Multifaceted role of GCN2 in tumor adaptation and therapeutic targeting.

Tumor cells voraciously consume nutrients from their environment to facilitate rapid proliferation, necessitating effective strategies to manage nutrient scarcity during tumor growth and progression. A pivotal regulatory mechanism in this context is the Integrated Stress Response (ISR), which ensures cellular homeostasis under conditions such as endoplasmic reticulum stress, the unfolded protein response, and nutrient deprivation. Within the ISR framework, the kinase GCN2 is critical, orchestrating a myriad of cellular processes including the inhibition of protein synthesis, the enhancement of amino acid transport, autophagy initiation, and angiogenesis. These processes collectively enable tumor survival and adaptation under nutrient-limited conditions. Furthermore, GCN2-mediated pathways may induce apoptosis, a property exploited by specific therapeutic agents. Leveraging extensive datasets from TCGA, GEO, and GTEx projects, we conducted a pan-cancer analysis to investigate the prognostic significance of GCN2 expression across diverse cancer types. Our analysis indicates that GCN2 expression significantly varies and correlates with both adverse and favorable prognoses depending on the type of cancer, illustrating its complex role in tumorigenesis. Importantly, GCN2 also modulates the tumor immune microenvironment, influencing immune checkpoint expression and the functionality of immune cells, thereby affecting immunotherapy outcomes. This study highlights the potential of targeting GCN2 with specific inhibitors, as evidenced by their efficacy in preclinical models to augment treatment responses and combat resistance in oncology. These findings advocate for a deeper exploration of GCN2's multifaceted roles, which could pave the way for novel targeted therapies in cancer treatment, aiming to improve clinical outcomes.

Establishment and verification of a TME prognosis scoring model based on the acute myeloid leukemia single-cell transcriptome.

The tumor microenvironment (TME) plays an important role in the occurrence and progression of Acute Myeloid Leukemia (AML). Single-cell sequencing has enabled researchers to explore the correlation between TME subgroups and tumor prognosis, distinguish the existence of drug-resistant subgroups of tumor cells, and unravel the complexity of the AML cellular heterogeneity. We used bone marrow immune cell enrichment analysis from public databases to screen prognostic genes, construct prognostic models, and validate their prognostic significance on independent external datasets and patient samples. A total of 18,251 single cells were obtained to establish prognostic scoring models for 10 key genes including CCL5, ETLS2, and IL2RA.The AML cases were divided into two groups: high-risk and low-risk. The low-risk group exhibited a higher survival rate than the high-risk group. The areas under curves (AUC) of 1-, 3- and 5-year survival curves in the TCGA and GEO training sets were greater than 0.8 and 0.6, respectively, indicating effective prediction. The model's prognostic efficacy was confirmed across multiple validation sets. It demonstrated increased expression of ETS2, CCL5, and IL2RA in AML samples compared to controls, which was associated with decreased overall survival (OS). This prognostic scoring model based on tumor immune infiltration provides a reference for developing novel treatment strategies for recurrent/refractory AML.

A comprehensive prognostic and immune infiltration analysis of UBA1 in pan-cancer: A computational analysis and in vitro experiments.

Ubiquitin like modifier activating enzyme 1 (UBA1) plays an important role in immune regulation and cellular function. However, the functional mechanism and role of UBA1 in pan-cancer have not been fully elucidated and its value in haematological tumours (diffuse large B cell lymphoma (DLBC/DLBCL) and acute myeloid leukaemia (AML/LAML)) has not been explored. We conducted a comprehensive analysis of the functional mechanism and role of UBA1 in pan-cancer using multiple databases, including differential expression analysis, clinical pathological staging analysis, prognosis analysis and immune analysis. Then, we confirmed the function of UBA1 in haematological tumours through cell experiments. The results showed that the expression of UBA1 was significantly increased in most cancers and the differential expression of UBA1 was mainly concentrated in digestive tumours, haematological tumours and brain tumours. Moreover, the high expression of UBA1 had poor prognosis in most tumours, which may be related to its involvement in various cancer-related pathways such as cell cycle, as well as its methylation level, protein phosphorylation level, immune cell infiltration and immune therapy response. Cell experiments have confirmed that UBA1 can significantly regulate the cycle progression and apoptosis of DLBCL cells and AML cells. Therefore, UBA1 may be a potential therapeutic target for haematological tumours. In summary, our study not only comprehensively analysed the functional mechanisms and clinical value of UBA1 in pan-cancer, but also validated for the first time the regulatory role of UBA1 in haematological tumours.

