Β2-microglobulin Levels Research Articles

Acute tubulointerstitial nephritis following coronavirus disease 2019 mRNA vaccination: a pediatric case report.

Coronavirus disease 2019 (COVID-19) mRNA vaccines have been linked to various kidney adverse events including acute tubulointerstitial nephritis (ATIN). This report describes a 15-year-old female who developed persistent fever and fatigue 54days after receiving her second dose of the BNT162b2 2 SARS-CoV-2 vaccine. She presented with elevated serum creatinine and urinary β2-microglobulin (β2MG) levels. Kidney biopsy revealed mononuclear infiltrate with some eosinophils, confirming the diagnosis of ATIN. Repeatedly positive lymphocyte transformation test results for the vaccine suggested a relationship between the vaccine and interstitial nephritis. Initially, treatment with prednisolone was effective. However, an increase in urinary β2MG level was observed 7months later, and the introduction of mycophenolate mofetil (MMF) allowed for the gradual reduction and eventual cessation of prednisolone. This case represents one of the rare pediatric instances of ATIN following COVID-19 vaccination. MMF can be an effective alternative in corticosteroid-dependent cases.

Clinical features and risk factors for outcome in hemodialysis patients with COVID-19 after complete liberalization of epidemic control in China.

Patients undergoing hemodialysis (HD) are highly vulnerable during the COVID-19 pandemic. We aimed to investigate the risk factors associated with the severity of COVID-19 and death after the complete liberalization of epidemic control in China. We followed the outcomes of the HD patients of Central Hospital of Dalian University of Technology, from December 6, 2022 to January 8, 2023. The non-contrast enhanced chest computed tomography (CT) was performed on all COVID-19-infected hospitalized patients. We recorded the patient's clinical characteristics, demographic features, vaccination history, treatments, and lung lesions. Odds ratios and 95% confidence intervals were calculated using logistic regression models to identify independent risk factors for COVID-19-related severity and mortality. This study included a total of 858 hemodialysis patients, of which 660 were infected with COVID-19. The mean age was (55.61±14.61) years, with a median (interquartile range) dialysis duration of 44.5 (69.5) months. Over half (60%) of the study participants were male, and the majority had hypertension as a comorbidity. Multivariable analysis revealed that age, pre-dialysis diastolic pressure, fever, white blood cell (WBC) count, potassium, β2-microglobulin level and calcium were independent risk factors for disease severity, while platelets, urea nitrogen and creatinine were identified as independent protective factors. Furthermore, total iron- binding capacity and vaccination were found to be independent protective factors against mortality, and WBC count was an independent risk factor for in-hospital mortality (p < 0.05). The most frequent CT finding among hospitalized patients with chest symptoms was patchy shadow or pleural effusion, observed in 64.8% of cases. More than half of the patients exhibited bilateral lung lesions, and over 60% involved two or more lobes. The majority of HD patients are susceptible to COVID-19. Demographic, clinical features and laboratory indicators can be used to predict the severity and mortality associated with COVID-19. Our findings will assist clinicians in identifying markers for the early detection of high mortality risk in HD patients with COVID-19.

Serum β2-microglobulin as an independent risk factor for mortality in patients with acute respiratory distress syndrome caused by bacterial infection

Acute respiratory distress syndrome (ARDS) is a heterogeneous disease with extremely high mortality. We hypothesized that the serum β2-microglobulin (β2MG) level would be elevated and be an independent risk factor for 28-day mortality in patients with ARDS caused by bacterial infection. We retrospectively enrolled 257 patients with ARDS caused by bacterial infection from January 1, 2015 to February 28, 2021. Patients were followed for up to 28 days and were divided into a survival group and non-survival group according to their clinical outcomes. The serum β2MG levels and other clinical data were collected. The relationship between β2MG levels and 28-day mortality was explored by performing a Cox regression analysis adjusted for age, updated Charlson comorbidity index, disorders of consciousness, septic shock, albumin level, cardiac troponin I level, procalcitonin level, lactic acid level, prothrombin time, partial pressure of arterial oxygen/fraction of inspired oxygen ratio, estimated glomerular filtration rate and Sequential Organ Failure Assessment. In this cohort, 96 patients died in 28 days, yielding a 28-day mortality of 37.4%. The median level of serum β2MG for all enrolled patients was 4.7 (interquartile range [IQR]: 2.9–8.5) mg/L. Higher β2MG levels were significantly associated with 28-day mortality when the β2MG level was analysed as a continuous variable (hazard ratio [HR]: 1.053; 95% confidence interval [CI] 1.004–1.104; P = 0.032) and when it was categorized into tertiles (HR: 3.241; 95% CI 1.180–8.905; P = 0.023). The β2MG level exhibited a high diagnostic accuracy for predicting 28-day mortality (area under the curve [AUC] = 0.732; 95% CI 0.673–0.785; sensitivity: 74.0%; specificity: 64.0%; P < 0.001). The level of serum β2MG is elevated and is an independent risk factor of 28-day mortality in patients with ARDS caused by bacterial infection.

