Long-term risk of autoimmune diseases after mRNA-based SARS-CoV2 vaccination in a Korean, nationwide, population-based cohort study.

The long-term association between mRNA-based coronavirus disease 2019 (COVID-19) vaccination and the development of autoimmune connective tissue diseases (AI-CTDs) remains unclear. In this nationwide, population-based cohort study involving 9,258,803 individuals, we aim to determine whether the incidence of AI-CTDs is associated with mRNA vaccination. The study spans over 1 year of observation and further analyses the risk of AI-CTDs by stratifying demographics and vaccination profiles and treating booster vaccination as time-varying covariate. We report that the risk of developing most AI-CTDs did not increase following mRNA vaccination, except for systemic lupus erythematosus with a 1.16-fold risk in vaccinated individuals relative to controls. Comparable results were reported in the stratified analyses for age, sex, mRNA vaccine type, and prior history of non-mRNA vaccination. However, a booster vaccination was associated with an increased risk of some AI-CTDs including alopecia areata, psoriasis, and rheumatoid arthritis. Overall, we conclude that mRNA-based vaccinations are not associated with an increased risk of most AI-CTDs, although further research is needed regarding its potential association with certain conditions.

Risk of lung diseases in patients with previous carbon monoxide poisoning: a nationwide population-based cohort study in the Republic of Korea.

INTRODUCTION: Carbon monoxide poisoning is associated with severe damage to various organs. In this study, we aimed to determine if previous carbon monoxide poisoning was associated with an increased risk of lung diseases. METHODS: The study population was derived from the National Health Insurance Service database of Korea between 1 January 2002 and 31 December 2021. Adults with carbon monoxide poisoning, with at least one visit to medical facilities between 2002 and 2021, were included. For comparison, an equal number of matched controls with the same index date were selected from the database. RESULTS: A total of 28,618 patients with carbon monoxide poisoning and 28,618 matched controls were included in this study. Approximately 42.8 per cent of the patient and control groups were female, with a mean age of 51.3 years. In patients with carbon monoxide poisoning, there was a significant increase in the risk of lung cancer (adjusted hazard ratio, 1.84; 95 per cent confidence interval, 1.42-2.39; P < 0.001), chronic obstructive pulmonary disease (adjusted hazard ratio, 1.60; 95 per cent confidence interval, 1.36-1.89; P < 0.001), pulmonary tuberculosis (adjusted hazard ratio, 1.46; 95 per cent confidence interval, 1.13-1.88; P = 0.003), and non-tuberculous mycobacterial infection (adjusted hazard ratio, 1.54; 95 per cent confidence interval, 1.01-2.36; P = 0.047). DISCUSSION: In this retrospective cohort study, previous carbon monoxide poisoning was associated with an increased risk of lung cancer, chronic obstructive pulmonary disease, pulmonary tuberculosis, and non-tuberculous mycobacterial infection. Further studies are needed to confirm such an association in other populations and the risk of lung diseases due to the toxic effect of carbon monoxide from different sources. CONCLUSIONS: Previous carbon monoxide poisoning was associated with an increased risk of lung diseases, but the relative importance of the causes and sources of exposure was not known. The long-term management of survivors of acute carbon monoxide poisoning should include monitoring for lung cancer, chronic obstructive pulmonary disease, pulmonary tuberculosis, and non-tuberculous mycobacterial infection.

Relationship between proteinuria and changes in antepartum and postpartum choroidal thickness in patients with pre-eclampsia.

