Prediction of postpartum hemorrhage in pregnant women with immune thrombocytopenia: Development and validation of the MONITOR model in a nationwide multicenter study.

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.

Anticancer activity of Honokiol against lymphoid malignant cells via activation of ROS-JNK and attenuation of Nrf2 and NF-κB.

PURPOSE: To evaluate the effect of Honokiol (HK) in the ROS-JNK pro-apoptotic pathway and NF-κB, Nrf2 anti-apoptotic pathways, in order to seek a possible explanation for its anticancer efficacy. METHODS: The Raji and Molt4 cell lines were utilized for the determination of anticancer activity against lymphoid malignant cells. BALB/C nude mice, weighing 18-20g each and aged 4-5 weeks, were procured from the central animal house facility. For establishing non-Hodgkin lymphoma in BALB/C, the nude mice were subcutaneously administered 1×10(7) Raji cells, suspended in 0.2 mL sterile PBS on the back. The mice were then randomly divided into 3 groups (6 mice in each group). HK cytotoxicity was determined using the colorimetric MTT assay. RESULTS: In colorimetry-based MTT assay, the cytotoxicity of HK was determined at different time intervals, in lymphoid malignant Raji and Molt4 cell lines. HK exhibited prominent cytotoxicity against Raji cell lines with IC50 of 0.092 ± 0.021 µM. In Molt4 cells, the administration of HK caused significant cytotoxicity with IC50 of 0.521 ± 0.115 µM. The treatment of HK caused significant increase in the activity of reactive oxygen species (ROS) in Raji cells at various time intervals. Moreover, the level of NF-κB was significantly reduced in the presence of HK, which could be easily understood by a decreased level of p-65. Furthermore, in the presence of ROS inhibitor NAC (10mM) for 24 hrs, the JNK pathway was markedly activated, together with inhibition of NF-κB activity and a reduced level of Nrf2 expression. To further confirm the in vitro results by in vivo activity, HK was observed to inhibit the proliferation of Raji cells in vivo, which might be attributable to its inhibitory effect against the progression of the tumor (p<0.05). CONCLUSION: The present study suggests that HK causes considerable induction of apoptosis in lymphoid malignant cells, both in vitro and in vivo, whereas the generation of ROS might serve as an underlying mechanism for inducing apoptosis.

BCR-ABL tyrosine kinase inhibitor pharmacophore model derived from a series of phenylaminopyrimidine-based (PAP) derivatives.

To reveal novel insights into the inhibition of BCR-ABL tyrosine kinase, pharmacophore mapping studies were performed for a series of phenylaminopyrimidine-based (PAP) derivatives, including imatinib (Gleevec). A seven-point pharmacophore model with one hydrophobic group (H), two hydrogen bond donors (D) and four aromatic rings (R) was developed using phase (pharmacophore alignment & scoring engine). The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of 0.886 and a survival score of 4.97 for training set molecules. The model showed excellent predictive power, with a correlation coefficient of Q(2)=0.768 for an external test set of ten molecules. The results obtained from our studies provide a valuable tool for designing new lead molecules with potent activity.

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.

Acute Mesenteric Ischemia in Patients with COVID-19: Review of the literature.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global health emergency. In addition to common respiratory symptoms, some patients with COVID-19 infections may experience a range of extra-pulmonary manifestations, such as digestive system involvement. Patients with COVID-19 have been reported to suffer from acute mesenteric ischemia (AMI) that is associated with disease-related severity and mortality. However, in the context of COVID-19, the exact cause of AMI has yet to be clearly defined. This review provides a comprehensive overview of the available data and elucidates the possible underlying mechanisms linking COVID-19 to AMI, in addition to highlighting therapeutic approaches for clinicians. Finally, given the severe global impact of COVID-19, we emphasize the importance of coordinated vaccination programs.

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.

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.

