Combined platelet-to-lymphocyte ratio and blood-brain barrier biomarkers as indicators of disability in acute neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a complex neuroinflammatory disease characterized by severe disability. In this study, we investigated the relationship between cerebrospinal fluid (CSF)/serum albumin quotient (Qalb) and platelet to lymphocyte ratio (PLR) in assessing disease severity. METHOD: A retrospective analysis of 72 NMOSD patients and 72 healthy controls was conducted, and patients were divided into two groups based on their Expanded Disability Status Scale (EDSS) scores. RESULTS: NMOSD patients had significantly higher levels of serum PLR, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and C-reactive protein (CRP) compared to healthy controls (all P<0.01). Patients in the EDSS≥4 group exhibited significantly elevated levels of Qalb, QIgG, QIgA, QIgM, and PLR (P=0.000, P<0.0001, P=0.0019, P=0.0001, respectively). Spearman's correlation test revealed significant positive associations between Qalb, QIgG, QIgA, QIgM, PLR, and EDSS score. Specifically, Qalb (r=0.571; P<0.001), QIgG (r=0.551; P<0.001), QIgA (r=0.519; P<0.001), and QIgM (r=0.541; P<0.001) demonstrated significant positive correlations with EDSS score, while PLR exhibited a moderate positive correlation (r=0.545; P<0.001) with EDSS score and a mild positive association (r=0.387; P<0.001) with Qalb. The increase of Qalb was positively correlated with the increased EDSS score (r=0.528, P=0.001), as well as the increase of QIgG (r=0.509, P=0.001), and the increase of QIgA (r=0.4989, P=0.03). ROC analysis indicated that Qalb, QIgG, QIgA, QIgM, and PLR levels could effectively serve as indicators of NMOSD severity (all P<0.0001). Multivariate analysis confirmed the independent significance of Qalb and PLR in assessing disease severity (P=0.000). CONCLUSION: These findings provide valuable insights into the risk and pathogenesis of NMOSD and highlight the potential of Qalb and PLR as independent markers for disease severity assessment in NMOSD patients.

Association of X-linked TLR-7 gene polymorphism with the risk of knee osteoarthritis: a case-control study.

Knee osteoarthritis (OA) is the most prevalent type of OA, and Toll-like receptor 7 (TLR7) may lead to the pathogenesis of OA. Recently, X-linked TLR7 polymorphism has been confirmed to be associated with arthritis. However, there is a lack of studies on TLR7 gene polymorphism associated with knee OA susceptibility. The current study aimed to determine whether TLR7 gene polymorphism is associated with the risk of knee OA. Genotyping of two polymorphic sites (rs3853839 and rs179010) in the TLR7 gene was performed in 252 OA patients, and 265 healthy controls using the SNaPshot sequencing technique. Data were analyzed statistically by Chi-square tests and logistic regression. Rs3853839-C allele showed frequencies of 28% and 27% in the healthy control and female knee OA groups, respectively. The differences were not statistically significant (P > 0.05). The rs3853839-CG genotype frequency was significantly lower in the female knee OA group as compared to the healthy control group (OR 0.60; 95%CI 0.36-0.99; P = 0.044). In the male hemizygote population, the rs3853839-CC showed significantly lower frequencies in the male knee OA group as compared to the healthy control group (OR 0.35; 95%CI 0.17-0.71; P = 0.0025). Regarding rs179010, there were no differences in the genotype distribution and allele frequencies between OA patients and healthy subjects under any models (P > 0.05). Stratified analysis showed that the frequency of the rs3853839-CG genotypes was lower in high Kellgren-Lawrence grades (KLG) (OR 0.48; 95%CI 0.21-1.08; P = 0.066), and significantly lower in OA patients with effusion synovitis (OR 0.38; 95%CI 0.17-0.88; P = 0.013). TLR7 rs3853839 polymorphism may play a role in the susceptibility of knee OA in the Chinese Han Population and may be associated with OA severity and the risk of effusion synovitis in Knee OA.

