Risk of severe illness of COVID‐19 patients with NAFLD and increased NAFLD fibrosis scores

BackgroundThere is still little knowledge about the association of liver fibrosis with the clinical outcomes of COVID‐19 patients with non‐alcoholic fatty liver disease (NAFLD). The aim of the study was to determine the association of NAFLD fibrosis score (NFS)–determined liver fibrosis with clinical outcomes of COVID‐19 patients with NAFLD.MethodsThe NAFLD was diagnosed by the Hepatic Steatosis Index (HSI) in the absence of other causes of chronic liver diseases. NFS was used to evaluate the severity of liver fibrosis.ResultsA total of 86 COVID‐19 patients with NAFLD were included. The median age was 43.5 years, and 58.1% of patients were male. Thirty‐eight (44.2%) patients had advanced liver fibrosis according to the NFS. Multivariate analysis indicated that concurrent diabetes (odds ratio [OR] 8.264, 95% confidence interval [CI] 1.202–56.830, p = 0.032) and advanced liver fibrosis (OR 11.057, 95% CI 1.193–102.439, p = 0.034) were independent risk factors of severe illness in COVID‐19 patients with NAFLD.ConclusionNAFLD patients with NFS‐determined advanced liver fibrosis are at higher risk of severe COVID‐19.     

Fatty liver index predicts incident risk of prediabetes,type 2 diabetes and non-alcoholic fatty liver disease (NAFLD)

AimsTo investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up.MethodsAt baseline (in 2001) 2020 participants, males and females, aged 24–39 years, were stratified according to body mass index (BMI), normal weight (<25 kg/m²), overweight (≥25–<30 kg/m²), or obese (≥30 kg/m²) and FLI (as high FLI ≥60 or low FLI <60). We examined the incidence of prediabetes/type 2 diabetes and NAFLD (ultrasound assessed) over 10 years to 2011 to determine the relative impact of FLI and BMI.Results514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes (n = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9–10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups.ConclusionsAn increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.

Key messages

• Obesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes.
• Additionally, NAFLD is more prevalent in people with prediabetes and type 2 diabetes when compared to age- and BMI-matched individuals.
• The presence of a raised fatty liver index (FLI) confers a significantly increased risk of developing prediabetes, type 2 diabetes and NAFLD above that conferred by being overweight/obese.
• The degree of elevation of FLI can risk stratify for incident prediabetes and type 2 diabetes in people with obesity.

     

Does the FT3-to-FT4 ratio easily predict the progression of NAFLD and NASH cirrhosis?

BackgroundFactors causing progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH) and liver cirrhosis remain relatively unknown. We aimed to evaluate the power and effectiveness of the free triiodothyronine (FT3)-to-free thyroxine (FT4) ratio to predict non-alcoholic fatty liver disease (NAFLD)/liver fibrosis and NASH cirrhosis severity.MethodsPatients (n = 436) with NASH-associated liver cirrhosis (n = 68), patients with liver biopsy-proven NAFLD (n = 226), or healthy participants (n = 142) were enrolled between January 2010 and January 2020. The aspartate aminotransferase-to-thrombocyte ratio (APRI), NAFLD fibrosis score, albumin–bilirubin score (ALBI), aspartate aminotransferase (AST)-to-alanine aminotransferase (ALT) ratio, FT3-to-FT4 ratio, and Fibrosis-4 (FIB-4) were calculated and evaluated.ResultsAll parameters were significantly higher in NASH cirrhosis than in the healthy group. Body mass index, ALT, fasting insulin, homeostatic model assessment for insulin resistance, and triglyceride levels were significantly higher in liver biopsy-proven NAFLD than in the healthy group. The APRI, NAFLD fibrosis score, ALBI, AST-to-ALT ratio, FT3-to-FT4 ratio, and FIB-4 were significantly higher in the NASH cirrhosis group than in the healthy group. In patients with biopsy-proven NAFLD, the FT3-to-FT4 ratio was significantly lower than in the healthy group.ConclusionThe FT3-to-FT4 ratio is an effective and useful indicator to predict NAFLD/liver fibrosis and NASH cirrhosis severity.     