Pre-eclampsia (PE) is a hypertensive disorder characterised by systemic vascular resistance and endothelial dysfunction. It is known to influence choroidal thickness (CT). No previous studies have explored the antepartum and postpartum changes in CT with respect to the protein-creatinine ratio (PCR), a measure of proteinuria that is a clinical hallmark of PE. This study evaluated the correlations between antepartum and postpartum CT and the PCR in patients with PE. In this retrospective study, sixty-six eyes (66 patients) were analysed. The patients were divided into two groups according to the median PCR value (2.36 mg/mg): low PCR group (< 2.36 mg/mg) and high PCR group (≥ 2.36 mg/mg). Ophthalmologic clinical data were collected and assessed. We observed higher antepartum CT and higher mean arterial pressure in high PCR group than in low PCR group. Moreover, postpartum CT decreased significantly in high PCR group. In the multivariate analysis, CT changes were correlated with antepartum CT and antepartum PCR after logarithm transformation. In conclusion, a greater decrease in CT was observed in high PCR group than in low PCR group. Further, the antepartum PCR showed a correlation with the extent of CT reduction.

Hybrid operating rooms and the risk of postoperative hypothermia in pregnant women with placenta previa: A retrospective cohort study.

BACKGROUND: Births at advanced maternal ages (≥ 35 years) are increasing. This has been associated with a higher incidence of placenta previa, which increases bleeding risk. Hybrid operating rooms, designed to accommodate interventions and cesarean sections, are becoming more prominent because of their dual capabilities and benefits. However, they have been associated with increased postoperative hypothermia in pediatric settings; moreover, this has not been studied in pregnant women with placenta previa. METHODS: This retrospective cohort study included pregnant women diagnosed with placenta previa who underwent elective cesarean section under general anesthesia between May 2019 and 2023. The patients were categorized according to the operating room type. The primary outcome was to determine whether the hybrid operating room is a risk factor for immediate postoperative hypothermia, defined as a tympanic membrane temperature below 36.0°C. The secondary outcomes were the effects of immediate postoperative hypothermia on the durations of postanesthetic care unit and postoperative hospital stays and incidence of complications. RESULTS: Immediate postoperative hypothermia (tympanic membrane temperature < 36.0°C) was more prevalent in the hybrid than in the standard operating room group (20% vs. 36.6%, p = 0.033), with a relative risk of 2.86 (95% confidence interval 1.24-6.64, p < 0.001). Patients undergoing surgery in the hybrid operating room who experienced immediate postoperative hypothermia stayed longer in the postanesthetic care unit (26 min vs. 40 min, p < 0.001) and in the hospital after surgery (4 days; range 3-5 vs. 4 days; range 4-11, p = 0.021). However, the complication rates of both groups were not significantly different (11.3% vs 7.3%, p = 0.743). CONCLUSION: Hybrid operating rooms may increase the risk of postoperative hypothermia. Postoperative hypothermia is associated with prolonged postanesthetic care unit and hospital stays. Preventing hypothermia in patients in hybrid operating rooms is of utmost importance.

Global, Regional, and National Epidemiology of Alopecia Areata: A Systematic Review and Modelling Study.

BACKGROUND: Alopecia areata (AA) is a chronic autoimmune disease that leads to a high psychiatric, economic, and systemic disease burden. A comprehensive understanding of AA epidemiology is essential for evaluating healthcare source utilization; however, there is a lack of systematic approach for summarizing epidemiologic data on AA. OBJECTIVES: To systematically investigate the global, regional, and national incidence and prevalence of AA. METHODS: A structured search was conducted using the Ovid MEDLINE, EMBASE, Cochrane Library, Web of Science, SciELO, and Korean journal databases from their inception date to October 4, 2023. Studies that reported the prevalence or incidence of AA were included. We used a Bayesian hierarchical linear mixed model to analyse the prevalence estimates. The primary outcomes of our study were the global, regional, and national prevalence of physician-diagnosed AA for overall population, adults, and children. The incidence data were summarised descriptively. RESULTS: In total, 88 studies from 28 countries were included in the analysis. The reported incidence of alopecia areata tended to be higher in adults aged 19-50 years, and this trend was consistent with its estimated prevalence. The reported prevalence in overall population tended to be higher in men compared to in women. The estimated lifetime prevalence of AA was 0.10% (95% credible intervals, 0.03%-0.39%) in the general population worldwide, 0.12% (95% credible intervals, 0.02%-0.52%) in adults, and 0.03% (95% credible intervals, 0.01%-0.12%) in children. The estimated prevalence was highest in the Asian region and lowest in the African region. CONCLUSIONS: In this study, 48% of the total Global Burden of Disease regions had insufficient data reporting the prevalence or incidence of AA. Further studies are needed to provide epidemiological information on middle- and low-income countries. Our study can serve as a crucial reference in terms of healthcare policy decisions.

