Objective
To evaluate Pneumocystis jirovecii pneumonia (PJP) infection risk in patients with systemic lupus erythematosus (SLE) in Taiwan.
Methods
We identified 24,367 patients with SLE from the ...National Health Insurance research database between 1997 and 2012 and compared the PJP incidence rates (IRs) with those in 243,670 age‐ and sex‐matched non‐SLE controls. PJP risk in the patients was evaluated using a Cox multivariate proportional hazards model.
Results
The SLE patients exhibited a significantly higher PJP risk than the controls, with an IR of 2.63 per 10,000 person‐years and IR ratio of 27.65 (95% confidence interval 17.2–45.3; P < 0.001). Male sex (hazard ratio HR 2.42, P < 0.01), end‐stage renal disease (ESRD; HR 1.74, P = 0.01), recent use of mycofenolate mofetil (MMF; HR 4.43, P < 0.001), intravenous steroid pulse therapy (HR 108.73, P < 0.001), and average oral dosage of >7.5 mg/day prednisolone or equivalent treatment (HR 4.83, P < 0.001) were associated with PJP in SLE, whereas hydroxychloroquine use reduced its risk (HR 0.51, P = 0.01). Of note, cyclophosphamide was not associated with PJP infection in the multivariate Cox proportional hazard model.
Conclusion
Patients with SLE have a considerably high PJP risk. Cyclophosphamide does not increase PJP risk. Male sex, ESRD, MMF use, intravenous steroid pulse therapy, and oral prednisolone or equivalent treatment (>7.5 mg/day) are risk factors for PJP, whereas hydroxychloroquine use reduces PJP risk.
•The estimated prevalence of sarcopenia in RA was 31%, without significant differences between various living area and diagnostic modalities.•Disease duration, DAS28 and HAQ were predictors of ...sarcopenia development in patients with RA.•Functional limitation, CRP and RF seropositivity were identified as additional risk factors.
Sarcopenia is an ever-increasingly recognized entity in aging or chronically-ill individuals. A recent surge of researches came out on sarcopenia in rheumatoid arthritis (RA). However, the results varied widely. We tried to assess the prevalence of and associated factors with sarcopenia in patients with RA.
We searched the investigations dealing with the prevalence of and associated factors with sarcopenia in RA from PubMed, EMBASE, CENTRAL, EBSCOhost, Airiti Library, CEPS, CNKI and J-STAGE from the inception to January 11, 2020. Effects regarding prevalence and associated factors were extracted and evaluated by random-effects model. Sensitivity analysis was also performed.
Seventeen studies containing 3,140 RA subjects were identified. After exclusion of outliers, the pooled prevalence of sarcopenia was 31%. Neither ongoing-study districts nor diagnostic modalities affected prevalence significantly. Any associated factors being mentioned in at least two publications were analyzed, yielding functional limitation (Steinbrocker stage III/IV), high CRP and RF seropositivity as the significant risk factors. Based on disease durations, we carried out meta-regression and found DAS28 and HAQ are predictive models. There was no alteration in the interpretation of results from sensitivity analysis after removal of any studies skewed in sampling distribution.
The prevalence of sarcopenia in patients with RA is high, compared to that in general counterparts. Disease duration rather than age, residing area or diagnostic modalities influences sarcopenia development; DAS28 and HAQ predict occurrence. High index of suspicion to facilitate early detection of sarcopenia in RA patients is important.
Suppression of cardiac iinflammasome, which can be inhibited by Farnesoid X receptor (FXR) agonist, can ameliorate cardiac inflammation and fibrosis. Increased cardiac inflammasome decrease the ...abundance of regulatory T (Treg) cells and exacerbate cardiac dysfunction. Interaction between cardiomyocytes and Treg cells is involved in the development of nonalcoholic steatohepatitis (NASH)-related cardiac dysfunction.
This study evaluates whether the FXR agonist obeticholic acid (OCA) treatment improves NASH-associated cardiac dysfunction.
The in vivo and in vitro mechanisms and effects of two weeks of OCA treatment on inflammasome and Treg dysregulation-related cardiac dysfunction in NASH mice (NASH-OCA) at systemic, tissue and cellular levels were investigated.