SNCA is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients.

Cuprotosis related genes (CRGs) have been proved to be potential therapeutic targets for coronavirus disease 2019 (COVID-19) and cancer, but their immune and molecular mechanisms in COVID-19 infection in Diffuse Large B-cell Lymphoma (DLBC/DLBCL) patients are rarely reported. Our research goal is first to screen the key CRGs in COVID-19 through univariate analysis, machine learning and clinical samples. Secondly, we determined the expression and prognostic role of key CRGs in DLBCL through pan-cancer analysis. We validated the expression levels and prognosis using multiple datasets and independent clinical samples and validated the functional role of key CRGs in DLBCL through cell experiments. Finally, we validated the expression levels of CRGs in COVID-19 infected DLBCL patients samples and analyzed their common pathways in COVID-19 and DLBCL. The results show that synuclein-alpha (SNCA) is the common key differential gene of COVID-19 and DLBCL. DLBCL cells confirm that high expression of SNCA can significantly promote cell apoptosis and significantly inhibit the cycle progression of DLBCL. High expression of SNCA can regulate the binding of major histocompatibility complexes (MHCs) and T cell receptor (TCR) by regulating immune infiltration of Dendritic cells, effectively enhancing T cell-mediated anti-tumor immunity and clearing cancer cells. In conclusion, SNCA may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our study provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL patients.

Zuberitamab, an innovative anti-CD20 monoclonal antibody, for patients with primary immune thrombocytopenia in China: a randomized, double-blind, placebo-controlled, phase 2 study.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease, and rituximab (RTX) induces long-term effect as second-line treatments. Zuberitamab is an innovative anti-CD20 monoclonal antibody, which was first developed in China and launched in diffuse large B lymphoma. This study aimed to investigate the safety, efficacy, and anticipated therapeutic dose of zuberitamab in Chinese ITP patients. Methods: This randomised, double-blind, placebo-controlled, phase 2 study was conducted at 26 hospitals in China. Eligible patients were aged 18-70 years, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous treatment and had a pre-treatment platelet count of <30 × 109/L. Patients randomly received zuberitamab in a dose escalation (100/300/600 mg) or placebo once-weekly for 4 weeks and followed up to 24 weeks. The primary endpoint is the proportion of patients with a platelet count ≥50 × 109/L at week 8. Secondary endpoints include the proportion of patients with platelet counts ≥50 × 109/L or ≥100 × 109/L at least once within week 12/24, the proportion of patients experiencing platelets increased twice more than baseline as well as ≥30 × 109/L at least once during the treatment. Adverse events, pharmacokinetic, B cell depletion and immunogenicity were also assessed. This study is registered with https://www.chictr.org.cn/as ChiCTR2100050513. Findings: From October 2021 to March 2023, 50 patients were screened for eligibility, of whom 32 patients were enrolled and randomly assigned to placebo (n = 4), zuberitamab 100 mg (n = 10), 300 mg (n = 8) and 600 mg (n = 10) groups. The primary endpoint (PLT ≥50 × 109/L at week 8) was achieved by 40% of patients in the 100 mg group, while none in the other groups. Within 12 weeks, the proportions of patients in each treatment group achieving at least one instance of platelet count ≥50 × 109/L or ≥100 × 109/L or an increase twice more than baseline as well as ≥30 × 109/L were (70%, 38%, 50%), (60%, 13%, 30%), and (80%, 50%, 70%) in zuberitamab 100/300/600 mg groups, respectively. By week 24, the proportions of patients achieving these secondary endpoints remained relatively stable or showed a mild increase of around 10%. The anticipated therapeutic dose of zuberitamab was 100 mg. The plasma concentration of zuberitamab showed an increasing trend with dose (100 mg-600 mg) and linear pharmacokinetic behavior. CD19+ B cells and CD20+ B lymphocytes rapidly declined to 0% within one week and consistently maintained reduced levels throughout the entire treatment phase in three groups. Adverse events occurred in all patients with most of them were mild to moderate, no severe infections occurred. A slight decrease in immunoglobulins was observed in the 600 mg group, but gradually recovered at week 20. Three patients (2 in 100 mg and 1 in 600 mg group) were tested positive for anti-zuberitamab antibodies. We also observed that women, disease duration <12 months, and MAIPA + patients may have higher response rates. Interpretation: This study preliminarily confirmed that 100 mg zuberitamab was safe and effective in treating ITP and was recommended to support further investigation. Funding: National Natural Science Foundation of China and Zhejiang Bioray Biopharmaceutical Co. Ltd.

