Serum globulin is a novel predictor of mortality in patients undergoing peritoneal dialysis.

Serum globulin, which is composed mainly of immunoglobulins and acute phase proteins, can be considered as reflecting the inflammatory state. We conducted the present study to investigate the role of globulin in mortality risk in patients undergoing peritoneal dialysis (PD). The study participants were categorized by the median globulin value (2.8 g/dL) as the high globulin group (≥ 2.8 g/dL), and low globulin group (< 2.8 g/dL). Serum globulin is calculated by the equation: (serum total protein-serum albumin). The area under the curve (AUC) by the receiver operating characteristics curve analysis was calculated to compare the mortality prediction capacity of globulin with that of ferritin, and WBC counts. Among the 554 patients, 265 (47.83%) were men, the mean age was 52.91 ± 15.54 years and the body mass index was 23.44 ± 3.88 kg/m2. Multivariate Cox models showed the high globulin group had higher mortality risks of all-cause and cardiovascular disease (CVD), compared with the low globulin group with adjusted HRs of 2.06 (95% CI 1.39-3.05) and 1.94 (95% CI 1.18-3.16), respectively. The AUC of univariate and multivariate models for all-cause mortality resulted in higher AUC values for globulin than for ferritin and white blood cell (WBC) counts. In patients undergoing PD, the serum globulin can serve as a novel and independent determinant of predicting overall and CVD- associated mortality.

Pediatric Prediction Model for Low Immunoglobulin G Level Based on Serum Globulin and Illness Status.

Hypogammaglobulinemia is a condition that requires prompt diagnosis and treatment. Unfortunately, serum immunoglobulin (Ig) measurements are not widely accessible in numerous developing countries. Serum globulin is potentially the best candidate for screening of low IgG level (IgGLo) due to its high availability, low cost, and rapid turnover time. However, multiple factors may influence the probability of prediction. Our study aimed to establish a simple prediction model using serum globulin to predict the likelihood of IgGLo in children. For retrospective data of patients who were suspected of having IgGLo, both serum IgG and globulin were simultaneously collected and measured. Potential factors interfering with serum globulin and IgG levels were investigated for their impact using bivariate binary logistic regression. A multivariate binary logistic regression was used to generate a formula and score to predict IgGLo. We obtained 953 samples from 143 pediatric patients. A strong positive correlation between serum globulin and IgG levels was observed (r=0.83, p < 0.001). A screening test model using serum globulin and illness status was constructed to predict IgGLo. The formula for predicting IgGLo was generated as follows; Predicted score = (2 x globulin (g/dl)) - illness condition score (well=0, sick=1). When the score was <4, the patient has the probability of having IgGLo with a sensitivity of 0.78 (0.71, 0.84), a specificity of 0.71 (0.68, 0.74), PPV of 0.34 (0.29, 0.40) and NPV of 0.94 (0.92, 0.96). This formula will be useful as rapid and inexpensive screening tool for early IgGLo detection, particularly in countries/locations where serum IgG measurement is inaccessible.

Macrophages secrete murinoglobulin-1 and galectin-3 to regulate neutrophil degranulation after myocardial infarction.

Inflammation presides early after myocardial infarction (MI) as a key event in cardiac wound healing. Ischemic cardiomyocytes secrete inflammatory cues to stimulate infiltration of leukocytes, predominantly macrophages and neutrophils. Infiltrating neutrophils degranulate to release a series of proteases including matrix metalloproteinase (MMP)-9 to break down extracellular matrix and remove necrotic myocytes to create space for the infarct scar to form. While neutrophil to macrophage communication has been explored, the reverse has been understudied. We used a proteomics approach to catalogue the macrophage secretome at MI day 1. Murinoglobulin-1 (MUG1) was the highest-ranked secreted protein (4.1-fold upregulated at MI day 1 vs. day 0 pre-MI cardiac macrophages, p = 0.004). By transcriptomics evaluation, galectin-3 (Lgals3) was 2.2-fold upregulated (p = 0.008) in MI day 1 macrophages. We explored the direct roles of MUG1 and Lgals3 on neutrophil degranulation. MUG1 blunted while Lgals3 amplified neutrophil degranulation in response to phorbol 12-myristate 13-acetate or interleukin-1ß, as measured by MMP-9 secretion. Lgals3 itself also stimulated MMP-9 secretion. To determine if MUG1 regulated Lgals3, we co-stimulated neutrophils with MUG1 and Lgals3. MUG1 limited degranulation stimulated by Lgals3 by 64% (p < 0.001). In vivo, MUG1 was elevated in the infarct region at MI days 1 and 3, while Lgals3 increased at MI day 7. The ratio of MUG1 to Lgals3 positively correlated with infarct wall thickness, revealing that MUG1 attenuated infarct wall thinning. In conclusion, macrophages at MI day 1 secrete MUG1 to limit and Lgals3 to accentuate neutrophil degranulation to regulate infarct wall thinning.

