[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Pulmonary nuclear protein of the testis midline carcinoma:a case report].

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare malignant epithelial tumor that typically occurs in the midline regions such as the head, neck, and mediastinum. This tumor is characterized by rapid development, aggressive growth, and strong invasiveness. Due to its short duration, most patients are diagnosed at advanced stages, often leading to rapid mortality. Although reports on pulmonary NUT carcinoma are uncommon, this article presents a case of pulmonary NUT carcinoma in which the patient repeatedly expectorated bronchial casts and tumor tissue. Additionally, a comprehensive review of relevant literature from recent years is provided to enhance understanding of this disease.

[Application and clinical significance of intercellular proximity labeling technique in chronic myelogenous leukemia].

Objective: This study aimed to explore the application of interaction-dependent fucosyl-biotinylation (FucoID), a chemical biology-based proximity labeling technique, in capturing tumor antigen-specific T cells and its clinical value in chronic myelogenous leukemia (CML) . Methods: Flow cytometry and fluorescence microscopy were employed to evaluate the experimental parameters for FucoID in CML. Peripheral blood samples were obtained from 14 newly diagnosed CML patients in the chronic phase. These samples underwent flow cytometry-based sorting and were subsequently labeled with FucoID to facilitate the isolation of tumor cells and T cells, followed by the immunophenotypic identification of tumor antigen-specific T cells. Finally, the diagnostic and therapeutic potential of FucoID in CML was assessed. Results: Initially, the experimental parameters for FucoID in CML were established. The proportion of CD3(+) T cells in patients was (8.96±6.47) %, exhibiting a marked decrease compared with that in healthy individuals at (38.89±22.62) %. The proportion of tumor-specific antigen-reactive T cells was (3.34±4.49) %, which demonstrated interpatient variability. In addition, the proportion of tumor-specific antigen-active T cells in CD4(+) T cells was (3.95±1.72) %, which was generally lower than the proportion in CD8(+) T cells at (5.68±2.18) %. Compared with those in tumor-specific antigen-nonreactive T cells, CCR7(-)CD45RA(-) effector memory T cells and CCR7(-)CD45RA(+) effector T cells were highly enriched in tumor-specific antigen-reactive T cells. Moreover, the intensity of tumor immune reactivity in patients exhibited a significant correlation with white blood cell count (WBC) and hemoglobin (HGB) levels in peripheral blood, while no such correlation was observed with other clinical baseline characteristics. Conclusion: The combination of FucoID and flow cytometry enables the rapid identification and isolation of tumor antigen-specific T cells in CML. The successful application of this method in CML and the implications of our findings suggest its potential clinical value in the field of hematologic malignancies.

[The consistency of skeletal muscle mass measured by CT at L1 and L3 levels and the correlation of skeletal muscle density at L1 level with prognosis in dialysis patients].

Objective: To investigate the consistency of skeletal muscle mass by CT at 1st lumbar vertebrae (L1) and 3rd lumbar vertebrae (L3) levels and the correlation of skeletal muscle density (SMD) at L1 level with prognosis in dialysis patients. Methods: A total of 1 020 patients who underwent initial dialysis and had CT examination data in four centers (Zhongda Hospital Affiliated to Southeast University, the Third Affiliated Hospital of Soochow University, Taizhou People's Hospital Affiliated to Nanjing Medical University and the Affiliated Hospital of Yangzhou University) from January 2014 to December 2019 were retrospectively collected. The skeletal muscle index (SMI) and SMD at L1 and L3 CT images were measured and calculated in patients with both L1 and L3 level CT images. The consistency of SMI and SMD at L1 and L3 levels was analyzed, and the cut-off value of SMI and SMD at L1 level for predicting all-cause mortality and their correlation with the prognosis of dialysis patients were studied. Cox regression model was used to analyze the risk factors for all-cause death and cardiac death. Results: A total of 383 patients had both L1 and L3 level images, including 233 males and 150 females. The average SMD value of 16 samples (4.2%) exceeded the 95% consistency limit range (-8.71 to 7.75 HU), and the average SMI value of 15 samples (3.9%) exceeded the 95% consistency limit range (-20.45 to 9.53 HU). The optimal cut-off value of SMD at L1 level for predicting all-cause mortality was 36.46 HU and the area under curve (AUC) of receiver operating characteristic (ROC) curve was 0.658 (95%CI: 0.596-0.721, P<0.001), with the sensitivity and specificity of 83.8% and 57.5%, respectively. SMI at L1 level was not significantly associated with all-cause mortality (P=0.299). Multivariate Cox regression analysis showed that low SMD at L1 level was associated with all-cause mortality (HR=2.861, 95%CI: 1.576-5.193, P=0.001) and cardiac death (HR=3.771, 95%CI:1.462-9.724, P=0.006). Conclusions: SMD at L1 levelis consistent with SMD at L3 level and can be used to evaluate muscle mass. Low SMD is a risk factor for mortality in dialysis patients.