Association between the liver fat score (LFS) and cardiovascular diseases in the national health and nutrition examination survey 1999–2016

BackgroundThe liver fat score (LFS) has been proposed to be a simple non-invasive marker of non-alcoholic fatty liver disease (NAFLD), which is highly prevalent in the general population. We tested its association with cardiovascular diseases (CVDs) and prognosis.Methods17,244 adult participants from the National Health and Nutrition Examination Survey 1999–2016 were included. LFS is calculated from variables including serum aspartate transaminase/alanine transaminase (AST/ALT) ratio, fasting serum aspartate transaminase (AST) level, fasting serum insulin level, presence of metabolic syndrome and diabetes mellitus. In cross-sectional analysis, logistic regression was used to examine the association of the LFS with coronary heart disease (CHD), myocardial infarction (MI), congestive heart failure (CHF), stroke and angina pectoris. Mortality during follow-up was analysed using Cox proportional hazard regression.ResultsLFS was associated with CHD (adjusted odds ratio [OR]: 1.09 per standard deviation [SD], 95% confidence interval [95% CI]: 1.03–1.15) (p = .003), CHF (1.11, 1.04–1.18) (p = .003) and angina pectoris (1.08, 1.02–1.13) (p = .005). LFS was not associated with MI or stroke, but was associated with increased all-cause and cardiovascular mortality with hazard ratios (HRs) of 1.10 (95% CI: 1.07–1.13) (p < .001) and 1.12 (95% CI: 1.06–1.17) (p < .001), respectively.ConclusionsNAFLD is usually asymptomatic, but this large study of a large general population shows that LFS is associated with CHD, CHF, angina pectoris, cardiovascular and all-cause mortality. Determining the LFS is worthwhile, as it identifies people with NAFLD, who may also be at increased cardiovascular risk.

Key Messages

• Liver fat score (LFS), a non-invasive marker of non-alcoholic fatty liver disease (NAFLD), is associated with coronary heart disease (CHD), congestive heart failure (CHF) and angina.
• LFS is also associated with increased cardiovascular and all-cause mortality.
• Determining the LFS is worthwhile as it identifies people with NAFLD as well as increased cardiovascular risk.

     

Gamma‐Glutamyl Transpeptidase‐to‐Platelet ratio predicts liver fibrosis in patients with concomitant chronic hepatitis B and nonalcoholic fatty liver disease

ObjectivesThe aim of this study was to compare the correlation of gamma‐glutamyl transpeptidase‐to‐platelet ratio (GPR), aspartate aminotransferase‐to‐platelet ratio index (APRI), fibrosis index‐4 (FIB‐4), and liver stiffness measurement (LSM) in the diagnosis of liver fibrosis, and perform a diagnostic value of GPR for predicting fibrosis in CHB patients with NAFLD.MethodsA retrospective study was conducted on CHB patients concurrent with NAFLD between September 2019 and December 2020. They were divided into control group (LSM ≤ 9.7 kpa) and fibrosis group (LSM ≥ 9.8 kpa). Demographic data were collected; ALT, AST, and PLT were also detected. LSM was measured by transient elastography (TE). The GPR, APRI, and FIB‐4 were calculated. The correlation between GPR, APRI, FIB‐4, and LSM was compared. The accuracy of predicting liver fibrosis using GPR, APRI, and FIB‐4 was assessed.ResultsEighty‐five CHB patients with NAFLD were enrolled. Multivariate analysis showed that age (p = 0.005), GGT (p = 0.001), and PLT (p = 0.013) were the independent risk factors for LSM. The GPR (p = 0.008), APRI (p = 0.001), and FIB‐4 (p = 0.001) values in fibrosis group were higher than control group. Pearson linear correlation was used to analyze the correlations between LSM and GPR, APRI, and FIB‐4. LSM was correlated with GPR, APRI, and FIB‐4. The AUCs of GPR, APRI, and FIB4 were 0.805, 0.766, and 0.826 in assessing liver fibrosis, respectively. No significant differences in the areas of GPR were comparable to that of APRI and FIB‐4.ConclusionGPR has a good correlation with LSM in assessing liver fibrosis and can be used as a noninvasive index for the assessment of liver fibrosis in patients with concomitant CHB and NAFLD.     

A comparative study on roles of natural killer T cells in two diet-induced non-alcoholic steatohepatitis-related fibrosis in mice