B-313 Assessment of β2-microglobulin concentration in pleural effusions

Abstract Background β2-microglobulin (β2-m) is a biomarker used in serum for different types of pathologies. It has been described that lymphocyte activation processes us tuberculosis infections, AIDS virus or cytomegalovirus infections, can produce an increase in the concentration of this marker. As a tumor marker is useful in lymphomas diagnosis. In the bibliography has reported that processes involving renal failure lead to a significant increase in its concentration. In patients with renal failure and treated with hemodialysis, have been described medians twenty times the upper reference limit. The objective is to assess whether the concentration of (β2-m) in pleural fluid is affected by the same factors as in serum. Methods We analyzed 303 pleural effusions (PE) samples from undiagnosed patients with pleural effusion. β2-microglobulin levels were prospectively measured by electrochemiluminescence (ECLIA) assays (Cobas c702, Roche Diagnostics®). Glomerular filtration rate (GFR) was calculated by CKD-EPI equation. The diagnostic performance of β2-microglobulin was evaluated by receiver operating characteristic (ROC) curve analysis. Statistical analyses were performed using SPSS software. Results Pleural fluid of 303 patients (104 female, 204 male) were collected. The median age was 72 ± 10,6 years. For all samples β2-m median concentration was 5,85 mg/L (IQR:3.4 -6.45).When we compared all results according to kidney failure values; GFR &amp;gt;60mL/min β2-m median concentration was 4,12mg/L and if GFR &amp;lt;60 mL/min, β2-m was 8,62g/L significant difference have found (p&amp;lt;0,001). Comparing results between malignant pleural effusions (MPE) (n=96) and benign pleural effusions (BPE) (n=207), MPE median concentration was 5.38 mg/L and 6.07mg/L significant difference (p&amp;lt;0,001). Benign pathologies associated with pleural effusions, tuberculosis samples had the highest concentration of β2-m. Tuberculosis samples (n=6) had a normal distribution, obtaining a value [mean (SD)] of 7.28 mg/mL (2,13) mg/mL. For tuberculosis samples and patients without renal failure (n=5) (GFR&amp;gt;60 mL/min), the area under the ROC curve was 0.98 (95% CI: 0.88-0.98) (p&amp;lt;0.005). For β2-m cut-off point was 5.150 mg/L, a sensitivity of 100%, specificity of 16%, positive predictive value (PPV) of 14% and negative predictive value (NPV) of 100% were obtained. Patients with lymphomas present the highest concentration in the group of malignant pleural effusions, but further investigations could not be performed due to the small sample size. Conclusions Based on the results obtained from our present study, it can be concluded that β2-microglobulin marker in pleural effusions has significant association with glomerular filtration rate, as well as occurs in serum. Higher concentrations were found in patients with GFR&amp;gt;60 mL/min and tuberculosis. Using 5,15 mg/L cut-off point, 100% of NPV was obtained.

Clinical Features and Prognosis of Patients with Diffuse Large B-Cell Lymphoma of the Breast

To explore the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) of the breast. The clinical data of 28 DLBCL patients admitted to Shanxi Provincial Cancer Hospital from January 2013 to January 2023 were retrospectively analysed, including 13 cases of primary breast DLBCL (PB-DLBCL) and 15 cases of secondary breast DLBCL (SB-DLBCL), and the data of their clinical manifestations, laboratory tests, pathological examinations, treatment protocols, and follow-up were statistically analyzed. There were significant differences in IPI score, LDH level and β2- microglobulin between PB-DLBCL and SB-DLBCL patients (P < 0.05). Among the 23 patients with breast DLBCL who received regular treatment, 13 patients achieved complete remission (9 patients with PB-DLBCL and 4 patients with SB-DLBCL) after initial treatment. By the end of follow-up, 11 patients relapsed or progressed (5 patients with PB-DLBCL and 6 patients with SB-DLBCL) and 9 patients died (3 patients with PB-DLBCL and 6 patients with SB-DLBCL). The 5-year OS rate was (75.0±15.3)% in PB-DLBCL group and (32.3±17.1)% in SB-DLBCL group. The 5-year PFS rate was （59.1±19.8）% in PB-DLBCL and 0% in SB-DLBCL group. The 5-year OS rate and PFS rate of PB-DLBCL patients were higher than those of SB-DLBCL patients (P < 0.05); the 5-year OS rate of the combined central preventive treatment group was higher than that of the chemotherapy group (P < 0.05). Breast DLBCL is divided into two categories: PB-DLBCL and SB-DLBCL. Compared with SB-DLBCL, PB-DLBCL has the characteristics of lower IPI score, LDH, and β2-microglobulin levels. PB-DLBCL patients have a longer survival period. In addition, the prognosis of patients receiving central preventive treatment is more optimistic.