The OCA treatment suppressed the serum and cardiac inflammasome levels, reduced the cardiac infiltrated CD3+ T cells, increased the cardiac Treg-represented anti-inflammatory cytokines (IL-10/IL-10R) and improved cardiac inflammation, fibrosis and function decreased left ventricle (LV) mass and increased fractional shortening (FS) in NASH-OCA mice. The percentages of OCA-decreased cardiac fibrosis and OCA-increased FS were positively correlated with the percentage of OCA-increased levels of cardiac FXR and IL-10/IL-10R. In the Treg cells from NASH-OCA mice spleen, in comparison with the Treg cells of the NASH group, higher intracellular FXR but lower inflammasome levels, and more proliferative/active and less apoptotic cells were observed. Incubation of H9c2 cardiomyoblasts with Treg-NASHcm supernatant of Treg from NASH mice as condition medium (cm), increased inflammasome levels, decreased the proliferative/active cells, suppressed the intracellular FXR, and downregulated differentiation/contraction marker. The Treg-NASHcm-induced hypocontractility of H9c2 can be attenuated by co-incubation with OCA, and the OCA-related effects were abolished by siIL-10R pretreatment.
Chronic FXR activation with OCA is a potential strategy for activating IL-10/IL-10R signalling, reversing cardiac regulatory T cell dysfunction, and improving inflammasome-mediated NASH-related cardiac dysfunction.
Medical personnel need to learn occupational safety knowledge in clinical workplaces, not only to ensure their own safety, but also to further ensure patients safety. Based on Human-centered ...artificial intelligence (HAI) technology, this study will provide HAI-based occupational safety training system for two training topics, Needle Stick/Sharps Injury (NSSI) prevention and appropriate Clinical Waste Management (CWM). From April 2018 to December 2021, this clinical occupational safety HAI training is used by 342 medical personnel (doctors and non-doctors). This study aims to investigate the learning performance and effectiveness including decreasing anxiety and increasing mastering level of users. This study shows that, for the first-time and feel-friendly users of this HAI training system, not only can they achieve significant learning improvement, but they can also effectively decrease their anxiety and increase their mastery level of clinical work safety knowledge and skill. In terms of learning performance and effectiveness, this study found that doctors are significantly benefited by the HAI training system in contrast to non-doctors.
In obesity, there are no effective therapies for parallel immune and metabolic abnormalities, including systemic/tissue insulin-resistance/inflammation, adiposity and hepatic steatosis. Caffeine has ...anti-inflammation, antihepatic steatosis, and anti-insulin resistance effects. In this study, we evaluated the effects and molecular mechanisms of 6 wk of caffeine treatment (HFD-caf) on immunological and metabolic abnormalities of high-fat diet (HFD)-induced obese rats. Compared with HFD vehicle (HFD-V) rats, in HFD-caf rats the suppressed circulating immune cell inflammatory TNFα, MCP-1, IL-6, intercellular adhesion molecule 1 (ICAM-1), and nitrite profiles were accompanied by decreased liver, white adipose tissue (WAT), and muscle macrophages and their intracellular cytokine levels. Metabolically, the increase in metabolic rates reduced lipid accumulation in various tissues, resulting in reduced adiposity, lower fat mass, decreased body weight, amelioration of hepatic steatosis, and improved systemic/muscle insulin resistance. Further mechanistic approaches revealed an upregulation of tissue lipogenic (SREBP1c, fatty acid synthase, acetyl-CoA carboxylase)/insulin-sensitizing (GLUT4 and p-IRS1) markers in HFD-caf rats. Significantly, ex vivo experiments revealed that the cytokine release by the cocultured peripheral blood mononuclear cell (monocyte) and WAT (adipocyte), which are known to stimulate macrophage migration and hepatocyte lipogenesis, were lower in HFD-V groups than HFD-caf groups. Caffeine treatment simultaneously ameliorates immune and metabolic pathogenic signals present in tissue to normalize immunolgical and metabolic abnormalities found in HFD-induced obese rats.