DLD is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients.

Since the discovery of copper induces cell death(cuprotosis) in 2022, it has been one of the biggest research hotspots. cuprotosis related genes (CRGs) has been demonstrated to be a potential therapeutic target for cancer, however, the molecular mechanism of CRGs in coronavirus disease 2019 (COVID-19) infected in DLBCL patients has not been reported yet. Therefore, our research objective is first to elucidate the mechanism and role of CRGs in COVID-19. Secondly, we conducted univariate and multivariate analysis and machine learning to screen for CRGs with common expression differences in COVID-19 and DLBCL. Finally, the functional role and immune mechanism of genes in DLBCL were confirmed through cell experiments and immune analysis. The research results show that CRGs play an important role in the occurrence and development of COVID-19. Univariate analysis and machine learning confirm that dihydrolipoamide dehydrogenase (DLD) is the common key gene of COVID-19 and DLBCL. Inhibiting the expression of DLD can significantly inhibit the cycle progression and promote cell apoptosis of DLBCL cells and can target positive regulation of Lysine-specific demethylase 1 (LSD1, also known as KDM1A) to inhibit the proliferation of DLBCL cells and promote cell apoptosis. The immune analysis results show that high-expression of DLD may reduce T cell-mediated anti-tumor immunity by regulating immune infiltration of CD8 + T cells and positively regulating immune checkpoints LAG3 and CD276. Reducing the expression of DLD can effectively enhance T cell-mediated anti-tumor immunity, thereby clearing cancer cells and preventing cancer growth. In conclusion, DLD may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our research provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL.

GPX4 is a potential diagnostic and therapeutic biomarker associated with diffuse large B lymphoma cell proliferation and B cell immune infiltration.

At present, GPX4's role in the occurrence and development of diffuse large B lymphoma (DLBCL) is rarely reported. This study's purpose is to explore GPX4's significance in the diagnosis, treatment, and pathological mechanisms of DLBCL. The TIMER 2.0, GEPIA, and GEO databases were used to analyze GPX4's expression levels in DLBCL tissue, peripheral blood, and single cells, and evaluate its potential performance as a therapeutic and diagnostic marker. Cell experiments validate GPX4's role in DLBCL cells. And revealed the potential mechanism of GPX4's action from three aspects: immunity, pathogenic gene expression, and protein interaction. The results indicate that GPX4 can be used as a biomarker for treatment and diagnosis (FC > 1.5, P < 0.05, AUC>0.8, KM-P value < 0.05). In single cell data, GPX4 also showed high expression in immune cells. Besides, cell experiments have confirmed that GPX4's high expression can inhibit DLBCL cells' proliferation. Meanwhile, we found a negative correlation between GPX4 and the 16 core DLBCL's pathogenic genes, and a significant negative correlation with immune B cell infiltration. In summary, GPX4 can serve as a potential therapeutic and diagnostic marker for DLBCL. GPX4's high expression can lead to a good prognosis in DLBCL patients, which may be related to its inhibition of cancer cell proliferation, high expression of key pathogenic genes, and infiltration of immune B cells.

Allo-HSCT with TBI-based preconditioning for hepatosplenic T-cell lymphoma: two case reports and systematic review of literature.

Hepatosplenic T cell lymphoma (HSTCL) is a particularly difficult-to-treat form of lymphoma, with many patients exhibiting primary resistance to chemotherapy. At present, no effective strategy for treating relapsed and refractory HSTCL has been established, with treatment being hampered by questions of how best to overcome chemoresistance to allow patients to attain more durable therapeutic benefits. While there have been marked advances in immunotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the primary approaches to curing HSTCL. Of patients who undergo immunochemotherapeutic treatment, many are resistant to conventional chemotherapeutic drugs yet remain sensitive to radiotherapy. We selected to employ a transplant pretreatment regimen consisting of total -body irradiation (TBI) and administered this regimen to two patients with HSTCL. Both patients achieved complete remission (CR) after transplantation, demonstrating extended periods without disease recurrence. We systematic reviewed previously published instances involving allo-HSCT in patients with HSTCL. We have found a total of 67 patients who have received allo-HSCT. In general, age<45 and the status of CR at HSCT may have a more favorable prognosis. Although the impact of TBI on prognosis was not found to be substantial, patients in the TBI group had higher 3-year overall survival (66.7% vs. 71.1%) and 5-year overall survival (58.4% vs. 71.1%) compared to patients in the non-TBI group. In addition, the relapse rate of the TBI group is approximately half that of the non-TBI group. This regimen is well tolerated and associated with low recurrence rates or complications, suggesting that it represents a viable pretreatment regimen for young HSTCL patients undergoing allogeneic HSCT.