Assessment of B2-Microglobulin Analysis for Renal Insufficiency in Iraqi β-Thalassemia Major Patients

Background: Beta-thalassemia is the most prevalent genetic hemoglobin apathy in the world. It is caused by a reduction or absence of beta-globin chain production, which is typically a portion of adult hemoglobin (HbA, which is α2β2). This genetic anomaly will lead to a rapid erythrocyte turnover, severe anemia, and compensatory ineffective erythropoiesis. The purpose of the current research is to reveal diagnostic, and predictive biomarkers that can be performed to detect the decline in renal function in β-thalassemia major patients with early stage renal impairment with high sensitivity and specificity, ascertain changes in B2-microglobulin as a biomarker in β-thalassemia patient. Objective: The samples were collected from Karama Hospital-Genetic Hematology Center/Baghdad during the period from the 1st of September 2022 until the 1st of January 2023. Methods: The patient group consisted of 45 patients with β-thalassemia major with repeated blood transfusion and the control group consisted of 45 individuals who seemed to be healthy. Age ranged between (18-35) years (for patients and control). The serum samples were used to measure biochemical parameters, S.Creatinine, blood urea, and Urine B2-microglobulin were measured from urine samples. B2-microglobulin level in Urine was estimated by Sandwich enzyme-linked immunosorbent assay (ELISA) technique, while serum Blood Urea and Serum Creatinine concentration were calculated by Colorimetric Kit by Spectrophotometer method, and Ferritin level in blood was estimated by BioMrieux Mini Vidas. Results: The statistical examination was carried out using SPSS software. B2-microglobulin biomarkers in the thalassemia Patient group were significantly higher than those in the control group (p&lt;0.001). While serum ferritin, B.Urea and S.Cr increased in patient groups compared to the control group (p&lt;0. 005). Conclusions: All parameters included in this study are significantly higher in β-thalassemia patients than in healthy subjects. Renal hemosiderosis and asymptomatic renal dysfunction are prevalent among β-thalassemia major patients with repeated blood transfusions, which are not found in routine renal investigations.

Effect of central dialysis fluid delivery system on markers of inflammation in hemodialysis patients

BackgroundThe utilization of ultrapure dialysate has been shown to decrease dialysate contamination and mitigate inflammatory responses. The central dialysate delivery system (CDDS) has the potential to attain a level of purity similar to ultrapure dialysate. Nevertheless, there is limited research examining the impact of CDDS on inflammation in comparison to single-patient dialysis fluid delivery system(SPDDS). This study aims to investigate the effects of CDDS utilizing ultrapure dialysate on ameliorating the microinflammatory state in hemodialysis patients.MethodA retrospective cohort clinical study enrolled a total of 125 hemodialysis patients, with 58 patients from the CDDS unit and 67 patients from the SPDDS unit. Each participant was monitored for a period of 6 months, and the repeated measurement data was analyzed using a generalized linear mixed models (GLMM).ResultsThe average age of the studty cohort was 56.22 ± 12.64 years. The GLMM analysis showed a significant time*group interaction effect on hs-CRP changes over the follow-up period (β = -1.966, FTime* CDDS group = 13.389, P < 0.001). A linear mixed model analysis with random slope showed that a different slope was observed between CDDS group and SPDDS group (βCDDS =—0.793; βSPDDS = 0.791), indicating a decreased hs-CRP levels in CDDS group, while increased in the SPDDS group over the follow-up period. However, no significant time*group interaction effect were observed on albumin and β2-microglobulin levels during follow-up period(β2-microglobulin: β = -0.658, FTime* CDDS group = 1.228, P = 0.269; albumin: β = 0.012, FTime* CDDS group = 1.429, P = 0.233).ConclusionUsing ultrapure dialysate in the CDDS is associated with an improvement in hs-CRP levels compared to standard dialysate, which might confer long-term clinical advantages.

Protection Effect of Soy Isoflavones (Genistein and Daidzein) on Hematologic Parameters in Acute Kidney Injury

Background: Acute kidney injury (AKI) is a severe, high-morbidity condition with limited effective preventative and therapeutic strategies despite advancements in understanding and treatment. Specific Background: Rhabdomyolysis-induced acute kidney injury (AKI) presents significant challenges in renal research, but soy isoflavones, particularly GN and DZ, have shown potential in mitigating oxidative stress and inflammation. Knowledge Gap: Soy isoflavones, while potentially providing renal protection, their impact on renal and hematologic parameters in glycerol-induced AKI models has not been thoroughly studied. Aims: The study evaluated the effectiveness of soy isoflavones in regulating renal and hematologic parameters in a glycerol-induced AKI rat model, assessing their potential as therapeutic agents. Results: The study involving adult female Wistar rats showed that pretreatment with glycerol or dihydroxystilbene significantly reduced urinary β2-microglobulin, albumin, BUN, and serum creatinine levels in the AKI-induced group, reversing hematological changes. Novelty: The study explores the protective effects of soy isoflavones on renal function and hematologic parameters in AKI, highlighting GN's superior efficacy over DZ. Implications: Soy isoflavones, particularly GN, may be potential preventive or therapeutic strategies for AKI caused by rhabdomyolysis, warranting further research for clinical applications. Highlights: GN and DZ reduce kidney damage in glycerol-induced AKI. GN is more effective than DZ in kidney and blood parameters. Soy isoflavones could treat or prevent AKI. Keywords: Acute kidney injury, soy isoflavones, glycerol-induced AKI, renal protection, hematologic parameters