[Exploration and expectation of magnetic resonance imaging in the evaluation of prostate cancer].

With the progress of imaging technology, magnetic resonance imaging (MRI) has become the preferred imaging method for prostate cancer due to its excellent soft tissue resolution and the capability of multiparametric and multi-planar imaging. This paper briefly describes the current application and research progress of MRI in the preoperative qualitative diagnosis, staging assessment and postoperative recurrence monitoring of prostate cancer. The purpose is to deepen the understanding of clinicians and radiologists on the value of MRI in prostate cancer, and to promote the exploration of MRI in the management of prostate cancer.

[Diagnostic value of multiparametric MRI-based models in the assessment of extra-prostatic extension of prostate cancer].

Objective: To evaluate the diagnostic value of multiparametric magnetic resonance imaging (mpMRI) based models in the assessment of extra-prostatic extension (EPE) of prostate cancer. Methods: This retrospective study included 168 consecutive men with prostate cancers [aged 48 to 82 (66.6±6.8) years] who underwent radical prostatectomy and preoperative mpMRI examinations at the First Medical Center of the PLA General Hospital from January 2021 to February 2022. According to European Society of Urogenital Radiology (ESUR) score, EPE grade and mEPE score, all cases were independently evaluated by two radiologists, with disagreement reviewed by a senior radiologist as the final result. The diagnostic performance of each MRI-based model for pathologic EPE prediction was assessed using receiver operating characteristic curve (ROC), and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. The weighted Kappa test was used to evaluate the inter-reader agreement of each MRI-based model. Results: A total of 62 (36.9%) prostate cancer patients had pathologic confirmed EPE after radical prostatectomy. The AUC of ESUR score, EPE grade and mEPE score for predicting pathologic EPE were 0.836 (95%CI: 0.771-0.888), 0.834 (95%CI: 0.769-0.887) and 0.785 (95%CI: 0.715-0.844), respectively. The AUC of ESUR score and EPE grade were both superior to that of mEPE score with significant differences (all P<0.05), while there was no significant difference between the ESUR score and EPE grade models (P=0.900). EPE grading and mEPE score had good inter-reader consistency, with weighted Kappa values of 0.65 (95%CI: 0.56-0.74) and 0.74 (95%CI: 0.64-0.84), respectively. The inter-reader consistency of ESUR score was moderate, and the weighted Kappa value was 0.52 (95%CI: 0.40-0.63). Conclusion: All MRI-based models showed good preoperative diagnostic value in predicting EPE, among which the EPE grade resulted in more reliable performance with substantial inter-reader agreement.

Retraction Note: MicroRNA-375 accelerates the invasion and migration of colorectal cancer through targeting RECK.

The article "MicroRNA-375 accelerates the invasion and migration of colorectal cancer through targeting RECK", by L.-J. Wei, D.-M. Bai, Z.-Y. Wang, B.-C. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (11): 4738-4745-DOI: 10.26355/eurrev_201906_18055-PMID: 31210300 has been retracted by the authors for the following reasons: This paper has been questioned on PubPeer (https://pubpeer.com/publications/0E5B55962B277F3D0ABBC0451DAAB3). In particular, concerns were raised about Figure 3 and Table I. Unfortunately, the authors are not able to confirm nor deny this concern as they did not find the primary data for figures. The authors decided to study this experiment again to deliver more precise results. After consultation among the authors, in line with the rigorous attitude towards scientific research, authors agreed that it was necessary to withdraw the article and make further research and improvement. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18055.

[Value of clear cell likelihood score in differentiation between renal oncocytoma and clear cell renal cell carcinoma].