Clinical Features of 50 Patients With Primary Adrenal Lymphoma.

Background and Objective: Primary adrenal lymphoma is a rare, progressive, easily misdiagnosed adrenal tumor with a poor prognosis. There are limited data on its clinical characteristics, and these have been derived from small sample studies. This study aimed to identify the clinical characteristics and prognosis of primary adrenal lymphoma. Methods: This single-center study retrospectively analyzed data of 50 primary adrenal lymphoma patients treated between January 2008 and January 2018. Demographic information, biochemical indexes, computed tomography images, pathological findings, treatment regimens, and prognostic factors were analyzed. Results: The median age of onset was 60.3 years, and 30 (60.0%) of 50 patients were male. Abdominal pain was the most common symptom, followed by incidentaloma and B symptoms. On average, patients presented with elevated lactate dehydrogenase (348 IU/L, normal range 110-220 IU/L) and hydroxybutyrate dehydrogenase levels (287 IU/L, normal range 72-182 IU/L) and decreased high-density lipoprotein cholesterol levels (0.88 mmol/L, normal range > 0.9 mmol/L). Bilateral lesions in the adrenal glands were observed in 30 (60.0%) patients. Computed tomography showed that 42 (84%) patients had signs of infiltration. Diffuse large B-cell lymphoma was present in 44 (88%) patients. Immunohistochemistry revealed that 70.6% (12/17), 89.5% (17/19), 92.0% (23/25), and 68.8% (11/16) of patients were positive for MYC, p53, BCL2, and both MYC and BCL2, respectively. Combined chemotherapy was associated with a good prognosis. Conclusions: Early diagnosis of primary adrenal lymphoma depends on a combination of biochemical examination, imaging studies, and pathological biopsy, and combined chemotherapy may lead to a better prognosis.

A NOVEL GLUCOCORTICOID RECEPTOR MUTATION IN PRIMARY GENERALIZED GLUCOCORTICOID RESISTANCE DISEASE.

Objective: Primary generalized glucocorticoid resistance (PGGR) is a rare hereditary disease characterized by generalized partial target-tissue insensitivity to glucocorticoids. To date, few cases have been reported, and more cases, especially involving other races, are needed to fully understand this disease. Methods: This study presented a novel glucocorticoid receptor mutation in a PGGR pedigree. The index patient was a 14-year-old male with fatigue, hypokalemia, hypertension, and polyuria. Eleven family members were available for the genetic screen. Next-generation sequencing and Sanger sequencing were used to identify the mutation. We systematically investigated the molecular mechanism through which the mutation impaired glucocorticoid signal transduction in COS-7 cells. Results: The index patient carried a de novo homo-zygous mutation within exon 6 (c.1652C>A, p.551S>Y), whereas eight family members carrying a heterozygous mutation were all phenotypically silent. The affinity of the human glucocorticoid receptor (hGR) for the ligand was 1.97-fold lower in the patient than in the family members. Mutant hGRα (551Y) displayed a 3.2-fold reduction in its ability to transactivate glucocorticoid-responsive genes. When exposed to the same concentration of dexamethasone, hGRα (551Y) displayed a reduced ability to trans-locate into the nucleus and decreased levels of hGR dimer formation and could not effectively induce the glucocorticoid response element to regulate the transcription of related genes. After 2 years of dexamethasone treatment, the volume of the left and right adrenal glands of the index subject decreased by 55.6% and 32.4%, respectively. The pituitary volume decreased by 18.9%. During the 2-year follow-up, none of the heterozygous carriers developed hypertension or hypokalemia. Conclusion: We described a novel homozygous glucocorticoid receptor mutation causing PGGR. This homozygous mutation leads to hypertension and hypokalemia, but its heterozygous mutation has no relevant clinical symptoms. Abbreviations: ACTH = adrenocorticotropic hormone; DBD = DNA-binding domain; GR = glucocorticoid receptor; GRE = glucocorticoid response element; hGR = human glucocorticoid receptor; LBD = ligand-binding domain; PGGR = primary generalized glucocorticoid resistance.