Vitamin D deficiency and up-regulated TNFα-related signals are reported to be involved in abnormalities including intestinal hyper-permeability, bacterial translocation, systemic/portal endotoxemia, ...intestinal/adipose tissue/hepatic inflammation, and hepatic steatosis in nonalcoholic steatohepatitis (NASH). This study aims to explore the molecular mechanisms and effects of chronic calcitriol 1,25-(OH)2D3, hormonal form of vitamin D on gut-adipose tissue-liver axis abnormalities using a high-fat diet (HFD)-fed rat model of NASH. In HFD-fed obese rats on a 10-week calcitriol (0.3 μg/kg/TIW) or vehicle treatment (NASH-vit. D and NASH-V rats) reigme, various in vivo and in vitro experiments were undertaken. Through anti-TNFα-TNFR1-NFκB signaling effects, chronic calcitriol treatment significantly restored plasma calcitriol levels and significantly improved vitamin D receptor (VDR) expression in monocytes and the small intestine of NASH-vit. D rats. Significantly, plasma and portal endotoxin/TNFα levels, bacterial translocation to mesenteric lymph nodes, plasma DX-4000-FITC, fecal albumin-assessed intestinal hyper-permeability, over-expression of TNFα-related immune profiles in monocytes, inflammation of intestinal/mesenteric adipose tissue (MAT)/liver and hepatic steatosis were improved by chronic calcitriol treatment of NASH rats. Additionally, in vitro experiments with acute calcitriol co-incubation reversed NASH-V rat monocyte supernatant/TNFα-induced monolayer barrier dysfunction in caco-2 cells, cytokine release from MAT-derived adipocytes, and triglyceride synthesis by lean-V rat hepatocytes. Using in vivo and in vitro experiments, our study reported calcitriol signaling in the gut as well as in adipose tissue. Meanwhile, our study suggests that restoration of systemic and intestinal vitamin D deficiency using by chronic vitamin D treatment effectively reduces TNFα-mediated immunological abnormalities associated with the gut-adipose tissue-liver axis and hepatic steatosis in NASH rats.
In advanced cirrhosis, the TNFα-mediated intestinal inflammation and bacteria dysbiosis are involved in the development of inflammation and vasoconstriction-related renal dysfunction. In colitis and ...acute kidney injury models, activation of SIRT1 attenuates the TNFα-mediated intestinal and renal abnormalities. This study explores the impacts of intestinal SIRT1 deficiency and TNFα-mediated intestinal abnormalities on the development of cirrhosis-related renal dysfunction. Systemic and renal hemodynamics, intestinal dysbiosis cirrhosis dysbiosis ratio (CDR) as marker of dysbiosis, and direct renal vasoconstrictive response (renal vascular resistance (RVR) and glomerular filtration rate (GFR)) to cumulative doses of TNFα were measured in bile duct ligated (BDL)-cirrhotic ascitic mice. In SIRT1
-BDL-ascitic mice, the worsening of intestinal dysbiosis exacerbates intestinal inflammation/barrier dysfunction, the upregulation of the expressions of intestinal/renal TNFα-related pathogenic signals, higher TNFα-induced increase in RVR, and decrease in GFR in perfused kidney. In intestinal SIRT1 knockout groups, the positive correlations were identified between intestinal SIRT1 activity and CDR. Particularly, the negative correlations were identified between CDR and RVR, with the positive correlation between CDR and GFR. In mice with advanced cirrhosis, the expression of intestinal SIRT1 is involved in the linkage between intestinal dysbiosis and vasoconstriction/hypoperfusion-related renal dysfunction through the crosstalk between intestinal/renal TNFα-related pathogenic inflammatory signals.
Graft failure resulting from rejection or any other adverse event usually originates from an aberrant and/or exaggerated immune response and is often catastrophic in renal transplantation. So, it is ...essential to monitor patients' immune status for detecting a rejection/graft failure early on.
We monitored the sequence change of complementary determining region 3 (CDR3) in B-cell receptor (BCR) immunoglobulin heavy-chain (
) immune repertoire (iR) in 14 renal transplant patients using next-generation sequencing (NGS), correlating its diversity to various clinical events occurring after transplantation.
in peripheral blood mononuclear cells was sequenced along the post-transplantation course by NGS using the iRweb server.