Globulin and albumin to globulin ratio precisely diagnose periprosthetic joint infection and determine the timing of second-stage reimplantation.

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most challenging complications of total joint arthroplasty (TJI). An early and accurate diagnosis of PJI is associated with better treatment outcomes. However, whether the platelet-related markers and globulin-related markers can be used to assist the diagnosis of PJI remains elusive. METHODS: A total of 206 patients who underwent revision hip or knee arthroplasty in our institution were divided into two groups: 79 patients in PJI group and 127 patients in aseptic failure group. The levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet-related markers including platelet count (PLT), mean platelet volume (MPV), plateletcrit (PCT) and PLT to MPV ratio (PMR) and globulin-related markers such as globulin (GLB), albumin to globulin ratio (AGR) and PLT to AGR ratio were compared. The diagnostic value was measured using area under the curve (AUC) after constructing receiver operating characteristic (ROC) curves. The potential of each marker for determining the timing of second-staged reimplantation was also evaluated. RESULTS: Significantly increased levels of ESR, CRP, PLT, PCT, PMR, GLB and PLT to AGR ratio were identified in PJI group, while decreased levels of MPV and AGR were also found. The diagnostic values of all platelet-related markers and GLB were considered as fair, and good diagnostic values of AGR and PLT to AGR ratio were found, which were comparable to those of ESR and CRP. The levels of GLB and AGR can also be used to predict negative culture result and the timing of second-stage reimplantation. CONCLUSIONS: Globulin and albumin to globulin ratio were found to have good diagnostic values for PJI, and they can precisely predict the culture results and persistent infection.

Association of serum globulin with all-cause mortality in incident hemodialysis patients.

BACKGROUND: Serum globulin is a major component of total protein and can be elevated in inflammatory disease states. While inflammation is common in hemodialysis patients and associated with mortality and morbidity, the association between serum globulin and mortality has never been examined in hemodialysis patients. METHODS: In a retrospective cohort of 104 164 incident hemodialysis patients treated by a large dialysis organization from 2007 to 2011, we explored the association between baseline serum globulin, albumin: globulin (A:G) ratio and serum protein levels and all-cause, cardiovascular and infection-related mortality with adjustments for demographic variables and laboratory markers of malnutrition and inflammation using Cox proportional hazards models. RESULTS: Patients with a globulin concentration >3.8 g/dL had a higher all-cause and infection-related mortality risk {hazard ratio [HR] 1.11 [95% confidence interval (CI) 1.06-1.16] and HR 1.28 [95% CI 1.09-1.51], respectively} in the fully adjusted model when compared with the reference group of 3.0- <3.2 g/dL. In addition, patients with an A:G ratio <0.75 had a 45% higher all-cause mortality hazard [HR 1.45 (95% CI 1.38-1.52)] and patients with total serum protein <5.5 g/dL had a 34% higher risk of death [1.34 (95% CI 1.27-1.42)] when compared with the reference (A:G ratio 1.05- <1.15 and total serum protein 6.5- <7 g/dL). CONCLUSIONS: Among incident hemodialysis patients, a higher globulin level was associated with a higher mortality risk independent of other markers of malnutrition and inflammation, including albumin. A lower A:G ratio and serum protein was also associated with a higher mortality hazard. The mechanisms that contribute to elevated serum globulin should be further explored.

