Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study.

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

Performance of the 2019 ACR/EULAR Classification Criteria for IgG4-Related Disease in a Large Chinese Cohort.

OBJECTIVE: The purpose of this research was to ascertain the effectiveness of the newly established criteria for classifying IgG4-related disease (IgG4-RD), as applied to a large Chinese cohort in real-world clinical settings. METHODS: Patient data were procured from the digital health records of 4 prominent academic hospitals. The criterion standard for identifying IgG4-RD patients was from a seasoned rheumatologist. The control group consisted of individuals with other ailments such as cancer, other forms of pancreatitis, infectious diseases, and illnesses that mimic IgG4-RD. RESULTS: A total of 605 IgG4-RD patients and 760 mimickers were available for analysis. The 2019 EULAR/ACR criteria have a sensitivity of 69.1% and a specificity of 90.9% in this large Chinese cohort. IgG4-RD had a greater proportion of males (55.89% vs 36.25%, p < 0.001), an older average age at diagnosis (54.91 ± 13.44 vs 48.91 ± 15.71, p < 0.001), more pancreatic (29.59% vs 6.12%, p < 0.001) and salivary gland (63.30% vs 27.50%, p < 0.001) involvement, and a larger number of organ involvement (3.431 ± 2.054 vs 2.062 ± 1.748, p < 0.001) compared with mimickers. CONCLUSIONS: The 2019 EULAR/ACR criteria are effective in classifying IgG4-RD in Chinese patients, demonstrating high specificity and moderate sensitivity.

Tacrolimus prevents complement-mediated Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis of mesenchymal stem cells from immune thrombocytopenia.

The abnormal immunomodulatory functions of mesenchymal stem cells (MSCs) have been implicated in the development of immune thrombocytopenia (ITP). Recent studies have suggested important effects of complement on immune cell function. However, whether complement modulates bone marrow MSCs function in ITP is poorly defined. Tacrolimus has recently been applied to the treatment of autoimmune diseases. Here, we explored whether impaired ITP-MSCs could be targeted by tacrolimus. Our results showed that the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome was activated in ITP MSCs with complement deposition (MSCs-C+ ) and initiated caspase-1-dependent pyroptosis. Transcriptome sequencing results showed abnormal fatty acid metabolism in MSCs-C+ . Enhanced fatty acid ß-oxidation and reactive oxygen species production activated the NLRP3 inflammasome. Adipocytes derived from MSCs-C+ secreted less adiponectin. Adiponectin promoted the differentiation of megakaryocytes and inhibited the destruction of platelets. Tacrolimus inhibited NLRP3 inflammasome activation and MSCs-C+ pyroptosis in vitro and in vivo. Tacrolimus plus danazol elicited a higher sustained response than danazol monotherapy in corticosteroid-resistant patients with ITP. Our findings demonstrate that the activation of the NLRP3 inflammasome in ITP MSCs mediated by complement could be inhibited by tacrolimus, which might be a potential new therapy for ITP.

NLRP3 Inflammasome as a Therapeutic Target for Atherosclerosis: A Focus on Potassium Outflow.

Atherosclerosis is a risk factor for various cardiovascular diseases, and is linked to high rates of morbidity and mortality across the globe. Although numerous complex processes are involved in the development and progression of atherosclerosis, the exact mechanisms behind its pathogenesis remain unclear. Inflammation and endothelial cell damage exert a lasting effect on atherosclerosis, causing lipid and fibrous tissue accumulation in the intima of the artery to form plaques, and subsequently promoting atherosclerosis. Nod-like receptor protein 3 (NLRP3) inflammatory corpuscle is thought to be the link between lipid metabolism and inflammation. Long Potassium outflow is a vital activator of NLRP3, with a simultaneous effect as a start-up and adjustment. The majority of existing drugs for atherosclerosis targeting the NLRP3 signaling pathway target IL-1, whereas drugs targeting the critical link of potassium efflux are relatively new. This review discusses the NLRP3 inflammatory corpuscle as a critical regulator of the immunological inflammatory pathway in atherosclerosis. Moreover, current knowledge on NLRP3 inflammatory corpuscle start and activation pathways were integrated, emphasizing potassium-involved outflow-related proteins. We highlight potential treatment approaches for NLRP3 inflammatory corpuscle pathways, specifically targeting potassium outflow channels of targeted drugs. Collectively, these insights indicate that targeting the NLRP3 inflammatory corpuscle is a vital anti-inflammatory therapy for treating atherosclerosis.

