OBJECTIVE: The aim of this study is to identify risk factors contributing to central nervous system (CNS) invasion and to validate the suitability of the Central Nervous System International Prognostic Index (CNS-IPI) for individuals afflicted with diffuse large B-cell lymphoma (DLBCL).
METHODS: Based on the presence or absence of CNS invasion, 365 patients were stratified into two groups: the CNS group and the non-CNS group. The clinical data of the patients were retrospectively analyzed using univariate and multivariate analysis, and the differences in survival curves were compared. The dependent variable in this study was the presence or absence of CNS invasion, while the independent variables included age, stage, extranodal involvement, renal/adrenal involvement, and others. Statistical methods included the chi-squared test and Fisher\'s exact test for intergroup comparison and binary logistic regression for multi-factor analysis. The related risk factors were modeled using the Cox proportional hazards model. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was used to compare the differences between survival curves. The optimal cutoff value of beta-2 (β2)-microglobulin was determined through the utilization of a receiver operating characteristic (ROC) curve. All P values were bidirectional, and P < 0.05 was considered statistically significant. Both SPSS 23.0 (IBM Inc., Armonk, NY, USA) and RStudio (R software version 4.0.2, R Project for Statistical Computing) software were used for data processing RESULTS: The five factors of the CNS-IPI were related to the prognosis of patients with CNS invasion. Bone involvement, albumin < 40 g/L, and P53 protein (+) were the risk factors for CNS invasion in patients with DLBCL. However, prognostic factors such as double strike, testicular involvement, breast involvement, uterine involvement, and bone marrow involvement did not apply to these patients. It was also discovered that elderly patients with DLBCL with reduced albumin levels were more susceptible to CNS invasion. Furthermore, extranodal involvement at multiple sites and elevated beta-2 (β2) microglobulin were independent prognostic factors CONCLUSION: Patients older than 60 years with DLBCL and decreased albumin are at increased risk for CNS invasion. In addition to the five factors in the CNS-IPI, bone involvement, albumin levels < 40 g/L, and P53 protein expression are risk factors affecting the prognosis of CNS invasion in patients with DLBCL.

BACKGROUND: Sjögren\'s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrates in the exocrine glands. Carpal tunnel syndrome (CTS) is suggested to be more frequent among SS patients than in the general population. The aim of this study was to seek associations between the CTS and the laboratory and clinical findings of SS patients.
METHODS: Fifty patients diagnosed with primary SS (pSS) were examined. Clinical evaluation by a rheumatologist and electrophysiological studies were conducted. Data on laboratory tests results was collected. Control group consisted of 50 sex and age-matched individuals with osteoarthritis (OA).
RESULTS: Out of 50 patients in the study group 27 (54%) were diagnosed with CTS. The prevalence of CTS among 50 individuals in the control group was 8%. Among pSS patients with CTS the joint involvement was not more common than in those from the non-CTS group [15 vs. 13 (p = 0.945)]. There was an expected difference in sleep disorders [18 vs. 9 (p = 0.012)] and paresthesia [23 vs. 13 (p = 0.024)]. The major finding was a significant difference in elevated beta2-microglobulin (B2MG) [23 vs. 13 (p = 0.024)]. Other studied factors, suggested in the literature as significant in the pSS-related neuropathy, were not statistically different between the groups.
CONCLUSIONS: Our study confirms that CTS is more prevalent among pSS patients than in the general population and suggests that a new approach is required towards the pathogenesis of this phenomenon. We hypothesize that CTS is more associated with an overall disease activity than joint involvement as such.

BACKGROUND: Gliomas are the deadliest malignant tumors of the adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and that it exerts a range of oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether serum B2M levels can be used in the diagnosis and prognosis of gliomas.
METHODS: Medical records from 246 glioma patients were retrospectively analyzed. The relationship between preoperative serum B2M levels and clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- and multivariate Cox regression, assessed the association between B2M levels, systemic inflammatory markers, and glioma patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic significance of these biomarkers specifically for glioblastoma (GBM).
RESULTS: Patients with malignant gliomas exhibited elevated preoperative serum B2M levels. Glioma patients with high serum B2M levels experienced shorter survival times. Multivariate Cox analysis determined the relationship between B2M levels (hazard ratio = 1.92, 95% confidence interval: 1.05-3.50, P = 0.034) and the overall survival of glioma patients. B2M demonstrated superior discriminatory power in distinguishing between GBM and non-GBM compared to inflammation indicators. Moreover, postoperative serum B2M levels were lower than preoperative levels in the majority of glioma patients.
CONCLUSIONS: High preoperative serum B2M levels correlated with malignant glioma and a poor prognosis. Serum B2M shows promise as a novel biomarker for predicting patient prognosis and reflecting the therapeutic response.