BackgroundImmune responses are important in the progression of non-alcoholic fatty liver disease (NAFLD). Natural killer T (NKT) cells are main components of the innate immune system that modulate immunity. However, the role of NKT cells in NAFLD remains controversial.ObjectiveWe aimed to investigate the role of NKT cells in non-alcoholic steatohepatitis (NASH)-related fibrosis in fast food diet (FFD)- and methionine choline-deficient (MCD) diet-induced mouse models.MethodsHepatic NKT cells were analysed in wild-type (WT) and CD1d-/- mice fed FFD or MCD diets. Hepatic pathology, cytokine profiles and liver fibrosis were evaluated. Furthermore, the effect of chronic administration of α-galactosylceramide (α-GalCer) on liver fibrosis was investigated in both FFD- and MCD-treated mice.ResultsFFD induced a significant depletion of hepatic NKT cells, thus leading to mild to moderate NASH and early-stage fibrosis, while mice fed MCD diets developed severe liver inflammation and progressive fibrosis without a significant change in hepatic NKT cell abundance. FFD induced a similar liver fibrogenic response in CD1d-/- and WT mice, while MCD induced a higher hepatic mRNA expression of Col1α1 and TIMP1 as well as relative fibrosis density in CD1d-/- mice than WT mice (31.8 vs. 16.3, p = .039; 40.0 vs. 22.6, p = .019; 2.24 vs. 1.59, p = .036). Chronic administration of α-GalCer induced a higher hepatic mRNA expression of TIMP1 in MCD-treated mice than controls (36.7 vs. 14.9, p = .005).ConclusionNKT cells have protective roles in NAFLD as the disease progresses. During diet-induced steatosis, mild to moderate NASH and the early stage of fibrosis, hepatic NKT cells are relatively depleted, leading to a proinflammatory status. In severe NASH and the advanced stage of liver fibrosis, NKT cells play a role in inhibiting the NASH-related fibrogenic response. Chronic administration of α-GalCer induces NKT cell anergy and tolerance, which may play a role in promoting the liver fibrogenic response.     

Effects of PPM1K rs1440581 and rs7678928 on serum branched-chain amino acid levels and risk of cardiovascular disease

ObjectiveThis study aimed to investigate the effects of PPM1K rs1440581 and rs7678928 single nucleotide polymorphisms (SNPs) on the serum branched-chain amino acids (BCAAs) levels and cardiovascular disease (CVD) risk.MethodsAnthropometric and biochemical examinations were performed at baseline and the end of 4 years in 234 individuals who were randomly recruited from the Diabetes Prevention Programme in Huai’an and received lifestyle intervention and follow up for 4 years. Serum BCAAs (leucine, isoleucine and valine (Val)) levels were measured by hydrophilic interaction chromatography-tandem mass spectrometric method and the PPM1K rs1440581 and rs7678928 were detected by high-throughput SNP genotyping at baseline. The associations of rs1440581 and rs7678928 with serum BCAA levels and risk for CVD after 4 years were further evaluated.ResultsThe distribution frequencies of PPM1K rs1440581 and rs7678928 met the Hardy-Weinberg equilibrium (p> .05). The baseline serum levels of Val (p = .022) and total BCAAs (p = .026) in subjects with rs1440581 CC genotype were higher than in those with TT genotype. There were no significant differences in the serum levels of BCAAs among subjects with different genotypes of rs7678928. After 4-year follow-up, the subjects with rs1440581 CC genotype had higher systolic blood pressure (SBP) (p = .027), diastolic blood pressure (DBP) (p = .019), triglycerides (TGs) (p = .019) and lower high-density lipoprotein cholesterol (HDL-c) (p = .008) than those with TT genotype, and had higher AST level than those with TT (p = .030) or TC (p = .003) genotype; the subjects with rs7678928 TT genotype had higher SBP (p = .039) and DBP (p = .019) and lower HDL-c than those with CC (p = .017) genotype. Lifestyle intervention had little influence on the serum levels of fasting plasma glucose (FPG), TG, HDL-c, alanine aminotransferase (ALT), AST and creatinine (CREA) in subjects with rs1440581 CC genotype or rs7678928 TT genotype (p> .05). The incidences of CVD and non-alcoholic fatty liver disease (NAFLD) in subjects with rs1440581 CC genotype were higher than in those with TT genotype; the incidence of CVD in subjects with rs7678928 TT genotype was higher than in those with CC (p < .05) genotype.ConclusionsAllele C of PPM1K rs1440581 was associated with elevated serum Val, total BCAAs and CVD risks. rs1440581 CC genotype may be a better marker than baseline serum BCAAs in predicting the risk for CVD.Trial registrationDiabetes Prevention Programme in Huai’an of Huai’an Second People''s Hospital, ChiCTR-TRC-14005029.

KEY MESSAGE

1. Allele C of PPM1K rs1440581 was relevant to elevated serum Val and total BCAAs.
2. PPM1K rs1440581 CC and rs7678928 TT genotypes were associated with CVD risk.
3. PPM1K rs1440581 CC genotype carriers were more likely to have liver injury and develop NAFLD.