Serum Globulin Is Associated with Endoscopic Findings and Mucosal Healing in Japanese Patients with Ulcerative Colitis.

BACKGROUND: Serum globulin is an inflammation marker. To date, no evidence regarding the association between serum globulin and disease activity in patients with ulcerative colitis has been reported. AIMS: We evaluated the association between serum globulin and endoscopic activity in patients with ulcerative colitis. METHODS: Serum globulin was divided into tertiles based on the distribution of study subjects (low globulin, ≤ 2.7 g/dl (reference); moderate globulin, 2.7-3.1 g/dl; and high globulin, > 3.1 g/dl). A single endoscopic specialist evaluated the endoscopic findings, and mucosal healing was based on Mayo endoscopic subscore. RESULTS: A total of 277 patients with ulcerative colitis were included in the study. Serum globulin was independently positively associated with diminished or absent vascular markings [moderate: adjusted odds ratio (OR) 3.70 (95% confidence interval, CI: 1.82-7.88) and high: adjusted OR 2.40 (95%CI: 1.20-4.94), p for trend = 0.005]. A similar positive association between globulin and erosion was found [high: adjusted OR 2.00 (95%CI: 1.05-3.86)]. Serum globulin was independently inversely associated with mucosal healing [moderate: adjusted OR 0.37 (95%CI: 0.18-0.73) and high: adjusted OR 0.31 (95%CI: 0.14-0.64), p for trend = 0.001] and adjusted partial mucosal healing [moderate: OR 0.51 (95%CI: 0.26-0.98), p for trend = 0.048]. The inverse association between globulin and mucosal healing was significant in the low but not the high C-reactive protein group. CONCLUSIONS: In patients with ulcerative colitis, serum globulin was significantly positively associated with endoscopic activity, and was significantly inversely associated with mucosal healing, especially in the low C-reactive protein group.

The prognostic value of the pretreatment serum albumin to globulin ratio for predicting adverse pathology in patients undergoing radical prostatectomy for prostate cancer.

PURPOSE: Few studies have demonstrated the clinical significance of pretreatment serum albumin and globulin in prostate cancer (PCa). This study evaluated the association between the pretreatment albumin to globulin ratio (AGR) and clinicopathologic characteristics of nonmetastatic PCa in a large multicenter setting in Korea. MATERIALS AND METHODS: This study involved 742 patients with nonmetastatic PCa who underwent radical prostatectomy (RP) in seven institutions between January 2011 and December 2012. The AGR was calculated as follows: albumin/(total protein-albumin). Patients were divided into low and high AGR groups by a cutoff value from a receiver operating characteristic curve analysis. RESULTS: The best cutoff for the AGR was set at 1.53. The area under the curve of the AGR was 0.624 (95% confidence interval, 0.557-0.671; p<0.001). Patients who had a lower pretreatment AGR (<1.53) were identified as the low AGR group (n=398, 53.6%) and the remaining patients as the high AGR group (n=344, 46.4%). Preoperative AGR was significantly lower in patients with non-organ-confined disease (≥pT3) than in those with organ-confined disease (≤pT2) (p<0.001). The low AGR group had higher aggressive pathologic Gleason scores (pGS) (≥8) than did the high AGR group (p=0.016). Furthermore, the AGR was an independent prognostic factor for high pGS (≥8) and non-organ-confined disease (≥pT3), according to multivariate logistic regression analysis. CONCLUSIONS: A low AGR was closely associated with nonconfined disease (≥pT3) and high pGS (≥8). AGR can be a useful serological marker for predicting adverse pathology in patients with nonmetastatic PCa who undergo RP.

Associations between the thyroid panel and serum protein concentrations across pregnancy.