Association of high serum β2-microglobulin levels with poor functional outcomes in patients with acute ischemic stroke: A cohort study.

We evaluated the association between serum β2-microglobulin (β2M) levels and prognosis in patients with acute ischemic stroke (AIS) and determined whether the association was affected by any clinical variables. This prospective study included 533 patients with AIS who were admitted to the Hospital of Nanhua Affiliated with the University of South China for treatment from June 1, 2021, to July 31, 2022. Using multiple regression modeling, the association between serum β2M levels and poor functional outcomes-which were classified as being modified Rankin Scale scores of 3 to 6 (composite score of death and major disability), 3 to 5 (major disability), and 6 (death)-were assessed 3 months after stroke onset. At the 3-month follow-up assessment, 209 (47.39%) participants had poor functional outcomes: major disabilities in 150 (34.01%) cases and deaths in 59 (13.38%). After adjusting for important covariates, the group with serum β2M levels in the highest quartile had the highest proportion of individuals with modified Rankin Scale scores of 3 to 6 (odds ratio [OR], 3.54; 95% confidence interval [CI], 1.35-9.33), 3 to 5 (OR, 2.95; 95% CI, 1.21-7.16), or 6 (OR, 1.02; 95% CI, 0.29-3.64) compared with the group having serum β2M levels in the lowest quartiles. The risk prediction for the combined outcome of death and major disability improved after incorporating β2M levels into models that included conventional risk factors. Subgroup analysis revealed a significant impact on the association between serum β2M levels and poor functional outcomes only in patients with AIS whose time from onset to hospitalization was <12 hours (P for interaction < .05). Elevated serum β2M levels were associated with poor functional outcomes in patients with AIS, possibly affected by the time from onset to hospitalization.

Aseptic meningitis with recurrent headache episodes, vomiting, and central fever as first manifestation of isolated neurosarcoidosis: a case report

BackgroundNeurosarcoidosis is a rare entity, usually within the context of systematic sarcoidosis. Isolated neurosarcoidosis and especially a manifestation with pachymeningitis is a notable rarity.Case ReportA 26-year-old patient presented to the emergency department with acute onset, recurrent episodes of occipital headaches spreading over the whole cranium and vomiting without food consumption, for three days. The clinical examination did not reveal any neurological deficits. The laboratory exams showed no pathological findings. A CT examination with angiography did not detect any acute intracranial or vessel pathology. A lumbar puncture was performed to rule out subarachnoid hemorrhage. The results showed a lymphocytic pleocytosis of 400/µL, elevated protein levels of 1077 mg/dL and reduced glucose levels (CSF: 55 mg/dL, Serum: 118 mg/dL). Extensive infectiological examinations did not reveal any signs of infection, including Borrelia spp. and M. tuberculosis. No positive auto-antibodies or vasculitis-related auto-antibodies were detected. The CSF analysis showed negative oligoclonal bands but an isolated increase in β2-microglobulin, neopterin, and IL-2R levels. The MRI examination revealed a dural gadolinium-enhancement, pronounced in the basal cerebral structures and the upper segment of the cervical spine, consistent with neurosarcoidosis. Corticosteroid treatment rapidly led to a significant improvement of the symptoms. No systemic manifestations of sarcoidosis were found.ConclusionsThis case report aims to highlight aseptic meningitis with atypical, acute onset headache attacks as a possible manifestation of isolated neurosarcoidosis. Neurosarcoidosis is a clinical entity that requires prompt treatment to avoid permanent neurological deficits.

