Β2-microglobulin Research Articles

Beta-2-Microglobulin Maintains Overall Survival Prediction in Binet a Stage Chronic Lymphocytic Leukemia Patients with Compromised Kidney Function in Both Treatment Eras of Chemoimmunotherapy and Targeted Agents

Background: Elevated beta-2-microglobulin (B2M) plasma levels commonly imply a higher CLL-IPI risk category for short overall survival (OS), but the risk model was not adjusted for compromised kidney function and not validated in Binet A stage CLL patients. Methods: CLL patients were identified from 2000 to 2022 at Innsbruck University Hospital, Austria. B2M levels, CLL-IPI risk stratification, and kidney function were assessed. Treatment modalities in case of disease progression and OS data during follow-up were evaluated. Results: A total of 259 Binet A stage CLL patients were identified; 16.9% (n = 44/259) presented with concurrent chronic kidney disease (CKD, GFR < 60 mL/min). Median OS was 170 months and was similar in CKD and non-CKD patients (p = 0.25). The CLL-IPI facilitated prognostic segregation in both CKD (p = 0.02) and non-CKD patients (p = 0.008). Although more frequently elevated in CKD patients (44.1% versus 10.6%, p < 0.001), B2M > 3.5 mg/L remained associated with inferior OS in this subgroup (p = 0.03). Contrary to the CLL-IPI, the prognostic value of B2M alone was also maintained in CLL patients diagnosed and potentially treated frontline in the era of targeted agents (2014–2022, p = 0.03). Conclusions: B2M retains its prognostic value for OS in early-stage CLL patients with concurrent CKD and still represents a promising covariate for up-coming prognostic models to identify patients at high risk for inferior OS in the era of targeted agents.

Survival Outcomes of Patients with Primary Plasma Cell Leukemia in the Era of Proteasome Inhibitors and Immunomodulatory Agents: A Real-Life Multicenter Analysis.

In this study, we aimed to obtain real-life data on the use of antimyeloma agents, which significantly increase overall survival (OS) in multiple myeloma (MM) patients, in primary plasma cell leukemia (pPCL) patients with a poor prognosis. Data from 53 patients who were diagnosed with pPCL between 2011-2020 and who used at least one proteasome inhibitor (PI) and/or immunomodulatory (IMID) agent were analyzed retrospectively. Depending on the year of pPCL diagnosis, 20% leukocytes or ≥2×109/L plasma cells in the peripheral blood were used. The median age of the patients was 58 years, and 23 (43.4%) patients were over 65 years of age. For first-line treatment, PI or IMID alone was used in 31 (58.5%) patients, and PI and IMID were used simultaneously in 15 (28.3%) patients. Additionally, 21 (39.6%) patients received transplantation, and 13 (24.5%) patients received maintenance treatment. The median progression-free survival was 4 (1-42) months. When patients whose primary disease was refractory to first-line therapy were excluded, the duration of treatment was 6.5 months. The median OS was 15 months, with a median follow-up of 15 months. Only 7 (13.2%) of the patients were alive at the last follow-up visit. Those with higher beta-2 microglobulin levels and ISS stage 3 and nontransplant patients receiving first-line treatment had shorter OS (p=0.005, p=0.02 and p=0.008, respectively). Otherwise, the concomitant use of PIs and IMIDs, the addition of chemotherapy to induction therapy, and the response to induction therapy or maintenance therapy did not affect OS. In our study, as in previous similar studies, we could not see the increased survival trend in pPCL which is observed in MM. New studies are needed for pPCL patients, which is likely to increase with the new diagnostic criteria, based on current agents and information in MM.

Association of uremic toxins and systemic inflammation with depression and anxiety among hemodialysis patients in Montenegro.