Establishing any characteristic associations between the serum parameters of thyroid function and serum proteins in pregnancy may aid in elucidating the role of the thyroid gland in the regulation of pregnancy-specific metabolic processes and in selecting candidate biomarkers for use in their clinical assessment. Concentrations of thyroid stimulating hormone (TSH), free tri-iodothyronine (fT3) and free thyroxine (fT4), six electrophoretically separated protein fractions (albumin, alpha-1-, alpha2-, beta-1-, beta-2- and gamma-globulins), representative proteins-albumin (ALB), transferrin (TRF), alpha-2-macroglobulin (AMG) and ceruloplasmin (CER) were measured in 136 serum samples from 65 women in their consecutive trimesters of pregnancy. The concentrations of TSH, fT4 and fT3 were significantly correlated (p < 0.05) with the concentrations of the albumin, alpha-2- and beta-1 globulin fractions. Significant correlations (p < 0.05) which were positive between fT4 and ALB and negative between fT4 and TRF were established throughout pregnancy. Significant negative correlations (p < 0.05) were demonstrated for fT3 with alpha-2-globulin, AMG and CER. Changes in the serum concentrations of thyroid hormones seen between the trimesters were found to correlate with the concentrations of high-abundance serum proteins. Opposite directions of correlations between fT4 and ALB and fT4 and TRF observed throughout pregnancy may indicate the shared biological role of these parameters in maintaining maternal homeostasis and they suggest their potential use in the clinic as a simple biomarker panel. A negative correlation of fT3 with CER in the second trimester possibly reflects their involvement in the active regulation of metabolic processes.

Crossing the Antarctica: Exploring the Effects of Appetite-Regulating Hormones and Indicators of Nutrition Status during a 93-Day Solo-Expedition.

Future deep space astronauts must maintain adequate nutrition despite highly stressful, isolated, confined and dangerous environments. The present case-study investigated appetite regulating hormones, nutrition status, and physical and emotional stress in a space analog condition: an explorer conducting a 93-day unsupported solo crossing of Antarctica. Using the dried blood spot (DBS) method, the subject drew samples of his blood on a regular basis during the expedition. The DBSs were later analyzed for the appetite regulating hormones leptin and adiponectin. Energy intake and nutritional status were monitored by analysis of albumin and globulin (including their ratio). Interleukin-6 (IL-6) was also analyzed and used as an energy sensor. The results showed a marked reduction in levels of the appetite-reducing hormone, leptin, and the appetite stimulating hormone, adiponectin, during both extreme physical and psychological strain. Nutrition status showed a variation over the expedition, with below-normal levels during extreme psychological strain and levels abutting the lower bounds of the normal range during a phase dominated by extreme physical hardship. The IL-6 levels varied substantially, with levels above the normal range except during the recovery phase. It was concluded that a daily intake of 5058 to 5931 calories seemed to allow recovery of both appetite and nutritional status between extreme physical and psychological hardship during a long Arctic expedition. Furthermore, IL-6 may be a sensor in the muscle-liver, muscle-fat and muscle-brain crosstalk. These results may help guide nutrition planning for future astronaut crews, mountaineers and others involved in highly demanding missions.

Preoperative Albumin-Globulin Ratio and Its Association with Perioperative and Long-Term Outcomes in Patients Undergoing Pancreatoduodenectomy.

BACKGROUND: Systemic inflammatory response is involved in natural progression of cancers by different pathways. Albumin-globulin ratio (AGR) has been reported to have impact on prognosis in various solid tumors. OBJECTIVE: To study the significance of AGR on perioperative and long-term outcomes in patients undergoing PD. METHODS: This is a post hoc analysis of the pancreatic surgery database from January 2012 to March 2017. Cutoff value for AGR was calculated by using the receiver operating curve, and the study cohort was divided into group I (AGR ≥1) and group II (AGR <1). Two groups were compared for perioperative and long-term survival outcomes. RESULTS: Two groups were comparable with respect to clinicodemographic variables. Groups I and II had similar perioperative outcomes (p > 0.05) like median hospital stay (14 vs. 15 days), clinically relevant postoperative pancreatic fistula (16.6 vs. 15.7%), hemorrhage (3.1 vs. 2.6%), bile leak (1.4 vs. 0.65%), overall morbidity (30.1 vs. 28.9%), and postoperative mortality (2.7 vs. 3.9%). With a median follow-up of 3 years, median survival, overall survival, and disease-free survival were similar in both groups. CONCLUSION: AGR at the cutoff value of ≥1 was not associated with adverse perioperative and long-term oncological outcomes after PD.

