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Background. Extramedullary disease (EMD), an infrequent manifestation of multiple myeloma (MM), can present at diagnosis or develop during the disease course. EMD can be clinically divided into bone-related EMD (EMD-B) and soft tissue-related EMD (EMD-S). The purpose of our study is to investigate the clinical characteristics, survival outcomes, and prognostic factors of MM patients with EMD. Methods. A total of 155 MM patients with EMD were ultimately enrolled in our study by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan–Meier survival curves and log-rank test for overall survival (OS) and myeloma-specific survival (MSS) were conducted to compare each potential variable. Variables with a p value 1 representing adverse prognostic factors. Results. The median age at diagnosis was 63 years old. EMD-B occurred in 99 patients (63.90%), while EMD-S occurred in 56 cases (36.10%). Patients with EMD-S had a significant survival disadvantage in MSS (HR = 1.844, 95% CI 1.117–3.042, p = 0.017) and OS (HR = 1.853, 95% CI 1.166–2.942, p = 0.009) compared to those with EMD-B. Patients with EMD interval ≤24 months were at higher risk of death than those with EMD at diagnosis in MSS (HR = 1.885, 95% CI 1.175–3.346, p = 0.042) and in OS (HR = 1.33, 95% CI 1.119–2.529, p = 0.036). Patients with EMD interval >24 months were at a lower risk of death as opposed to those with EMD at diagnosis. Conclusion. Age at MM diagnosis, site of EMD, and time interval from diagnosis to EMD occurrence were independent prognostic factors in MM patients with EMD. EMD-B bore a better prognosis than EMD-S.

IntroductionAutophagy functions as a prosurvival mechanism in multiple myeloma (MM).The objective of this research was to establish an autophagy-related gene (ARG) signature for predicting the survival outcomes of MM patients with TP53 mutations.Material and methodsInformation about MM patients with TP53 mutations was downloaded from Gene Expression Omnibus (GEO) database. Cox proportional hazard regression was employed to determine the independent prognostic ARG and construct a risk signature. Time-dependent receiver-operating characteristic (t ROC) curve was used to explore the predictive accuracy of the prognostic model. A nomogram was constructed to give a more precise prediction of the probability of 5-year, 8-year and 10-year overall survival (OS). In addition, we utilized the CIBERSORT algorithm to explore the distribution difference of 22 immune-infiltrating cells.ResultsThree differentially expressed ARGs (CASP8, MAPK8, RB1CC1) were finally incorporated to construct the risk model. Area under the curve (AUC) of corresponding tROC curve for 5-year,8-year and 10-year OS were 0.735, 0.686 and 0.662, respectively. MM patients were categorized into high and low-risk group in accordance with the median threshold value (-1.724549). ARG-based risk score model was an independent prognostic element correlated with OS, giving an hazard ratio (HR) of 3.29 (95%CI 2.35-4.60, PConclusionsWe established a three-ARGs risk signature which manifested an independent prognostic factor. The nomogram was testified to perform well in forecasting the long-term survival of TP53-mutated MM patients.