Comparing the diagnostic accuracy of PCR-reverse blot hybridization assay and conventional fungus study in superficial fungal infection of the skin: A systematic review.

BACKGROUND: In superficial fungal infections, prompt diagnosis and treatment are essential to prevent the spread of infection and minimise the impact on patients' quality of life. Traditional diagnostic methods, such as KOH smear and fungal culture, have limitations in terms of sensitivity and turnaround time. Recently, the PCR-reverse blot hybridization assay (PCR-REBA) has been developed for the direct detection of dermatophyte DNA. However, there is a lack of information assessing the diagnostic accuracy of PCR-REBA. OBJECTIVES: This systematic review aimed to evaluate the diagnostic accuracy of PCR-REBA in superficial fungal infections compared to conventional and molecular methods. METHODS: The comprehensive search containing Ovid MEDLINE and Embase databases was conducted on 7 August 2022. Two reviewers independently reviewed the included articles. Quality assessment was performed using the Newcastle-Ottawa Scale tool. RESULTS: The included studies were conducted in Korea (five studies) and the Netherlands (two studies), all of which were conducted in a single institution. The quality assessment of these studies indicated low risk of bias. When compared to the potassium hydroxide (KOH) smear and fungus culture, the sensitivity of PCR-REBA ranged from 85% to 100%, and the positive predictive values ranged from 58.9% to 100%. When compared to the RT-PCR, the sensitivity of PCR-REBA ranged from 93.3% to 100%, and the positive and negative predictive values were 91.6%-99.6% and 81.0%-89.1%, respectively. CONCLUSIONS: The PCR-REBA shows promise as a valuable diagnostic tool for dermatophytosis, offering practical and cost-effective benefits.

The impact of C-reactive protein-to-albumin ratio on mortality in patients with acute kidney injury requiring continuous renal replacement therapy: A multicenter retrospective study.

INTRODUCTION: C-reactive protein-to-albumin ratio (CAR) is a prognostic marker in various diseases that represents patients' inflammation and nutritional status. Here, we aimed to investigate the prognostic value of CAR in critically ill patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). METHODS: We retrospectively collected data from eight tertiary hospitals in Korea from 2006-2021. The patients were divided into quartiles according to CAR levels at the time of CRRT initiation. Cox regression analyses were performed to investigate the effect of CAR on in-hospital mortality. The mortality prediction performance of CAR was evaluated using the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: In total, 3995 patients who underwent CRRT were included, and the in-hospital mortality rate was 67.3% during the follow-up period. The 7-day, 30-day, and in-hospital mortality rates increased toward higher CAR quartiles (all P < 0.001). After adjusting for confounding variables, the higher quartile groups had an increased risk of in-hospital mortality (quartile 3: adjusted hazard ratio [aHR], 1.26, 95% confidence interval [CI], 1.10-1.43, P < 0.001; quartile 4: aHR, 1.22, 95% CI, 1.07-1.40, P = 0.003). CAR combined with APACHE II or SOFA scores significantly increased the predictive power compared to each severity score alone for the AUC, NRI, and IDI (all P < 0.05). CONCLUSIONS: A high CAR is associated with increased in-hospital mortality in critically ill patients requiring CRRT. The combined use of CAR and severity scores provides better predictive performance for mortality than the severity score alone.

Discovery of 3-Phenyl Indazole-Based Novel Chemokine-like Receptor 1 Antagonists for the Treatment of Psoriasis.