Clinical Characteristics, Serological and Radiological Longitudinal Changes of Patients with COVID-19.

BACKGROUND: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) began in Wuhan and rapidly spread globally. The speed and scope of the spread of COVID-19 makes it urgent to define clinical characteristics, serological and radiological changes of the affected patients. METHODS: Seven patients with laboratory-confirmed COVID-19 who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University Yuedong Hospital from January 2020 to March 2020 were retrospectively enrolled and their clinical features, serological and radiological longitudinal changes were analyzed. RESULTS: Among the 7 patients, all (100%) had a clear epidemiological history. The most common symptoms were respiratory symptoms 6 (85.7%), and only 2 (28.6%) of the patients had fever at their first visit. The cohort included 4 (57.1%) common types and 3 (42.9%) severe types. Two (28.6%) common type patients developed to severe type in a short time. All of the 7 patients (100%) had abnormal liver function, normal renal function, and normal procalcitonin. The detection time of specific antibody in 7 patients was 5 - 13 days after symptoms. Before the specific antibody could be detected, the absolute value of lymphocytes decreased in 2 (28.6%) common type cases transferred to severe type cases accompanied with obvious progress in pulmonary imaging. The phenomenon of decreased albumin and elevated globulin occurred in 6 patients (85.7%). The predominant pattern of lung lesions observed was bilateral (71.4%) and mainly near the pleura at the first diagnosis. Bilateral pulmonary involvement occurred in 6 cases (85.7%) during the course of disease. In 4 cases (57.1%) with obvious pulmonary lesions, the absolute value of lymphocytes decreased, albumin decreased, and globulin increased during the course of the disease. CONCLUSIONS: Serum specific antibodies can be detected within 2 weeks of onset. Close observation of the dynamic changes of absolute value of blood lymphocytes, serum albumin, and globulin which were related to pulmonary imaging changes in patients will contribute to assessment of COVID-19.

Prognostic value of the preoperative albumin-globulin ratio in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

OBJECTIVE: To assess the value of preoperative albumin to globulin ratio for predicting pathologic and oncological outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy in a large multi-institutional cohort. MATERIALS AND METHODS: Preoperative albumin to globulin ratio was assessed in a multi-institutional cohort of 2492 patients. Logistic regression analyses were performed to assess the association of the albumin to globulin ratio with pathologic features. Cox proportional hazards regression models were performed for survival endpoints. RESULTS: The optimal cut-off value was determined to be 1.4 according to a receiver operating curve analysis. Lower albumin to globulin ratios were observed in 797 patients (33.6%) compared with other patients. In a preoperative model, low preoperative albumin to globulin ratio was independently associated with nonorgan-confined diseases (odds ratio 1.32, P = 0.002). Patients with low albumin to globulin ratios had worse recurrence-free survival (P < 0.001), cancer-specific survival (P = 0.001) and overall survival (P = 0.020) in univariable and multivariable analyses after adjusting for the effect of standard preoperative prognostic factors (recurrence-free survival: hazard ratio (HR) 1.31, P = 0.001; cancer-specific survival: HR 1.31, P = 0.002 and overall survival: HR 1.18, P = 0.024). CONCLUSIONS: Lower preoperative albumin to globulin ratio is associated with locally advanced disease and worse clinical outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. As it is difficult to stage disease entity, low preoperative serum albumin to globulin ratio may help identify those most likely to benefit from intensified care, such as perioperative systemic therapy, and the extent and type of surgery.

A renewed understanding of anti-human globulin reagents: interference constraints using an optimization method in pretransfusion compatibility tests.

Anti-human globulin (AHG) reagents are widely applied in pretransfusion compatibility tests. The accuracy of detection with AHG reagents is mainly affected by irregular antibodies or cold agglutinins in blood samples, which are related to the human complement system. Although much has been written about various types and applications of AHG reagents, their characteristics, interference factors and optimal selection in pretransfusion compatibility tests still need to be further clarified. Here, we review clinical practice and basic studies that describe each AHG reagent, summarize the advantages and disadvantages of using different AHG reagents in the presence of cold agglutinins or complement-fixing antibodies, explore the potential mechanisms by which the complement system influences detection with AHG reagents and address the question of how to optimally select AHG reagents for clinically significant antibody detection.