Objective: To evaluate the value of clear cell likelihood score (ccLS) in identifying renal oncocytoma (RO) and clear cell renal cell carcinoma (ccRCC). Methods: Retrospective data of pathologically confirmed 43 RO patients [24 men and 19 women, aged 22-77 (54±14) years] between February 2008 and September 2021 and 43 ccRCC patients [30 men and 13 women, aged 29-78 (56±12) years] between May and July 2021 were consecutively included in the department of radiology, Chinese PLA General Hospital. Two radiologists used ccLS to assess each case independently, and disagreements were resolved by consensus. The ability of ccLS to identify RO and ccRCC was examined by the receiver operating characteristic (ROC) curve which identified the best optimal diagnostic cut-off values, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Results: The mean tumor diameter was 3.8 cm in RO patients and 3.7 cm in ccRCC patients. Central scar and segmental enhancement inversion (SEI) were more frequently observed in the RO group compared to the ccRCC group [53.5% (23∶43) versus 11.6% (5∶43) and 41.9% (18∶43) versus 7.0% (3∶43), respectively], with statistical differences (P<0.001). The ccLS scores in the RO group ranged from 1 to 4, while 79.0% of the cases were 3. The ccLS scores in the ccRCC group ranged from 2 to 5, while 72% of the cases were 4. The scores of the two groups were statistically different (P<0.001). The ccLS showed the best performance when the threshold was 4 according to the ROC curve. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of ccLS for distinguishing RO from ccRCC were 83.7%, 90.7%, 87.2%, 90.0%, and 84.8%, respectively, and the area under the ROC curve value was 0.879. Conclusion: The ccLS has credible sensitivity and specificity in differentiating renal oncocytoma from clear cell carcinoma, which may be helpful for the preoperative diagnosis.

[Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study].

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

[Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study].

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

[Clinical and genetic characteristics of patients with newly diagnosed acute promyelocytic leukemia: a single-center retrospective of 790 cases].

Objective: To retrospectively analyze the data of Chinese patients with newly diagnosed acute promyelocytic leukemia (APL) to preliminarily discuss the clinical and cytogenetic characteristics. Methods: From February 2004 to June 2020, patients with newly diagnosed APL aged ≥ 15 years who were admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College were chosen. Clinical and laboratory features were retrospectively analyzed. Results: A total of 790 cases were included, with a male to female ratio of 1.22. The median age of the patients was 41 (15-76) years. Patients aged between 20 and 59 predominated, with 632 patients (80%) of 790 patients classified as low and intermediate risk and 158 patients (20%) of 790 patients classified as high risk. The white blood cell, platelet, and hemoglobin levels at diagnosis were 2.3 (0.1-176.1) ×10(9)/L, 29.5 (2.0-1220.8) ×10(9)/L, and 89 (15-169) g/L, respectively, and 4.8% of patients were complicated with psoriasis. The long-form type of PML-RARα was most commonly seen in APL, accounting for 58%. Both APTT extension (10.3%) and creatinine>14 mg/L (1%) are rarely seen in patients at diagnosis. Cytogenetics was performed in 715 patients with newly diagnosed APL. t (15;17) with additional chromosomal abnormalities were found in 155 patients, accounting for 21.7%; among which, +8 was most frequently seen. A complex karyotype was found in 64 (9.0%) patients. Next-generation sequencing was performed in 178 patients, and 113 mutated genes were discovered; 75 genes had an incidence rate>1%. FLT3 was the most frequently seen, which accounted for 44.9%, and 20.8% of the 178 patients present with FLT3-ITD. Conclusions: Patients aged 20-59 years are the most common group with newly diagnosed APL. No obvious difference was found in the ratio of males to females. In terms of risk stratification, patients divided into low and intermediate risk predominate. t (15;17) with additional chromosomal abnormalities accounted for 21% of 715 patients, in which +8 was most commonly seen. The long-form subtype was most frequently seen in PML-RARα-positive patients, and FLT3 was most commonly seen in the mutation spectrum of APL.

[A study on treatment timing selection and short-term efficacy prediction with changes in cytokine levels before and after non-biological artificial liver treatment in acute-on-chronic liver failure].