Chronic myelomonocytic leukemia-associated pulmonary alveolar proteinosis: A case report and review of literature.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare condition that can cause progressive symptoms including dyspnea, cough and respiratory insufficiency. Secondary PAP is generally associated with hematological malignancies including chronic myelomonocytic leukemia (CMML). To the best of our knowledge, this is the first reported case of PAP occurring secondary to CMML. CASE SUMMARY: We report the case of a 63-year-old male who presented with a recurrent cough and gradually progressive dyspnea in the absence of fever. Based upon clinical symptoms, computed tomography findings, bone marrow aspiration, flow cytometry studies and cytogenetic analyses, the patient was diagnosed with PAP secondary to CMML. He underwent whole lung lavage in March 2016 to alleviate his dyspnea, after which he began combined chemotherapeutic treatment with decitabine and cytarabine. The patient died in January 2020 as a consequence of severe pulmonary infection. CONCLUSION: This case offers insight regarding the mechanistic basis for PAP secondary to CMML and highlights potential risk factors.

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Acute myeloid leukemia during pregnancy: a single institutional experience with 17 patients and literature review.

Management of acute myeloid leukemia during pregnancy (P-AML) is a challenging endeavor with limited evidence-based information available. To truly achieve the goal of improving P-AML patients, additional evidence-based research is necessary. We retrospectively reviewed cases of 17 patients diagnosed with P-AML, including seven for acute promyelocytic leukemia (APL) from January 2012 to June 2019. Among the non-APL, 90% patients (9/10) ended pregnancy prior to induction chemotherapy. The median intervals between diagnosis and start of chemotherapy were 5 days (range 1-14 days). Four patients elected to delay chemotherapy by more than one week. Of the seven APL patients, six received all-trans retinoic acid (ATRA) before the diagnostic molecular results. Five patients underwent cesarean sections (CS) and all newborns were alive (four preterm and one full-term deliveries). Overall, approximately 94% of the patients (16/17) are currently alive in remission. To treat P-AML patients in a safer manner, balancing the risk of progressing to advanced disease and proceeding with pregnancy is required. We consider a slight delay (less than 14 days) in the termination of pregnancy may not differ the prognosis to patients with non-APL. For APL, patients will benefit from prompt administration of ATRA for highly suspected cases.

Salvage tigecycline in high risk febrile neutropenic patients with hematological malignancies: a prospective multicenter study.

The purpose of this prospective, multi-center study was to examine the efficacy and safety of tigecycline as empirical treatment in neutropenic patients with hematological malignancies who failed to respond to first-line antibiotics. A total of 125 patients with persistent fever (>72 h) despite first-line antibiotics received empirical treatment with tigecycline (loading dose of 100 mg, followed by 50 mg every 12 h). The use of other antimicrobial agents was not restricted. Treatment success rate was 68.0%. Subgroup analysis revealed a success rate of 73.1% in patients with pneumonia and 35.3% in patients with bacteremia. Toxicities were moderate with gastrointestinal symptoms being the main side effects. In conclusion, tigecycline-based antibacterial regimen was a justifiable empirical treatment in febrile neutropenic patients who failed to respond to first-line antibiotics except those with bacteremia. For patients with bacteremia, trials on higher-dose of tigecycline are needed.

[Prognostic Value of Morphology and Hans Classification in Diffuse Large B Cell Lymphoma].

OBJECTIVE: To investigate the prognostic value of morphology and Hans classification in diffuse large B cell lymphoma（DLBCL）. METHODS: Clinical data of 249 patients diagnosed with DLBCL in our hospital and Hangzhou Xixi hospital during Jan 2006 to Dec 2016 were analyzed retrospectively. These patients were classified into 3 groups: immunoblastic variant（IB） group, centroblastic variant（CB） group and others group according to the cell morphology. And DLBCL was also divided into GCB（germinal center B-cell-like）or non-GCB（non-germinal center B-cell-like） group by analyzing the expression of CD10, BCL6 and MUM1 (GCB: CD10 +,BCL6+-,MUM1+-/CD10-,BCL6+,MUM1-；non-GCB：CD10-,BCL6-,MUM1+-/CD10-,BCL6+,MUM1+). RESULTS: The univariate analysis displayed that the age，LDH level，IPI，IB，non-GCB，B-symptoms and rituximab all could influence the OS and EFS, the CR rate of CB subtype patients was significantly higher than that of the patients with IB subtype （68.3% vs 38.9%)(P=0.02）. IB subtype was the in dependent prognostic factor for both EFS and OS in the whole study. In multivariate analysis, IPI and IB were the independent prognostic factors for OS and EFS. IB subtype was also an independent prognostic factor in EFS and OS with or without rituximab. The expression of BCL2 and BCL6 was related with prognosis in R-CHOP, but not in CHOP treated patients. Other markers (CD5, CD10, IRF4/MUM1, HLA-DR and Ki-67 proliferation index) were not of the significant prognostic value for DLBCL. When accepted rituximab, the GCB and non-GCB were not different significantly for prognosis. However, the non-GCB group showed a poor prognosis without using rituximab （EFS P=0.020；OS P=0.020）. Multivariate Cox models showed that OS and EFS were not significantly different between GCB and non-GCB group, however, the IB subtype had a very significantly poor prognosis in OS and EFS (P=0.001, P=0.002). When the analysis was restricted to DLBCL with CB morphology only, no prognostic value was observed in Hans classification. CONCLUSION: The subtype of immunoblast is a major risk factor in patients treated with CHOP or R-CHOP. There is a significant association between the Hans classification and the morphologic subclassification. Results of this study have supplemented the data for the prognostic factor of DLBCL and demonstrated that the cytomorphologic diagnosis can be reproducible.