Cancer related nutritional and inflammatory markers as predictive parameters of immediate postoperative complications and long-term survival after hepatectomies.

BACKGROUND: The overall survival (OS), disease-free survival (DFS) and complications after liver resections is unsatisfactory. Cancer-related malnutrition and inflammation have an effect on survival but not studied/not clear on postoperative complications. METHODS: We retrospectively analyzed prospectively maintained database of 309 patients. The outcome variables included complications in terms of Clavien-Dindo (CD) Score, OS and DFS; We studied effect of preoperative albumin globulin ratio (AGR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and aspartate transaminase to platelet ratio index (APRI) and dynamic change from pre-operative to postoperative value (Delta-AGR, Delta-NLR, Delta-PLR and Delta-APRI) on complications, OS and DFS. RESULTS: Total 98 patients (31.71%) had postoperative complications. Fifty patients had CD 1 & 2 and 35 (11.33%) had CD 3 & 4, and 13 (4.12%) had mortality (CD 5). Low AGR, high NLR, high PLR and high Delta-AGR and high Delta-APRI predicted increased major complications. Preoperative high NLR predicted worse OS and low AGR predicted worse OS and DFS. Delta-APRI showed trends towards worse OS and DFS. CONCLUSION: These serum inflammatory markers can predict immediate postoperative complications. Preoperative AGR and preoperative NLR can predict survival after liver resections. High Delta-AGR, which is a new entity, is predicting more postoperative complications and needs further detailed studies.

Physical Features and Vital Signs Predict Serum Albumin and Globulin Concentrations Using Machine Learning.

OBJECTIVE: Serum protein concentrations are diagnostically and prognostically valuable in cancer and other diseases, but their measurement via blood test is uncomfortable, inconvenient, and costly. This study investigates the possibility of predicting albumin, globulin, and albumin-globulin ratio from easily accessible physical characteristics (height, weight, Body Mass Index, age, gender) and vital signs (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure, pulse) using advanced machine learning techniques. METHODS: We obtained albumin concentration, globulin concentration, albumin-globulin ratio and predictor information (physical characteristics, vital signs) from physical exam records of 46,951 healthy adult participants in Hangzhou, China. We trained a computational model to predict each serum protein concentration from the predictors and then evaluated the predictive accuracy of each model on an independent portion of the dataset that was not used in model training. We also determined the relative importance of each feature within the model. RESULTS: Prediction accuracies were r=0.540 (95% CI: 0.539-0.540; Pearson r) for albumin, r=0.250 (95% CI: 0.249-0.251) for globulin, and r=0.373 (95% CI: 0.372-0.374) for albumin-globulin ratio. The most important predictive features were age (100% ± 0.0%; mean ± 95% CI of normalized importance), gender (34.4% ± 0.7%), pulse (25.6% ± 1.3%) and Body Mass Index (24.4% ± 2.3%) for albumin, pulse (83.7% ± 3.8%) for globulin, and age (99.2% ± 1.0%), gender (59.2% ± 1.7%), Body Mass Index (46.1% ± 4.2%) and height (40.0% ± 3.8%) for albumin-globulin ratio. CONCLUSIONS: Our models predicted serum protein concentrations with appreciable accuracy showing the promise of this approach. Such models could serve to augment existing tools for identifying "at-risk" individuals for follow-up with a blood test.

Albumin-to-globulin ratio (AGR) as a potential marker of predicting lupus nephritis in Chinese patients with systemic lupus erythematosus.

