Baseline and on-treatment HBcrAg levels as predictors of HBeAg seroconversion in chronic hepatitis B patients treated with antivirals.

HBeAg seroconversion is an important treatment endpoint. We aimed to identify predictors of seroconversion using serum HBsAg and hepatitis B core-related antigen (HBcrAg) in HBeAg-positive patients treated with nucleos(t)ide analogs (NAs). Data and samples from 70 HBeAg-positive patients treated with entecavir or tenofovir between January 2007 and December 2017 were retrospectively analysed. The mean follow-up period was 11 years. The predictive power for HBeAg seroconversion of HBcrAg levels at baseline and 2 years after antiviral therapy was determined using receiver operating curve analysis. Twenty-one patients (30%) achieved HBeAg seroconversion at a mean of 28 (range, 12-84) months after antiviral treatment. The median baseline HBcrAg and HBsAg levels were 6.9(5.7-7.0) vs. 5.8(5.5-6.5) log10 U/mL (p = .006), 4.9(4.5-5.1) vs. 4.5(4.1-5.0) log10 IU/mL (p = .044) in the no seroconversion group and seroconversion group, respectively. In the multivariate analysis, the serum HBcrAg levels at baseline and 2 years after antiviral therapy were predictive factors for HBeAg seroconversion ([HR]; 0.326; [CI], 0.111-0.958; p = .042 and HR, 0.4555; CI, 0.211-0.984; p = .045). HBcrAg levels≤6.5log10 U/mL at baseline and ≤5.3log10 U/mL at 2 years after antiviral therapy had sensitivities of 53.1% and 69.8%, specificities of 95.2% and 70.6%, positive predictive values of 82.6% and 50.0%, and negative predictive values of 82.6% and 84.5%, respectively, with AUROCs of 0.712 (95%CI, 0.596-0.830) and 0.745 (95%CI, 0.599-0.891) for predicting HBeAg seroconversion. In chronic hepatitis B patients treated with NAs, HBcrAg levels≤6.5log10 U/mL at baseline and ≤5.3log10 U/mL at 2 years after antiviral therapy were useful predictive factors of HBeAg seroconversion.

Causes for Retraction in the Biomedical Literature: A Systematic Review of Studies of Retraction Notices.

BACKGROUND: Many studies have evaluated the prevalence of different reasons for retraction in samples of retraction notices. We aimed to perform a systematic review of such empirical studies of retraction causes. METHODS: The PubMed/MEDLINE database and the Embase database were searched in June 2023. Eligible studies were those containing sufficient data on the reasons for retraction across samples of examined retracted notices. RESULTS: A 11,181 potentially eligible items were identified, and 43 studies of retractions were included in this systematic review. Studies limited to retraction notices of a specific subspecialty or country, journal/publication type are emerging since 2015. We noticed that the reasons for retraction are becoming more specific and more diverse. In a meta-analysis of 17 studies focused on different subspecialties, misconduct was responsible for 60% (95% confidence interval [CI], 53-67%) of all retractions while error and publication issues contributed to 17% (95% CI, 12-22%) and 9% (95% CI, 6-13%), respectively. The end year of the retraction period in all included studies and the proportion of misconduct presented a weak positive association (coefficient = 1.3% per year, P = 0.002). CONCLUSION: Misconduct seems to be the most frequently recorded reason for retraction across empirical analyses of retraction notices, but other reasons are not negligible. Greater specificity of causes and standardization is needed in retraction notices.

A Cross-Sectional Investigation of the Association between Arterial Stiffness and Depressive Symptoms, Anxiety Symptoms, and Quality of Life.

Background and Objectives: Previous studies have assessed the association between arterial stiffness and depressive and anxiety symptoms, but the results were inconsistent. We aimed to conduct a cross-sectional study to assess the relationship between arterial stiffness, depressive and anxiety symptoms, and quality of life. Materials and Methods: We analyzed the 2014-2015 Korea Institute of Sport Science Fitness Standards project data. Brachial-ankle pulse wave velocity (baPWV) was measured to assess arterial stiffness. High baPWV was defined as a baPWV higher than 1400 cm/s. Participants completed Beck's depressive symptoms inventory (BDI), Beck's anxiety symptoms inventory (BAI), and the World Health Organization's Quality of Life Questionnaire (WHOQOL-Bref). We performed a logistic regression analysis by adjusting confounding factors and used the inverse probability of treatment weighting (IPTW) method. Results: 1936 participants were included in the analysis (men 43.9%, median age 47). Participants with a high baPWV had higher odds of depressive symptoms compared to those with a normal baPWV (aOR 1.920, 95% CI 1.062-3.472, p = 0.031; IPTW OR 2.637, 95% CI 1.219-5.704, p = 0.014). In addition, baPWV was significantly associated with depressive symptoms in the IPTW model in men but not in women (OR 2.497, 95% CI 1.004-6.207, p = 0.049). High baPWV was not associated with anxiety symptoms in all models, but it was associated with poor QOL in women (OR 4.561, 95% CI 1.465-14.199, p = 0.009). Conclusions: High baPWV was associated with higher odds of depressive symptoms, especially in men. Our study suggests a modest association between arterial stiffness and depressive symptoms in Korean adults.