[Expression of CD30 in Diffuse Large B Cell Lymphoma and Its Clinical Significance].

OBJECTIVE: To evaluate the expression and clinical significance of tumor necrosis factor receptor (TNFR) superfamily protein CD30 in diffuse large B cell lymhoma (DLBCL). METHODS: The CD30 expression, clinical characteristics and prognosis of 63 patients with DLBCL, NOS out of 149 patients with DLBCL admitted in our hospital between January 2008 and December 2012 were analyzed retrospectively. RESULTS: no significant relationship existed between CD30 expression and clinical features, such as age, sex, B symptoms, staging, ECOG PS, LDH level, extranodal site involvement, IPI, GCB or non GCB type, bone marrow involvement. By univariate analysis, the clinical factors associated with general OS and EFS, included CD30, ECOG PS, B symptoms, extranodal site involvement, LDH level, IPI, bone marrow involvement and rituximab. Univariate analysis in GCB DLBCL indicated that CD30 had no significant effect on OS and EFS. However, univariate analysis in non-GCB DLBCL indicated CD30 was associated with longer OS (P=0.037) and showed a tendency of better EFS (P=0.067). In multivariate analysis, IPI and CD30 were independent prognostic factors for OS (IPI: P=0.000, 95%CI 0.042-0.374, CD30: P=0.044, 95%CI 1.055-60.613), and IPI also was independent prognostic factors for EFS (P=0.000, 95%CI 0.040-0.360). CD30+ and DLBCL have a tendency of better EFS (P=0.050, 95%CI 0.996-56.501). CONCLUSION: CD30 expression level correlates with the prognosis of DLBCL and has a certain clinical value, which may be a new prognostic index of DLBCL.

[Action mechanism of lenalidomide in hematological malignancies - review].

Immunomodulatory drug lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide is a 4-amino-glutamyl analogue of thalidomide that has emerged as a drug with activity against various hematological and solid malignancies. It is approved by FDA in USA for clinical use in myelodysplastic syndromes with deletion of chromosome 5q and multiple myeloma. Studies have shown that lenalidomide exert anti-tumor activity probably by various mechanisms in hematologic malignancies, such as immunomodulation, anti-angiogenesis and effects on signal transduction. In this article, the progresses of study on these problems are reviewed.

[Expression and activity of membrane surface tissue factor in peripheral blood cells of patients with cerebral infarction].

This study was aimed to investigate the expression and activity of membrane surface tissue factor (TF) of monocytes and platelets in peripheral blood cells from patients with cerebral infarction and their clinical significance. The TF expressions in monocytes and platelets from 25 patients with cerebral infarction were detected by flow cytometry, the TF activity was detected by chromogenic reaction method, and compared with 24 normal people used as control. The results showed that the TF expressions of monocytes and platelets in peripheral blood cells from patients with cerebral infarction were significantly higher than that in normal controls (p<0.01), and TF activity was also higher in patients than that in controls (p<0.01). In conclusion, the expression and activity of membrane surface in patients with cerebral infarction were enhanced, the hematocyte-derived tissue factor as a trigger in coagulation pathway is involved in pathological thrombosis in patients with cerebral infarction.