The association of COVID-19 with diffuse large B-cell lymphoma: a Mendelian randomization study.

With the outbreak of coronavirus disease 2019 (COVID-19), there has been an increasing focus on exploring the relationship between SARS-CoV-2 infection and tumors. However, there is no consensus on the association between COVID-19 and lymphoma. In this study, genome-wide association study (GWAS) summary data sets for COVID-19 and lymphoma were obtained from the OPEN GWAS website. Single nucleotide polymorphisms (SNPs) were selected as genetic instrument variants for fulling P < 5 × 10-8 and linkage disequilibrium [LD] r2 < 0.001. Both palindromic and outlier SNPs were removed. Cochran's Q test, the MR‒Egger intercept test, and leave-one-out analysis were employed to assess the sensitivity of the effect of COVID-19 on lymphoma. The results showed that COVID-19 patients with very severe respiratory symptoms have an increased risk of developing diffuse large B-cell lymphoma (IVW, OR = 1.765, 95% CI 1.174-2.651, P = 0.006). There was no association between COVID-19 with very severe respiratory symptoms and Hodgkin's lymphoma or other types of non-Hodgkin's lymphoma. No horizontal or directional pleiotropy was observed in the Mendelian randomization analysis. In conclusion, SARS-CoV-2 infection with very severe respiratory symptoms may be a potential risk factor for diffuse large B-cell lymphoma (DLBCL), and follow-up studies with larger samples are needed.

The efficacy and safety of low-dose rituximab in immune thrombocytopenia: a systematic review and meta-analysis.

Rituximab has been frequently used as a second-line treatment for patients with immune thrombocytopenia (ITP). Recently, several studies have proposed low-dose (100 mg or 100mg/m2 per week for 4 weeks) rituximab instead of the standard dose of 375mg/m2 per week for 4 weeks to treat ITP patients. The aim of this review was to systematically evaluate the efficacy and safety of low-dose rituximab for patients with ITP. Pubmed, Web of Science, Cochrane Library and Embase were searched to identify the clinical studies published in full text or abstract that met the predefined inclusion criteria. Efficacy analysis was restricted to the studies enrolling five or more patients. While safety analysis was evaluated based on all the studies reported adverse events. Nine studies (329 patients) were included for effect assessment of low-dose rituximab treatment on the patients with ITP. The pooled overall response rate was 63% (95% CI, 0.54-0.71) while the pooled complete response was 44% (95% CI, 0.33-0.55). Thirty-one patients were reported to experience adverse effects associated with rituximab, among them 30 cases suffered mild to moderate side-effects (grade1-2). Only one patient developed into interstitial pneumonia (grade3). No death was reported. Low-dose rituximab exhibited a satisfactory efficacy and safety profile, indicating that this regimen is a promising therapy for ITP, and should be further investigated through randomized clinical trials with standard-dose rituximab.

The prognostic role of lymphocyte to monocyte ratio (LMR) in patients with Myelodysplastic Neoplasms.

BACKGROUND: Previous studies validated the prognostic significance of lymphocyte to monocyte ratio (LMR) in patients with solid tumors and some hematologic malignancies. However, the correlation between LMR and Myelodysplastic Neoplasms (MDS) was unclear. The study intends to investigate the prognostic impact of LMR on MDS patients. METHODS: 91 newly diagnosed MDS patients were included in this retrospective study. The cut-off of LMR was 3.2 by X-Tile. All patients were divided into the low LMR group (<3.2) and the high LMR group (≥3.2). Clinical characteristics were compared between the two groups. RESULTS: Patients in the high LMR group (n = 67) had better OS (P = 0.007) from the Kaplan-Meier survival curves. The results of the univariate analysis demonstrated that LMR was a prognostic factor for OS [hazard ratio (HR) = 2.070, 95%CI 1.201-3.571, P = 0.009]. After multivariate cox analysis, low LMR was confirmed to be an independent predictor of poor OS in MDS patients (HR = 1.872, 95%CI 1.084-3.230, P = 0.024). CONCLUSIONS: LMR, a representative marker of systematic inflammation and immune response, has potential prognostic significance in MDS patients.