Background To evaluate the efficacy and safety of rituximab-based combination therapy for Waldenstrom macroglobulinemia (WM), we conducted this meta-analysis by pooling the rates of overall response, major response, complete response, and grade ≥3 hematological adverse events. Methods and materials We searched for relevant studies in the databases of PubMed, Web of Science, Embase, and the Cochrane Library. The qualitative assessment of all the included articles was conducted with reference to the Newcastle-Ottawa Scale. A random-effects model was selected to perform all pooled analyses. Results We identified altogether 22 studies with a total of 806 symptomatic WM patients enrolled. The pooled analysis indicated that the rituximab-based combination therapy achieved an overall response rate (ORR) of 84% (95% CI: 81%-87%), a major response rate (MRR) of 71% (95% CI: 66%-75%), and a complete response rate (CRR) of 7% (95% CI: 5%-10%). Rituximab plus conventional alkylating agents-containing chemotherapy (subgroup A) yielded an ORR of 86% (95% CI: 81%-89%), an MRR of 74% (95% CI: 69%-79%), and a CRR of 8% (95% CI: 4%-14%). Rituximab plus purine analog (subgroup B) resulted in an ORR of 85% (95% CI: 79%-89%), an MRR of 74% (95% CI: 66%-81%), and a CRR of 9% (95% CI: 4%-15%). Rituximab plus proteasome inhibitor (subgroup C) resulted in an ORR of 86% (95% CI: 81%-90%), an MRR of 68% (95% CI: 58%-77%), and a CRR of 7% (95% CI: 3%-11%). Rituximab plus immunomodulatory drug (subgroup D) attained relatively lower response rates, with an ORR of 67% (95% CI: 51%-81%), an MRR of 56% (95% CI: 27%-83%), and a CRR of 5% (95% CI: 1%-12%). Common grade ≥3 hematological adverse events consisted of neutropenia (33%, 95% CI: 17%-52%), thrombocytopenia (7%, 95% CI: 3%-11%), and anemia (5%, 95% CI: 3%-9%). Conclusion Rituximab in combination with an alkylating agent, purine analog, or proteasome inhibitor is highly effective with tolerable hematological toxicities for WM.

Background: Previous studies have revealed that quantitative hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (qAnti-HBc) levels can be used as predictors of treatment response in both interferon-α and nucleoside analogue therapies. Few data have been published regarding the relationship between quantitative HBsAg or Anti-HBc levels and liver fibrosis stages in patients with chronic hepatitis B (CHB). Methods: We conducted a cross-sectional study of treatment-naïve CHB patients. A total of 624 CHB patients were recruited. We assessed the serum HBsAg and qAnti-HBc levels, HBV DNA levels, HBV genotypes, BCP/PC mutations, histological fibrosis staging by Scheuer classification. Results: In HBeAg (+) patients, the S0-1 subjects had significantly higher serum HBsAg and lower qAnti-HBc levels than the S2-4 subjects (both p 0.05). Serum qAnti-HBc levels showed a moderate positive correlation with fibrosis scores (r = 0.383, p

Background: Primary lymphoma of bone (PLB) is an extremely rare malignancy arising in the skeletal system. There is no consensus over the best definition of PLB. Most of the published articles are single-institutional retrospective studies with a limited sample size. The rarity of PLB and discrepancies on diagnostic criteria has resulted in a vague understanding of PLB. Methods We retrospectively analyzed the clinical characteristics and prognostic factors of 2558 PLB patients who were registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2016. Survival rates were calculated using the Kaplan–Meier method. The effects of various factors on survival outcomes were analyzed by using the log-rank test. Univariate and multivariate analyses were conducted by using the Cox proportional hazards model to determine independent prognostic factors. Results: The median follow-up time of all eligible patients was 58 months. There seemed no sex preponderance in PLB incidence. The most involved sites are axial skeletons. The most common histological subtype was diffuse large B-cell lymphoma. The 3-, 5-, 10-, and 20-year overall survival (OS) rates were 70.70%, 65.70%, 54.40% and 39.50%, respectively. PLB patients whose primary tumor sites were appendicular and craniofacial skeletons had a significant survival advantage [hazard ratio (HR) = 0.694, 95% confidence interval (CI) 0.552–0.872; HR = 0.729, 95% CI 0.597–0.889, respectively] over those with axial skeletons as primary tumor sites. Patients with Hodgkin lymphoma, non-Hodgkin lymphoma (NHL)–mature B-cell lymphoma, and NHL-precursor-cell lymphoblastic lymphoma also had a significant OS advantage (HR = 0.392, 95% CI 0.200–0.771; HR = 0.826, 95% CI 0.700–0.973; and HR = 0.453, 95% CI 0.223–0.923, respectively). Patients with Ann Arbor stage III–IV at diagnosis were at higher risk of death than those with stage I–II (HR = 1.348, 95% CI 1.107–1.641). Chemotherapy was an independent favorable prognostic factor (HR = 0.734, 95% CI 0.605–0.890). Conclusions: Primary anatomic site, histology type, higher Ann Arbor stage and chemotherapy were independent prognostic factors. Chemotherapy played a pivotal role in PLB treatment.