     

Use of GP73 in the diagnosis of non-alcoholic steatohepatitis and the staging of hepatic fibrosis

ObjectiveTo evaluate the utility of Golgi protein 73 (GP73) in the diagnosis of non-alcoholic steatohepatitis (NASH) and hepatic fibrosis (HF) staging.MethodsNinety-one patients with non-alcoholic fatty liver disease (NAFLD) were allocated to NAFL (n = 46) and NASH (n = 45) groups according to their NAFLD activity score (NAS), and there were 30 healthy controls. Serum GP73 was measured by ELISA, GP73 protein expression was evaluated using immunohistochemistry, and FibroScan was used to determine liver hardness.ResultsThe serum GP73 concentrations of the NAFL and NASH groups were significantly higher than those of controls. GP73 expression in the liver of the patients gradually progressed from absent or low to moderate or high. Serum GP73 positively correlated with liver expression, and the serum and liver GP73 of the patients positively correlated with FibroScan value and HF stage. There was a strong positive correlation of the combination of alanine aminotransferase, gamma glutamyl transferase and GP73 with NASH. The combination of serum GP73 and FibroScan value was found to predict NASH (NAS > 4) and advanced HF (stage ≥2) in patients with NAFLD using receiver operating characteristic analysis.ConclusionSerum GP73 may be useful in the diagnosis of NASH and the staging of HF.     

Relationship between AGT rs2493132 polymorphism and the risk of coronary artery disease in patients with NAFLD in the Chinese Han population

ObjectiveTo investigate the relationship between angiotensin (AGT) rs2493132 gene polymorphism and the risk of developing non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population.MethodsPolymerase chain reaction was performed to determine AGT genotypes. Anthropometric and clinical data were investigated and statistically analyzed in the clinical laboratory department of Qingdao Municipal Hospital.ResultsThe AGT rs2493132 CT + TT genotype was an important risk factor for CAD in patients with NAFLD and NAFLD + CAD in healthy controls. The AGT rs2493132 T allele increased the risk of NAFLD + CAD in healthy controls. The AGT rs2493132 CT + TT genotype and T allele also significantly increased the risk of CAD in patients with NAFLD after adjustments for age, sex, and body mass index. In addition, AGT rs2493132 T allele carriers showed higher total cholesterol (TC) and low-density lipoprotein (LDL) levels compared with non-carriers.ConclusionsThe AGT rs2493132 CT + TT genotype and T allele significantly increased the risk of developing CAD in patients with NAFLD in the Chinese Han population. The AGT rs2493132 T allele was associated with increased serum TC and LDL levels.     

Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study

ObjectiveEvaluating the prevalence of long-COVID symptoms in patients with a history of mild or asymptomatic infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the factors associated with developing long-COVID.DesignA nationwide cohort study. Using a centralized database, we have identified patients with and without a history of SARS-CoV-2 infection 1–6 months before data collection. Patients were asked to fill out an online questionnaire through text messages.SettingIsraeli general practice.Subjects2755 persons participated in the study in September 2021 (a response rate of 7.5%): 819 with and, 936 without a history of SARS-CoV-2 infection.Main outcome measuresWe asked patients to provide details about their demographic status, medical history, COVID-related variables and the presence of long-COVID symptoms.ResultsMost prevalent long-COVID symptoms were decreased smell sensation (35.1% vs. 4.3%, p < 0.001), decreased taste sensation (25.2% vs. 3.2%, p < 0.001), memory disturbances (36.9% vs. 14.4%, p < 0.001), dyspnea (24.2% vs. 10.7%, p < 0.001) and arthralgia (33% vs. 16.3%, p < 0.001). Risk factors associated with long-COVID included female gender, symptomatic COVID-19, overweight or obesity and the presence of dyslipidemia. About 34.6% of participants reported not returning to their baseline health condition after the acute illness.ConclusionLong-COVID is frequently seen following a mild symptomatic COVID-19 infection and, to a lesser extent, following an asymptomatic SARS-CoV-2 infection. Primary care physicians should be aware of these symptoms and consider this option in their differential diagnosis. Health policymakers should expect a significant impact of this syndrome on public health.

Key Points

• Long-COVID has emerged as a significant health problem with a serious impact on normal daily function
• • Long-COVID symptoms were evident in patients with mild symptomatic disease and in asymptomatic patients to a lesser extent.
• • Risk factors for having Long-COVID symptoms include female gender, symptomatic disease, increased BMI, and the presence of dyslipidemia.
• • Fatigue, dyspnea, weakness, decreased libido, weight changes, memory, and sleep disturbances were associated with not returning to the baseline health state.