Objective: To investigate the efficacy and diagnostic accuracy of changes in cytokine levels before and after non-biological artificial liver (referred to as ABL) treatment in patients with acute-on-chronic liver failure (ACLF) in order to establish a basis for treatment timing selection and short-term (28d) prognosis. Methods: 90 cases diagnosed with ACLF were selected and divided into a group receiving artificial liver treatment (45 cases) and a group not receiving artificial liver treatment (45 cases). Age, gender, first routine blood test after admission, liver and kidney function, and procalcitonin (PCT) of the two groups were collected. The 28-day survival of the two groups was followed-up for survival analysis. The 45 cases who received artificial liver therapy were further divided into an improvement group and a deterioration group according to the clinical manifestations before discharge and the last laboratory examination results as the efficacy evaluation indicators. Routine blood test, coagulation function, liver and kidney function, PCT, alpha fetoprotein (AFP), ß-defensin-1 (HBD-1), 12 cytokines and other indicators were analyzed and compared. A receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic efficacy of the short-term (28 d) prognosis and an independent risk factors affecting the prognosis of ACLF patients. According to different data, Kaplan-Meier method, log-rant test, t-test, Mann-Whitney U test, Wilcoxon rank-sum test, χ2 test, Spearman rank correlation analysis and logistic regression analysis were used for statistical analysis. Results: The 28-day survival rate was significantly higher in ACLF patients who received artificial liver therapy than that of those who did not receive artificial liver therapy (82.2% vs. 61.0%, P<0.05). The levels of serum HBD-1, alpha interferon (IFN-α) and interleukin-5 (IL-5) after artificial liver treatment were significantly lower in ACLF patients than those before treatment (P<0.05), while liver and coagulation function were significantly improved compared with those before treatment (P<0.05), and there was no statistically significant difference in other serological indexes before and after treatment (P＞0.05). Before artificial liver treatment, serum HBD-1 and INF-α levels were significantly lower in the ACLF improvement group than in the deterioration group (P<0.05) and were positively correlated with the patients' prognosis (deteriorating) (r=0.591, 0.427, P<0.001, 0.008). The level of AFP was significantly higher in the improved ACLF group than that in the deterioration group (P<0.05), and was negatively correlated with the prognosis (deteriorating) of the patients (r=-0.557, P<0.001). Univariate logistic regression analysis showed that HBD-1, IFN-α and AFP were independent risk factors for the prognosis of ACLF patients (P=0.001, 0.043, and 0.036, respectively), and that higher HBD-1 and IFN-α levels were associated with lower AFP level and a deteriorating prognosis. The area under the curve (AUC) of HBD-1, IFN-α, and AFP for short-term (28d) prognostic and diagnostic efficacy of ACLF patients was 0.883, 0.763, and 0.843, respectively, and the sensitivity and specificty was 0.75, 0.75, and 0.72, and 0.84, 0.80, and 0.83, respectively. The combination of HBD-1 and AFP had further improved the diagnostic efficiency of short-term prognosis of ACLF patients (AUC=0.960, sensitivity and specificity: 0.909 and 0.880 respectively). The combination of HBD-1+IFN-α+AFP had the highest diagnostic performance, with an AUC of 0.989, sensitivity of 0.900, and specificity of 0.947. Conclusion: Artificial liver therapy can effectively improve the clinical symptoms and liver and coagulation function of patients with ACLF; remove cytokines such as HBD-1, IFN-α, and IL-5 in patients with liver failure; delay or reverse the progression of the disease; and improve the survival rate of patients. HBD-1, IFN-α, and AFP are independent risk factors affecting the prognosis of ACLF patients, which can be used as biological indicators for evaluating the short-term prognosis of ACLF patients. The higher the level of HBD-1 and/or IFN-α, the higher the risk of disease deterioration. Therefore, artificial liver therapy should be started as soon as possible after the exclusion of infection. In diagnosing the prognosis of ACLF, HBD-1 has higher sensitivity and specificity than IFN-α and AFP, and its diagnostic efficiency is greatest when combined with IFN-α and AFP.

[Observational study of chronic myeloid leukemia Chinese patients who discontinued tyrosine kinase inhibitors in the real-world].

