarker in non-cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: COVID-19-associated fungal infections seem to be a concerning issue. The aim of this study was to assess the incidence of fungal infections, the possible risk factors, and their effect on outcomes of critically ill patients with COVID-19. Methods: A retrospective observational study was conducted in the COVID-19 ICU of the First Respiratory Department of National and Kapodistrian University of Athens in Sotiria Chest Diseases Hospital between 27 August 2020 and 10 November 2021. Results: Here, 178 patients were included in the study. Nineteen patients (10.7%) developed fungal infection, of which five had COVID-19 associated candidemia, thirteen had COVID-19 associated pulmonary aspergillosis, and one had both. Patients with fungal infection were younger, had a lower Charlson Comorbidity Index, and had a lower PaO2/FiO2 ratio upon admission. Regarding health-care factors, patients with fungal infections were treated more frequently with Tocilizumab, a high regimen of dexamethasone, continuous renal replacement treatment, and were supported more with ECMO. They also had more complications, especially infections, and subsequently developed septic shock more frequently. Finally, patients with fungal infections had a longer length of ICU stay, as well as length of mechanical ventilation, although no statistically significant difference was reported on 28-day and 90-day mortality. Conclusions: Fungal infections seem to have a high incidence in COVID-19 critically ill patients and specific risk factors are identified. However, fungal infections do not seem to burden on mortality. [ABSTRACT FROM AUTHOR]

Background: Epicardial fat volume (EFV) has been reported to be associated with coronary artery disease (CAD). CAD is the leading cause of myocardial ischemia and myocardial ischemia is closely related to major adverse cardiovascular events. We hypothesized that EFV could provide incremental value to traditional risk factors and coronary artery calcium score (CACS) in predicting myocardial ischemia in Chinese patients with suspected CAD. Methods: We retrospectively studied 204 Chinese patients with suspected CAD who underwent single-photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) combined with computed tomography (CT). Pericardial contours were manually defined, and EFV was automatically calculated. A reversible perfusion defect with summed difference score (SDS) ≥ 2 was defined as myocardial ischemia. Results: The myocardial ischemia group had higher EFV than normal MPI group (137.80 ± 34.95cm3 vs. 106.63 ± 29.10 cm3, P <.001). In multivariable logistic regression analysis, high EFV was significantly associated with myocardial ischemia [odds ratio (OR): 8.30, 95% CI: 3.72-18.49, P <.001]. Addition of EFV to CACS and traditional risk factors could predict myocardial ischemia more effectively, with larger AUC.82 (P <.001), positive net reclassification index.14 (P =.04) and integrated discrimination improvement.14 (P <.001). The bootstrap resampling method (times = 500) was used to internally validation and calculate the 95% confidence interval (CI) of the AUC (95% CI.75-.87). The calibration curve for the probability of myocardial ischemia demonstrated good agreement between prediction and observation. Conclusions: In Chinese patients with suspected CAD, EFV was significantly associated with myocardial ischemia, and improved prediction of myocardial ischemia above traditional risk factors and CACS. [ABSTRACT FROM AUTHOR]