     

Prevalence and related factors of hyperuricaemia in Chinese children and adolescents: a pooled analysis of 11 population-based studies

Background and aimsHyperuricaemia can lead to gout and is associated with an increased risk of cardiometabolic disease. We aimed to investigate the prevalence of hyperuricaemia and its related factors in Chinese children and adolescents.MethodsWe pooled data from 11 population-based studies comprising 54,580 participants aged 3–19 years. The sex- and age-standardized prevalence of hyperuricaemia was estimated overall and by sex, age, weight status, geographic region and survey year.ResultsSerum uric acid (SUA) increased gradually from 3 to 11 years with no significant sex difference, and then increased dramatically during 11–15 years. The estimated overall prevalence of hyperuricaemia was 23.3% (26.6% in boys and 19.8% in girls, p < .001). The prevalence increased with growing age (3.7, 9.8, 15.8, 35.5 and 31.7% among children aged 3–5, 6–8, 9–11, 12–15 and 16–19 years, respectively, p for trend < .001) and with increasing weight status (18.2, 37.6, 50.6 and 64.5% among children with non-overweight, overweight, obesity and extreme obesity, respectively, p for trend < .001). The prevalence was higher in North than in South (24.2 vs. 19.7%, p < .001), and increased markedly from 16.7% during 2009–2015 to 24.8% during 2016–2019. In multivariable regression analyses, sex, age, obesity, region and survey year were independently associated with odds of hyperuricaemia.ConclusionsThe prevalence of hyperuricaemia in Chinese children and adolescents is unexpectedly high. The findings suggest an urgent need to implement effective interventions to reduce risk of hyperuricaemia in Chinese youths.

KEY MESSAGES

• Question: What is the prevalence of hyperuricaemia in Chinese children and adolescents?
• Findings: In this large pooled cross-sectional study comprising >50,000 children and adolescents aged 3–19 years, we found that the prevalence of hyperuricaemia was high in overall population and subgroups of sex, age, obesity, region and survey year.
• Meaning: Our findings indicate that hyperuricaemia is an important health problem in Chinese children and adolescents, and effective intervention strategies are needed to reduce its burden.

     

Relationship between exercise motivation and social support in a support facility for persons with disabilities in Japan

PurposeExercise motivation (EM) is related to individual capabilities and social support. However, in support facilities for people with disabilities, it is susceptible to a lack of social support. In this study, we classified EM into Autonomous Motivation (AM) and controlled motivation (CM) and then examined the influence of social support.MethodThirty-three residents from a support facility for people with disabilities in Japan participated in this study. We conducted a hierarchical multiple regression analysis in which age, gender and time since admission were entered in Step 1, mobility and self-efficacy as individual capabilities in Step 2, and family support, facility support and peer support as social support in Step 3.ResultA significant increase in variance from Step 2 to Step 3 was found for both AM (ΔR² = 0.504, ΔF = 12.18, p < .001) and CM (ΔR² = 0.269, ΔF = 3.491, p = .031). The results also showed that AM was higher among those with high family and facility support, and CM was higher among those with low family and high peer support.ConclusionsSocial support was a more significant predictor of EM among participants than individual capabilities.

KEY MESSAGES

• Among residents of support facilities for people with disabilities, assessing not only individual capabilities but also social support status can lead to better understandings of exercise motivation (EM).
• To enhance facility residents’ autonomous motivation (AM), it is necessary to intervene after evaluating family and facility support.
• When family support is not readily available among facility residents, efforts should be made to encourage residents to interact with each other to increase peer support.

     

Correlation between dietary selenium intake and stroke in the National Health and Nutrition Examination Survey 2003–2018

BackgroundEpidemiologic evidence of the effect of dietary selenium intake on stroke risk remains controversial. This study aimed to examine the cross-sectional correlation between dietary selenium intake and the risk of stroke in adults.Materials and methodsWe retrospectively analysed 39,438 participants from the National Health and Nutrition Examination Survey 2003–2018, aged 20–85 years. Participants were divided into quartiles depending on daily dietary selenium intake: quartile 1 (0–77 μg), quartile 2 (77–108 μg), quartile 3 (108–148 μg), and quartile 4 (148–400 μg). The dose-response relationship was assessed using the restricted cubic spline function.ResultsThe adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of stroke were 0.70 (0.55, 0.88) for participants in quartile 2, 0.71 (0.53, 0.93) for quartile 3, and 0.61 (0.43, 0.85) for quartile 4 compared with that in quartile 1. p-Value for trend through quartiles was .007. A non-linear negative correlation between dietary selenium intake and stroke was observed in the threshold effect analysis and restricted cubic spline function (p-value for non-linearity < .001). An initial decrease in odds of stroke lower than 105 μg/day selenium intake (0.61 [0.44, 0.85], p = .004) was followed by a platform beyond 105 μg/day (0.97 [0.81, 1.16], p = .723). In the subgroup analysis, adjusted ORs (95% CIs) of stroke were 0.51 (0.36, 0.70) for female participants, 0.63 (0.40, 0.99) for participants with age <60 years, 0.63 (0.47, 0.85) for participants with poverty-income ratio < 2.14, 0.66 (0.50, 0.87) for participants with overweight and obesity, 0.66 (0.52, 0.84) for participants with hypertension, 0.72 (0.53, 0.97) for participants without diabetes, and 0.72 (0.56, 0.92) for non-anaemic participants.ConclusionsDietary selenium had a negative and non-linear correlation with the risk of stroke in adults. The correlation varied across different population subgroups.