Chemokine-like receptor 1 (CMKLR1)─a G protein-coupled receptor─has functional roles in the immune system and related diseases, including psoriasis and metabolic diseases. Psoriasis is a chronic inflammatory disease characterized by skin redness, scaliness, and itching. In this study, we sought to develop novel CMKLR1 antagonists by screening our in-house GPCR-targeting compound library. Moreover, we optimized a phenylindazole-based hit compound with antagonistic activities and evaluated its oral pharmacokinetic properties in a murine model. A structure-based design on the human CMKLR1 homology model identified S-26d as an optimized compound that serves as a potent and orally available antagonist with a pIC50 value of 7.44 in hCMKLR1-transfected CHO cells. Furthermore, in the imiquimod-induced psoriasis-like mouse model, oral administration of S-26d for 1 week significantly alleviated modified psoriasis area and severity index scores (severity of erythema, scaliness, skin thickness) compared with the control group.

Correlation between Severity of Idiopathic Epiretinal Membrane and Irvine-Gass Syndrome.

A higher risk of pseudophakic cystoid macular edema (PCME) has been reported in patients with preoperative idiopathic epiretinal membrane (ERM); however, whether the formation of PCME depends on the grade of ERM has not been well established. We conducted a retrospective case-control study of 87 eyes of 78 patients who were preoperatively diagnosed with idiopathic ERM and had undergone cataract surgery. Patients were divided into two groups: PCME and non-PCME groups. After cataract surgery, the ERM status was graded using the Gass and Govetto classifications. Both the central macular thickness (CMT) and ERM grade increased after surgery, and higher preoperative CMT and ERM grades were found in the PCME group. The association between higher-grade ERM and the development of PCME was significant in the Govetto classification (grade 2, odds ratio (OR): 3.13; grade 3, OR: 3.93; and grade 4, OR: 16.07). The study results indicate that close attention should be given to patients with ERM with the presence of an ectopic inner foveal layer before cataract surgery.

The impact of severe depression on the survival of older patients with end-stage kidney disease.

Background: Incidence of depression increases in patients with end-stage kidney disease (ESKD). We evaluated the association between depression and mortality among older patients with ESKD, which has not been studied previously. Methods: This nationwide prospective cohort study included 487 patients with ESKD aged >65 years, who were categorized into minimal, mild-to-moderate, and severe depression groups based on their Beck Depression Inventory-II (BDI-II) scores. Predisposing factors for high BDI-II scores and the association between the scores and survival were analyzed. Results: The severe depression group showed a higher modified Charlson comorbidity index value and lower serum albumin, phosphate, and uric acid levels than the other depression groups. The Kaplan-Meier curve revealed a significantly lower survival in the severe depression group than in the minimal and mild-to-moderate depression groups (p = 0.011). Multivariate Cox regression analysis confirmed that severe depression was an independent risk factor for mortality in the study cohort (hazard ratio, 1.39; 95% confidence interval, 1.01-1.91; p = 0.041). Additionally, BDI-II scores were associated with modified Charlson comorbidity index (p = 0.009) and serum albumin level (p = 0.004) in multivariate linear regression. Among the three depressive symptoms, higher somatic symptom scores were associated with increased mortality. Conclusion: Severe depression among older patients with ESKD increases mortality compared with minimal or mild-to-moderate depression, and patients with concomitant somatic symptoms require careful management of their comorbidities and nutritional status.

Serum and urine metabolomic biomarkers for predicting prognosis in patients with immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most prevalent form of glomerulonephritis worldwide. Prediction of disease progression in IgAN can help to provide individualized treatment based on accurate risk stratification. METHODS: We performed proton nuclear magnetic resonance-based metabolomics analyses of serum and urine samples from healthy controls, non-progressor (NP), and progressor (P) groups to identify metabolic profiles of IgAN disease progression. Metabolites that were significantly different between the NP and P groups were selected for pathway analysis. Subsequently, we analyzed multivariate area under the receiver operating characteristic (ROC) curves to evaluate the predictive power of metabolites associated with IgAN progression. RESULTS: We observed several distinct metabolic fingerprints of the P group involving the following metabolic pathways: glycolipid metabolism; valine, leucine, and isoleucine biosynthesis; aminoacyl-transfer RNA biosynthesis; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism. In multivariate ROC analyses, the combinations of serum glycerol, threonine, and proteinuria (area under the curve [AUC], 0.923; 95% confidence interval [CI], 0.667-1.000) and of urinary leucine, valine, and proteinuria (AUC, 0.912; 95% CI, 0.667-1.000) showed the highest discriminatory ability to predict IgAN disease progression. CONCLUSION: This study identified serum and urine metabolites profiles that can aid in the identification of progressive IgAN and proposed perturbed metabolic pathways associated with the identified metabolites.

