Associations of lactate dehydrogenase with risk of renal outcomes and cardiovascular mortality in individuals with diabetic kidney disease.

OBJECTIVE: This study aimed to investigate the role of the lactate dehydrogenase (LDH) in the development of end-stage renal disease (ESRD) and the cardiovascular mortality in individuals with diabetic kidney disease (DKD). METHODS: Two cohorts were recruited in this study. We explored the correlation between LDH and renal injury in individuals with DKD in using a Cohort 1. Additionally, we validated this correlation in the NHANES database and further investigated its association with the risk of cardiovascular mortality in Cohort 2 which also comprised individuals with DKD. RESULTS: In cohort 1, multivariate Cox regression analysis demonstrated that individuals in DKD with higher LDH were independently associated with an increased risk of ESRD compared to those with lower LDH (HR = 2.11; 95 % CI, 1.07-4.16). In cohort 2, linear regression models showed that LDH affects the level of albumin-creatinine ratio (ACR) (ß = 2.95, P = 0.001). Additionally, multivariate Cox regression analysis results showed that an increase in LDH per 1-standard deviation (SD) was associated with a 27 % increased risk of cardiovascular mortality (HR = 1.27; 95 % CI, 1.09-1.48). CONCLUSIONS: LDH levels are associated with renal injury and progression to ESRD, as well as being an independent risk factor for cardiovascular in individuals with DKD.

Non-immune system comorbidity in neuromyelitis optica spectrum disorders.

Comorbidities may influence the clinical features, prognosis, and treatment outcomes of neuromyelitis optica spectrum disorders (NMOSD). The aim of this study was to determine the status of non-immune system comorbidities in patients with NMOSD and the effect on treatment response and prognosis. We retrospectively collected data from all patients who met the 2015 NMOSD diagnostic criteria from the NMOSD database established by our center. Patients were divided into positive and negative groups based on the presence of non-immune disease comorbidities. Patient data, clinical characteristics, treatment response, prognosis, and mortality were compared between the two groups. A total of 138 patients with NMOSD plus comorbidities were included, and 404 patients without comorbidities were selected as controls. The average age at onset was older (45 years vs 38 years, P < 0.001), the mean body mass index was higher (23.12 vs 22.04, P = 0.042) and more patients experienced relapse after immunotherapy (68.5 % vs 54.5 %, P = 0.020) in the comorbidity group than in the non-comorbidity group. Multifocal central nervous system lesions as an initial symptom was more common in the comorbidity group than in the non-comorbidity group (30.4 % vs 18.32 %, P = 0.003). Further, more patients experienced severe vision attacks (28.3 % vs 15.8 %, P = 0.003) and severe motor attacks (30.4 % vs 11.9 %, P < 0.001) in the comorbidity group than in the non-comorbidity group. In conclusion, patients with NMOSD with comorbidities tended to be older, less responsive to treatment, and at a higher risk of vision loss and paralysis.

Granzyme B in circulating CD8+ T cells as a biomarker of immunotherapy effectiveness and disability in neuromyelitis optica spectrum disorders.

Background and objective: Neuromyelitis optica spectrum disorders (NMOSD) are chronical inflammatory demyelinating diseases of the central nervous system (CNS) and the underlying mechanism remains unclear. Several recent studies have demonstrated that T cells play a pivotal role in the pathogenesis of NMOSD.In this study, we investigated CD8+ T cell phenotypes and levels of the cytotoxic protein granzyme B (GzmB), as well as their potential clinical application in NMOSD. Methods: In this study, 90 peripheral blood samples were collected from 59 NMOSD patients with seropositive anti-aquaporin-4 (AQP4) antibodies and 31 sex- and age-matched healthy donors (HDs). Flow cytometry was used to detect circulating levels of GzmB and CD8+ T cell subpopulations, including naïve (TN, CCD7+CD45RA+), central memory (TCM, CCD7+CD45RA-), effector memory (TEM, CCD7-CD45RA-), terminal differentiation effector memory cells (TEMRA, CCD7-CD45RA+) in both groups. The associations between GzmB levels in CD8+T cells and clinical characteristics of NMOSD were evaluated. Results: NMOSD patients exhibited significantly decreased proportions of CD8+TN cells and increased proportions of highly differentiated CD8+T cells (TEMRA) compared with HDs. In addition, levels of GzmB in CD8+ T cells were markedly higher in NMOSD patients than in HDs. Moreover, we observed that high proportions of GzmB-expressing CD8+ T cells were more common in patients with a poor response to immunotherapies, and showed a good potential to distinguish poor responders from responders (ACU=0.89). Clinical correlation analysis indicated that high levels of GzmB in CD8+ T cells were not only related to severe disability but also significantly associated with increased serum levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP). Multivariate linear regression analyses further suggested that GzmB expression in CD8+ T cells was predominantly associated with disability and immunotherapy effectiveness in NMOSD, independent of the sex, age, and disease phase. Transcription factor T-bet in CD8+ T cells were also significantly elevated in NMOSD and were associated with increasing number of circulating CD8+TEMRA cells and GzmB-expressing CD8+T cells. Conclusions: Our study support the involvement of GzmB-expressing CD8+ T cells in the inflammatory response in patients with NMOSD and provide a potential biomarker for disease immunotherapy effectiveness and disability progression.