KEY MESSAGES

• Dietary selenium had a negative and non-linear correlation with the risk of stroke in adults.
• Non-linear negative correlation trends were observed in subpopulations of females, age <60 years, poverty-income ratio <2.14, overweight and obesity, hypertension, non-diabetes, and non-anaemia.
• Dietary selenium intake of approximately 105 μg per day has an optimum effect on stroke.

     

Clinical profiles of SS-ILD compared with SS-NILD in a Chinese population: a retrospective analysis of 735 patients

BackgroundInterstitial lung disease (ILD) is a serious complication in patients with Sjögren’s syndrome (SS). Most studies on primary SS (pSS) with ILD are limited in sample size, and studies on secondary SS (sSS) with ILD are rare. This study aimed to elucidate both primary and secondary SS-associated ILD (SS-ILD) based on a large cohort.MethodsThe medical records of hospitalized patients diagnosed with SS at the Second Xiangya Hospital of Central South University from January 2010 to May 2020 were retrospectively reviewed. Clinical manifestations, medical history, biological results and imaging data were collected.ResultsOf the 735 SS patients enrolled in this study, 563 (76.6%) were diagnosed with pSS, 172 (23.4%) were diagnosed with sSS. Additionally, 316 (43.0%) were diagnosed with SS-ILD. No significant difference was found between the pSS and sSS groups concerning the incidence of ILD (p = .718). Factors associated with SS-ILD were older age (p < .001), male sex (p = .032), female sex at menopause (p = .002), Raynaud’s phenomenon (p < .001), low levels of albumin (p = .010) and respiratory symptoms (p < .001). The SS-ILD group showed higher counts of platelets (p < .001). The three most frequent high-resolution CT (HRCT) findings of SS-ILD were irregular linear opacities (42.7%), grid shadows (30.7%) and pleural thickening (28.5%). NSIP (56.3%) was the most frequent HRCT pattern. Compared with pSS patients with ILD (pSS-ILD) patients, sSS patients with ILD (sSS-ILD) patients had a higher incidence of proteinuria (p < .001) and hypercreatinaemia (p = .013), a higher level of erythrocyte sedimentation rate (ESR) (p = .003), low levels of complement 3 (C3) (p = .013), lymphocytes (p = .009) and leukocytes (p = .024), and worse DLCO (%Pred) (p = .035).ConclusionsILD is a common pulmonary involvement in both pSS patients and sSS patients. Older age, male sex, female sex at menopause, Raynaud’s phenomenon, low albumin levels and respiratory symptoms are risk factors associated with SS-ILD. NSIP is important HRCT feature of SS-ILD. sSS-ILD patients showed worse laboratory results and pulmonary function.

KEY MESSAGE

• Older age, male sex, female sex at menopause, Raynaud’s phenomenon, low albumin levels and respiratory symptoms are risk factors associated with SS-ILD.
• SS-ILD patients show higher counts of platelets and less purpura.
• sSS-ILD patients have worse laboratory results and pulmonary function.

     

Prediabetes as a risk factor for major adverse cardiovascular events

IntroductionType II diabetes mellitus (DM) is a proinflammatory process and a known risk factor for major adverse cardiac events (MACE). The same inflammatory markers may be present in prediabetes (pDM); however, the relationship between pDM by HbA1c and MACE is not well studied. We sought to see if pDM increases one’s risk for MACE.MethodsWe retrospectively studied patients at Beaumont Health, Michigan between 2006 and 2020. We divided patients into groups (G1–G5) based on haemoglobin A1c (HbA1c) trends over the study period as follows: G1: pDM patients who remained pDM; G2: pDM who progressed into DM; G3: pDM who normalized their HbA1c; G4: patients who maintained a normal HbA1c; and G5: patients with HbA1c persistently in the DM range. We compared MACE between the groups by univariate and multivariate regression analyses.ResultsA total of 119,271 patients were included in the study (G1: N = 13,520, G2: N = 6314, G3: N = 1585, G4: N = 15,018, G5: N = 82,834). Pairwise comparison revealed a statistically significant increase in the odds of MACE in all groups compared to those with normal HbA1c values (G4; p < .001). After adjusting for baseline characteristics, multivariate regression revealed elevated odds of MACE in patients with persistent pDM (G1; aOR = 1.087, p = .002) and diabetes (G2/G5; aOR = 1.25 and aOR = 1.18, p < .001) compared to individuals with normal HbA1c values.ConclusionPrediabetes is a risk factor for MACE. Normalization of HbA1c values appears to decrease the adjusted risk for MACE and should be the goal in patients with pDM.