Comparison of the Effectiveness of Intravitreal Bevacizumab Injections with and without Simultaneous Cataract Surgery in Diabetic Patients with Macular Edema.

Intravitreal bevacizumab (IVB), often injected during cataract surgery, is currently the main treatment for diabetic macular edema. This retrospective study aimed to compare the effectiveness of IVB injections alone and during cataract surgery in patients with diabetic macular edema. We examined 43 eyes in 40 patients who underwent cataract surgery with simultaneous IVB injections 3-12 months after IVB injections alone. Best-corrected visual acuity and central subfield macular thickness (CMT) were measured 1-month post-injection. The CMTs of the same eyes with IVB-only first and combined-treatment procedures later were 384 ± 149 vs. 315 ± 109 µm pretreatment (p = 0.0002), and after 1 month, they were 319 ± 102 vs. 419 ± 183 µm (p < 0.0001). In the IVB-only procedure, 56.1% of eyes had CMT < 300 µm 1 month after the injection compared to 32.5% after the combined treatment. Therefore, on average, when IVB was administered during cataract surgery, CMT increased, whereas after IVB injection alone, it effectively decreased. More prospective trials with large sample sizes are needed to evaluate the effectiveness of IVB injection performed simultaneously with cataract surgery.

Factors Predicting Older People's Acceptance of a Personalized Health Care Service App and the Effect of Chronic Disease: Cross-Sectional Questionnaire Study.

BACKGROUND: Mobile health (mHealth) services enable real-time measurement of information on individuals' biosignals and environmental risk factors; accordingly, research on health management using mHealth is being actively conducted. OBJECTIVE: The study aims to identify the predictors of older people's intention to use mHealth in South Korea and verify whether chronic disease moderates the effect of the identified predictors on behavioral intentions. METHODS: A cross-sectional questionnaire study was conducted among 500 participants aged 60 to 75 years. The research hypotheses were tested using structural equation modeling, and indirect effects were verified through bootstrapping. Bootstrapping was performed 10,000 times, and the significance of the indirect effects was confirmed through the bias-corrected percentile method. RESULTS: Of 477 participants, 278 (58.3%) had at least 1 chronic disease. Performance expectancy (ß=.453; P=.003) and social influence (ß=.693; P<.001) were significant predictors of behavioral intention. Bootstrapping results showed that facilitating conditions (ß=.325; P=.006; 95% CI 0.115-0.759) were found to have a significant indirect effect on behavioral intention. Multigroup structural equation modeling testing the presence or absence of chronic disease revealed a significant difference in the path of device trust to performance expectancy (critical ratio=-2.165). Bootstrapping also confirmed that device trust (ß=.122; P=.039; 95% CI 0.007-0.346) had a significant indirect effect on behavioral intention in people with chronic disease. CONCLUSIONS: This study, which explored the predictors of the intention to use mHealth through a web-based survey of older people, suggests similar results to those of other studies that applied the unified theory of acceptance and use of technology model to the acceptance of mHealth. Performance expectancy, social influence, and facilitating conditions were revealed as predictors of accepting mHealth. In addition, trust in a wearable device for measuring biosignals was investigated as an additional predictor in people with chronic disease. This suggests that different strategies are needed, depending on the characteristics of users.

Platelet-to-Lymphocyte Ratio and In-Hospital Mortality in Patients With AKI Receiving Continuous Kidney Replacement Therapy: A Retrospective Observational Cohort Study.

