bFGF could be a biomarker of malignancy in RS3PE syndrome: an ambispective single-center cohort analysis of 51 patients

Objectives Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare inflammatory arthritis, with a higher incidence of malignancy. The aim of this study is to identify biomarkers for predicting malignancy in RS3PE. Methods A total of 51 patients with RS3PE from September 2007 to May 2019 were retrospectively reviewed and followed for up to 5 years, with 15 patients with osteoarthritis (OA) and 14 patients with elderly-onset rheumatoid arthritis (EORA) as disease controls. Serum levels of angiogenesis cytokines were measured by electrochemiluminescent immunoassay and Luminex Human Magnetic Assay. Clinical data and laboratory parameters were analyzed to identify risk factors for malignancy. Results A total of forty-eight RS3PE patients (94.1%) were available with follow-up data; 8 patients (16.7%) were diagnosed with malignancy, of which 6 patients were hematological tumor; and 2 patients were solid tumors. Serum levels of basic fibroblast growth factor (bFGF) were exclusively higher in RS3PE patients with malignancy [14.21 (7.52, 23.18) ng/mL] than RS3PE patients without malignancy [4.32 (2.88, 7.42) ng/mL], OA [3.20 (2.20, 5.30) ng/mL], and EORA [3.20 (2.20, 5.30) ng/mL]. The optimal cut-off value of bFGF for malignancy was 10ng/mL in RS3PE. Logistic regression analysis indicated that elevation of bFGF was a risk factor for malignancy in RS3PE. Conclusions This study indicated that bFGF was elevated in RS3PE patients with malignancy and could serve as a biomarker for predicting paraneoplastic RS3PE.

Addressing Enzymatic-Independent Tumor-Promoting Function of NAMPT via PROTAC-Mediated Degradation

The rate-limiting enzyme of salvage pathway for NAD+ synthesis, NAMPT, is aberrantly overexpressed in a variety of tumor cells and is a poor prognosis factor for patient survival. NAMPT plays a major role in tumor cell proliferation, acting concurrently as an NAD+ synthase and unexpectedly, an extracellular ligand for several tumor-promoting signaling pathways. While previous efforts to modulate NAMPT activity were limited to enzymatic inhibitors with low success in clinical studies, protein degradation offers a possibility to simultaneously disrupt NAMPT enzyme activity and ligand capabilities. Here, we report the development of two highly selective NAMPT-targeted proteolysis-targeting chimeras (PROTACs), which promoted rapid and potent NAMPT degradation in a cereblon-dependent manner in multiple tumor cell lines. Notably, both PROTAC degraders outperform a clinical candidate, FK866, in killing effect on hematological tumor cells. These results emphasize the importance and feasibility of applying PROTACs as a better strategy for targeting proteins like NAMPT with dual tumor-promoting functions, which are not easily achieved by conventional enzymatic inhibitors.

A review and content analysis of apps for hematological diseases using Mobile Application Rating Scale (MARS). (Preprint)