Rationale and design of REGULATE: an observational study protocol for relationship between plasma metabolome and the efficacy of systemic glucocorticoid in acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) significantly increases the mortality of patients with COPD. Guidelines have recommended systemic glucocorticoid as a regular treatment. Recently, evidence has shown that systemic glucocorticoid cannot be a benefit to all of the patients with AECOPD. Thus, the problem that how the clinicians can screen the patients who can benefit from systemic glucocorticoid needs to be solved urgently. This study is aimed to detect the metabolic biomarkers and metabolic pathways that are related to the efficacy of systemic glucocorticoid and contribute to the precise treatment of COPD. METHODS AND DESIGN: In this study, we will utilize ultraperformance liquid chromatography/mass spectrometry (LC-MS) and gas chromatography/mass spectrometry (GC-MS) methods for the analysis of the metabolites in AECOPD patients and compare the metabolites profiles between patients with systemic glucocorticoid treatment success group and treatment failure group. We aim to detect the metabolic biomarkers and metabolic pathways that are related to the efficacy of systemic glucocorticoid and contribute to the precise treatment of COPD. DISCUSSION: Previous studies have found that plasma metabolome changed significantly after dexamethasone treatment in healthy participants. Furthermore, inter-person variability was high and remained uninfluenced by treatment, suggesting the potential of metabolomics for predicting the efficacy and side effects of systemic glucocorticoid. Therefore, we hypothesized that metabolome changes in patients with AECOPD may be associated with the efficacy of systemic glucocorticoid. Trial registration Clinicaltrials.gov registration number NCT04710849. Registered 15 January 2021, https://clinicaltrials.gov/ct2/show/NCT04710849 .

Menin inhibitors for acute myeloid leukemia: latest updates from the 2023 ASH Annual Meeting.

Recent developments in menin inhibitors for relapsed or refractory acute myeloid leukemia (AML) were highlighted at the 2023 ASH Annual Meeting. Notably, revumenib showed promising efficacy, achieving a 100% ORR when combined with decitabine/cedazuridine and venetoclax. These findings underscore the potential of menin inhibitors in transforming AML treatment, particularly in genetically defined subgroups, offering hope for improved patient outcomes. Ongoing studies, like KOMET-008, further explore the synergistic potential of menin inhibitors in combination regimens, shaping future AML management strategies.

The Application of Mendelian Randomization in Cardiovascular Disease Risk Prediction: Current Status and Future Prospects.

Cardiovascular disease (CVD), a leading cause of death and disability worldwide, and is associated with a wide range of risk factors, and genetically associated conditions. While many CVDs are preventable and early detection alongside treatment can significantly mitigate complication risks, current prediction models for CVDs need enhancements for better accuracy. Mendelian randomization (MR) offers a novel approach for estimating the causal relationship between exposure and outcome by using genetic variation in quasi-experimental data. This method minimizes the impact of confounding variables by leveraging the random allocation of genes during gamete formation, thereby facilitating the integration of new predictors into risk prediction models to refine the accuracy of prediction. In this review, we delve into the theory behind MR, as well as the strengths, applications, and limitations behind this emerging technology. A particular focus will be placed on MR application to CVD, and integration into CVD prediction frameworks. We conclude by discussing the inclusion of various populations and by offering insights into potential areas for future research and refinement.

Severe/critical COVID-19 early warning system based on machine learning algorithms using novel imaging scores.

BACKGROUND: Early identification of severe/critical coronavirus disease 2019 (COVID-19) is crucial for timely treatment and intervention. Chest computed tomography (CT) score has been shown to be a significant factor in the diagnosis and treatment of pneumonia, however, there is currently a lack of effective early warning systems for severe/critical COVID-19 based on dynamic CT evolution. AIM: To develop a severe/critical COVID-19 prediction model using a combination of imaging scores, clinical features, and biomarker levels. METHODS: This study used an improved scoring system to extract and describe the chest CT characteristics of COVID-19 patients. The study also took into consideration the general clinical indicators such as dyspnea, oxygen saturation, alternative lengthening of telomeres (ALT), and androgen suppression treatment (AST), which are commonly associated with severe/critical COVID-19 cases. The study employed lasso regression to evaluate and rank the significance of different disease characteristics. RESULTS: The results showed that blood oxygen saturation, ALT, IL-6/IL-10, combined score, ground glass opacity score, age, crazy paving mode score, qsofa, AST, and overall lung involvement score were key factors in predicting severe/critical COVID-19 cases. The study established a COVID-19 severe/critical early warning system using various machine learning algorithms, including XGBClassifier, Logistic Regression, MLPClassifier, RandomForestClassifier, and AdaBoost Classifier. The study concluded that the prediction model based on the improved CT score and machine learning algorithms is a feasible method for early detection of severe/critical COVID-19 evolution. CONCLUSION: The findings of this study suggest that a prediction model based on improved CT scores and machine learning algorithms is effective in detecting the early warning signals of severe/critical COVID-19.