ST11 KPC-2-Producing Klebsiella pneumoniae Isolated from Patient with Acute Myelocytic Leukemia.

Background: The emergence of the ST11-CRKP (ST11-CRKP) strain is expected to become a serious public health problem in China. As one of the most serious complications in patients with acute myeloid lymphoma, infections can cause systemic infection and life-threatening sepsis, seriously affecting the morbidity, mortality, and quality of life of patients. Thus, ST11-CRKP infections in patients with acute myeloid lymphoma are worthy of our attention. Aim: To investigate the occurrence and genetic characteristics of the ST11-CRKP from a patient with acute myeloid lymphoma. Methods: Species identification was determined by MALDI-TOF MS. Antimicrobial susceptibility testing (AST) was conducted by VITEK 2 system with AST-N335 panel. Whole-genome sequencing was performed on the Illumina NovaSeq 6000 platform. Phylogenetic analyses were performed using Snippy based on the core-genome SNPs. Findings: S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot and Whole-genome analysis indicated blaKPC-2 genes were located on plasmids with a conserved genetic environment. Moreover, the eight ST11-CRKP strains carry a variety of antimicrobial resistance genes (ARGs) and virulence factors. The ability of biofilm formation of eight strains was verified by a crystal violet assay. Core genome single-nucleotide polymorphism (cgSNP) analysis suggesting a possible bacterial translocation event. Conclusion: We performed a comprehensive analysis of ST11-CRKP strains from a patient with acute myelocytic leukemia. Our study emphasized the need for continuous surveillance of ST11-CRKP in the clinic especially in the immunocompromised population.

Application of recombinant human thrombopoietin in pregnant women with immune thrombocytopenia: a single-center experience of four patients and literature review.

The management of pregnant women with immune thrombocytopenia who fail to respond to corticosteroids and intravenous immunoglobulin is an intractable clinical challenge because of the limited availability of evidence-based information. Recombinant human thrombopoietin (rhTPO) is recommended for refractory immune thrombocytopenia (ITP). To date, however, few studies have investigated rhTPO treatment during pregnancy. We retrospectively reviewed four cases who were diagnosed with ITP and treated with rhTPO during pregnancy in our center from January 2015 to June 2020. Of the four cases, two (50%) responded to rhTPO treatment. No adverse events were noted in the newborns. Our findings indicate that rhTPO treatment is safe for patients with refractory gestational ITP, and that subcutaneous injection is a convenient delivery method that does not lead to adverse events. Thus, rhTPO may be a viable alternative treatment option for patients with refractory gestational ITP who do not respond to first-line therapies.

Andrographolide induced ferroptosis in multiple myeloma cells by regulating the P38/Nrf2/HO-1 pathway.

Andrographis paniculata is used as a functional food in Asia. Andrographolide (Andro), a diterpene lactone isolated from Andrographis paniculata, has been reported to have potent anticancer activity. Multiple myeloma (MM), the second most common malignant tumor in hematology, is incurable. Ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation, has shown potential in the treatment of various cancers. However, previous studies have not demonstrated whether Andro inhibits the development of MM via ferroptosis or any other mechanism. In the present study, we observed that Andro induced cell death, G0/G1 cell cycle arrest and evoked oxidative stress in MM cells. Interestingly, these phenomena were accompanied by increases in intracellular and mitochondrial Fe2+ and lipid peroxidation levels. Furthermore, treatment with ferroptosis inhibitors rescued Andro-induced cell death, which indicated that ferroptosis contributed to this phenomenon. Mechanistic examination showed that Andro may block the Nrf2/HO-1 signaling pathway by activating P38, thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in MM cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM.

A first case of successful using of ibrutinib in treating paraneoplastic pemphigus related bronchiolitis obliterans concurrent with CLL.