Association between sarcopenia and quality of life among adults aged ≥ 65 years from low- and middle-income countries.

BACKGROUND: Sarcopenia has been associated with a lower quality of life (QoL). However, studies on this association from low- and middle-income countries (LMICs) are scarce. AIMS: To examine the association between sarcopenia and QoL, in a large nationally representative sample of older adults from six LMICs. METHODS: Cross-sectional, community-based data from the WHO study on global ageing and adult health (SAGE) were analysed. Non-severe sarcopenia was defined as having low skeletal muscle mass (SMM) and weak handgrip strength but no slow gait speed, while severe sarcopenia was defined as having low SMM, weak handgrip strength, and slow gait speed. QoL was assessed with the 8-item WHO QoL instrument (range 0-100) with higher scores representing better QoL. Multivariable linear regression analysis was conducted. RESULTS: Data on 14,585 people aged ≥ 65 years were analyzed [mean (SD) age 72.6 (11.5) years; 55.0% female]. After adjustment for potential confounders, compared to no sarcopenia, severe sarcopenia was associated with a significant - 3.37 points [95% CI - 5.56, - 1.18] lower QoL score. Non-severe sarcopenia was not significantly associated with lower QoL. DISCUSSION: The association between sarcopenia and QoL observed in our study may be explained by factors such as functional impairment and disability related with sarcopenia. CONCLUSIONS: In this large representative sample of older adults from multiple LMICs, compared to no sarcopenia, only severe sarcopenia was associated with a significantly lower QoL score. Interventions to prevent or manage sarcopenia among older adults in LMICs may contribute to better QoL in this population.

Genetic Polymorphism of PTPN22 in Autoimmune Diseases: A Comprehensive Review.

It is known that the etiology and clinical outcomes of autoimmune diseases are associated with a combination of genetic and environmental factors. In the case of the genetic factor, the SNPs of the PTPN22 gene have shown strong associations with several diseases. The recent exploding numbers of genetic studies have made it possible to find these associations rapidly, and a variety of autoimmune diseases were found to be associated with PTPN22 polymorphisms. Proteins encoded by PTPN22 play a key role in the adaptative and immune systems by regulating both T and B cells. Gene variants, particularly SNPs, have been shown to significantly disrupt several immune functions. In this review, we summarize the mechanism of how PTPN22 and its genetic variants are involved in the pathophysiology of autoimmune diseases. In addition, we sum up the findings of studies reporting the genetic association of PTPN22 with different types of diseases, including type 1 diabetes mellitus, systemic lupus erythematosus, juvenile idiopathic arthritis, and several other diseases. By understanding these findings comprehensively, we can explain the complex etiology of autoimmunity and help to determine the criteria of disease diagnosis and prognosis, as well as medication developments.

Sarcopenia is an independent risk factor for short-term mortality in patients undergoing transjugular intrahepatic portosystemic shunt.

BACKGROUND: Sarcopenia is common in patients with cirrhosis and is a risk factor for increased mortality. Transjugular intrahepatic portosystemic shunt (TIPS) placement has been utilized in cirrhosis patients with decompensation. We investigated the role of sarcopenia in predicting mortality in patients undergoing TIPS. METHODS: We conducted a single-center retrospective study of 232 patients with cirrhosis who underwent TIPS between January 2010 and December 2015. Sarcopenia was defined by the psoas muscle index (PMI) cutoff value, calculated based on dynamic time-dependent outcomes using X-tile software. Kaplan-Meier analysis demonstrated the difference in survival in the sarcopenia group versus the non-sarcopenia group. . Univariate and multivariate analyses were used to identify the relationship between sarcopenia and post-TIPS mortality during a follow-up period of 1 year. RESULTS: For TIPS indications, 111 (47.84%) patients had refractory ascites, 69 (29.74%) patients had variceal bleeding, 12 (5.17%) patients had ascites, and 40 (17.24%) for other indications. The mean PMI was 4.40 ±â€…1.55. Sarcopenia was defined as a PMI value of <4.36 in males, and <3.23 in females. Sarcopenia was present in 96 (41.38%) of patients. . Kaplan-Meier analysis showed thatsarcopenia is associated with worse survival (log-rank P < 0.01). Multivariate Cox regression analysis showed that sarcopenia is independently associated with worse survival during the 1-year follow-up period with an hazard ratio of 2.435 (95% CI 1.346-4.403) (P < 0.01), after adjusting for age, BMI, indications for TIPS, etiology for cirrhosis, and MELD score and stratified by sex. CONCLUSION: Sarcopenia is an independent risk factor for 1-year mortality in patients undergoing TIPS and should be considered when patients are evaluated as a candidate for TIPS.