Left-versus-right-adrenal-volume ratio as a screening index before adrenal venous sampling to identify unilateral primary aldosteronism patients.

OBJECTIVES: The current study aimed to investigate the value of the computed tomography-based left-versus-right adrenal gland volume ratio (L/Rv) in screening patients with unilateral primary aldosteronism. METHODS: The current study recruited 114 patients who underwent successful adrenal venous sampling (AVS) and adrenal computed tomography at West China Hospital of Sichuan University. The patients were divided into three groups according to the AVS results: AVS-left, AVS-bilateral, and AVS-right primary aldosteronism. The volumes of the left and right adrenal glands were semiautomatically calculated. The L/Rv of each patient was computed, and its value in identifying unilateral primary aldosteronism was analyzed. RESULTS: The mean value of the L/Rv was larger in AVS-left patients and smaller in AVS-right patients than that in AVS-bilateral patients. In AVS-left primary aldosteronism patients, the cutoff value of the L/Rv with the highest Youden index was 1.344 [area under the curve (AUC) 0.851, sensitivity 80.0%, specificity 78.1%]. The optimal cutoff value was 1.908, of which 46.0% (23/50) of AVS-left primary aldosteronism patients could be identified (specificity 100.0%). In AVS-right primary aldosteronism patients, the cutoff value of the L/Rv with the highest Youden index was 1.267 (AUC 0.868, specificity 72.8%, sensitivity 87.9%). The optimal cutoff value was 0.765, of which 27.3% (9/33) of AVS-right primary aldosteronism patients could be identified (specificity 100.0%). Patients with L/Rv more than 1.908 or less than 0.765 had higher complete success rate postsurgery. CONCLUSION: Although not perfect, the L/Rv is an applicable index to screen unilateral primary aldosteronism patients for surgery. Primary aldosteronism patients, even those aged more than 35 years, with an L/Rv more than 1.908 or less than 0.765 can be spared AVS before surgery.

THE POTENTIAL CLINICAL APPLICATION OF A LOWER BILATERAL ADRENAL LIMB WIDTH RATIO (L/RW) IN PATIENTS WITH BILATERAL PRIMARY HYPERALDOSTERONISM.

Objective: This study investigated the characteristics of the adrenal limbs of primary aldosteronism (PA) patients and evaluated the value of the adrenal limb width measurement for the differentiation of unilateral PA from bilateral PA. Methods: A total of 122 PA patients (93 unilateral PA, ages ranged from 23 to 72 years; 29 bilateral PA, ages ranged from 30 to 68 years) who had undergone successful adrenal venous sampling (AVS) and adrenal gland computed tomography (CT) scan were retrospectively included. The maximum width of each adrenal gland limb (normal area on CT images) was measured, the left adrenal limb width to right adrenal limb width ratio (L/Rw) was calculated, and its potential value in the differentiation of unilateral PA and bilateral PA was analyzed. Results: The mean widths of the left adrenal limbs and the right adrenal limbs were 0.52 ± 0.10 cm and 0.43 ± 0.09 cm in unilateral PA patients, versus 0.52 ± 0.10 cm and 0.49 ± 0.12 cm in bilateral PA patients. The L/Rw ratio was 1.22 ± 0.24 in unilateral PA patients and 1.11 ± 0.23 in bilateral PA patients (P<.05). In the subgroup of PA patients over 55 years of age, compared with AVS, the sensitivity and specificity of the L/Rw ratio at 1.06 for subtype classification were 75% and 82%, respectively. Conclusion: A lower L/Rw ratio, referring to the ratio of the left adrenal limb width to the right adrenal limb width, may be a predictor of bilateral PA, especially in PA patients over 55 years of age. Abbreviations: APA = aldosterone-producing adenoma; AVS = adrenal venous sampling; BAH = bilateral adrenal hyperplasia; BMI = body mass index; CT = computed tomography; L/Rw = ratio of left adrenal limb width to right adrenal limb width; PA = primary aldosteronism.