KEY MESSAGES

• Patients with prediabetes (pDM) are at increased risk for major cardiovascular events.
• Normalization of HbA1c in pDM patients may have a clinically significant benefit, in terms of lowering the MACE risk.
• Prediabetes patients who progress into diabetes mellitus may represent a particularly high-risk group.

     

Long-term outcomes after coronary artery bypass surgery in patients with rheumatoid arthritis

ObjectiveTo investigate the long-term outcomes of coronary artery bypass grafting surgery (CABG) in patients with rheumatoid arthritis (RA).MethodsPatients with RA (n = 378) were retrospectively compared to patients without RA (n = 7560), all treated with CABG in a multicentre, population-based cohort register study in Finland. The outcomes were studied with propensity score-matching adjustment for baseline features. The median follow-up was 9.7 years.ResultsDiagnosis of RA was associated with an increased risk of mortality after CABG compared to patients without RA (HR 1.50; CI 1.28–1.77; p < .0001). In addition, patients with RA were in higher risk of myocardial infarction during the follow-up period (HR 1.61; CI 1.28–2.04; p < .0001). Cumulative rate of repeated revascularization after CABG was 14.4% in RA patients and 12.0% in control patients (p = .060). Duration of RA before CABG (p = .011) and preoperative corticosteroid usage in RA (p = .041) were independently associated with higher mortality after CABG. There were no differences between the study groups in 30-d mortality or in the post-operative usage of cardiovascular medications.ConclusionsRA is independently associated with worse prognosis in coronary artery disease treated with CABG. Preoperative corticosteroid use and longer RA disease duration are additional risk factors for mortality.

Key messages

• Patients with rheumatoid arthritis (RA) have impaired long-term outcomes after coronary artery bypass surgery (CABG).
• Glucocorticoid use before CABG and duration of RA are associated with higher mortality.
• Special attention should be paid in secondary prevention of cardiovascular disease in RA patients after CABG.

     

Predictive value of HDL function in patients with coronary artery disease: relationship with coronary plaque characteristics and clinical events

BackgroundHDL is endowed with several metabolic, vascular, and immunoinflammatory protective functions. Among them, a key property is to promote reverse cholesterol transport from cells back to the liver. The aim of this study was to estimate the association of scavenger receptor class B type I (SR-BI)- and ATP binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux (the two major routes for cholesterol efflux to HDL) with the presence, extent, and severity of coronary artery disease (CAD), vascular wall remodelling processes, coronary plaque characteristics, and the incidence of myocardial infarction in the different subgroups of patients from the CAPIRE study.MethodsPatients (n = 525) from the CAPIRE study were divided into two groups: low-risk factors (RF), with 0–1 RF (n = 263), and multiple-RF, with ≥2 RFs; within each group, subjects were classified as no-CAD or CAD based on the segment involvement score (SIS) evaluated by coronary computed tomography angiography (SIS = 0 and SIS > 5, respectively). SR-BI- and ABCA1-mediated cholesterol efflux were measured using the plasma of all patients.ResultsSR-BI-mediated cholesterol efflux was significantly reduced in patients with CAD in both the low-RF and multiple-RF groups, whereas ABCA1-mediated cholesterol efflux was similar among all groups. In CAD patients, multivariable analysis showed that SR-BI-mediated cholesterol efflux <25^th percentile predicted cardiovascular outcome (odds ratio 4.1; 95% CI: 1.3–13.7; p = .019), whereas ABCA-1-mediated cholesterol efflux and HDL-C levels significantly did not. Despite this finding, reduced SR-BI-mediated cholesterol efflux was not associated with changes in high-risk plaque features or changes in the prevalence of elevated total, non-calcified, and low-attenuation plaque volume.ConclusionSR-BI-mediated cholesterol efflux capacity is lower in patients with diffuse coronary atherosclerosis. In addition, a lower SR-BI-mediated cholesterol efflux capacity is associated with the worst clinical outcomes in patients with CAD, independently of atherosclerotic plaque features.