The purpose of this study was to examine the association between uremic toxins, inflammation, depression and anxiety among hemodialysis patients in Montenegro. The cross-sectional study included 88 patients undergoing hemodialysis. Depression and anxiety symptoms were assessed by Patient Health Questionnaire (PHQ-9) and Beck Anxiety Inventory (BAI). The standard laboratory methods were used to measure uremic toxins and systemic inflammation (C-reactive protein, Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR)). Clinically significant depression (PHQ-9 ≥ 10) and anxiety (BAI ≥16) were found in 55.7% and 27.2%, respectively. Logistic regression analyses revealed that serum urea, beta 2-microglobulin (B2M), and systemic inflammation (CRP, NLR, PLR) were significantly and independently associated with depressive symptoms, whereas serum urea, creatinine, uric acid, B2M, and systemic inflammation (CRP nad NLR) were associated with anxiety symptoms. Depressive symptoms and anxiety are common among hemodialysis patients in Montenegro, and are associated with increased levels of systematic inflammation, serum urea, and beta 2-microglobulin.

The Usefulness of Lordosis Load Test and Urinary Biochemistry in the Diagnosis of Orthostatic Proteinuria.

Introduction Renal disease is commonly suspected in patients with proteinuria. Renal biopsy might be considered based on the patient's clinical history and the results of diagnostic tests. However, as orthostatic proteinuria is benign and requires no treatment, it is important to obtain a diagnosis without renal biopsy whenever possible. Therefore, up to now, for the diagnosis of orthostatic proteinuria, in addition to resting urinalysis evaluation (disappearance of proteinuria), we have performed the lordosis load test and urine biochemistry of the samples showing peak proteinuria in a lordosis load test. Method We retrospectively enrolled all patients who visited the pediatric department and underwent the lordosis load test at Kanazawa Medical Center between 2011 and 2020. In the present study, samples with the highest concentrations of protein after the lordosis load test were subjected to general urinary biochemistry and urinary sediment analysis. Patients were followed up with the lordosis load test for several years. Results Enrolled in the study were 68 patients with OP. The mean age at the time of diagnosis was 11.5 years (range, six to 16 years). General urinary tests, urinary sediment, and urinary biochemistry including N-acetyl-beta-D-glucosaminidase (NAG), alpha1-microglobulin(α1MG), and beta 2-microglobulin (β2MG) were normal in all patients with orthostatic proteinuria except one case who was a premature baby. Conclusion If proteinuria disappears after two hours of rest, and urinary biochemistry of the samples showing peak proteinuria in the lordosis load test is normal, orthostatic proteinuria can be diagnosed more accurately.

Causal relationship between beta-2 microglobulin and B-cell malignancies: genome-wide meta-analysis and a bidirectional two-sample Mendelian randomization study.

Beta-2 microglobulin (β2M) is acknowledged as a prognostic biomarker for B-cell malignancies. However, insights into the impact of β2M on B-cell malignancy risk, and vice versa, are limited. We conducted a genome-wide meta-analysis (GWMA), bidirectional two-sample Mendelian randomization (TSMR) analysis, and pathway enrichment analysis to explore the causal relationship between β2M and B-cell malignancies and the underlying biological processes. The GWMA identified 55 lead SNPs across five genomic regions (three novel: WDR72, UMOD, and NLRC5) associated with β2M. In the UKB, genetically predicted β2M showed a positive association with diffuse large B-cell lymphoma (DLBCL; odds ratio [OR]: 1.742 per standard deviation increase in β2M; 95% confidence interval [CI]: 1.215-2.498; P = 3.00 × 10-3; FDR = 7.50× 10-3) and Hodgkin lymphoma (HL; OR: 2.270; 95% CI: 1.525-3.380; P = 5.15 × 10-5; FDR =2.58 × 10-4). However, no associations were found with follicular lymphoma (FL), chronic lymphoid leukemia (CLL), or multiple myeloma (MM). Reverse TSMR analysis revealed no association between genetically predicted B-cell malignancies and β2M. In FinnGen, β2M was found to be associated with an increased risk of DLBCL (OR: 2.098; 95% CI: 1.358-3.242; P = 8.28 × 10-4; FDR = 4.14 × 10-3), HL (OR: 1.581; 95% CI: 1.167-2.142; P = 3.13 × 10-3; FDR = 5.22 × 10-3), and FL (OR: 2.113; 95% CI: 1.292-3.455; P = 2.90 × 10-3; FDR = 5.22 × 10-3). However, no association was found with CLL or MM. Reverse TSMR analysis indicated that genetically predicted DLBCL, FL, and MM may perturb β2M levels. Pathway enrichment analysis suggested that the innate immune system represents a convergent biological process underlying β2M, DLBCL, and HL. Our findings suggested that elevated levels of β2M were associated with an increased risk of DLBCL and HL, which is potentially linked to dysfunction of the innate immune system.