Relationship between the Clinical Characteristics in Patients with Neuromyelitis Optica Spectrum Disorders and Clinical Immune Indicators: A Retrospective Study.

Objective: T lymphocytes, complement, and immunoglobulin play an important role in neuromyelitis optica spectrum disorders (NMOSD). As common clinical examination indicators, they have been used as routine indicators in many hospitals, which is convenient for being carried out in clinical work, but there are few articles of guiding significance for clinical practice. The purpose of this study was to study the relationship between commonly used immune indicators and clinical characteristics in patients with NMOSD. Methods: We compared clinical characteristics and clinical immune indicators in 258 patients with NMOSD and 200 healthy controls (HCs). We used multiple linear regression to study the relationship between immunotherapy, disease phase, sex, age, AQP4-IgG, and immune indicators. In addition, lymphocyte subsets were compared before and after immunotherapy in 24 of the 258 patients. We explored the influencing factors and predictors of severe motor disability. Results: The percentages of CD3 ratio (71.4% vs. 73.8%, p = 0.013), CD4 ratio (38.8% vs. 42.2%, p < 0.001), and CD4/CD8 ratio (1.43 vs. 1.66, p < 0.001) in NMOSD patients were significantly lower than those in the HC group. In addition, complement C4 (0.177 g/L vs. 0.221 g/L, p < 0.001) and peripheral blood IgG (10.95 g/L vs. 11.80 g/L, p = 0.026) in NMOSD patients were significantly lower than those in the HC group. CD3 percentage was correlated with blood collection age and disease stage; CD8 percentage was correlated with blood collection age, disease stage, and treatment; CD4/CD8 percentage was correlated with blood collection age and treatment; complement C4 was correlated with blood collection age and sex; and IgG was correlated with disease stage and treatment. Twenty-four patients before and after treatment showed that the percentages of CD3 ratio (74.8% vs. 66.7%, p = 0.001) and CD8 ratio (32.4% vs. 26.2%, p < 0.001) after treatment in NMOSD patients were significantly increased, and the percentage of CD3 before treatment was moderately negatively correlated with ARR (r = −0.507, p = 0.011). Binary logistic regression analysis showed that peripheral blood complement C3 is a serious influencing factor for severe motor disability (EDSS score ≥ 6 points). Peripheral blood complement C3 and C4 are predictors of severe motor disability (p < 0.05). Conclusion: Our results suggest that peripheral blood T lymphocytes, C3, C4 and immunoglobulin are convenient and routine clinical indicators that are convenient for implementation in clinical work. They have certain reference values for disease staging, recurrence, drug efficacy, and motor disability. They have improved our understanding of clinical immune indicators for NMOSD patients, but whether they can be used as biomarkers for clinical prognosis remains to be further studied.

Sexual dysfunction in patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease that causes fatigueable muscle weakness. Sexual dysfunction (SD) is a common condition, but the association between SD and MG remains poorly understood. METHODS: An observational study was conducted to explore SD incidence and risk factors in MG patients. The study enrolled 158 MG patients and 161 age- and sex-matched healthy individuals. SD was investigated using the Female Sexual Function Inventory (FSFI), the abridged International Index of Erectile Function-5 (IIEF-5), and the Chinese Index of Premature Ejaculation-5 (CIPE-5). The mental health was evaluated using Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA). RESULTS: A total of 52 male patients and 106 female patients were finally included. The average age of these patients was 41.82 ± 10.44 years. The incidence of female SD was significantly higher in MG patients (48.11%) than in healthy people (22.64%) (P < 0.001). The incidence of SD in male MG patients was also higher. Age and depression were significantly correlated with decreased libido, wakefulness, lubrication, orgasm, and satisfaction scores, indicating that these are risk factors for SD. Age (OR:1.13, CI%:1.06-1.21, P < 0.001) and HAMD scores (OR:1.53, CI%:1.0-2.13, P = 0.011) are independent risk factors for SD of MG patients. CONCLUSION: SD is a common problem in MG, and its severity does not change with the severity of the disease. Age and depression are risk factors for sexual dysfunction.