[Efficacy and safety analysis of venetoclax combined with hypomethylating agents for the treatment of higher-risk myelodysplastic syndromes in the real world].

Objective: To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) . Methods: From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis. Results: ①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five naïve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions: There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

[Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center].

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

[Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase].

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

[Advances in clinical diagnosis and treatment of drug-induced liver injury in children].

Drug-induced liver injury (DILI) is one of the most common adverse drug reactions that may seriously threaten the health of children and is receiving increasing clinical attention day by day. There is still no independent diagnosis and treatment guideline for DILI in children, but its clinical features are not completely similar to those in adults. This article reviews the epidemiology, clinical features, diagnosis, and treatment progress in order to provide a reference for the management of DILI in children.

[Simultaneous detection of 7 important Rickettsiales pathogens by TaqMan-probe quantitative real-time PCR].

Objective: To establish and optimize a TaqMan-probe quantitative real-time PCR (qPCR) assay for the detection of 7 important Rickettsiales pathogens and simultaneous identification of the infection types. Methods: Based on the ompB gene of Rickettsia prowazekii, Rickettsia mooseri and spotted fever group rickettsiae, the groEL gene of Orientia tsutsugamushi, the 16S rRNA of Ehrlichia chaffeensis, the gltA gene of Anaplasma phagocytophilum and the com1 gene of Coxiella burnetii, we synthesized primers and TaqMan-probes and optimized the reaction system and reaction process to same solution. The sensitivity, specificity and reproducibility of this assay were evaluated and the assay was used for the detection of simulated and actual samples. Results: The Ct value of the standard curves of the 7 pathogens showed a good linear relationship with the number of DNA copies (all R2 >0.990 0), the minimum detection limit was 10 copies/µl, showing good specificity. In the 96 tick nucleic acid extracts, Coxiella burnetii was detected in 1 sampleand spotted fever group Rickettsiae was detected in 3 samples. In the 80 blood samples from patients with undefined febrile illness, Orientia tsutsugamushi was detected in 1 sample and spotted fever group rickettsiae was detected in 2 samples. Conclusions: In this study, based on the established TaqMan-probe qPCR assay, the reaction system and reaction condition of the 7 important pathogens of Rickettsiales were optimized to the same solution. This method overcomes the shortcomings of using different reaction systems and reaction conditions for different pathogens, which can precisely identify the species of 7 important pathogens of Rickettsiales in clinical sample detections and is important for the infection type identification and laboratory detection time reduction to facilitate precise treatment of the patients.

[Epidemiological characteristics of typhus in China, 1950-2021].

Objective: To analyze the epidemiological characteristics of typhus in China from 1950 to 2021, and discuss the challenges in typhus prevention and control in China and suggest future prevention and control strategies. Methods: Based on the reported data of typhus from 1950 to 2021 in China from the Infectious Disease History Database of China Public Health Science Data Center and the National Notifiable Infectious Disease Reporting Information System of Chinese Center for Disease Control and Prevention, we conducted a descriptive statistical analysis. Mann-Kendall test and circular distribution method were used to analyze the incidence, mortality and case fatality of typhus to reveal the temporal, spatial and population distributions and diagnosis of typhus in China. Results: From 1950 to 2021, a total of 452 965 typhus cases and 7 339 typhus deaths were reported in China, with the cases numbers exceeding 10 000 in 14 years of the 1950s, 1960s and 1980s, respectively. Since 1990s, the reported cases and incidence rate of typhus have decreased dramatically and the most cases were sporadic. However, the reported typhus cases in Anhui, Hubei, Hunan Provinces showed significant uptrends. Although typhus could occur all the year round, but the seasonality was observed with the incidence mainly in summer and autumn. For different provinces from the north to the south, the peaks of typhus' monthly incidence tended to shift to earlier dates. The male to female ratio of the cases was 1.01∶1 (18 529∶18 366). However, more cases occurred in women in recent years. The cases aged ≤9 years accounted for the highest proportion (18.9%), but the number of cases aged ≥50 years showed an upward trend. Most cases were farmers with the proportion increasing year by year. Moreover, the cases in students and scattered-living children also accounted for relatively higher proportions. The median of the interval between onset and diagnosis of typhus was 6 days. Most cases were clinically diagnosed, while the proportion of laboratory-confirmed cases was low and most laboratory cases were confirmed by Well-Felix reaction. Conclusions: Although the incidence and mortality of typhus in China has decreased significantly, the risk for local typhus outbreaks still exists. The prevention and control of typhus still face many challenges. It is indispensable to strengthen the pathogen detection and surveillance for typhus in China.

[Comparison of three different measurement methods to determine resting energy expenditure in patients with decompensated hepatitis B cirrhosis].

Objective: To compare the differences to determine resting energy expenditure (REE) measured with indirect calorimetry and REE predicted by formula method and body composition analyzer in patients with decompensated hepatitis B cirrhosis, so as to provide theoretical guidance for the implementation of precision nutrition intervention. Methods: Patients with decompensated hepatitis B cirrhosis who were admitted to Henan Provincial People's Hospital from April 2020 to December 2020 were collected. REE was determined by the body composition analyzer and the H-B formula method. Results: were analyzed and compared to REE measured by the metabolic cart. Results A total of 57 cases with liver cirrhosis were included in this study. Among them, 42 were male, aged (47.93 ± 8.62) years, and 15 were female aged (57.20 ± 11.34) years. REE measured value in males was (1 808.14 ± 201.47) kcal/d, compared with the results calculated by the H-B formula method and the measured result of body composition, and the difference was statistically significant (P = 0.002 and 0.003, respectively). REE measured value in females was (1 496.60 ± 131.28) kcal/d, compared with the results calculated by the H-B formula method and the measured result of body composition, and the difference was statistically significant (P = 0.016 and 0.004, respectively). REE measured with the metabolic cart had correlation with age and area of visceral fat in men (P = 0.021) and women (P = 0.037). Conclusion: Metabolic cart use will be more accurate to obtain resting energy expenditure in patients with decompensated hepatitis B cirrhosis. Body composition analyzer and formula method may underestimate REE predictions. Simultaneously, it is suggested that the effect of age on REE in H-B formula should be fully considered for male patients, while the area of visceral fat may have a certain impact on the interpretation of REE in female patients.