OBJECTIVES: To evaluate a potential role of albumin-to-globulin ratio (AGR) in the development of lupus nephritis (LN) and determine the potential to use AGR as a marker for future LN in systemic lupus erythematosus (SLE) patients. METHODS: 194 newly diagnosed SLE patients without renal impairment were followed. The clinical data were collected and analyzed at the time of initial diagnosis of SLE and the end of follow-up. We compared baseline characteristics between those who did or did not develop LN on follow-up. Univariate and multivariate Cox hazard analysis were used to identify predictors of lupus nephritis. RESULTS: Among the 194 newly diagnosed SLE patients without renal impairment, 26 (13.40%) patients were diagnosed with LN during a median follow-up of 53.87 months. On univariate Cox analysis, patients with the history of alopecia, higher SBP, lower AGR, lower CRP, lower C3, lower C4, higher anti-dsDNA Ab, presence of ANA homogeneous patterns or higher SLEDAI had an increased probability of developing LN. In a multivariate model, the history of alopecia (adjust hazard ratio, aHR = 3.614, 95%CI 1.365-9.571 P = 0.010), lower AGR (aHR = 6.968, 95%CI 1.873-25.919, P = 0.004), lower CRP (aHR = 4.230, 95%CI 1.591-11.247, P = 0.004) and higher level of anti-dsDNA (aHR = 2.675, 95%CI 1.008-7.093, P = 0.048) were independently associated with an increased risk of developing LN after adjusting for covariates. CONCLUSION: Our findings indicated that SLE patients with low AGR, low CRP, high anti-dsDNA and the history of alopecia were more likely to develop LN in the course of SLE. AGR shown the greatest hazard for developing LN among them, it may be a strong predictor.

Dynamic biomarkers indicate the immunological benefits provided by Ganoderma spore powder in post-operative breast and lung cancer patients.

BACKGROUND: T lymphocyte are a strong indicator of treatment immune response. This study was aimed to determine the utility of T lymphocyte subsets, cytokines and inflammatory biomarkers in predicting the immunological benefits of Ganoderma spore powder (G. lucidum) in post-operative patients with breast and lung cancer. METHODS: We prospectively evaluated 120 breast and lung cancer patients with or without G. lucidum. T lymphocyte subsets with relative cytokines were detected using flow cytometry and PCR and assessed by Spearman correlation analysis. The relationships between albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) with G. lucidum treatment and prognosis were analyzed using Kaplan-Meier and Cox regression methods. RESULTS: The prevalence of CD3 + CD4 + , CD3 + HLADR- types was higher in G. lucidum group compared to control, whilst CD4 + CD25 + Treg, CD3 + HLADR + cell types was lower. IL-12 levels were significantly higher during the treatment period which negatively impacted levels of IL-10. Other immunosuppressive factors such as COX2 and TGF-ß1 had lower prevalence in treated patients. Correlation analysis showed a positive relationship between IL-10 and CD28. IL-2 was positively related to TGF-ß1, whilst it was negatively related to CD3. Kaplan-Meier analysis suggested that low AGR/high NLR was related to poor progression free survival (PFS) and overall survival (OS). A combination of high AGR and low NLR may predicted treatment benefits associated with PFS and OS. CONCLUSIONS: Our findings show that T lymphocyte subsets combined with relevant cytokines and AGR/NLR inflammatory predictors may help to identify patients most likely to benefit from the immunological enhancements from G. lucidum treatment.

Calculated globulin as a screening tool for hypogammaglobulinaemia or paraproteins in hospitalized patients.

BACKGROUND: Calculated globulin fraction is derived from the liver function tests by subtracting albumin from the total protein. Since immunoglobulins comprise the largest component of the serum globulin concentration, increased or decreased calculated globulins and may identify patients with hypogammaglobulinaemia or hypergammaglobulinaemia, respectively. METHODS: A retrospective study of laboratory data over 2.5 years from inpatients at three tertiary hospitals was performed. Patients with paired calculated globulins and immunoglobulin results were identified and clinical details reviewed. The results of serum electrophoresis testing were also assessed where available. RESULTS: A total of 4035 patients had paired laboratory data available. A calculated globulin ≤20 g/L (<2nd percentile) had a low sensitivity (5.8%) but good positive predictive value (82.5%) for hypogammaglobulinaemia (IgG ≤5.7 g/L), with a positive predictive value of 37.5% for severe hypogammaglobulinaemia (IgG ≤3 g/L). Paraproteins were identified in 123/291 (42.3%) of patients with increased calculated globulins (≥42 g/L) who also had a serum electrophoresis performed. Significantly elevated calculated globulin ≥50 g/L (>4th percentile) were seen in patients with either liver disease (37%), haematological malignancy (36%), autoimmune disease (13%) or infections (9%). CONCLUSIONS: Calculated globulin is an inexpensive and easily available test that assists in the identification of hypogammaglobulinaemia or hypergammaglobulinaemia which may prompt further investigation and reduce diagnostic delays.