Changes in urinary renal injury markers in children with Mycoplasma pneumoniae pneumonia and a prediction model for related early renal injury

BackgroundThis study aims to analyse changes in urinary kidney injury markers in children with Mycoplasma pneumoniae pneumonia (MPP), investigate the risk factors for MPP-related acute kidney injury (AKI) and establish a model to predict MPP-related AKI.MethodsNinety-five children were enrolled based on the study’s inclusion and exclusion criteria. They were divided into a severe MPP (SMPP) group and a non-SMPP group and then into an AKI group and a non-AKI group according to the presence of AKI. A univariate logistic regression analysis was performed to explore the early risk factors for AKI. Based on a multivariate logistic regression analysis and a least absolute shrinkage and selection operator regression analysis, appropriate variables were selected to establish a prediction model, and R 4.2.2 software was used to draw nomograms and generate a dynamic nomogram website.ResultsSeven urinary kidney injury markers were abnormally elevated in the SMPP group and the non-SMPP group: urinary N-acetyl-β-D-glucosaminidase (NAG), β2-microglobulin, α1-microglobulin, retinol-binding protein, urinary immunoglobulin G, urinary transferrin and urinary microalbumin. Sixteen children were identified with AKI during hospitalisation. The AKI group had higher levels of urinary NAG, α1-microglobulin, β2-microglobulin, urinary microalbumin, urinary transferrin and retinol-binding protein than the non-AKI group (P < 0.05). The MPP-related AKI prediction model consists of four indicators (serum immunoglobulin M [IgM], C-reactive protein [CRP], urine NAG and sputum plug presence) and a dynamic nomogram.ConclusionUrinary kidney injury markers are often elevated in children with MPP; urinary NAG is the marker most likely to be elevated, and it is especially evident in severe cases. The nomogram of the prediction model, comprising serum IgM, CRP, urinary NAG and sputum plug presence, can predict the probability of AKI in children with MPP.

Clinical Characteristics Analysis of EBV-associated Hemophagocytic Lymphohistiocytosis Patients with Acute Kidney Injury

To analyze the clinical characteristics of patients with Epstein-Barr virus(EBV)-associated hemophagocytic lymphohistiocytosis(HLH) with acute kidney injury(AKI). EBV-HLH patients who were hospitalized in our hospital from January 2014 to December 2020 were collected, and their clinical characteristics, treatment, concurrent acute kidney injury and prognosis were retrospectively analyzed. In this study, the incidence of AKI complicated by EBV-HLH was 65.5%, and the 28-day mortality rate was 15.3%. Compared with non-AKI group, patients in the AKI group had higher levels of bilirubin, lactate dehydrogenase, creatinine, urea nitrogen, and β2-microglobulin（β2-MG）, poorer coagulation, and lower soluble IL-2 receptor （sCD25）. Patients in the AKI group had a higher proportion of chemotherapy, transplantation, mechanical ventilation, and the application of vasoactive medications, and were hospitalized for longer periods of time, with higher in-hospital mortality rates and 28-day mortality rates. Patients in the AKI group were analyzed in subgroups according to the Kidney Disease Improving Global Outcomes （KDIGO）classification, and the levels of leukocytes, bilirubin, albumin, creatinine, urea nitrogen, β2-MG, activated partial thromboplastin time （APTT）, and prothrombin time activity （PTA）were more responsive to the severity of the patient's condition. KDIGO grade 2 and 3 had higher proportions of receiving transplants, diuretics, organ support (mechanical ventilation, application of vasoactive medications, and renal replacement therapy), and admissions to the intensive care unit （ICU）, and with higher in-hospital mortality rates and 28-day mortality rates. Regression analysis found that creatinine, β2-MG, APTT, transplantation, and chemotherapy were independent risk factors for the development of AKI; the application of vasoactive drugs was both an independent risk factor for the development of AKI and for death at 28 days; and chemotherapy, length of hospitalization, and HGB and fibrinogen levels were protective factors for death at 28 days. AKI in EBV-HLH has high incidence and high rate of progression to severe disease and death, early attention should be given and strengthened in order to carry out early treatment and improve the prognosis of patients.

Superior detection of low-allele burden Janus kinase 2 V617F mutation and monitoring clonal evolution in myeloproliferative neoplasms using chip-based digital PCR

The JAK2 V617F is a prevalent driver mutation in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph−MPNs), significantly affecting disease progression, immunophenotype, and patient outcomes. The World Health Organization (WHO) guidelines highlight the JAK2 V617F mutation as one of the key diagnostic criterions for Ph−MPNs. In this study, we analyzed 283 MPN samples with the JAK2 V617F mutation to assess the effectiveness of three detection technologies: chip-based digital PCR (cdPCR), real-time quantitative PCR (qPCR), and next-generation sequencing (NGS). Additionally, we investigated the relationship between JAK2 V617F mutant allele burden (% JAK2 V617F) and various laboratory characteristics to elucidate potential implications in MPN diagnosis. Our findings demonstrated high conformance of cdPCR with qPCR/NGS for detecting % JAK2 V617F, but the mutant allele burdens detected by qPCR/NGS were lower than those detected by cdPCR. Moreover, the cdPCR exhibited high sensitivity with a limit of detection (LoD) of 0.08% and a limit of quantification (LoQ) of 0.2% for detecting % JAK2 V617F in MPNs. Clinical implications were explored by correlating % JAK2 V617F with various laboratory characteristics in MPN patients, revealing significant associations with white blood cell counts, lactate dehydrogenase levels, and particularly β2-microglobulin (β2-MG) levels. Finally, a case report illustrated the application of cdPCR in detecting low-allele burdens in a de novo chronic myeloid leukemia (CML) patient with a hidden JAK2 V617F subclone, which expanded during tyrosine kinase inhibitor (TKI) treatment. Our findings underscore the superior sensitivity and accuracy of cdPCR, making it a valuable tool for early diagnosis and monitoring clonal evolution.