B-141 Analysis of risk factors and construction of prediction model for pneumonia in patients with pneumoconiosis based on the clinical laboratory indexes

Abstract Background Pneumoconiosis has been the leading industrial disease in China. Pneumonia is one of the common comorbidities for patients with pneumoconiosis, which may lead to the worse condition and poor prognosis. Timely and accurate diagnosis is necessary to retard the pneumonia progression in pneumoconiosis patients. Due to the similarity of clinical features between pneumoconiosis and pneumonia, clinical laboratory tests are needed for assessing the hazard of pneumonia occurrence in patients with pneumoconiosis. Therefore, we aim to explore the risk factors of pneumonia from laboratory test indexes for patients with pneumoconiosis, construct prediction model, and evaluate its feasibility. Methods A total of 243 patients with pneumoconiosis from the General Hospital of Xuzhou Mining Group from September 2021 to August 2023 were selected as the modeling set, which was further separated as the non-pneumonia group and the pneumonia group. Nineteen laboratory test indexes related to inflammation, tumor markers, renal function, and blood routine examination were compared between the two groups. The univariate and multivariate Logistic analysis was used to screen out risk factors and construct the prediction model. Two hundred and twenty-eight patients with pneumoconiosis from General Hospital of Xuzhou Mining Group (Yi'an Branch) were enrolled as the validation set. The predictive efficiency of the model on pneumonia for patients with pneumoconiosis was evaluated through Hosmer-Lemeshow(H-L)test and receiver operating characteristic (ROC) curve. Results C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), β2 microglobulin, creatinine, urea, neutrophil percentage, lymphocyte percentage, and lymphocyte count in pneumonia group were significant different from those in non-pneumonia group (<0.05). Logistic regression analysis suggested that CRP (OR=3.883, <0.001), IL-6 (OR=1.217, =0.003), IL-8 (OR=1.215, =0.002) and β2-microglobulin (OR=2.838, =0.002) were independent risk factors for pneumonia in patients with pneumoconiosis. The prediction model was constructed as Logit (P) =1.357×CRP+0.196×IL-6+0.195×IL-8+1.043×β2-microglobulin-9.772. The H-L test demonstrated that there was no significantly difference between predicted values and the true values. The areas under ROC curves of the model in the modeling set and the validation set were 0.909 and 0.848. The sensitivity was 86.8% and 75.6%, and accuracy 82.1% and 79.7%, respectively. Conclusions CRP, IL-6, IL-8, and β2-microglobulin were independent risk factors of pneumonia for pneumoconiosis patients. The risk model constructed by laboratory test indexes showed a good predictive performance, which might provide laboratory evidence for the pneumonia diagnosis in patients with pneumoconiosis.

Evaluation of Serum Beta-2 Microglobulin (B2M) in Patients with CKD and People Living with HIV (PLHIV) and CKD

Evaluation of Serum Beta-2 Microglobulin (B2M) in Patients with CKD and People Living with HIV (PLHIV) and CKD

Time to lymphoma treatment within 24 months in 'watch and wait' follicular lymphoma is associated with inferior outcomes: A multicentre analysis.