The causal effect of inflammatory bowel disease on diffuse large B-cell lymphoma: two-sample Mendelian randomization study.

Background: It has been reported that inflammatory bowel disease (IBD) is associated with an increased risk of malignancies, including lymphoma. A number of large observational studies have been devoted to exploring the causal link between IBD and malignant lymphoma. However, no consensus exists on whether there is a causal relationship between IBD and malignant lymphoma. Methods: The summary dataset of the IBD and lymphoma genome-wide association studies (GWAS) was obtained from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) were selected as genetic instrumental variants (IVs) for fulling P < 5 × 10-8 and linkage disequilibrium (LD) of r2 = 0.001 in the IBD GWAS. The proxy SNPs with LD of r2 > 0.8 were identified. Palindromic SNPs and outlier SNPs were excluded. The assessments of sensitivity employed the Cochran's Q test, Mendelian randomization (MR)-Egger intercept test, and leave-one-out analysis. Results: The MR analysis results proved the causality of IBD on diffuse large B-cell lymphoma (DLBCL). The risk of developing DLBCL is increased by 28.6% in patients with IBD [odds ratio (OR)IVW = 1.286, 95% confidence interval (CI) 1.066-1.552, P = 0.009]. The results of the subgroup analysis showed that Crohn's disease (ORIVW = 1.218, 95% CI 1.030-1.441, P = 0.021) rather than ulcerative colitis (ORIVW = 1.206, 95% CI 0.984-1.478, P = 0.072) had a causal effect on DLBCL. No horizontal and directional pleiotropy was observed in the MR studies. Conclusions: The above MR study concluded that IBD itself is causally responsible for DLBCL, especially Crohn's disease. Further investigations are needed to elucidate the mechanism underlying this direct causal link.

Clinical significance of prognostic nutritional index in myelodysplastic syndrome.

BACKGROUND: Prognostic nutritional index has been found to be related to the clinical outcomes of patients with cancer. However, its role in myelodysplastic syndromes (MDS) patients is unclear. We aimed to assess the value of nutritional status in predicting the prognosis of MDS patients. METHODS: Totally 121 MDS patients were analyzed retrospectively. The prognostic nutritional index (PNI) was used to assess nutritional status of the patients. The bio-informatics tool X-tile was used to define the threshold, and accordingly patients were divided into PNIlow and PNIhigh groups, the characteristics were compared between two groups. RESULTS: The PNIhigh was associated with better OS (Overall Survival) than PNIlow in MDS patients (Median OS, 28.03 months versus 19.63 months, P = 0.0205). But there were no statistical differences in PFS (Progression-Free-Survival) between the two groups (P = 0.9373). The univariable and multivariable COX proportional hazard analysis adjusted for age, gender, platelet count, HB level and IPSS-R scores, and the results showed that PNI is a useful index in the evaluation of the OS of MDS (HR 0.588, 95%CI 0.374-0.926, P = 0.024). CONCLUSION: PNI would be a simple and immediately available tool for predicting the prognosis of MDS.

Clinical outcomes and characteristics of patients with TP53-mutated myelodysplastic syndromes.