Pulmonary Tuberculosis and Risk of Lung Cancer: A Systematic Review and Meta-Analysis.

Pulmonary tuberculosis (TB) is a known risk factor for lung cancer. However, a detailed analysis of lung cancer type, age, sex, smoking, and TB burden associated with geographic and socioeconomic status has not been performed previously. We systematically appraised relevant observational studies reporting an association between pulmonary TB and lung cancer. All studies were included in the primary analysis, and studies that used robust TB diagnostic methods, such as validated medical diagnostic codes, were included in the secondary analysis. Thirty-two articles were included. The association between the history of pulmonary TB and diagnosis of lung cancer was statistically significant (OR 2.09, 95% CI: 1.62-2.69, p < 0.001). There was a high heterogeneity (I2 = 95%), without any publication bias. The analysis indicated a high association in advanced articles describing stringent pulmonary TB diagnosis (OR 2.26, 95% CI: 1.29-3.94, p = 0.004). The subgroup analyses suggested a significant association in countries with medium or high TB burdens, from East Asia and the Pacific region, and upper-middle income countries. Heterogeneity within the subgroups remained high in a majority of the subgroup analyses. A meta-regression analysis revealed that younger patients showed a significantly higher association between TB and lung cancer (regression coefficient = 0.949, p < 0.001). The history of pulmonary TB is an independent risk factor for lung cancer, especially in younger patients diagnosed with pulmonary TB. Clinicians should be aware of this association while treating young patients with a history of pulmonary TB.

Neurocognitive Effects of Chemotherapy for Colorectal Cancer: A Systematic Review and a Meta-Analysis of 11 Studies.

PURPOSE: Chemotherapy-related cognitive impairment (CRCI) is a controversial concept not much explored on colorectal cancer patients. MATERIALS AND METHODS: We identified 11 prospective studies: eight studies on 696 colorectal cancer patients who received chemotherapy and three studies on 346 rectal cancer patients who received neoadjuvant chemoradiotherapy. Standardized mean differences (SMDs) of neuropsychological test results and the cognitive quality-of-life scale were calculated using random effect models. A meta-regression was conducted to investigate the association between mean study population age and effect sizes. RESULTS: The association between chemotherapy and cognitive impairment was not clear in colorectal cancer patients (SMD, 0.003; 95% confidence interval, ‒0.080 to 0.086). However, a meta-regression showed that older patients are more vulnerable to CRCI than younger patients (ß=‒0.016, p < 0.001). CONCLUSION: Chemotherapy has an overall positive negligible effect size on the cognitive function of colorectal patients. Age is a significant moderator of CRCI.

Functional proteomics study reveals that N-Acetylglucosaminyltransferase V reinforces the invasive/metastatic potential of colon cancer through aberrant glycosylation on tissue inhibitor of metalloproteinase-1.

N-Acetylglucosaminyltransferase-V (GnT-V) has been reported to be up-regulated in invasive/metastatic cancer cells, but a comprehensive understanding of how the transferase correlates with the invasive/metastatic potential is not currently available. Through a glycomics approach, we identified 30 proteins, including tissue inhibitor of metalloproteinase-1 (TIMP-1), as a target protein for GnT-V in human colon cancer cell WiDr. TIMP-1 was aberrantly glycosylated as characterized by the addition of beta1,6-N-acetylglucosamine, polylactosaminylation, and sialylation in GnT-V-overexpressing WiDr cells. Compared with normal TIMP-1, the aberrantly glycosylated TIMP-1 showed the weaker inhibition on both matrix metalloproteinase (MMP)-2 and MMP-9, and this aberrancy was closely associated with cancer cell invasion and metastasis in vivo as well as in vitro. Integrated data, both of TIMP-1 expression level and aberrant glycosylation, could provide important information to aid to improve the clinical outcome of colon cancer patients.

Identification of target proteins of N-acetylglucosaminyl-transferase V and fucosyltransferase 8 in human gastric tissues by glycomic approach.

To understand better the mechanism underlying gastric cancer and search for potential markers for gastric cancer prognosis, the proteomic analysis of gastric cancer tissues was conducted using two-dimensional gel electrophoresis and lectin blot, followed by electrospray ionization-mass spectrometry. These approaches permitted identification of glyco- or putative glycosylated proteins which may be associated with tumorigenesis. The proteins identified include molecules involved in sugar metabolism, signal transduction, proteolysis, and stress, as well as several unknown proteins, which were aberrantly glycosylated as evidenced by the L-phytohemagglutinin blot.