Some 'watch and wait' (W&W) FL patients suffer from rapid progression in a short term. Herein, we sought to identify these patients and also develop a risk score to screen them at diagnosis. Between 2008 and 2022, a total of 411 FL patients managed by the W&W strategy from 16 cancer centres were retrospectively enrolled in this study, and their time to lymphoma treatment (TLT) and progression-free survival (PFS) were evaluated. Thirty-five percent of W&W FL patients experienced TLT within 24 months (TLT24) after diagnosis. Their 5-year PFS rate was significantly lower than those without treatment at 24 months (62.3% vs. 89.5%). In multivariable analysis, five factors were identified as independent predictors of TLT24: stages III-IV, β2 microglobulin ≥3 mg/L, lymphocyte-to-monocyte ratio <3.8, bone marrow involvement and spleen enlargement (above umbilical line). Their AUCs for TLT24 were 0.76 (95% CI, 0.70-0.82) in the training cohort and 0.76 (95% CI, 0.67-0.85) in the validation cohort respectively. Risk groups were also associated with PFS (p < 0.001). In FL patients initially managed by W&W, TLT24 was associated with poor outcomes. This multivariable model helps screening for predicting TLT24, which may be useful to identify candidates for early interventional treatment.

Understanding Cisplatin Pharmacokinetics and Toxicodynamics to Predict and Prevent Kidney Injury.

Cisplatin is a common platinum-based chemotherapeutic that induces acute kidney injury (AKI) in about 30% of patients. Pharmacokinetic/toxicodynamic (PKTD) models of cisplatin-induced AKI have been used to understand risk factors and evaluate potential mitigation strategies. While both traditional clinical biomarkers of kidney function [e.g. serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and creatinine clearance (CrCl)] and newer subclinical biomarkers of kidney injury [e.g. urinary kidney injury molecule 1 (KIM-1), beta-2 microglobulin (B2M), neutrophil gelatinase-associated lipocalin (NGAL), calbindin, etc.] can be used to detect cisplatin-induced AKI, published PKTD models are limited to using only traditional clinical biomarkers. Previously identified risk factors for cisplatin nephrotoxicity have included dose, age, sex, race, body surface area, genetics, concomitant medications, and comorbid conditions. However, the relationships between concentrations and PK of platinum and biomarkers of kidney injury have not been well elucidated. This review discusses the evaluation of cisplatin-induced nephrotoxicity in clinical studies, mouse models, and in vitro models, and examines the available human PK and TD data. Improved understanding of the relationships between platinum PK and TD, in the presence of identified risk factors, will enable the prediction and prevention of cisplatin kidney injury. Significance Statement As cisplatin treatment continues to cause AKI in a third of patients, it is critical to improve the understanding of the relationships between platinum PK and nephrotoxicity as assessed by traditional clinical and contemporary subclinical TD markers of kidney injury. Prediction and prevention of cisplatin-induced nephrotoxicity will be advanced by the evolving development of PKTD models that incorporate kidney injury biomarkers with enhanced sensitivity and include covariates that can impact risk of developing cisplatin-induced AKI.

The Vitamin C Level in Cases with Hematological Malignancies

Background: Oxidative stress plays a significant role in the pathogenesis of hematological malignan-cies. Vitamin C, known for its antioxidant properties, has garnered attention in this context. There-fore, we investigated vitamin C levels in patients with hematological malignancies and evaluated the relationship between vitamin C levels and response to treatment. Materials and Methods: Our study examined 150 cases of hematological malignancies and 30 he-althy cases. The vitamin C levels of patients with hematological malignancies were compared with those of the healthy group. Results: Vitamin C levels in cases of acute myeloblastic leukemia (n=30) (p&amp;lt;0.001), acute lympho-blastic leukemia (n=30) (p&amp;lt;0.001), Hodgkin lymphoma (n=30) (p&amp;lt;0.001), diffuse large B-cell lympho-ma (n=30) (p&amp;lt;0.001), and multiple myeloma (n=30) (p&amp;lt;0.001) were significantly lower compared to healthy individuals. There was a significant relationship between vitamin C levels and the response to treatment in cases with acute myeloblastic leukemia, acute lymphoblastic leukemia, Hodgkin lymphoma, diffuse large B-cell lymphoma, and multiple myeloma (p=0.020, p=0.020, p=0.040, p&amp;lt;0.001, p&amp;lt;0.001, respectively). In Hodgkin and non-Hodgkin lymphoma cases, a negative correla-tion was found between vitamin C levels and LDH and beta-2 microglobulin levels (p=0.001; p=0.008; p=0.017; p=0.019, respectively). Conclusions: Our study underscores the lower levels of vitamin C in patients with hematological malignancies compared to healthy individuals. Furthermore, the findings suggest that vitamin C levels could serve as a potential biomarker for predicting the response to treatment in these cases.