OBJECTIVE: To explore the clinical outcomes and characteristics of TP53-mutated primary myelodysplastic syndromes (MDS). METHODS: A total of 74 de novo primary MDS patients who were diagnosed and treated in the Department of Hematology of our hospital from January 2018 and September 2021 were analyzed retrospectively. All patients had evaluable blood cell counts, mean corpuscular volume (MCV), lactate dehydrogenase (LDH), bone marrow (BM) morphology, biopsy, and MDS-related 20-gene mutations sequencing. In addition, 69 of 74 patients had complete cytogenetic analysis through conventional chromosome analysis and fluorescence in-situ hybridization. RESULTS: Patients were divided into two cohorts, the TP53-mutated type (TP53Mut) group (n = 19) and TP53 wild type (TP53WT) group (n = 55). Compared with the TP53WT group, patients in the TP53Mut group had higher ratios of cytogenetic abnormalities (82.4% vs. 30.8%, P < 0.001), with 5q- karyotype (64.70% vs. 38.5%, P < 0.001), complex karyotype(CK) (64.70% vs. 38.5%, P < 0.001), HR-MDS (94.7% vs. 61.8%, P = 0.008), and acute myelogenous leukemia (AML) transformation (26.3% vs. 12.7%, P < 0.001). Interestingly, patients in the TP53Mut group had lower median MCV than the TP53WT group (94.40 fl vs. 101.90 fl, P = 0.008). Furthermore, MCV = 100 fl as cutoff, and found that MCV ≤ 100 fl was more common in the TP53Mut group (73.7% vs. 38.2%, P < 0.001). After 1-4 courses of HMA ± chemotherapy, the overall response rate of the TP53Mut group was higher than the TP53WT group (83.3% vs. 71.4%, P = 0.012). With the median follow-up 12.0 months (1-46 months), the results show that the median OS and leukemia-free survival (LFS) of TP53Mut group was significantly shorter than the TP53WT group (P = 0.0018; P = 0.0310). Results of multivariate Cox proportional hazard analyses show TP53 mutation was an independent prognostic factor for the OS (HR 2.724, 95%CI 1.099-6.750, P = 0.030). CONCLUSION: TP53-mutated primary MDS patients were associated with higher frequency of cytogenetic abnormalities, with 5q- karyotype, CK, AML transformation, higher risk IPSS-R, lower MCV and sensitive to HMA treatment, but worse survival.

Prognostic role of controlling nutritional status score in hematological malignancies.

BACKGROUND: Controlling nutritional status (CONUT) score, based on three indexes including serum albumin (ALB), total cholesterol (CHO), and absolute lymphocyte count (ALC), has been closely associated with the prognosis of cancer patients. Multiple studies revealed the significance of CONUT score in hematological malignancies, including diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), multiple myeloma (MM), and leukemia. OBJECTIVE: This review aimed to explore the prognostic role of CONUT score in hematological malignancies. METHODS: We conducted this review through Pubmed to summarize the published studies on the CONUT score in hematological malignancies, using the terms: Controlling nutritional status, CONUT score, hematological malignancy, lymphoma, multiple myeloma, and leukemia. RESULT: CONUT score can reflect not only the nutritional status but also the inflammatory status of patients with hematological malignancies. It can assist in predicting the survival of patients with DLBCL, PTCL, MM, adult T-cell leukemia (ATL), myelodysplastic syndrome (MDS), and acute myeloid leukemia with myelodysplasia related changes (AML-MRC). CONCLUSION: CONUT score plays an important role in predicting the prognosis of patients with hematological malignancies.

Prognostic Impact of Platelet-Large Cell Ratio In Myelodysplastic Syndromes.

Background: Myelodysplastic syndromes (MDSs) are a very heterogeneous group of myeloid disorders with high prevalence and risk of developing acute myeloid leukemia. The more accurate risk stratification can provide a better guidance of treatment. The platelet-large cell ratio (P-LCR) is a parameter reported in complete blood cell count tests, and was associated with many diseases, but its role in MDS is not clear. Purpose: This study aims to explore the impact of the P-LCR on the prognosis of patients with MDS, which is of great significance for clinical treatment. Methods: In the retrospective study, 122 newly diagnosed MDS patients were enrolled. We used the bioinformatics tool X-tile to define a P-LCR threshold of 36.7% to predict prognosis. Patients were divided into P-LCRlow and P-LCRhigh groups, and their characteristics were compared between the two groups. Results: Results show that the P-LCRlow was associated with worse overall survival (OS) than the P-LCRhigh patients (median OS, 18.53 months versus 25.77 months, p=0.0057), but there were no statistical differences in progression-free survival (PFS) between the two groups (p=0.2001). The results of univariate and multivariate Cox proportional hazard analyses adjusted for gender, bone marrow blast level, platelet count, and International Prognostic Scoring System scores showed that the P-LCR was useful in the evaluation of PFS [hazard ratio (HR) 0.212, 95%CI 0.064-0.702, p=0.011] and OS of MDS (HR 0.464, 95%CI 0.284-0.757, p=0.002). Conclusion: This study is the first report showing that the P-LCR would be a simple and immediately available biomarker for predicting the prognosis of MDS.