Paraneoplastic pemphigus (PNP) is a rare life-threatening disease which always associated with an underlying neoplasm. Tumor-related PNP most commonly precedes the detection of a hematological malignancy, with some cases seen during disease remission following cytotoxic drug therapy or radiotherapy. The lung is the most frequently-involved site in PNP, second only to the eyes, and involvement is seen in 59.2% to 92.8% of PNP cases. Bronchiolitis obliterans (BO) is the end stage of respiratory involvement and is regarded as life-threatening. The key point in treatment of PNP is to control the associated underlying hematologic neoplasia. High-dose systemic corticosteroids combined with other immunosuppressants are considered the first line of treatment. Other therapies that have shown beneficial effects include plasmapheresis, intravenous immunogloblin (IVIG), and more recently, daclizumab, alemtuzumab, and rituximab. There is no effective treatment for BO with PNP, and suppression of the cellular immune response may be necessary. Patients with PNP-BO associated with lymphoma mostly die within approximately 1 year. Herein, we reported a patient who diagnosed with PNP-BO concurrent with chronic lymphocytic leukemia. He was successful treated with ibrutinib and had achieved the longest survival which suggested that ibrutinib may be the best treatment choice for such patient.

Lichen myxedematosus associated with monoclonal gammopathy of undetermined significance: A case report and literature review.

Lichen myxedematosus (LM) is an idiopathic cutaneous mucinosis disorder, and monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic plasma cell disease with a monoclonal increase in globulin. Patients with LM combined with monoclonal gammopathy are normally diagnosed with scleromyxedema. However, we report a case of generalized papules combined with MGUS in a 78-year-old man who was eventually diagnosed with atypical or intermediate forms of LM because it only involved the skin, and the pathological type was not consistent with scleromyxedema. Few cases of atypical or intermediate forms of LM have been reported, so the course of atypical or intermediate forms of LM is unpredictable. We report the diagnosis and treatment of a case of atypical forms of LM to discuss the current understanding of the disease, hoping to provide a reference for clinical research on this disease.

Recombinant human thrombopoietin (rhTPO) of different dosing regimens for refractory/relapsed primary immune thrombocytopenia: a multicenter, randomized controlled trial and pharmacokinetics study.

Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count ≤30 × 109/L or >30 × 109/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 × 109/L, interquartile range [IQR] 23.0-295.0 × 109/L), followed by the 30000-U QOD group (57.5 × 109/L, IQR 9.0-190.0 × 109/L) (ANCOVA P < .001; P = .266 with baseline count as a covariate). The TRR on day 14 was also the highest in the 15000-U QD group (63.2%), followed by the 30000-U QOD group (59.7%). The rate of grade 3 and above adverse events did not differ among the four groups. There were no new safety concerns. All 4 regimens are safe and well-tolerated. The 30000-U QOD regimen is practically indistinguishable in efficacy to the 15000-U QD regimen.

What is the context? Relative thrombopoietin deficiency is implicated in primary immune thrombocytopenia (ITP), which is characterized by increased platelet destruction and impaired megakaryopoiesis.Patients who are innately unresponsive to or have relapsed after glucocorticoid treatment have limited treatment options.Recombinant human thrombopoietin (rhTPO) improves treatment response of primary ITP patients when added to high-dose dexamethasone.What is new? This trial sought to identify an optimal dosing regimen of rhTPO for patients who had failed or relapsed after glucocorticoid therapy.Of the 4 regimens, once daily 15000 U rhTPO for 14 injections yielded the greatest median increase in platelet count (167.5 × 10⁹/L) from baseline and attained the highest total response rate on day 14 (63.2%).30000 U rhTPO once every other day for 7 injections was effective in rapidly increasing platelet counts in the first 7 days.All 4 regimens were safe and well-tolerated.What is the impact? The 30000 U rhTPO once every other day regimen may offer an effective and safe regimen with less frequent injections, but future trials with longer follow-up are needed.

Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagy.

Multiple myeloma (MM) is an incurable hematological malignancy that lacks effective therapeutic interventions. Ferroptosis is a newly discovered form of cell death that has shown great potential for MM therapy. As a proteasome inhibitor and necroptosis inducer, shikonin (SHK) performs dual functions in MM cells. However, whether SHK inhibits the development of MM via ferroptosis or any other mechanism remains elusive. Here, we provide evidence that SHK treatment was capable of inducing ferroptosis and immunogenic cell death (ICD) in MM. The results showed that SHK treatment induced lactate dehydrogenase release, triggered cell death, evoked oxidative stress, and enhanced ferrous iron and lipid peroxidation levels. Furthermore, treatment with ferroptosis inhibitors reversed SHK-induced cell death, which indicated that ferroptosis contributed to this phenomenon. Meanwhile, ferroptosis was accompanied by the extracellular release of Adenosine 5'-triphosphate (ATP) and High mobility group protein B1 (HMGB1), which are characteristics of ICD. Further investigation showed that glutamic-oxaloacetic transaminase 1 (GOT1) acted as a critical mediator of SHK-induced ferroptosis by promoting ferritinophagy. In conclusion, our findings suggest that SHK exerts ferroptotic effects on MM by regulating GOT1-mediated ferritinophagy. Thus, SHK is a potential therapeutic agent for MM.