Prognostic value of albumin to globulin ratio in non-muscle-invasive bladder cancer.

PURPOSE: To investigate the prognostic value of preoperative serum albumin to globulin ratio (AGR) in patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of bladder tumor (TURB) with or without intravesical therapy (IVT). MATERIALS AND METHODS: We retrospectively reviewed 1,096 consecutive patients with NMIBC. Levels of albumin and globulin were obtained before TURB and used to calculate the preoperative AGR level. Multivariable Cox regression analyses were performed to assess the prognostic effect of preoperative AGR on oncologic outcomes. Subgroup analyses were performed in patients based on the European Association of Urology (EAU) risk groups for NMIBC. RESULTS: Low AGR levels were observed in 389 (35.5%) patients. The median follow-up was 63.7 months (IQR 25.3-111). On multivariable Cox regression analysis, low AGR was associated with increased risk of progression to muscle-invasive BCa (MIBC) (HR 1.81, 95% CI 1.22-2.68, P = 0.003). The addition of AGR only minimally improved the discrimination ability of a base model that included established clinicopathologic features (C-index = 0.7354 vs. C-index = 0.7162). Low preoperative AGR was not significantly associated with the risk of disease recurrence (P = 0.31). In subgroup analyses based on patients' EAU risk groups, low preoperative AGR was not associated with recurrence-free survival (RFS) (P = 0.59) or progression-free survival (PFS) (P = 0.22) in any of the risk groups. Additionally, in patients treated with Bacillus Calmette-Guerin (BCG) for intermediate- or high-risk NMIBC, low AGR failed to predict disease recurrence or progression. CONCLUSION: Preoperative serum AGR levels independently predicted the risk of disease progression in patients with NMIBC. However, it was not found to be associated with either RFS or PFS in NMIBC patients based on their EAU risk group. This marker seems to have a limited role in NMIBC at the present time. However, further research is needed to investigate this marker in combination with other systemic inflammatory markers to help improve prediction in this heterogeneous group of patients.

Preoperative Albumin-to-Globulin Ratio Predicts Prognosis in Hepatocellular Carcinoma: A Cohort Study Including Non-Hepatitis Virus-Infected Patients.

INTRODUCTION: We evaluated the prognostic significance of the preoperative albumin-to-globulin ratio (AGR) in patients with hepatocellular carcinoma (HCC) with various liver etiologies. METHODS: We retrospectively analyzed 157 patients with HCC between July 2010 and February 2021. The relationship between clinicopathological variables was investigated using univariate and multivariate analyses. Statistical significance was set at p < 0.05. RESULTS: The mean overall survival (OS) was 24.5 months. The 1-, 3-, and 5-year OS rates were 90.4%, 81.2%, and 68.7%, respectively. Patients were classified into 2 groups: AGR <1.16 (low-AGR group; n = 43) and AGR ≥1.16 (high-AGR group; n = 114). In univariate analysis, OS was significantly reduced in patients with a low AGR (AGR <1.16), an alpha-fetoprotein level ≥25 ng/mL, a tumor size ≥3.5 cm, microvascular invasion, and poor tumor differentiation. In multivariate analysis, a low AGR (hazard ratio [95% confidence interval]) (2.394 [1.092-5.213]; p = 0.030) and microvascular invasion (2.268 [1.019-5.169]; p = 0.045) were independent predictors of OS. DISCUSSION/CONCLUSION: A low AGR was significantly associated with poor OS in patients with HCC, regardless of liver etiology. This may assist in treatment stratification and better management of patients with HCC.