A life-threatening bleeding prediction model for immune thrombocytopenia based on personalized machine learning: a nationwide prospective cohort study.

Rare but critical bleeding events in primary immune thrombocytopenia (ITP) present life-threatening complications in patients with ITP, which severely affect their prognosis, quality of life, and treatment decisions. Although several studies have investigated the risk factors related to critical bleeding in ITP, large sample size data, consistent definitions, large-scale multicenter findings, and prediction models for critical bleeding events in patients with ITP are unavailable. For the first time, in this study, we applied the newly proposed critical ITP bleeding criteria by the International Society on Thrombosis and Hemostasis for large sample size data and developed the first machine learning (ML)-based online application for predict critical ITP bleeding. In this research, we developed and externally tested an ML-based model for determining the risk of critical bleeding events in patients with ITP using large multicenter data across China. Retrospective data from 8 medical centers across the country were obtained for model development and prospectively tested in 39 medical centers across the country over a year. This system exhibited good predictive capabilities for training, validation, and test datasets. This convenient web-based tool based on a novel algorithm can rapidly identify the bleeding risk profile of patients with ITP and facilitate clinical decision-making and reduce the occurrence of adversities.

Ethical review of off-label drugs during the COVID-19 pandemic.

High-quality scientific research is very important in attempting to effectively control the coronavirus disease 2019 (COVID-19) pandemic and ensure people's health and safety. Chloroquine (CQ) and hydroxychloroquine (HCQ) have received much attention. This article comprehensively investigates the ethical review of off-label CQ and HCQ research during the COVID-19 pandemic with regard to strictly abiding by review standards, improving review efficiency, ensuring the rights and interests of subjects and that ethics committees conduct independent reviews, and achieving full ethics supervision of research conducted during an emergency. Research must be both rigorous and prudent to ensure the best outcome, with the maximization of benefits as the core principle. Standardization of the application, implementation and ethical review processes are needed to prevent unnecessary risk.

Meta-Analysis of the Association Between Asthma and the Risk of Stroke.

Introduction: Asthma and stroke share many risk factors. Previous meta-analysis has indicated that asthma is associated with an increased risk of stroke. However, this study were limited by the small number of articles included and the lack of subgroup analyses of different stroke types and different populations. This meta-analysis aimed to synthesize evidence systematically to investigate the impact of asthma on stroke. Methods: We searched Medline (via PubMed), Web of Science and EMBASE databases and manually identified eligible studies (inception dates to December 25, 2021) that analyzed the association between asthma and stroke. We conducted quality assessment to evaluate the risk of bias of studies and sensitivity analyses to test the robustness of results. Results: We included 8 cohort studies and 10 cross-sectional studies comprised 3,011,016 participants. We found patients with asthma had a higher risk of stroke than patients without asthma [relative risk (RR): 1.34, 95% confidence interval (CI): 1.21-1.47]. Moreover, asthma significantly increased the risk of ischemic stroke (RR: 1.25, 95% CI: 1.06-1.47) without increasing the risk of hemorrhagic stroke (RR: 1.08, 95% CI: 0.87-1.34). Asthma increased the risk of stroke in both men (RR: 1.20, 95% CI: 1.10-1.32) and women (RR: 1.29, 95% CI: 1.12-1.48) with no significant difference between the sexes. We also found that patients with inactive asthma, child-onset asthma, or no smoking history did not have an increased risk of stroke. Conclusions: These results supported the finding that asthma could significantly increase the risk of stroke, but this impact was not consistent in different populations. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=290745, identifier: CRD42021290745.