Galectin-3, a microglia/macrophage-derived inflammatory mediator, plays a role in the stroke progression. In this single-center prospective study, we included 288 consecutive patients with a first-ever acute ischemic stroke to assess the association between galectin-3 serum level and clinical severity at admission and outcome at discharge by univariate and multivariate logistic regression. The results were presented as odds ratios (OR) and 95% confidence intervals (CI). Patients with high severity and poor outcomes had higher serum levels of galectin-3 (P

Lymphomatoid granulomatosis (LYG) is an extremely rare angio-centric and angio-destructive B-cell lymphoproliferative disease. Driven by Epstein-Barr virus (EBV), LYG predominantly involves the bilateral lungs. Commonly presenting as multiple nodules in the lung, pulmonary LYG can masquerade as various infectious diseases, vasculitis, lung cancer, or other metastatic neoplasm. It is difficult to be diagnosed and is always neglected by clinicians. No standardized therapeutic regimens for LYG has been established yet now. Hemophagocytic lymphohistiocytosis (HLH), a life-threatening condition caused by abnormal activation of macrophages and T-cells, is characterized by fever, hepatosplenomegaly, pancytopenia, hypercytokinemia, and the presence of hemophagocytosis within the bone marrow, liver, spleen, or other lymphatic tissue. We herein report a 55-year-old man with recurrent fever, severe jaundice, and multiple high-density opacities and nodules in both lungs, who was finally diagnosed with pulmonary LYG (Grade 3) manifested with secondary HLH. Administration of HLH-1994 protocol led to the rapid control of the symptoms caused by HLH. Rituximab-based combination therapy was useful yet LYG (Grade 3) progressed rapidly. This case demonstrates that tissue biopsy is essential for early pathological diagnosis and effective treatment of LYG.

Background: Multiple myeloma (MM) is the second most common hematological neoplasm. Wide administration of bortezomib significantly improves the survival of MM patients compared with conventional chemotherapy. Bromodomain-containing protein 4 (BRD4) inhibitors also have been demonstrated to retard cell proliferation and induce cellular apoptosis in various cancers. However, it is unclear whether the BRD4 inhibitor nitroxoline plus bortezomib has a synergistic anti-tumor effect on MM. Methods: Cell viability was determined via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and cell apoptosis were assessed via flow cytometry. Protein expression levels were determined via western blotting. The expression of apoptosis-related proteins in xenograft tissue were detected by means of immunohistochemistry. Results: Treatment with nitroxoline or bortezomib suppressed cell proliferation, and caused G0/G1 phase arrest and apoptosis in H929 and RPMI8226 cells. Furthermore, nitroxoline intensified the retardation of cell proliferation, as well as further enhanced the G0/G1 phase arrest and apoptosis induced by bortezomib in H929 and RPMI8226 cells. The western blot analysis revealed that nitroxoline or bortezomib treatment markedly diminished the levels of Bcl-2 and cyclin D1, and increased the levels of p21, Bax, cleaved PARP and cleaved caspase-3. Combination of these two agents was observed to result in further marked changes on these levels compared with nitroxoline or bortezomib treatment alone. What is more, in the xenograft tumor model, combinative treatment markedly inhibited tumor growth compared with the single drug treatment. Conclusion: Combination of bortezomib with nitroxoline has a synergistic anti-tumor activity in MM cells and may be a novel treatment method for MM.