Prognostic impact of the controlling nutritional status score in patients with hematologic malignancies: A systematic review and meta-analysis.

Background: An increasing number of studies have validated the prognostic significance of the controlling nutritional status (CONUT) score in patients with solid tumors. However, the extent of the correlation between the CONUT score and clinical outcomes of patients with hematologic malignancies is unclear. Objective: This study aimed to investigate the prognostic role of the CONUT score in patients with hematologic malignancies. Methods: All relevant articles published up to November 15, 2021, were identified by systematically searching PubMed, Embase, Web of Science, and Cochrane Library. Pooled hazard ratios (HRs) and 95% confidence intervals were used to quantitatively analyze the association between the CONUT scores and clinical outcomes of patients with hematologic malignancies. Subgroup and sensitivity analyses were performed. Funnel plots as well as Begg's and Egger's tests were used to assess publication bias. Results: Six studies with 1811 patients were included in the meta-analysis. The results showed that a high CONUT score was associated with worse overall survival (OS) (HR=1.34, 95%CI 1.14-1.59, P < 0.001) and progression-free survival (PFS) (HR=1.20, 95%CI 1.10-1.32, P < 0.001). Conclusions: The CONUT score is an independent prognostic factor in patients with hematologic malignancies. Systematic review registration: http://www.crd.york.ac.uk/prospero/, identifier CRD42021292621.

Prognostic value of the controlling nutritional status score in patients with myelodysplastic syndromes.

Background: Myelodysplastic syndromes (MDS) are a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The controlling nutritional status (CONUT) score, an easy-to-use tool for assessing the nutritional status, was reported as an independent prognostic factor in cancer patients. However, its role in patients with MDS is unclear. Objective: We aimed to explore the impact of CONUT score on the prognosis of patients with MDS, which is of great significance for clinical treatment. Methods: A total of 121 patients with MDS were analyzed. The CONUT score was calculated prior to therapy. The bio-informatics tool X-tile was used to define the CONUT score and the threshold of 4 points was determined to predict the prognosis. Patients were divided into CONUTlow and CONUThigh groups, and the characteristics were compared between two groups. Results: Results show that CONUTlow was associated with better overall survival (OS) than CONUThigh patients (Median OS, 30.20 vs. 19.63 months, p = 0.0003). However, there were no statistical differences in progression-free survival (PFS) between the two groups (p = 0.2683). Results of univariate and multivariate COX proportional hazard analysis adjusted for bone marrow blasts level, platelet count, International Prognostic Scoring System (IPSS) scores, gender, and hemoglobin (Hb) level showed that the CONUT score was useful in the evaluation standard of OS of MDS (hazard ratio (HR) 2.297, 95% CI 1.441-3.663, p < 0.001). Conclusions: The CONUT, as a novel immuno-nutritional biomarker, may be useful in predicting the OS of MDS.

Comparative study between two bleeding grading systems of immune thrombocytopenia purpura.

OBJECTIVE: To explore the relationship between platelet count and bleeding score in immune thrombocytopenia purpura (ITP) and compare the clinical practicability of two bleeding grading systems with adult patients with ITP. METHODS: A total of 204 patients were retrospectively analyzed with the ITP bleeding scale (IBLS) and the ITP bleeding assessment tool (version 2016) (ITP-2016). The correlation between the two bleeding score systems and the relations among the platelet counts were respectively analyzed. RESULTS: (1) There is a linear relationship between platelet count and bleeding score, no matter which scoring system it is based on (rs = -0.429, p < 0.001; rs = -0.331, p < 0.001, the analysis of the number of sites of Grade 1/2 bleeding were done; and rs = -0.466, p < 0.05, the analysis between platelet count and bleeding score by ITP-2016 respectively). (2) Platelet count and bleeding scores are negatively correlated in those with extremely low platelet counts ( < 10*109/L). The number of sites of Grade 2 bleeding and the ITP-2016 scores are negatively correlated with platelet counts (rs = -0.15 and rs = -0.244, p < 0.05, respectively). Significantly, there is no correlation between the platelet count and bleeding scores when the platelet count is more than 10*109/L. (3) It takes less time to score with ITP-2016 than IBLS (z = -3.825, P < 0.001). CONCLUSIONS: There is good responsiveness, strong assessment consistency, close correlation between ITP-2016 and IBLS. ITP-2016 takes less time-consuming in clinical application. It can be used as an effective tool of condition judgement, risk assessment and efficacy evaluation of patients with ITP.