Craters on the melanoma surface facilitate tumor-immune interactions and demonstrate pathologic response to checkpoint blockade in humans.

Immunotherapy leads to cancer eradication despite the tumor's immunosuppressive environment. Here, we used extended long-term in-vivo imaging and high-resolution spatial transcriptomics of endogenous melanoma in zebrafish, and multiplex imaging of human melanoma, to identify domains that facilitate immune response during immunotherapy. We identified crater-shaped pockets at the margins of zebrafish and human melanoma, rich with beta-2 microglobulin (B2M) and antigen recognition molecules. The craters harbor the highest density of CD8+ T cells in the tumor. In zebrafish, CD8+ T cells formed prolonged interactions with melanoma cells within craters, characteristic of antigen recognition. Following immunostimulatory treatment, the craters enlarged and became the major site of activated CD8+ T cell accumulation and tumor killing that was B2M dependent. In humans, craters predicted immune response to ICB therapy, showing response better than high T cell infiltration. This marks craters as potential new diagnostic tool for immunotherapy success and targets to enhance ICB response.

Regulatory CD4+ T cells redirected against pathogenic CD8+ T cells protect NOD mice from development of autoimmune diabetes.

In this study, we report a novel therapeutic approach redirecting antigen-specific CD4+ T cells recognizing a hybrid insulin peptide (BDC2.5 T cell receptor (TCR) transgenic CD4+ T cells) to attract and suppress islet-specific CD8+ T cells T cells in the non-obese diabetic (NOD) mouse model, and prevent the development of autoimmune diabetes. Purified BDC2.5 CD4+ T cells were induced to differentiate into regulatory T cells (Tregs). The Tregs were then electroporated with mRNA encoding chimeric human β2 microglobulin (hβ2m) covalently linked to insulin B chain amino acids 15-23 (designated INS-eTreg) or islet-specific glucose-6-phosphatase related protein (IGRP) peptide 206-214 (designated IGRP-eTreg). Immunoregulatory functions of these engineered regulatory T cells (eTregs) were tested by in vitro assays and in vivo co-transfer experiments with β-cell-antigen-specific CD8+ T cells in NOD.Scid mice or by adoptive transfer into young, pre-diabetic NOD mice. These eTregs were phenotyped by flow cytometry, and shown to have high expression of FoxP3, as well as other markers of Treg function, including IL-10. They suppressed polyclonal CD4+ T cells and antigen-specific CD8+ T cells (recognizing insulin or IGRP), decreasing proliferation and increasing exhaustion and regulatory markers in vitro. In vivo, eTregs reduced diabetes development in co-transfer experiments with pathogenic antigen-specific CD8+ T cells (INS-CD8+ or IGRP-CD8+ cells) into NOD.Scid mice. Finally, when the eTreg were injected into young NOD mice, they reduced insulitis and prevented spontaneous diabetes in the recipient mice. Our results suggest a novel therapeutic strategy to protect NOD mice by targeting antigen-specific cytotoxic CD8+ T cells, using redirected antigen-specific CD4+ Treg cells, to suppress autoimmune diabetes. This may suggest an innovative therapy for protection of people at risk of development of type 1 diabetes.

Association of cardiorenal biomarkers with mortality in metabolic syndrome patients: A prospective cohort study from NHANES.