Transcriptomic and proteomic differences in BTK-WT and BTK-mutated CLL and their changes during therapy with pirtobrutinib

AbstractCovalent Bruton tyrosine kinase inhibitors (cBTKis), which bind to the BTK C481 residue, are now primary therapeutics for chronic lymphocytic leukemia (CLL). Alterations at C481, primarily C481S, prevent cBTKi binding and lead to the emergence of resistant clones. Pirtobrutinib is a noncovalent BTKi that binds to both wild-type (WT) and C481S-mutated BTK and has shown efficacy in BTK-WT and -mutated CLL patient groups. To compare baseline clinical, transcriptomic, and proteomic characteristics and their changes during treatment in these 2 groups, we used 67 longitudinal peripheral blood samples obtained during the first 3 cycles of treatment with pirtobrutinib from 18 patients with CLL (11 BTK-mutated, 7 BTK-WT) enrolled in the BRUIN (pirtobrutinib in relapsed or refractory B-cell malignancies) trial. Eastern Cooperative Oncology Group performance status, age, and Rai stage were similar in both groups. At baseline, lymph nodes were larger in the BTK-mutated cohort. All patients achieved partial remission within 4 cycles of pirtobrutinib. Lactate dehydrogenase and β2-microglobulin levels decreased in both cohorts after 1 treatment cycle. Expression analysis demonstrated upregulation of 35 genes and downregulation of 6 in the BTK-mutated group. Gene set enrichment analysis revealed that the primary pathways enriched in BTK-mutated cells were involved in cell proliferation, metabolism, and stress response. Pathways associated with metabolism and proliferation were downregulated in both groups during pirtobrutinib treatment. Proteomic data corroborated transcriptomic findings. Our data identified inherent differences between BTK-mutated and -WT CLL and demonstrated molecular normalization of plasma and omics parameters with pirtobrutinib treatment in both groups.

Estimated Proximal Tubule Fluid Phosphate Concentration and Renal Tubular Damage Biomarkers in Early Stages of Chronic Kidney Disease

IntroductionAn increase in proximal tubule fluid phosphate concentration is caused by increased serum fibroblast growth factor 23 (FGF23) levels, which resulted in renal tubular damage in a mouse model of chronic kidney disease (CKD). However, few human studies have supported this concept. This study aimed to explore the association among estimated proximal tubule fluid phosphate concentration (ePTFp), serum FGF23 levels, and renal tubular damage biomarkers in middle-aged and older populations with mild decline in renal function. MethodsThis cross-sectional study included 218 participants aged ≥45 with CKD stages G2–G4. Anthropometric measurements, blood tests, spot urine biomarkers, renal ultrasonography, cardiovascular assessment, smoking status, and medication usage were obtained in the morning in fasted states. The ePTFp was calculated using serum creatinine, urine phosphate, and creatinine concentrations. Urinary β2-microglobulin and liver-type fatty acid-binding protein (L-FABP) levels were evaluated to assess renal tubular damage.Results: ePTFp, serum FGF23, urinary β2-microglobulin, and urinary L-FABP levels increased with CKD stage progression (stages G2, G3, and G4). However, serum and urine phosphate concentrations were comparable across the CKD stages. Univariate analysis revealed a stronger correlation of ePTFp with serum FGF23, urinary β2-microglobulin, and urinary L-FABP levels than with the corresponding serum and urine phosphate concentrations. Multivariate analyses demonstrated that increased ePTFp was independently associated with elevated serum FGF23 and urinary β2-microglobulin levels, even after adjusting for potential covariates, including the estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. ConclusionsOur results are consistent with the concept in mouse model and suggest that increased ePTFp are associated with increased serum FGF23 levels and renal tubular damage during the early stages of CKD.

Therapeutic Apheresis Using a β2-Microglobulin Removal Column Reduces Circulating Tumor Cell Count.