Key Messages

• Increased cholesterol efflux capacity, an estimate of HDL function, is associated with a reduced CVD risk, regardless of HDL-C levels.
• HDL-C levels are significantly lower in patients with CAD.
• Lower SR-BI-mediated cholesterol efflux capacity is observed in patients with diffuse coronary atherosclerosis and is associated with the worst clinical outcomes in patients with CAD, independently of atherosclerotic plaque features.

     

Influence of changes in body fat on clinical outcomes in a general population: a 12-year follow-up report on the Ansan–Ansung cohort in the Korean Genome Environment Study

BackgroundThe impact of the changes in the obesity status on mortality has not been established; thus, we investigated the long-term influence of body fat (BF) changes on all-cause deaths and cardiovascular outcomes in a general population.MethodsA total of 8374 participants were observed for 12 years. BF was measured at least two times using a bioimpedance method. The causes of death were acquired from the nationwide database. A major adverse cardiovascular event (MACE) was defined as a composite of myocardial infarction, coronary artery disease, stroke, and cardiovascular death. Standard deviations (SDs) were derived using a local regression model corresponding to the time elapsed between the initial and final BF measurements (SD_T) and were used to standardize the changes in BF (ΔBF/SD_T).ResultsThe incidence rates of all-cause death, cardiovascular death, and MACE were the highest in the participants with ΔBF/SD_T <−1 and lowest in the participants with ΔBF/SD_T ≥1. Multivariate Cox proportional hazard models adjusted for relevant covariates, including baseline obesity and physical activity, showed that the risks of all-cause deaths (hazard ratio [HR] 0.58; 95% confidence intervals [CI] 0.53–0.64), cardiovascular deaths (HR 0.63; 95% CI 0.51–0.78) and MACEs (HR 0.68; 95% CI 0.62–0.75) decreased as ΔBF/SD_T increased. Subgroup analyses showed that existing cardiovascular diseases weakened the associations between higher ΔBF/SD_T and better outcomes, while high physical activity and exercise did not impact the associations.ConclusionIncreasing BF was associated with a lower risk of all-cause death, cardiovascular death, and MACE in the general population.

Key messages

• Increasing body fat is associated with a lower risk of all-cause death, cardiovascular death, and major cardiovascular adverse events in a low-risk ageing general population, independently of physical activity, underlying cardiovascular disease burden, changes in muscle mass, and baseline obesity status.
• Fatness measured at baseline requires adjustment for the changes in fatness during the follow-up to reveal its impact on the clinical outcomes.

     

Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial

BackgroundThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir–ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19.MethodIn this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion.ResultsA total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days (p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days (p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups.Conclusions and relevancerSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.

Key messages

• There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.
• In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir–ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.

     

A possible association between early life factors and burden of functional bowel symptoms in adulthood

ObjectiveThe studies of early life factors and development of functional bowel diseases show inconsistent results. We therefore examined associations between certain early life factors and functional bowel symptoms in adulthood.DesignPopulation-based cross-sectional study.SettingWeight and height were measured and questionnaires were completed at the time point of enrollment in MOS.Subjects1013 participants in the Malmö Offspring Study (MOS) without organic bowel disease with data available from the Swedish Medical Birth Registry.Main outcome measuresAssociations were calculated between gestational age, birth weight, small-for-gestational-age and Apgar score from the Birth Registry, and symptoms according to the visual analog scale for irritable bowel syndrome (VAS-IBS) (abdominal pain, diarrhea, constipation, bloating and flatulence, vomiting and nausea, and symptoms’ influence on daily life) or self-reported IBS using logistic regression.ResultsIn all, 253 (25.0%) participants reported bowel symptoms during the past 2 weeks and 179 (17.7%) self-reported IBS; conditions which were strongly associated (p < 0.001). Female sex and chronic stress were two independent factors more common among participants with bowel symptoms compared with asymptomatic participants (p < 0.001). Early life factors were not associated with presence of overall bowel symptoms (p = 0.080), any specific bowel symptoms or self-reported IBS. Lower birth weight (p = 0.038) and being born small for gestational age (p = 0.043) were associated with severe influence of intestinal symptoms on daily life in adulthood.ConclusionsLower birth weight and small for gestational age are not associated with the presence of overall bowel symptoms but with more pronounced influence of such symptoms on daily adult life.

Key points

• Lower gestational age tended to be associated with functional bowel symptoms in adulthood.
• Lower birth weight and being small for gestational age are associated with increased negative influences of symptoms on daily life in adulthood.
• Patients born preterm or with low birth weights may be at increased risk to develop functional bowel symptoms later in life.