Approximately 20%-25% of the global adult population is affected by metabolic syndrome (MetS), highlighting its status as a major public health concern. This study aims to investigate the predictive value of cardiorenal biomarkers on mortality among patients with MetS, thus optimizing treatment strategies. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) cycles between 1999 and 2004, we conducted a prospective cohort study involving 2369 participants diagnosed with MetS. We evaluated the association of cardiac and renal biomarkers with all-cause and cardiovascular disease (CVD) mortality, employing weighted Cox proportional hazards models. Furthermore, machine learning models were used to predict mortality outcomes based on these biomarkers. Among 2369 participants in the study cohort, over a median follow-up period of 17.1 years, 774 (32.67%) participants died, including 260 (10.98%) from CVD. The highest quartiles of cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) and renal biomarkers (beta-2 microglobulin, [β2M]) were significantly associated with increased risks of all-cause mortality (hazard ratios[HRs] ranging from 1.94 to 2.06) and CVD mortality (HRs up to 2.86), after adjusting for confounders. Additionally, a U-shaped association was observed between high-sensitivity cardiac troponin T (Hs-cTnT), creatinine (Cr), and all-cause mortality in patients with MetS. Machine learning analyses identified Hs-cTnT,NT-proBNP, and β2M as important predictors of mortality, with the CatBoost model showing superior performance (area under the curve[AUC] = 0.904). Cardiac and renal biomarkers are significant predictors of mortality in MetS patients, with Hs-cTnT, NT-proBNP, and β2M emerging as crucial indicators. Further research is needed to explore intervention strategies targeting these biomarkers to improve clinical outcomes.

Proteomic Correlates and Prognostic Significance of Kidney Injury in Heart Failure With Preserved Ejection Fraction.

Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear. Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death or HF-related hospital admission in models adjusted for the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. We also assessed the relationship between the KI factor score and ~5000 plasma proteins, followed by pathway analysis. We validated our findings among HFpEF participants in the Penn Heart Failure Study. KI was associated with the risk of death or HF-related hospital admission independent of the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. Both the risk score and eGFR were no longer associated with death or HF-related hospital admission after adjusting for the KI factor score. KI was predominantly associated with proteins and biologic pathways related to complement activation, inflammation, fibrosis, and cholesterol homeostasis. KI was associated with 140 proteins, which reproduced across cohorts. Findings regarding biologic associations and the prognostic significance of KI were also reproduced in the validation cohort. KI is associated with adverse outcomes in HFpEF independent of baseline eGFR. Patients with HFpEF and KI exhibit a plasma proteomic signature indicative of complement activation, inflammation, fibrosis, and impaired cholesterol homeostasis.

Insomnia and sleep duration for kidney function: Mendelian randomization study

Objectives Extensive researches highlight the detrimental impact of sleep disorders such as insomnia and insufficient sleep duration on kidney function. However, establishing a clear causal relationship between insomnia, sleep duration, and kidney function remains challenging. This study aims to estimate this relationship using Mendelian randomization (MR). Methods Independent genetic variants strongly associated with insomnia (N = 462,341) and sleep duration (N = 460,099) were selected as instrumental variables from corresponding genome-wide association studies (GWAS). Kidney function parameters, including serum creatinine, estimated glomerular filtration rate by cystatin C (eGFRcys), acute renal failure (ARF), chronic renal failure (CRF), kidney injury molecule-1, neutrophil gelatinase associated lipocalin, microalbuminuria, cystatin C, and β2 microglobulin, were derived from GWAS databases. A two-sample MR study was conducted to assess the causal relationship between sleep disorders and kidney function, and multivariable MR was used to identify potential mediators. The inverse-variance weighted was used as the primary estimate. Results MR analysis found robust evidence indicating that insomnia and short sleep duration were associated with an increased risk of elevated serum creatinine, regardless of adjusting for obesity. Causal links between sleep duration and eGFRcys or cystatin C were also identified. While genetically predicted insomnia and sleep duration were found to potentially impact ARF, CRF, microalbuminuria, and β2 microglobulin, the p-values in multivariable MR analysis became nonsignificant. No pleiotropy was detected. Conclusions This study demonstrates a causal impact of insomnia on the risk of elevated serum creatinine and a positive effect of sleep duration on serum creatinine, eGFRcys, and cystatin C. Our findings also suggest their potential indirect effects on ARF, CRF, microalbuminuria, and β2 microglobulin mediated by obesity.