An elevated serum β2-microglobulin (β2M) level is indicative of impaired glomerular filtration and prerenal diseases, such as malignant tumors, autoimmune disorders, and liver diseases. An elevated serum β2M level has been shown to promote metastasis via the induction of epithelial-mesenchymal transition (EMT) in cancer cells. However, the therapeutic potential of targeting β2M remains unclear. Here, we aimed to investigate the efficacy of Filtor, a small polymethyl methacrylate fiber-based β2M removal column, in reducing the β2M level and suppressing cancer cell-induced EMT and metastasis. We assessed the effects of Filtor on the changes in metastasis based on the number of circulating tumor cells (CTCs), which reflects the post-EMT cancer cell population. We performed therapeutic apheresis using Filtor on a male patient with sinonasal neuroendocrine carcinoma, a female patient with a history of colorectal cancer, and another female patient with a history of pancreatic ductal adenocarcinoma. Significantly low serum β2M levels and CTC counts were observed immediately and 4 weeks after treatment compared with those in the pretreatment phase. Moreover, the CTC count immediately after therapeutic intervention was markedly reduced, likely because Filtor had trapped CTCs directly. These findings suggest that therapeutic apheresis with Filtor can prevent cancer metastasis and recurrence by directly removing CTCs.

Expression and Clinical Significance of LINC00475 in Multiple Myeloma

To investigate the relative expression level and clinical significance of LINC00475 in serum of patients with multiple myeloma (MM). The expression of LINC00475 in serum of 108 MM patients and five MM cell lines including RPMI 8226, NCI-H929, U266, OPM2 and CAG were detected by real-time fluorescence quantitative PCR. The diagnostic value of LINC00475 in MM was evaluated by receiver operating characteristic (ROC) curve analysis. The correlation of LINC00475 with patients' characteristics was analyzed. Compared with control groups, the expression of LINC00475 was up-regulated in serum of MM patients and MM cell lines (all P < 0.05). ROC curve analysis showed that the optimal cut-off value of LINC00475 was 262.4, the area under curve (AUC) was 0.924(95%CI : 0.884-0.964), and sensitivity and specificity was 83.3% and 91.7%, respectively, which indicated that LINC00475 had good evaluation value in MM patients. Compared with low-LINC00475 expression group, patients in high-LINC00475 expression group had higher levels of β2microglobulin (β2-MG) and Cystatin C (Cys-C) but lower albumin (ALB) (all P < 0.05). Compared with MM patients with International Staging System (ISS) stage I, the expression level of LINC00475 was significantly higher in patients with stage II and III (both P < 0.05). LINC00475 is helpful to distinguish MM patients from healthy adults, which is correlated with the prognostic indicators such as β2-MG, ALB, and ISS stage.

Clinical, Pathological and Immunohistochemical Characteristics of Patients with Primary Testicular Lymphoma Undergoing Orchiectomy: A Systematic Review and Meta-Analysis.

Primary testicular lymphoma (PTL) is a rare and aggressive malignant tumour with no specific clinical symptoms. Large-scale evidence-based medical evidence to guide preoperative diagnosis is lacking at present. This study aimed to analyse the clinical, pathological and immunohistochemical characteristics of patients with PTL undergoing testicular resection surgery. Literature on the clinical characteristics of patients with PTL undergoing orchiectomy was retrieved from databases, including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Data. The search covered all available records from the inception of these databases until December 31, 2023. Data extraction was followed by a meta-analysis using Stata 15.0 software. A total of 22 articles and 475 cases of PTL were included. The meta-analysis revealed that 58.1% of patients with PTL undergoing orchiectomy were under 60 years old, and 41.9% were 60 years or older. The lesion is mostly located on the right side (55.1%). Common symptoms included testicular swelling and falling swelling (91.3%), hydrocele testis (31.0%) and testicular pain (23.0%). Ann Arbor stages I-IV accounted for 53.3%, 16.7%, 14.8% and 15.7%, respectively. Diffuse large B-cell lymphoma (DLBCL) cases were higher at 95.5% than NK/T-cell lymphoma cases at 8.2%. Amongst DLBCL cases, 69.3% were non-germinal centre B-cell (GCB) subtype, and 27.6% were GCB subtype. Immunohistochemistry markers showed 95.9% CD3 negative, 94.9% CD10 negative, 94.4% CD20 positive, 88.4% multiple myeloma oncogene-1 (MUM-1) negative, 73.6% B-cell lymphoma-6 (BCL-6) negative and 66.5% BCL-2 positive. Laboratory findings indicated that 70.4% of patients had a tumour proliferating cell nuclear antigen (Ki67) index of ≥80%, 36.0% had increased serum lactate dehydrogenase level and 22.9% had increased serum β2-microglobulin level. PTL is rare, and it often occurs in elderly male patients. Common symptoms include testicular swelling and falling swelling, and the common histological type is DLBCL. Diagnosis should be based on histopathological characteristics and immunohistochemical examination.