BACKGROUND Hematological diseases are prevalent disorders associated with significant comorbidities and have a major impact on patient care. Concerning new tools for the care of these patients, the number of health apps aimed at hematological patients is growing. Currently, there are not quality analyses or classifications of apps for patients diagnosed with hematological diseases. OBJECTIVE Our objective was to analyze the characteristics and quality of apps designed for patients diagnosed with hematological diseases using the Mobile Application Rating Scale (MARS). METHODS We performed an observational, cross-sectional, descriptive study of all smartphone apps destined for patients diagnosed with hematological diseases. A search was conducted in March 2021, using the following terms: “anemia”, “blood cancer”, “blood disorder”, “hematological cancer”, “hematological malignancy”, “hematological tumor”, “hematology”, “hemophilia”, “hemorrhage”, “lymphoma”, “leukemia”, “multiple myeloma”, “thalassemia”, “thrombocytopenia”, and “thrombosis”. The apps identified were downloaded and evaluated by 2 independent researchers. General characteristics were registered and quality was analyzed using the MARS score. Interrater reliability was measured by using Cohen's kappa coefficient (κ). RESULTS We identified 2.100 apps in the initial search, and 88 apps met the criteria and were analyzed. Of these, 54 (61.36%) were available on Android, 26 (29.55%) on iOS, and 8 (9.09%) on both platforms. 6 apps (6.82%) required payment and 43 apps (48.86%) were updated in the last year. Only 23 apps (26.13%) were developed with the participation of health professionals. The apps were mainly informative (60; 68.18%), followed by preventive (23; 26.13%), and diagnostic (5; 5.68%). Most of the apps were intended for patients with anemia (23; 26.14%). The mean MARS score for the overall quality of the 88 apps was 3.03 (SD 1.14), ranging from 1.19 (lowest rated app) to 4.86 (highest rated app). Only 41 apps (46.59%) obtained a MARS score over 3 points (“acceptable quality”). Functionality was the best rated section, followed by aesthetics, engagement, information, and app subjective quality. The 5 apps with the highest MARS score were the following: “Multiple Myeloma Manager”, “Hodgkin Lymphoma Manager”, “Focus On Lymphoma”, “ALL Manager”, and “CLL Manager”. The analysis by the operating system, developers, and cost revealed statistically significant differences in the MARS score (P < .001, P <.001, and P=.049, respectively). Interrater agreement between the two reviewers was substantial (k=0.78). CONCLUSIONS There is great heterogeneity in the quality of apps for hematological patients. More than half of the apps do not meet acceptable criteria for quality and content. Most of them only provide information about the pathology, lacking interactivity and personalization options. The participation of health professionals in the development of these apps is low, although it is narrowly related to better quality.

bFGF could be a Biomarker of Malignancy in RS3PE Syndrome: an Ambispective Single Center Cohort Analysis of 51 Patients

ObjectivesRemitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare inflammatory arthritis, with a higher incidence of malignancy. The aim of this study is to identify biomarkers for predicting malignancy in RS3PE.MethodsA total of 51 patients with RS3PE from September 2007 to May 2019 were retrospectively reviewed and followed for up to 5 years, with 15 patients with osteoarthritis (OA) and 14 patients with elderly-onset rheumatoid arthritis (EORA) as disease controls. Serum levels of angiogenesis cytokines were measured by electrochemiluminescent immunoassay and Luminex Human Magnetic Assay. Clinical data and laboratory parameters were analyzed to identify risk factors for malignancy.ResultsA total of forty-eight RS3PE patients (94.1%) were available with follow-up data, 8 patients (16.7%) were diagnosed with malignancy, of which 6 patients were hematological tumor, and 2 patients were solid tumor. Serum levels of basic fibroblast growth factor (bFGF) were exclusively higher in RS3PE patients with malignancy [14.21 (7.52, 23.18) ng/mL] than RS3PE patients without malignancy [4.32 (2.88, 7.42) ng/mL], OA [3.20 (2.20, 5.30) ng/mL] and EORA [3.20 (2.20, 5.30) ng/mL]. The optimal cut-off value of bFGF for malignancy was 10ng/mL in RS3PE. Logistic regression analysis indicated that elevation of bFGF was a risk factor for malignancy in RS3PE.ConclusionsThis study indicated that bFGF was elevated in RS3PE patients with malignancy and could serve as a biomarker for predicting paraneoplastic RS3PE.

Comparison of Hospital- and Community-Acquired Septic Shock in Children: A Single-Center, Cohort, Retrospective Study

Background To explore differences between hospital- (HASS) and community-acquired septic shock (CASS) in patient characteristics, pathogens, complications, outcomes, and risk factors in pediatric intensive care unit (PICU) children. Methods This retrospective study enrolled septic shock children from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into HASS and CASS groups. After comparison, logistic regression analyses were used to identify risk factors for mortality. Results A total of 298 children were enrolled. 65.9% of HASS patients (N = 91) had hematological/tumor diseases and were mainly bloodstream infections of Gram-negative bacteria (47.3%). 67.7% of CASS (N = 207) had no obvious underlying disease and were mostly infected with Gram-positive bacteria (30.9%) of the respiratory or central nervous system. 28-day mortality was 62.6% and 32.7% in HASS and CASS groups, respectively (p < 0.001). The factor associated with 28-day mortality of HASS and CASS was MODS (OR:11.524; 95% CI: 2.140-62.051) and needed invasive mechanical ventilation therapy (OR:6.884; 95% CI: 1.499–31.624), respectively. Conclusions The underlying diseases, pathogens, complications, prognosis and mortality varied widely. 28-day mortality is associated with MODS and need for invasive mechanical ventilation therapy in HASS and CASS patients.

TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss

Background To investigate the effect of TriBAFF-CAR-T cells on hematological tumor cells. Methods TriBAFF-CAR-T and CD19-CAR-T cells were co-cultured with BAFFR-bearing B-cell malignancies at different effector/target ratios to evaluate the anti-tumor effects. In vivo, TriBAFF-CAR-T and CD19-CAR-T cells were intravenously injected into Raji-luciferase xenograft mice. CD19 antigens losing lymphoblasts was simulated by Raji knocking out CD19 (CD19KO) to investigate the effect of TriBAFF-CAR-T cells on CD19KO Raji. Results Both TriBAFF-CAR-T and CD19-CAR-T cells significantly induced the lysis of Raji, BALL-1, and Jeko-1. Moreover, when CD19-CAR-T cells specifically caused the lysis of K562 with overexpressed CD19, the lethal effect of TriBAFF-CAR-T cells was also specific for BAFFR-bearing K562 with increasing levels of interleukin-2 and INF-γ. The TriBAFF-CAR-T have the same effect with CD19-CAR-T cells in treating Raji xenofraft mice. TriBAFF-CAR-T cells also have great effect in CD19KO Raji cells. Conclusions In this study, we successfully constructed novel TriBAFF-CAR-T cells to eliminate BAFFR-bearing and CD19 antigen loss in hematological tumor cells.

Prognostic Role of the Activated p-AKT Molecule in Various Hematologic Malignancies and Solid Tumors: A Meta-Analysis

Cancer is one of the main causes of human death worldwide. Recently, many studies have firmly established the causal relationship between oxidative stress and cancer initiation and progression. As a key protein in PI3K/Akt signaling pathway, p-AKT (phosphorylated Akt) participates in the process of oxidative stress and plays a prognostic role in various hematologic tumors and solid tumors. We conducted a comprehensive search of the PubMed, Embase and Cochrane libraries to identify studies published in the past decade involving cancer patients expressing p-AKT that reported overall survival (OS) during follow-up. In this study, 6,128 patients in total were evaluated from 29 enrolled articles, and we concluded that overexpression of p-AKT was closely related to worse OS in cancer patients with a hazard ratio (HR) of 2.33 (95% CI: 1.67–4.00). Furthermore, we conducted a subgroup analysis, and the results indicated that overexpression of p-AKT was associated with worse OS in hematological tumor (HR: 1.64, 95% CI: 1.41–1.92), and solid tumor (HR: 2.44, 95% CI: 1.61–5.26). High expression of p-AKT is related to poor prognosis of various hematologic tumors and solid tumors.

HLA-DPA1 gene is a potential predictor with prognostic values in multiple myeloma

Background Multiple myeloma (MM) is an incurable hematological tumor, which is closely related to hypoxic bone marrow microenvironment. However, the underlying mechanisms are still far from fully understood. We took integrated bioinformatics analysis with expression profile GSE110113 downloaded from National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database, and screened out major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) as a hub gene related to hypoxia in MM. Methods Differentially expressed genes (DEGs) were filtrated with R package “limma”. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed using “clusterProfiler” package in R. Then, protein-protein interaction (PPI) network was established. Hub genes were screened out according to Maximal Clique Centrality (MCC). PrognoScan evaluated all the significant hub genes for survival analysis. ScanGEO was used for visualization of gene expression in different clinical studies. P and Cox p value < 0.05 was considered to be statistical significance. Results HLA-DPA1 was finally picked out as a hub gene in MM related to hypoxia. MM patients with down-regulated expression of HLA-DPA1 has statistically significantly shorter disease specific survival (DSS) (COX p = 0.005411). Based on the clinical data of GSE47552 dataset, HLA-DPA1 expression showed significantly lower in MM patients than that in healthy donors (HDs) (p = 0.017). Conclusion We identified HLA-DPA1 as a hub gene in MM related to hypoxia. HLA-DPA1 down-regulated expression was associated with MM patients’ poor outcome. Further functional and mechanistic studies are need to investigate HLA-DPA1 as potential therapeutic target.