Datasets covering VDJ regions of
indicated clonal diversity (D50) variations along the post-transplant course. Furthermore, principal component analysis showed the clustering of these sequence variations. A total of 544 shared sequences were identified before transplantation. D50 remained low in three patients receiving rituximab. Among them, one's D50 resumed after 3 m, indicating graft tolerance. The D50 rapidly increased after grafting and decreased thereafter in four patients without rejection, decreased in two patients with T-cell-mediated rejection (TCMR) and exhibited a sharp down-sliding after 3 m in two patients receiving donations after cardiac death (DCD). In another two patients with TCMR, D50 was low just before individual episodes, but either became persistently low or returned to a plateau, depending on the failure or success of the immunosuppressive treatments. Shared CDR3 clonal expansions correlated to D50 changes. Agglomerative hierarchical clustering showed a commonly shared CDR3 sequence and at least two different clusters in five patients.
Clonal diversity in
-
3 varied depending on clinical courses of 14 renal transplant patients, including B-cell suppression therapy, TCMR, DCD, and graft tolerance. Adverse events on renal graft failure might lead to different clustering of
iR. However, these preliminary data need further verification in further studies for the possible applications of iR changes as genetic expression biomarkers or laboratory parameters to detect renal graft failure/rejection earlier.
Introduction:
Infections are a leading cause of mortality in patients with systemic lupus erythematosus (SLE). Among various infections, invasive fungal infections (IFIs) have a particularly high ...mortality rate; however, studies examining IFIs in patients with SLE are limited.
Methods:
Patients diagnosed as having SLE between 1997 and 2012 were enrolled from Taiwan’s National Health Insurance Research Database along with age- and sex-matched non-SLE controls at a ratio of 1:10. IFIs were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification codes and validated by the prescriptions of systemic antifungal agents. The incidence rate (IR), incidence rate ratio (IRR), and all-cause mortality rate of IFIs and its subtypes were analyzed. A Cox multivariate regression model with time-dependent covariates was applied to analyze independent risk factors for IFIs.
Results:
A total of 24,541 patients with SLE and 245,410 non-SLE controls were included. We observed 445 IFI episodes in the SLE cohort, with an all-cause mortality rate of 26.7%. Candida spp. (52.8%) was the most common pathogen, followed by Cryptococcus spp. (18.2%) and Aspergillus spp. (18.2%). The IR of IFIs in the SLE cohort was 20.83 per 10,000 person-years, with an IRR of 11.1 95% confidence interval (CI): 9.8–12.6 relative to the non-SLE controls. Juvenile patients with SLE aged ⩽18 years had the highest IRR of 47.2 (95% CI: 26.9–86.8). Intravenous steroid therapy administered within 60 days (hazard ratio: 29.11, 95% CI: 23.30–36.37) was the most critical risk factor for overall IFIs and each of the three major fungal pathogens. Distinct risk factors were found among different IFI subtypes.
Conclusion:
Patients with SLE had a higher risk of IFIs, especially juvenile patients. Intravenous steroid therapy is the most critical risk factor for IFIs. This study provides crucial information for the risk stratification of IFIs in SLE.
Plain Language Summaries
Patients with systemic lupus erythematosus and physicians treating this patient group should be aware of the risk of invasive fungal infections.
Invasive fungal infections (IFIs) are a severe complication with a high mortality rate among patients with systemic lupus erythematosus (SLE); however, studies on this topic are scant. We performed a nationwide population-based study in Taiwan to estimate the incidence and mortality of and risk factors for IFIs. We found an incidence rate of 20.83 per 10,000 person-years for IFIs, with a mortality rate of 26.7%. Juvenile patients aged ⩽18 years had the highest relative risk of IFIs. Although candidiasis was the most common IFI, cryptococcosis and aspergillosis should be concerned in juvenile patients as well. Intravenous steroid therapy was the most critical risk factor for all IFIs, and different immunosuppressive agents posed different risks in patients for acquiring certain fungal pathogens.
Our findings provide pivotal epidemiological information and indicate risk factors for IFIs in patients with SLE. Age and exposure to specific immunosuppressants and steroids might help predict the risk of IFIs. Because the manifestation of these infections is sometimes indistinguishable from a lupus flare, physicians should be aware of this fatal complication, especially when patients are not responsive to immunosuppressive therapy. Early recognition, implication of diagnostic tools, and empirical antimicrobial agents can be the key to treating patients with IFIs. Additional studies are required to develop a risk management program for patients with SLE.
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