[Reaserch Advance on Bruton Tyrosine Kinase Inhibitors in the Treatment of B-Cell Tumors--Review].

Abstract　　In recent years, development of the targeted drugs according to the biological characteristics of tumors have provided more treatment options for tumor patients. It was found that the overactivation or abnormality of B cell receptor (BCR) signal pathway closely related to the occurrence and development of various B cell tumors, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). As a key kinase in the BCR pathway, BTK inhibitors have obvious anti-tumor effect when its activity is being inhibitered. Currently, BTK inhibitors developed include the first-generation Ibrutinib and the second-generation Acalabrutinib, which can be targeted at the inhibition of BTK and its downstream signaling pathway, and have important therapeutic value for a variety of B-cell tumors, such as CLL and partial non-Hodgkin's lymphoma (NHL). However, its side effects and drug-resistance also gradually emerged, effective drug combination therapy has shown a certain clinical activity. This reviews summarizes briefly the mechanism and status of BTK inhibitors in the treatment of various B-cell tumors.

[Research Advance on the Role of Spleen Tyrosine Kinase Inhibitors in Hematologic Malignancies].

Abstract　　Spleen tyrosine kinase (SYK) is not only a key kinase in the B-cell receptor (BCR) signaling pathway, but also a critical component of other signal transduction pathways such as Fc receptor, complement receptor and integrin. Abnormal activation of SYK closely related to the occurrence and development of hematological malignancies, thus targeting SYK has become a research hotspot. Several SYK inhibitors including Fostamatinib, Entospletinib and Cerdulatinib were being evaluated in clincal trials. As a second generation SYK inhibitor, Entospletinib has achieved good efficacy in lymphoid and myeloid hematologic tumors. Furthermore, Entospletinib can significantly relieve hematopoietic stem cell transplantation(HCT) related graft versus host disease (GVHD). In this review the role of SYK inhibitors in treatment of hematological malignancies is summarized brifely.

[Reaserch Advance on Inhibitor Targeting at the B-Cell Receptor Pathway in Chronic Lymphocytic Leukemia --Review].

Abstract　　Disregulated BCR signaling pathway plays an important role in the occurence and progress of chronic lymphocytic leukemia (CLL). As key kinases of BCR pathway, the Bruton tyrosine kinase (BTK), phosphoinositide 3-kinase (PI3K) and spleen tyrosine kinase (SYK) have become the focus of CLL targeted therapy. Over the past decade, drugs targeting of BCR pathway for CLL treatment have been continuously developed, including BTK inhibitors, PI3K inhibitors and SYK inhibitors. To date, the BTK inhibitor Ibrutinib, PI3K inhibitors Idelalisib and Duvelisib have been approved for CLL treatment, and some novel inhibitors are still in clinical trials. These targeted drugs are much less toxic than chemoimmunotherapy and show better efficacy in certain high-risk patients such as del 17P. These inhibitors targeted BCR pathway are increasingly prominent in CLL treatment and gradually replace traditional chemoimmunotherapy.

[Research Progress of m6A-Methylation in Acute Leukemia-Review].

OBJECTIVE: Epigenetic abnormalities play an important role in the pathogenesis of hematological malignancies, especially acute leukemia (AL). Similar to DNA methylation and histone modifications, RNA methylation is another important epigenetic modification. m6A methylation is one of the most prevalent and extensively studied RNA methylation. m6A methylation is involved in many biological and pathological process. Recent studies have found that m6A methylation is involved in the occurrence, development and drug-resistance of AL. This review focuses on the research progress of m6A methylation in AL.