Objective: This study aimed to observe whether the treatment-free remission (TFR) of second-generation tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) is better than imatinib (IM) . Methods: The clinical data of 274 CML patients who discontinued treatment and with complete clinical data were retrospectively studied from June 2013 to March 2021. Using both univariate and multivariate Cox proportional hazards regression models, risk factors influencing TFR outcomes after drug withdrawal in CML patients were assessed. Results: A total of 274 patients were enrolled, 140 patients were women (51.1%) , with a median age of 48 (9-84) years at the time of TKI discontinuation. Prior to TKI discontinuation, 172 (62.8%) patients were treated with IM, and 102 (37.2%) had received second-generation TKI treatment, including 73 patients who had shifted from IM to a second-generation TKI and 29 patients who used second-generation TKI as the first-line treatment. The rationale for converting to a second-generation TKI are as follows: 37 patients aimed deep molecular response (DMR) to achieve TFR, seven patients changed due to IM intolerance, and 29 patients changed because of failure to achieve the optimal treatment response. The use of the last type of TKI included 96 patients (94.1%) with nilotinib, three patients (2.9%) with dasatinib, and two patients (2%) with flumatinib, including one patient who changed to IM due to second-generation TKI intolerance. No statistical differences were found in the median age at diagnosis and TKI discontinuation, sex, Sokal score, IFN treatment before TKI, median time of TKI treatment to achieve DMR, and the reasons for TKI discontinuation between the second TKI and IM (P>0.05) .The median cumulative treatment time of TKI (71.5 months vs 88 months, P<0.001) , the last TKI median treatment time (60 months vs 88 months, P<0.001) , and the median duration of DMR (58 months vs 66 months, P=0.002) were significantly shorter in the second-generation TKI compared with IM. In the median follow-up of 22 (6-118) months after TKI discontinuation, 88 patients (32.1%) had lost their MMR at a median of 6 (1-91) months; of the 53 patients (60.2%) who lost MMR within 6 months, the overall TFR rate was 67.9%, and the cumulative TFR rates at 12 and 24 months were 70.5% and 67.5%, respectively. Withdrawal syndrome occurred in 26 patients (9.5%) . For patients who restarted TKI treatment, 72 patients (83.7%) achieved DMR again at a median treatment of 4 (1 to 18) months. The univariate analysis showed that the TFR rate of patients treated with second-generation TKI was significantly higher than those who were treated with IM (77.5% vs 62.2%, P=0.041) . A further subgroup analysis found that the TFR rate of the second-generation TKI patients was significantly higher than those treated with IM (80.8% vs 62.2%, P=0.026) . No significant difference was found in the second-generation TKI used as the first line treatment compared with those who were treated with IM (69.0% vs 62.2%, P=0.599) . The multivariate analysis results showed that second-generation TKI treatment was an independent prognostic factor affecting TFR in patients who discontinued TKI (RR=1.827, 95%CI 1.015-3.288, P=0.044) . Conclusion: In the clinical setting, more CML patients rapidly achieved TFR using second-generation TKI than IM treatment.

[Hyperkalemia in chronic kidney disease: old problems, new solutions].

Hyperkalemia, one of the common complications of patients with chronic kidney disease (CKD), contributes an crucial risk factor affecting the prognosis of patients. The prevention and treatment of hyperkalemia has long been a clinically important topic. This article reviews the diagnosis, treatment and management of CKD combined with hyperkalemia in order to standardize its clinical diagnosis and treatment, achieve early detection, early diagnosis and early treatment, and thus improve the prognosis of patients.

[Treatment status of tyrosine kinase inhibitors in Chinese patients with chronic myeloid leukemia in 2020].