Analysis of risk factors for changes of renal artery resistance indexes in gout patients by ultrasound colour Doppler.

Gout may disturb renal hemodynamics by promoting uric acid deposition; however, this relationship has not been elucidated with adequate clinical evidence. In this study, we measured the renal artery resistance index (ARI) in patients with gout to identify the risk factors and establish predictive models for elevated renal ARI in these patients. Renal artery ultrasound examination was performed in 235 primary gout patients and 50 healthy controls (HCs); subsequently, their renal interlobar ARI (RIARI), renal segmental ARI (RSARI) and overall intrarenal ARI (OIARI) were recorded. Each ARI > 0.7 was considered elevated. RIARI, RSARI and OIARI were higher in patients with gout than in HCs (all P < 0.001). Nineteen (8.1%), 24 (10.2%) and 18 (7.7%) patients had elevated RIARI, RSARI and OIARI scores, respectively. Multivariate logistic regression analyses disclosed that: age ≥ 60 years (P = 0.000), abnormal beta2 microglobulin (β2MG) (P = 0.028), and abnormal high-density lipoprotein cholesterol (HDLC) (P = 0.030) were independently associated with elevated RIARI; age ≥ 60 years (P = 0.000), and abnormal β2MG (P = 0.013) were independently related to elevated RSARI; abnormal total protein (TP) (P = 0.014) were independently linked with elevated OIARI in gout patients. Consequently, predictive models for elevated ARI were established using nomograms based on the aforementioned independent risk factors, which showed a satisfactory value for estimating elevated RIARI [area under the curve (AUC):0.929], RSARI (AUC: 0.926) and OIARI (AUC: 0.660) in patients with gout, as validated by receiver operating characteristic curves. Renal ARI were elevated in patients with gout, whose independent risk factors included older age and abnormal β2MG, HDLC and TP levels.

Effectiveness and safety of bortezomib-dexamethasone regimen in patients with multiple myeloma: A prospective observational study

Background: Bortezomib and dexamethasone (BD) regimen offers a promising therapeutic approach in multiple myeloma (MM) by inhibiting the proteolytic pathway of tumor cells. Aims and Objectives: This study aims to assess the safety profile and treatment outcomes of MM patients undergoing the BD regimen. Materials and Methods: This prospective observational study included MM patients who received BD regimen. Patients received bortezomib (1.3 mg/m2 intravenous) weekly for 4 weeks along with dexamethasone (40 mg orally) weekly for 4 weeks. Clinical assessments were performed after each cycle, and adverse drug reactions were graded according to National Cancer Institute criteria. Treatment outcomes were evaluated after the 4th cycle based on specific parameters. Results: Thirty-seven patients, with a mean age of 56.2 years, predominantly male (56.8%), were included. Common symptoms included bone pain, fatigue, weight loss, and appetite loss. Toxicities were mainly grade 1 and 2, with peripheral neuropathy (PN) being the most prevalent. The BD regimen exhibited a response rate of 65%, accompanied by significant improvements in bone marrow plasma cells, β2 microglobulin, immunoglobulin assay, and erythrocyte sedimentation rate. In addition, treatment improved performance status, in 51.4% of patients achieving scores above 90 on the Karnofsky scale. Conclusion: The BD regimen demonstrated notable efficacy and tolerability in MM treatment. However, it is associated with a higher risk of PN.

Development of a baculoviral CRISPR/Cas9 vector system for beta-2-microglobulin knockout in human pluripotent stem cells.