The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, β2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was -0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.

BACKGROUND: The removal of low- and medium-molecular-weight proteins has been improved with online hemodiafiltration (OL-HDF) and hemodialysis using high-flux membranes; however, the outcomes of patients with end-stage kidney disease (ESKD) undergoing dialysis treatment are still worse than in the general population. α1-Microglobulin (α1-m), with a molecular weight of 33,000 Da, may contribute to dialysis-related disorders and mortality. However, the removal is insufficient even with current OL-HDF using the polysulfone (PS) membrane, which is common in Japan. Polymethylmethacrylate (PMMA) membranes can remove medium- to high-molecular-weight proteins by adsorption. This study aimed to assess the efficacy of removing medium- to high-molecular-weight proteins, such as α1-m and β2-microglobulin (β2-m), through post-dilution OL-HDF with PMMA (Post-PMMA). The assessment was conducted in comparison to pre-dilution OL-HDF with PS (Pre-PS), using an open-label, single-arm study.
METHODS: Seven patients with ESKD on Pre-PS underwent Post-PMMA with replacement volume of 30 mL/min (low flow) and 50 mL/min (high flow). Clearance and removal rates of α1-m, β2-m, small molecules, inflammatory cytokines, and albumin were measured at 60 and 240 min of treatment.
RESULTS: Clearance rates of α1-m at 60 min were -2.8 ± 5.2 mL/min with Pre-PS, -0.4 ± 2.6 mL/min with Post-PMMA (low), and 0.6 ± 3.4 mL/min with Post-PMMA (high). The removal rate of α1-m was higher in Post-PMMA than that in Pre-HDF-PS (Post-PMMA [high] 17.7 ± 5.9%, Post-PMMA [low] 15.0 ± 5.6%, and Pre-PS 4.1 ± 5.5%). Adsorption clearance of β2-m was increased with Post-PMMA. Albumin leakage in Post-PMMA was not higher than that in Pre-PS.
CONCLUSIONS: The removal rate of α1-m with Post-PMMA was higher than that with Pre-PS. The PMMA membrane adsorbed β2-m, suggesting the removal effect of medium- to high-molecular-weight proteins by the adsorption method. Since Post-PMMA effectively removes α1-m without excessive albumin leakage, it will be useful for patients with ESKD, especially those with a poor nutritional status.

Expanded hemodialysis (HDx) is expected to provide enhanced permeability of medium-sized molecules, selective solute retention, and better internal retrofiltration. The primary objective of this study was to compare the efficiency for removal of β2-microglobulin with 3 different extracorporeal therapies (ETs): high-flux hemodialysis (HF), online hemodiafiltration (OL-HDF), and HDx. The secondary objective was to evaluate the efficiency of removal of other uremic toxins, including urea, phosphate, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-cresol.
This single-center, randomized, and cross-over study was performed. Patients were randomized to determine the initial modality of treatment, each period lasted 4 weeks and between one modality and another, there was a washout period of 1 week. Reduction ratios (RRs) of different-size molecules and albumin were calculated for the different ET.
Twenty-two patients were included, β2-microglobulin RR was greater during both OL-HDF and HDx as compared to HF (RR 62% vs. 73% vs. 27%, respectively, p = <0.0001), and there was no significant difference between HDx and OL-HDF (p = 0.09). A decrease in serum phosphate levels was observed in the HDx and OL-HDF periods, contrary to an increase in HF (-0.79 mg/dL vs. -1.02 mg/dL vs. + 0.11 mg/dL, respectively, p = <0.0001). There was no difference in RRs of other molecules (BUN, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-Cresol). There was no decrease in serum albumin in any ET.
HDx provides enhanced removal of β2-microglobulin and phosphate as compared to HF, and similar efficacy as with OL-HDF. HDx should be considered an alternative to chronic convective therapies.