Multiple functions of Ikaros in hematological malignancies, solid tumor and autoimmune diseases.

Ikaros, encoded by IKZF1 (Ikaros family zinc finger 1), is an important transcription factor in the control of lymphocyte specification and differentiation. Multiple functions of Ikaros have been exerted in almost all hematopoietic cell types, from stem cells to mature lymphoid and myeloid cells. Moreover, nonhematopoietic cells are also functional targets of Ikaros. Ikaros is essential for normal hematopoiesis, autoimmune and tumor suppression. Ikaros mutations were associated with lymphoblastic cells deficiency, autoimmunity and malignancies development, including hematological malignancies (leukemia) and solid tumors. This review focus on discuss the role of Ikaros in hematological malignancies, solid tumors and autoimmune diseases, and highlight the importance of Ikaros in cancer and immune diseases therapy.

Clinical analysis of hepatic angioleiomyoma: Two case reports.

RATIONALE: Angioleiomyoma is an uncommon benign tumor that originates from the vascular smooth muscle cells and contains thick-walled vessels. It can appear anywhere in the body but more frequently in the extremities (especially in the lower limbs) and rarely invades the internal organs. PATIENT CONCERNS: A 52-year-old Chinese woman was referred to our hospital because of finding liver neoplasm 2 weeks ago (case first) and a 64-year-old Chinese woman was admitted to hospital with enlargement of the hepatic neoplasm revealed in follow-up, who was diagnosed with angioleiomyoma of left kidney 2 years ago (case second). DIAGNOSIS: All patients were diagnosed with hepatic angioleiomyoma by pathological results. INTERVENTIONS: All patients received surgical treatment, with laparoscopic hepatectomy of the IVb segment in case 1 and laparoscopic hepatic left lateral lobectomy in case 2. OUTCOMES: The 2 patients have eventually recovered, and no recurrences or other complications have been observed so far. LESSONS: Because of atypical clinical symptoms, no specificity in laboratory examination, and lack of characteristic imaging findings, angioleiomyoma is easily misdiagnosed for another disease of the liver. But with complete resection, the prognosis is generally good.

The research progress of circular RNAs in hematological malignancies.

Objectives: Circular RNA (circRNA), a covalently closed loop structure lacking poly-adenylated tails, has attracted attention with the rapid development of its detection techniques such as bioinformatics and RNA sequencing. CircRNA plays important roles in several cell signaling pathways that are associated with cancer biogenesis, including acting as miRNA sponges, transcriptional regulators, protein adaptors and protein translators. The role of circRNA in hematological malignancy has been revealed recently. The purpose of this study was to explore the role of circRNA in hematological malignancy. Methods: A comprehensive literature review was conducted through Pubmed to summarize the published evidence on the circRNAs in hematological malignancies. English literature sources since 1976 were searched, using the terms circRNA, hematological malignancy. Results: CircRNAs can regulate the gene expression of hematological malignancies mainly through adsorbing several miRNAs. Some circRNAs are potential biomarkers and therapeutic targets in hematological malignancies, such as acute myloid leukemia (AML), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Conclusion: CircRNAs play an important biological function and have great diagnostic and prognostic value in hematological malignancies.

[Risk factors of nurses' occupational adaptability].

OBJECTIVE: To explore factors affecting occupational adaptability in nurses for offering basis to increase their occupational adaptability. METHODS: Five hundred and forty-five nurses were investigated with work ability index questionnaire and occupational stress instruments. RESULTS: There were many risk factors affecting occupational adaptability in nurses. The main variables that influenced occupational adaptability included work-overtime, mental load, social support, physical environment, and job hazards. The social support was the factor increasing the occupational adaptability of the nurses (P < 0.01, OR = 0.912). Five factors including work overtime, mental load, social support, physical environment and job hazards were introduced in the Logistic equation. The established functions were: Logit (P) = -11.357 + 1.011x(1) + 0.335x(2) - 0.076x(3) + 0.260x(4) + 0.129x(5). CONCLUSION: There are many risk factors affecting occupational adaptability in nurses. Relevant measures should be taken to promote the occupational adaptability in nurses to reduce the risk factors.