During the past decades, agents with novel mechanisms of action, such as monoclonal antibodies (MAbs) and histone deacetylase inhibitors (HDACis) have been applied to treat relapsed or refractory multiple myeloma (RRMM). The treatment outcomes of MAbs versus HDACi in combination with bortezomib or lenalidomide plus dexamethasone remain unknown. We conducted this meta-analysis to compare indirectly the efficacy and safety of MAbs and HDACis in combination with bortezomib or lenalidomide plus dexamethasone. Six trials (eight articles) were included in the meta-analysis with 3270 RRMM patients enrolled. We synthesized hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) for complete response (CR),very good partial response (VGPR), overall response (OR), progressive disease plus stable disease (PD + SD) and common at least grade 3 adverse events, and their corresponding 95%confidence intervals (95% CI). Treatment with MAbs in combination with bortezomib or lenalidomide plus dexamethasone resulted in longer PFS (HR 0.83, 95% CI: 0.66–0.98), fewer incidences of at least grade 3 thrombocytopenia (RR 0.35, 95% CI: 0.23–0.53), neutropenia (RR 0.70, 95% CI: 0.51–0.96), and sense of fatigue (RR 0.37, 95% CI: 0.17–0.82) than HDACis. The daratumumab plus bortezomib or lenalidomide and dexamethasone might significantly improve PFS in comparison with HDACis plus bortezomib or lenalidomide and dexamethasone (HR 0.55, 95% CI: 0.40–0.74). In conclusion, MAbs may be superior to HDACis in achieving longer PFS and may be better tolerated when in combination therapy with bortezomib or lenalidomide plus dexamethasone.

Background Accumulating evidence has indicated that the dysregulation of immunological environment has an important role in the pathogenesis of myelodysplastic syndromes (MDS). The previous studies about the levels of the inflammatory cytokines in MDS, such as TNF-α, IFN-γ, IL-6, IL-8, and IL-17, have yielded controversial results. Thus, we performed a meta-analysis to assess the levels of these inflammatory cytokines in MDS. Methods A systematic search in PubMed, MEDLINE, Cochrane Library, Web of Science, CNKI, and CBM was conducted to find eligible studies. Meta-analyses were performed using STATA 12.0 for Windows. Heterogeneity between included studies was assessed by I test. We chose SMD as the summary statistic. Results A total of 697 individuals from 11 studies were included in this study. Our results suggest the levels of TNF-α, IL-6, IL-8 were significantly higher in MDS patients compared with controls, SMD and 95%CI was 1.48 (0.60, 2.36), 0.71 (0.16, 1.25) and 0.69 (0.28, 1.09), respectively. Moreover, the levels of IL-17 have decreased in the high-risk MDS, the SMD and 95% CI was 2.96 (0.78, 5.15). Conclusion A close association between immunological microenvironment disorders and the pathogenesis of MDS was revealed in this meta-analysis. More importantly, the profiles of inflammatory cytokines appear to change along the progression of the disease.

Previous studies have shown that hepatitis B core antibody (anti-HBc) levels vary during different phases of disease in treatment-naïve chronic hepatitis B (CHB) patients and can be used as a predictor of both interferon-α and nucleoside analogue therapy response. However, there is no information on the association between the quantitative serum anti-HBc (qAnti-HBc) level and liver inflammation in CHB patients. Therefore, we investigated these relationships in a large cohort of treatment-naïve CHB patients. A total of 624 treatment-naïve CHB patients were included in the study. The serum qAnti-HBc level was moderately correlated with ALT and AST levels (P

Serum samples from endometrial cancer (EC) patients and healthy females were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to discover the potential diagnostic biomarker for detection of EC. A preliminary training set of spectra derived from 40 EC patients and 30 healthy women were used to develop a proteomic model that effectively discriminated cancer patients from healthy women. The training set had a specificity of 100% and sensitivity of 92.5% in the EC detection. A blind test set, including 20 new cancer cases and 10 healthy women, was used to validate the sensitivity and specificity of this multivariate model, which had a corresponding results of 60% in specificity and 75% in sensitivity, respectively. The combination of SELDI-TOF-MS with bioinformatics tools could help find new biomarkers and establish the detection of EC with high sensitivity and specificity.