暂无摘要。

Cadmium (Cd) is an environmental pollutant. Long-term exposure to Cd may lead to adverse health effects in humans. Our epidemiological studies showed that urinary Cd (U-Cd) concentrations increased from 2008 through 2014, although they decreased from 1986 through 2008. The aim of this study was to elucidate the long-term effects of the changing trend of cadmium exposure levels (U-Cd) on residents\' renal function within 30 years after Cd exposure ceased. In 2016, urine samples were collected from each subject by visiting 20 elderly Japanese people (9 females and 11 males) living in the Kakehashi River basin, a previously Cd-polluted area in Ishikawa, Japan. The geometric means of the β2-microglobulin (β2-MG) and urinary Cd (U-Cd) continued to increase from 2014 until 2016. Furthermore, Cd concentration and β2-MG in urine were still higher than those in the non-polluted areas in Japan. Multivariate linear regression was performed to associate β2-MG (dependent variable) and U-Cd with sex and age (independent variables). Significant correlations were found among age, U-Cd, and β2-MG, and these were clearer in females than in males. In summary, we propose that three decades after Cd exposure ceased, age is associated with β2-MG more strongly than Cd for bodily impact. Moreover, renal tubular dysfunction is irreversible and worsens after exposure to Cd, with females being more sensitive to exposure.

A strong correlation between lupus nephritis (LN), disease activity, and serum beta 2-microglobulin (b2MG) was observed. The current study examines the correlation between serum b2MG and renal involvement, damage score, and disease activity in systemic lupus erythematosus (SLE) patients. One hundred SLE patients from Ain Shams University Hospital were enrolled and categorized into two groups. Group I had 40 patients with negative b2MG, while Group II had 60 patients with positive b2MG levels. Medical history, clinical examination, and assessing disease activity based on SLE disease activity index (SLEDAI-2 K), and damage score were recorded for all patients. Laboratory examinations, such as serum b2MG, complete blood count, blood urea nitrogen (BUN), serum creatinine, glomerular filtration rate (GFR), urine analysis, 24 h urinary protein excretion, Antinuclear antibodies (ANA), anti-dsDNA antibody, and serum complement (C3, C4). BUN, 24 h urinary protein, serum creatinine, active urinary sediment, SLEDAI score, and damage score were all elevated in group II compared to group I (p < 0.001). There is a positive correlation between serum b2MG and 24 h urinary protein, BUN, serum creatinine, disease activity, and damage score (p < 0.001), while it was negatively correlated with GFR, C3, and C4 (p < 0.001). Serum b2MG has proven to be a predictor of LN in SLE patients (Sensitivity 92.45%, Specificity 74.47%), also being a predictor of the activity of the disease as well as damage index (Sensitivity 96.67%, Specificity 85%) (Sensitivity 92.45%, Specificity 74.47%), respectively. Serum b2MG level can be used as a valuable predictor for LN, clinical disease activity, and damage score.

BACKGROUND: β2-microglobulin has been showing to be vital that associated with brain function and neurological diseases. This study aimed to explore the expressions of β2-microglobulin in blood and urine of the patients with brain injury, and the effect of hyperbaric oxygen therapy on the content of β2-microglobulin.
METHODS: This prospective study included 54 patients with brain injury and 11 healthy controls. The patients were further assigned to two groups: the conscious disturbance group (n = 32) and the non-conscious disturbance group (n = 22) depending on the Glasgow Coma Scale (GCS). The patients received routine treatment and two courses of hyperbaric oxygen therapy (2.0ATA, 60 min, once a day, 10 days for a course). In the brain injury group, blood β2-microglobulin (β2MG) and urine β2-microglobulin (β2MU) were detected respectively before and after hyperbaric oxygen therapy (HBOT). Consciousness and cognitive scores were performed, correspondingly.
RESULTS: Compared with those of the control group, levels of β2MG and β2MU in the brain injury group were significantly increased before HBOT (P < 0.05). Whether it was before or after HBOT, β2MG\'s content in the conscious disturbance group was higher than that in the non-conscious disturbance group, while β2MU\'s content was obviously higher than that of the non-conscious disturbance group only before HBOT (P < 0.05). Besides, the β2MU\'s content in the conscious disturbance group was negatively correlated with GCS score (R = -0.351, P < 0.05) and β2MG\'s content in the non-conscious disturbance group was positively correlated with the MMSE score grade (R = 0.598, P < 0.05). The ROC curve was used to assess the evaluation of β2MG and β2MU for patients with impaired consciousness with the area under the curve (AUC) of β2MG and β2MU were 0.775 and 0.796, respectively.
CONCLUSIONS: The concentrations of blood β2-microglobulin and urinary β2-microglobulin were significantly increased in patients with brain injury. The concentrations of β2-microglobulin were correlated with the degree of consciousness and cognitive function. The changes tendency of β2-microglobulin may be considered as clinical monitoring index to evaluate the patient\'s disturbance of consciousness and cognitive degree, and provide a basis for early assessment of prognosis.