Derivation of hypoimmunogenic human cells from genetically manipulated pluripotent stem cells holds great promise for future transplantation medicine and adoptive immunotherapy. Disruption of beta-2-microglobulin (B2M) in pluripotent stem cells followed by differentiation into specialized cell types is a promising approach to derive hypoimmunogenic cells. Given the attractive features of CRISPR/Cas9-based gene editing tool and baculoviral delivery system, baculovirus can deliver CRISPR/Cas9 components for site-specific gene editing of B2M. Herein, we report the development of a baculoviral CRISPR/Cas9 vector system for the B2M locus disruption in human cells. When tested in human embryonic stem cells (hESCs), the B2M gene knockdown/out was successfully achieved, leading to the stable down-regulation of human leukocyte antigen class I expression on the cell surface. Fibroblasts derived from the B2M gene-disrupted hESCs were then used as stimulator cells in the co-cultures with human peripheral blood mononuclear cells. These fibroblasts triggered significantly reduced alloimmune responses as assessed by sensitive Elispot assays. The B2M-negative hESCs maintained the pluripotency and the ability to differentiate into three germ lineages in vitro and in vivo. These findings demonstrated the feasibility of using the baculoviral-CRISPR/Cas9 system to establish B2M-disrupted pluripotent stem cells. B2M knockdown/out sufficiently leads to hypoimmunogenic conditions, thereby supporting the potential use of B2M-negative cells as universal donor cells for allogeneic cell therapy.

Association between serum β2-microglobulin and left ventricular hypertrophy in patients with type 2 diabetes mellitus: A cross-sectional study.

Beta 2-microglobulin (β2-MG) is a component of the class I major histocompatibility complex (MHCI) and has recently been reported to be involved in type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, the association of β2-MG with left ventricular hypertrophy (LVH) in T2DM patients remains unknown. This study aims to investigate the correlation between serum β2-MG and LVH in T2DM patients. The retrospective analysis included 4602 eligible T2DM patients, divided into LVH and non-LVH groups based on echocardiography results. Serum β2-MG levels were measured, and participants were categorized into four groups (Q1-Q4) by their serum β2-MG quartile. The relationship of serum β2-MG level with LVH was evaluated using logistic regression, restricted cubic spline (RCS), subgroup analysis, and machine learning. The prevalence of LVH in T2DM patients was 31.12%. Each standard deviation increase in serum β2-MG level corresponded to a 1.17-fold increase in the prevalence of LVH [OR = 1.17, (95% CI: 1.05-1.31); p = 0.006]. When considering β2-MG as a categorical variable (quartile), Q3 [OR = 1.36, (95% CI: 1.09-1.69); p = 0.007] and Q4 [OR = 1.77, (95% CI: 1.36-2.31); p < 0.001] had a significantly higher prevalence of LVH than Q1. RCS analysis found a nonlinear association between β2-MG and LVH prevalence (p for nonlinearity <0.05). Additionally, machine learning results confirmed the importance of β2-MG for LVH in T2DM patients. Elevated serum β2-MG levels were likely to be associated with an increased prevalence of LVH in T2DM patients, suggesting its potential role in LVH development.

Unusual course of glyphosate-induced acute kidney injury: a case report of tubulointerstitial nephritis treated with steroids.

Glyphosate is a widely used herbicide that is generally considered safe; however, acute kidney injury (AKI) caused by glyphosate ingestion can be severe and require hemodialysis. We present a unique case of a 68-year-old Japanese man who developed AKI after accidental ingestion of glyphosate and required hemodialysis. Based on the clinical presentation and findings, the patient was diagnosed with renal AKI with severe tubulointerstitial damage. However, the precise pathogenesis of the tubulointerstitial damage remained unclear. An elevated beta-2 microglobulin level discovered by the urinalysis during admission raised the suspicion of tubulointerstitial nephritis caused by glyphosate. Gallium scintigraphy revealed accumulation in both kidneys. A renal biopsy revealed acute tubulointerstitial nephritis rather than acute tubular necrosis, which is commonly observed with glyphosate-induced renal injury. After initiating steroid therapy, his kidney function gradually improved and he was weaned from hemodialysis. This report is the first to describe glyphosate-induced acute tubulointerstitial nephritis that was successfully treated with immunosuppressive therapy. Furthermore, this report highlights the importance of steroid therapy for cases of persistent kidney injury after the discontinuation of agents associated with acute tubulointerstitial nephritis.