Rationale & Objective: The platelet-to-lymphocyte ratio (PLR) is a marker of inflammation and a predictor of mortality in a variety of diseases. However, the effectiveness of PLR as a predictor of mortality in patients with severe acute kidney injury (AKI) is uncertain. We evaluated the association between the PLR and mortality in critically ill patients with severe AKI who underwent continuous kidney replacement therapy (CKRT). Study Design: Retrospective cohort study. Setting & Participants: A total of 1,044 patients who underwent CKRT in a single center, from February 2017 to March 2021. Exposures: PLR. Outcomes: In-hospital mortality. Analytical Approach: The study patients were classified into quintiles according to the PLR values. A Cox proportional hazards model was used to investigate the association between PLR and mortality. Results: The PLR value was associated with in-hospital mortality in a nonlinear manner, showing a higher mortality at both ends of the PLR. The Kaplan-Meier curve revealed the highest mortality with the first and fifth quintiles, whereas the lowest mortality occurred with the third quintile. Compared with the third quintile, the first (adjusted HR, 1.94; 95% CI, 1.44-2.62; P < 0.001) and fifth (adjusted HR, 1.60; 95% CI, 1.18-2.18; P = 0.002) quintiles of the PLR group had a significantly higher in-hospital mortality rate. The first and fifth quintiles showed a consistently increased risk of 30- and 90-day mortality rates compared with those of the third quintile. In the subgroup analysis, the lower and higher PLR values were predictors of in-hospital mortality in patients with older age, of female sex, and with hypertension, diabetes, and higher Sequential Organ Failure Assessment score. Limitations: There may be bias owing to the single-center retrospective nature of this study. We only had PLR values at the time of initiation of CKRT. Conclusions: Both the lower and higher PLR values were independent predictors of in-hospital mortality in critically ill patients with severe AKI who underwent CKRT.

Association between smoking and all-cause mortality in Parkinson's disease.

We aimed to investigate the association between smoking status and all-cause mortality of Parkinson's disease (PD). Among the whole nationwide population data from Korea National Health Insurance Service, newly diagnosed PD was selected, and all-cause mortality was evaluated. The systematic review was performed through a literature search on the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases. Among 26,080 individuals with PD, there was no significant association between smoking status and all-cause mortality in a nationwide cohort study (ex-smoker, HR 0.1.03, 95% CI 0.97-1.10; current smoker, HR 1.06, 95% CI 0.96-1.16). The systematic review, including six prospective cohort studies, also found a nonsignificant association. PD smokers tended to have fewer deaths from neurologic causes but were significantly more likely to die from smoking-related cancers such as lung cancer. We presented a nonsignificant association between smoking and mortality of PD, and cigarette smoking is not recommended in individuals with PD.

Gut taste receptor type 1 member 3 is an intrinsic regulator of Western diet-induced intestinal inflammation.