Association Between Asthma and All-Cause Mortality and Cardiovascular Disease Morbidity and Mortality: A Meta-Analysis of Cohort Studies.

Background: Asthma and cardiovascular disease (CVD) share many risk factors. Previous meta-analyses indicated that asthma is associated with an increased risk of CVD and all-cause mortality, but these studies were limited by unstandardized search strategies and the number of articles included. Objective: We sought to systematically synthesize evidence investigating the impact of asthma on all-cause mortality and CVD morbidity and mortality. Methods: We searched in PubMed and EMBASE for observational cohort studies (inception dates to November 10, 2021) that had both asthma groups and control groups. We also manually searched the reference lists of correlative articles to include other eligible studies. Data for associations between asthma and all-cause mortality and CVD morbidity and mortality were needed. Results: We summarized the findings from 30 cohort studies comprising 4,157,823 participants. Asthma patients had increased CVD morbidity [relative risk (RR) = 1.28, 95% confidence interval (CI) = 1.16-1.40] and increased CVD mortality (RR = 1.25, 95% CI = 1.14-1.38). Asthma patients also had increased risk of all-cause mortality (RR = 1.38, 95% CI = 1.07-1.77). In subgroup analyses, female asthma patients had a higher risk of CVD morbidity and all-cause mortality than male asthma patients, and late-onset asthma patients had a higher risk of CVD morbidity than early-onset asthma patients. Conclusion: Asthma patients have increased risk of all-cause mortality and CVD morbidity and mortality. This information reminds clinicians to be aware of the risk of CVD and all-cause mortality in asthma patients. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, PROSPERO, identifier: CRD 42021290082.

Associations Between the Use of Renin-Angiotensin System Inhibitors and the Risks of Severe COVID-19 and Mortality in COVID-19 Patients With Hypertension: A Meta-Analysis of Observational Studies.

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share a target receptor with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The use of ACEIs/ARBs may cause angiotensin-converting enzyme 2 receptor upregulation, facilitating the entry of SARS-CoV-2 into host cells. There is concern that the use of ACEIs/ARBs could increase the risks of severe COVID-19 and mortality. The impact of discontinuing these drugs in patients with COVID-19 remains uncertain. We aimed to assess the association between the use of ACEIs/ARBs and the risks of mortality and severe disease in patients with COVID-19. A systematic search was performed in PubMed, EMBASE, Cochrane Library, and MedRxiv.org from December 1, 2019, to June 20, 2020. We also identified additional citations by manually searching the reference lists of eligible articles. Forty-two observational studies including 63,893 participants were included. We found that the use of ACEIs/ARBs was not significantly associated with a reduction in the relative risk of all-cause mortality [odds ratio (OR) = 0.87, 95% confidence interval (95% CI) = 0.75-1.00; I 2 = 57%, p = 0.05]. We found no significant reduction in the risk of severe disease in the ACEI subgroup (OR = 0.95, 95% CI = 0.88-1.02, I 2 = 50%, p = 0.18), the ARB subgroup (OR = 1.03, 95% CI = 0.94-1.13, I 2 = 62%, p = 0.48), or the ACEI/ARB subgroup (OR = 0.83, 95% CI = 0.65-1.08, I 2 = 67%, p = 0.16). Moreover, seven studies showed no significant difference in the duration of hospitalization between the two groups (mean difference = 0.33, 95% CI = -1.75 to 2.40, p = 0.76). In conclusion, the use of ACEIs/ARBs appears to not have a significant effect on mortality, disease severity, or duration of hospitalization in COVID-19 patients. On the basis of the findings of this meta-analysis, there is no support for the cessation of treatment with ACEIs or ARBs in patients with COVID-19.

Chronic Active Hepatitis B with COVID-19 in Pregnancy: A Case Report.

Currently, infection with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during pregnancy is a problem worthy of attention, especially in patients with underlying diseases. In this case report, we present a case of chronic active hepatitis B with COVID-19 in pregnancy. A 31-year-old woman at 29 weeks of gestation who had a history of chronic hepatitis B virus infection discontinued antiviral treatment, was admitted to the hospital with chronic active hepatitis B, and tested positive for SARS-CoV-2 infection. In this case, we applied liver protective and antiviral agents, and low-dose dexamethasone therapy to successfully treat the critically ill pregnant woman suffering from chronic active hepatitis B combined with COVID-19.