Objective: To investigate the current status of treatment choice and responses in patients with chronic myeloid leukemia (CML) in China. Methods: From the end of April to mid-May in 2020, a cross-sectional survey, by filling out a survey questionnaire, was conducted to explore the first-line choice of tyrosine kinase inhibitors (TKI) , current medications, drug switch and major molecular responses (MMR) as well as the variables associated with them in patients in China. Results: Data of 2933 respondents with CML from 31 provinces, municipalities, and autonomous regions across the country were included in this study. 1683 respondents (57.4%) were males. Median age was 38 (16-87) years old. 2481 respondents (84.6%) received imatinib as first-line TKI; 1803 (61.5%) , the original new drug (branded drug) . When completing the questionnaire, 1765 respondents (60.2%) were receiving imatinib; 1791 (61.1%) , branded drug. 1185 respondents (40.4%) had experienced TKI switch. With a median follow-up of 45 (3-227) months, 1417 of 1944 (72.9%) respondents with newly diagnosed CML in the chronic phase achieved MMR. Multivariate analysis showed that the respondents with urban household registration (OR=0.6, 95%CI 0.5-0.8, P<0.001) , ≥ bachelor degree (OR=0.5, 95%CI 0.4-0.7, P<0.001) , and in the advanced phase at diagnosis (OR=0.5, 95%CI 0.3-0.8, P=0.001) less preferred Chinese generic TKI, while the respondents from the central region in China more preferred Chinese generic TKI more than those from the eastern region (OR=1.7, 95%CI 1.4-2.0, P<0.001) . Moreover, the respondents in the advanced phase at diagnosis more preferred second-generation TKI (OR=5.4, 95%CI 3.6-8.2, P<0.001) ; those ≥60 years old, less preferred second-generation TKI (OR=0.4, 95%CI 0.2-0.7, P=0.002) . Being in the advanced phase at diagnosis (OR=2.2, 95%CI 1.6-3.2, P<0.001) , first-line choice of imatinib (OR=2.0, 95%CI 1.6-2.6, P<0.001) or Chinese generic drugs (OR=1.3, 95%CI 1.1-1.6, P=0.002) , longer interval from diagnose of CML to starting TKI treatment (OR=1.2, 95%CI 1.1-1.2, P<0.001) and longer duration of TKI therapy (OR=1.1, 95%CI 1.0-1.1, P<0.001) were significantly associated with TKI switch; urban household registration (OR=0.7, 95%CI 0.6-0.8, P<0.001) , ≥MMR (OR=0.6, 95%CI 0.5-0.8, P<0.001) and unknown response (OR=0.7, 95%CI 0.6-0.9, P=0.003) , no TKI switch. Female sex (OR=1.4, 95%CI 1.1-1.7, P=0.003) , urban household registration (OR=1.6, 95%CI 1.3-2.0, P<0.001) , front-line imatinib therapy (OR=1.4, 95%CI 1.1-1.9, P=0.016) and longer duration of TKI treatment (OR=1.2, 95%CI 1.2-1.3, P<0.001) were significantly associated with achieving a MMR or better response; age ≥ 60 years old (OR=0.7, 95%CI 0.4-1.0, P=0.047) and TKI switch (OR=0.6, 95%CI 0.5-0.7, P<0.001) , achieving no MMR. Conclusions: By 2020, the majority of Chinese CML patients received imatinib as the fist-line TKI therapy and continue to take it. More than half of TKIs were branded drugs. Socio-demographic characteristics and clinical variables affect their TKI choice, drug switch, and treatment response.

[Dasatinib combined with multi-agent chemotherapy regimen in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a prospective study from a single center].

Objective: This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) patients. Methods: This prospective, single-arm, and open clinical study enrolled 30 adult Ph(+) ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results: All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS (P=0.004) , HRFS (P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS (P=0.030) and EFS (P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions: The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph(+) ALL patients. Clinical trial registration: ClinicalTrials.gov, NCT02523976.

[Research status and prospect of novel biomarkers for diabetic kidney disease].

Diabetic kidney disease (DKD) is the most common chronic complication of diabetes mellitus and the major cause of end stage renal disease (ESRD). Prediction, early diagnosis and evaluation of disease progression are crucial to improve the prognosis of DKD. Estimated glomerular filtration rate (GFR) and urinary albumin excretion rate (AER) are the main diagnostic biomarkers of DKD. However, the sensitivity and specificity are insufficient. In recent years, more and more attention has been paid to the value of novel biomarkers of DKD. This article reviews the clinical studies of novel biomarkers of DKD, in order to provide reference for clinical diagnosis and prognosis evaluation of DKD.

Cytokine storm syndrome in coronavirus disease 2019: A narrative review.

Cytokine storm syndrome (CSS) is a critical clinical condition induced by a cascade of cytokine activation, characterized by overwhelming systemic inflammation, hyperferritinaemia, haemodynamic instability and multiple organ failure (MOF). At the end of 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, and rapidly developed into a global pandemic. More and more evidence shows that there is a dramatic increase of inflammatory cytokines in patients with COVID-19, suggesting the existence of cytokine storm in some critical illness patients. Here, we summarize the pathogenesis, clinical manifestation of CSS, and highlight the current understanding about the recognition and potential therapeutic options of CSS in COVID-19.