BACKGROUND: Long-term intake of a Western diet (WD), characterized by a high-fat content and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms by which dietary changes contribute to IBD development remain unknown. Therefore, we examined the influence of long-term intake of a WD on intestinal inflammation and the mechanisms by which WD intake affects IBD development. METHODS: Mice fed normal diet or WD for 10 weeks, and bowel inflammation was evaluated through pathohistological and infiltrated inflammatory cell assessments. To understand the role of intestinal taste receptor type 1 member 3 (TAS1R3) in WD-induced intestinal inflammation, cultured enteroendocrine cells harboring TAS1R3, subjected to RNA interference or antagonist treatment, and Tas1r3-deficient mice were used. RNA-sequencing, flow cytometry, 16S metagenomic sequencing, and bioinformatics analyses were performed to examine the involved mechanisms. To demonstrate their clinical relevance, intestinal biopsies from patients with IBD and mice with dextran sulfate sodium-induced colitis were analyzed. RESULTS: Our study revealed for the first time that intestinal TAS1R3 is a critical mediator of WD-induced intestinal inflammation. WD-fed mice showed marked TAS1R3 overexpression with hallmarks of serious bowel inflammation. Conversely, mice lacking TAS1R3 failed to exhibit inflammatory responses to WD. Mechanistically, intestinal transcriptome analysis revealed that Tas1r3 deficiency suppressed mTOR signaling, significantly increasing the expression of PPARγ (a major mucosal defense enhancer) and upregulating the expression of PPARγ target-gene (tight junction protein and antimicrobial peptide). The gut microbiota of Tas1r3-deficient mice showed expansion of butyrate-producing Clostridia. Moreover, an increased expression of host PPARγ-signaling pathway proteins was positively correlated with butyrate-producing microbes, suggesting that intestinal TAS1R3 regulates the relationship between host metabolism and gut microflora in response to dietary factors. In cultured intestinal cells, regulation of the TAS1R3-mTOR-PPARγ axis was critical for triggering an inflammatory response via proinflammatory cytokine production and secretion. Abnormal regulation of the axis was observed in patients with IBD. CONCLUSIONS: Our findings suggest that the TAS1R3-mTOR-PPARγ axis in the gut links Western diet consumption with intestinal inflammation and is a potential therapeutic target for IBD.

Catecholamine induces Kupffer cell apoptosis via growth differentiation factor 15 in alcohol-associated liver disease.

Chronic alcohol consumption often induces hepatic steatosis but rarely causes severe inflammation in Kupffer cells (KCs) despite the increased hepatic influx of lipopolysaccharide (LPS), suggesting the presence of a veiled tolerance mechanism. In addition to LPS, the liver is affected by several gut-derived neurotransmitters through the portal blood, but the effects of catecholamines on KCs have not been clearly explored in alcohol-associated liver disease (ALD). Hence, we investigated the regulatory roles of catecholamine on inflammatory KCs under chronic alcohol exposure. We discovered that catecholamine levels were significantly elevated in the cecum, portal blood, and liver tissues of chronic ethanol-fed mice. Increased catecholamines induced mitochondrial translocation of cytochrome P450 2E1 in perivenous hepatocytes expressing the ß2-adrenergic receptor (ADRB2), leading to the enhanced production of growth differentiation factor 15 (GDF15). Subsequently, GDF15 profoundly increased ADRB2 expression in adjacent inflammatory KCs to facilitate catecholamine/ADRB2-mediated apoptosis. Single-cell RNA sequencing of KCs confirmed the elevated expression of Adrb2 and apoptotic genes after chronic ethanol intake. Genetic ablation of Adrb2 or hepatic Gdf15 robustly decreased the number of apoptotic KCs near perivenous areas, exacerbating alcohol-associated inflammation. Consistently, we found that blood and stool catecholamine levels and perivenous GDF15 expression were increased in patients with early-stage ALD along with an increase in apoptotic KCs. Our findings reveal a novel protective mechanism against ALD, in which the catecholamine/GDF15 axis plays a critical role in KC apoptosis, and identify a unique neuro-metabo-immune axis between the gut and liver that elicits hepatoprotection against alcohol-mediated pathogenic challenges.

Is endotracheal tube displacement during head and neck extension due to ascending movement or tracheal lengthening? An observational ultrasonographic study.

Complications of the endotracheal tube (ETT) displacement during head and neck positional changes are related to not only the tip position but also the cuff pressure against the larynx. Here, we evaluated movement of the ETT cuff relative to laryngeal structures as well as tip displacement from the carina.Sixty-two patients scheduled for thyroidectomy were recruited. The distance from the cricoid cartilage to the upper margin of the cuff (CC) and that from the ETT tip to the carina (TC) were measured using ultrasonography and fiberoptic bronchoscopy, respectively, during flexion and extension. The total tracheal length (TTL) was defined as the combination of CC, TC, and the distance from the upper margin of the cuff to the tip.During flexion, the CC and TC were 1.5 ± 0.6 and 2.9 ± 1.0 cm respectively. Seven patients (11.7%) exhibited excessively deep intubation. After adjusting the cuff position under ultrasonography (CC = 0), the tip position was corrected in 96.7%. While the TC increased by 2.1 ± 1.0 cm after the positional change in extension, the CC decreased by 0.6 ± 0.7 cm because the TTL lengthened (1.4 ± 1.1 cm). Four patients (6.7%) exhibited excessive cuff displacement beyond the cricoid cartilage, which could have been corrected under ultrasonography.In conclusion, the ETT cuff displaced toward the larynx in a less degree than the tip did from the carina due to the tracheal lengthening during head and neck extension. Nevertheless, we suggest that ultrasonographic assessment of cuff position may avoid ETT misplacement. Trial registration https://cris.nih.go.kr/ (approval no. KCT0005319); registered on May 14, 2019.