Tumor immune cell infiltration score based model predicts prognosis in multiple myeloma.

The tumor microenvironment plays an important role in various processes, including tumorigenesis, cancer progression, and metastasis. Immune signatures have been identified and verified for use in diagnosis and prognosis prediction. We used single-sample Gene Set Enrichment Analysis to evaluate tumor immune cell infiltration score (TIICs) and verify their prognostic significance in both training and validation cohorts and using this information to build a prognostic model. A total of 1281 samples were obtained for further evaluation of the immune enrichment scores of 28 immune cells, showing that Th17 cell contributed most significantly to survival. Using the median TIICs as a cutoff to divide the samples into two groups, we found that the high-TIICs group was associated with favorable outcomes in both the training and validation sets. We then constructed a prognostic model to predict the 6, 8, and 10-year survival outcomes. Further analysis showed that immune score and tumor purity were higher in the high-TIICs group, while the matrix score was lower in this group. Forty-two differentially expressed genes were identified between the two groups. This new prognostic model based on immune cell infiltration indicates the potential for TIICs in predicting prognosis and as targets for treatment.

Fatal left atrial air embolism as a complication of percutaneous transthoracic lung biopsy: A case report.

BACKGROUND: Computed tomography (CT)-guided percutaneous lung biopsy is a common protocol in the context of diagnostic thoracic oncology, but entails a risk of complications including systematic air embolism (SAE). While SAE is often well tolerated, it can be difficult to treat and may result in rapid mortality in some cases. CASE SUMMARY: We report a rare case of left atrial SAE in a 71-year-old woman who underwent a CT-guided lung biopsy of a pulmonary nodule in the posterior basal segment of the right lower lobe. Shortly following needle extraction, she experienced a mild cough, hemoptysis, rapid-onset unconsciousness, and cardiopulmonary arrest. Cardiopulmonary resuscitation was immediately performed, but the patient died 40 min after the procedure. A closer review of collected CT scans revealed the presence of a large volume of air within the left atrium. CONCLUSION: Although SAE is generally well tolerated and asymptomatic, interventional radiologists must be aware of the risk of fatal outcomes and establish appropriate emergency management protocols. In this report, the characteristics, mechanisms, and treatment recommendations associated with SAE are discussed in an effort to improve the survival of affected patients.

A Novel Prognostic Scoring Model for Myelodysplastic Syndrome Patients With SF3B1 Mutation.

The outcomes of myelodysplastic syndrome (MDS) patients with SF3B1 mutation, despite identified as a favorable prognostic biomarker, are variable. To comprehend the heterogeneity in clinical characteristics and outcomes, we reviewed 140 MDS patients with SF3B1 mutation in Zhejiang province of China. Seventy-three (52.1%) patients diagnosed as MDS with ring sideroblasts (MDS-RS) following the 2016 World Health Organization (WHO) classification and 118 (84.3%) patients belonged to lower risk following the revised International Prognostic Scoring System (IPSS-R). Although clonal hematopoiesis-associated mutations containing TET2, ASXL1 and DNMT3A were the most frequent co-mutant genes in these patients, RUNX1, EZH2, NF1 and KRAS/NRAS mutations had significant effects on overall survival (OS). Based on that we developed a risk scoring model as IPSS-R×0.4+RUNX1×1.1+EZH2×0.6+RAS×0.9+NF1×1.6. Patients were categorized into two subgroups: low-risk (L-R, score <= 1.4) group and high risk (H-R, score > 1.4) group. The 3-year OS for the L-R and H-R groups was 91.88% (95% CI, 83.27%-100%) and 38.14% (95% CI, 24.08%-60.40%), respectively (P<0.001). This proposed model distinctly outperformed the widely used IPSS-R. In summary, we constructed and validated a personalized prediction model of MDS patients with SF3B1 mutation that can better predict the survival of these patients.

Prednisone plus IVIg compared with prednisone or IVIg for immune thrombocytopenia in pregnancy: a national retrospective cohort study.

Background: The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP). Methods: Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone. Results: Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8-195 days), whereas that in the combination group was 14 days (range, 6-85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone. Conclusion: These findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.