#1235 Comparative effect on bone remodeling and inflammation biomarkers of citrate dialysate and bicarbonate dialysate in HDF-OL patients

Abstract Background and Aims Hemodialysis (HD) treatment increases the inflammatory state of chronic kidney disease (CKD), which is associated with dysregulation of mineral bone metabolism. Reduced inflammation and increased bone formation have been described in Hemodiafiltration (HDF) compared with conventional HD. On the other hand, HD and OL-HDF using citrate-enriched dialysate are known to be safe and anti-inflammatory. However, the effects of post-dilution OL-HDF with citrate dialysate compared to bicarbonate dialysate on biomarkers of bone formation and resorption have not been studied. We aimed to compare the effect of bone remodeling markers and inflammation of different dialysates (citrate vs bicarbonate) in post dilution OL- HDF treatment. Method A total of 33 patients on conventional HD with bicarbonate citrate were included. At month 1, 18 patients, who did not require individualized adjustment of the dialysate composition such as potassium, were changed to HD with citrate dialysate and 15 patients remained with bicarbonate dialysate. By the second month, however, all patients were on OL-HDF with no change in buffer dialysate. Pre-dialysis blood samples were taken in both treatment groups at baseline (prior to the initiation of citrate dialysate in 18 patients), and at the first, second and fifth months after the introduction of citrate. Measurements of mineral homeostasis (calcium, phosphate, magnesium, parathyroid hormone, intact parathyroid hormone), inflammation (interleukin-6, β2-microglobulin, C-reactive protein) and bone remodeling markers (carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX), as a biomarker of bone resorption and procollagen type 1 N-terminal pro-peptide (P1NP), as a biomarker of bone formation) were performed. All samples were collected before a mid-week dialysis session. Mineral homeostasis measurements were also performed before and after HD at the first and second month of the switch to citrate dialysate. Normally distributed data were presented as mean (standard deviation, SD) and median (interquartile range). Intra-subjects comparisons were analyzed using paired sample t-test or Wilcoxon signed-rank test. Comparisons between groups were analyzed using Mann-Whitney U test. Statistical analyses were performed using the SPSS (version 15.0, Chicago, IL, USA). p-value &amp;lt; 0.05. Results Overall, 75.7% (n = 25) of the subjects were male, the median age was 69 years (SD: 12) and 39.3% suffered diabetes (n = 13). Patients on citrate and bicarbonate dialysates were comparable for age, sex, comorbidities, months on dialysis and anemia control. Baseline mineral, bone remodeling and inflammation markers before HD, were also comparable in both groups. Only patients on bicarbonate dialysate had higher β2-microglobulin levels at baseline. Changes in serum levels of mineral, bone remodeling and inflammatory biomarkers at 5 months compared to baseline for both groups are shown in Table 1. After 5 months of follow-up, a 22% trend-reduction (p = 0.08) in P1NP as bone formation biomarker was observed in patients on citrate dialysate compared to those on bicarbonate dialysate. In addition, the fold change observed in CTX as parameter of bone resorption was attenuated in the citrate dialysate group (11% vs 116% in the bicarbonate dialysate group, p &amp;lt; 0.001). β2-microglobulin levels decreased significantly in both groups at 5 months but It is explained by the known effect of OL-HDF treatment on the inflammatory state of dialysis patients. Conclusion In patients on OL-HDF treatment the use of the citrate as dialysate may provide a benefit in bone remodeling by reducing bone resorption and trend to balance the bone formation/resorption. However, our results are in line with previous studies, where caution should be adopted in patients with very high parathyroid hormone levels, as this may be enhanced by reduced mineral turnover.

Elimination of Medium/High Molecular Weight Solutes. Comparison of High Flow Hemodialysis with Extended Hemodialysis

Introduction: Post-dilution online hemodiafiltration is the most efficient extracorporeal depurative treatment of CKD. Recently a new type of membrane has been developed, with a higher cut-off point also called a medium cut-off point, which has the capacity to eliminate higher molecular weight molecules in hemodialysis. The hemodialysis performed with these membranes has been called “Expanded Hemodialysis”. Objective: Compare the purifying efficacy of medium and high molecular weight molecules in patients dialyzed with high-flux hemodialysis, VitaPES 210HF, and with patients treated with expanded hemodialysis with the medium cut-off dialyzer, Elisio-HX. We also assessed the effect that the increased removal of inflammatory mediators by MCO hemodialysis had on fecal Calprotectin levels. Patients and methods: This is a prospective observational cross-over study in which 8 prevalent hemodialysis patients were followed for two months. Blood levels of IL-6, C-reactive protein (CRP), β2-microglobulin, Kappa and Lambda immunoglobulin light chains, and serum albumin were determined before and after each hemodialysis session. Results: The percentage of reduction of medium and higher molecular weight molecules: β2microglobulin, IL-6, Kappa and Lambda chains and CRP were higher with the Elisio-21HX dialyzer compared to the VitaPES 210HF dialyzer. There was no difference in albumin clearance between the two dialyzers. Fecal calprotectin levels were lower in patients dialyzed with Elisio-21HX. Conclusion: The medium cutoff dialyzer, Elisio-HX, is more efficient in the elimination of medium/high molecular weight molecules than the VitaPES HF high-flux dialyzer, with the same albumin elimination. Improving inflammation at the local intestinal level with lower levels of fecal Calprotectin.