Bacteroides vulgatus SNUG 40005 Restores Akkermansia Depletion by Metabolite Modulation.

BACKGROUND & AIMS: Weight loss and exercise intervention have been reported to increase the interaction between Bacteroides spp and Akkermansiamuciniphila (Am), although the underlying mechanisms and consequences of the interaction remain unknown. METHODS: Using a healthy Korean twin cohort (n = 582), we analyzed taxonomic associations with host body mass index. B vulgatus strains were isolated from mice and human subjects to investigate the strain-specific effect of B vulgatus SNUG 40005 (Bvul) on obesity. The mechanisms underlying Am enrichment by Bvul administration were investigated by multiple experiments: (1) in vitro cross-feeding experiments, (2) construction of Bvul mutants with the N-acetylglucosaminidase gene knocked out, and (3) in vivo validation cohorts with different metabolites. Finally, metabolite profiling in mouse and human fecal samples was performed. RESULTS: An interaction between Bvul and Am was observed in lean subjects but was disrupted in obese subjects. The administration of Bvul to mice fed a high-fat diet decreased body weight, insulin resistance, and gut permeability. In particular, Bvul restored the abundance of Am, which decreased significantly after a long-term high-fat diet. A cross-feeding analysis of Am with cecal contents or Bvul revealed that Am enrichment was attributed to metabolites produced during mucus degradation by Bvul. The metabolome profile of mouse fecal samples identified N-acetylglucosamine as contributing to Am enrichment, which was confirmed by in vitro and in vivo experiments. Metabolite network analysis of the twin cohort found that lysine serves as a bridge between N-acetylglucosamine, Bvul, and Am. CONCLUSIONS: Strain-specific microbe-microbe interactions modulate the mucosal environment via metabolites produced during mucin degradation in the gut.

Serum and urine metabolomic biomarkers for predicting prognosis in patients with immunoglobulin A nephropathy

Immunoglobulin A nephropathy (IgAN) is the most prevalent form of glomerulonephritis worldwide. Prediction of disease progression in IgAN can help to provide individualized treatment based on accurate risk stratification. Methods: We performed proton nuclear magnetic resonance-based metabolomics analyses of serum and urine samples from healthy controls, non-progressor (NP), and progressor (P) groups to identify metabolic profiles of IgAN disease progression. Metabolites that were significantly different between the NP and P groups were selected for pathway analysis. Subsequently, we analyzed multivariate area under the receiver operating characteristic (ROC) curves to evaluate the predictive power of metabolites associated with IgAN progression. Results: We observed several distinct metabolic fingerprints of the P group involving the following metabolic pathways: glycolipid metabolism; valine, leucine, and isoleucine biosynthesis; aminoacyl-transfer RNA biosynthesis; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism. In multivariate ROC analyses, the combinations of serum glycerol, threonine, and proteinuria (area under the curve [AUC], 0.923; 95% confidence interval [CI], 0.667–1.000) and of urinary leucine, valine, and proteinuria (AUC, 0.912; 95% CI, 0.667–1.000) showed the highest discriminatory ability to predict IgAN disease progression. Conclusion: This study identified serum and urine metabolites profiles that can aid in the identification of progressive IgAN and proposed perturbed metabolic pathways associated with the identified metabolites.