Analysis of the Safety and Pregnancy Outcomes of Fertility-sparing Surgery in Ovarian Malignant Sex Cord-stromal Tumours: A Multicentre Retrospective Study.

AIMS: To assess the difference in survival between fertility-sparing surgery (FSS) and radical surgery and explore pregnancy outcomes after FSS in stage I malignant sex cord-stromal tumours (MSCSTs). MATERIALS AND METHODS: We carried out a multicentre retrospective cohort study on patients who were diagnosed with MSCSTs and the tumour was confined to one ovary. The patients were divided into FSS and radical surgery groups. Inverse probability of treatment weighting (IPTW) was used to balance variables between the two groups. Kaplan-Meier analysis was used to compare the difference in disease-free survival (DFS). Univariate and multivariate Cox regression analysis was used to find risk factors of DFS. Univariate logistic regression analysis was used to assess risk factors of pregnancy. RESULTS: In total, 107 patients were included, of whom 54 (50.5%) women underwent FSS and 53 (49.5%) received radical surgery. After IPTW, a pseudo-population of 208 was determined and all of the covariates were well balanced. After a median follow-up time of 50 months (range 7-156 months), 10 patients experienced recurrence and two died. There was no significant difference in DFS between the two groups, both in unweighted (P = 0.969) or weighted cohorts (P = 0.792). In the weighted cohort, stage IC (P = 0.014), tumour diameter >8 cm (P = 0.003), incomplete staging surgery (P = 0.003) and no adjuvant chemotherapy (P < 0.001) were the four high-risk factors associated with a shorter DFS. Among 14 patients who had pregnancy desire, 11 (78.6%) women conceived successfully; the live birth rate was 76.9%. In univariate analysis, only adjuvant chemotherapy (P = 0.009) was associated with infertility. CONCLUSIONS: On the premise of complete staging surgery, FSS is safe and feasible in early stage MSCSTs with satisfactory reproductive outcomes.

Risk factors for prolongation of ileostomy closure operation.

OBJECTIVE: Understanding factors for prolonged operative time is essential for surgery. This study aims at identifying the factors related to prolonged ileostomy closure operation time. PATIENTS AND METHODS: The data of 88 patients who underwent ileostomy reversal in the Department of Gastrointestinal Surgery of Jiaxing First Hospital between January 2018 and October 2021 were retrospectively analyzed. Prolonged operation time was defined as operative time >65 minutes. The Chi-square test was used to compare data between patients with normal operative time (≤65 minutes) and patients with prolonged operative time. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with prolonged ileostomy closure operation time. RESULTS: Among the 88 patients (mean age: 62.78 years), median ileostomy retention time was 127.50 (range: 61.00-1,192.00) days. The operation time ranged from 35.00 minutes to 125.00 minutes. Prolonged ileostomy closure time occurred in 41 (46.6%) patients. In univariate analysis, the factors associated with prolonged operation time were body mass index (BMI) ≥25 kg/m2, previous history of abdominal surgery, and manual suture. History of serious complications after the primary operation was associated with shorter operation time. In multivariate analysis, the independent risk factors for prolonged operation time were BMI ≥25 kg/m2 (OR = 4.552, 95% CI: 1.369-15.136, p = 0.013), previous history of abdominal surgery (OR = 4.377, 95% CI: 1.394-13.739, p = 0.011), and manual suture (OR = 3.941, 95% CI: 1.181-13.154, p = 0.026). CONCLUSIONS: Overweight, previous history of abdominal surgery, and manual suture appear to be risk factors for prolonged operative time for ileostomy closure.

[Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera].

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

[Analysis of the efficacy and safety of low-dose aspirin in preventing renal artery stenosis in kidney transplantation].

Objective: To evaluate the clinical value of aspirin as a prophylactic for transplant renal artery stenosis (TRAS). Methods: From January 2017 to November 2019, clinical data of 307 patients who had undergone renal transplant in Zhengzhou University People's Hospital were collected. Patients were divided into two groups: the treatment group (124 recipients who had taken oral aspirin 100 mg/d after transplant) and the control group (183 recipients who had not taken aspirin after transplant). The general data, incidence of initially diagnosed and confirmed TRAS, type of renal artery anastomosis vessels, duration of stenosis, location of stenosis, and complications were compared between the two groups. The treatment group was further divided into two subgroups, the early group (92 recipients) and the delayed group (32 recipients), according to the time of starting aspirin after operation. Subgroup analysis was performed. Results: Among all 307 patients included, there were 241 males and 66 females, aged 19-64 years. There were no statistical difference between the treatment and control groups in terms of gender, age, comorbidities, number of arterial vessels, type of graft, and acute rejection all P>0.05. Among 46 initially diagnosed TRAS patients, 13 (10.5%) and 33 (18.0%) cases were in the treatment and control group respectively, with no statistically significant difference in stenosis rate (P>0.05). The number of confirmed TRAS patients was 1 (0.8%) and 24 (13.1%) in the treatment and control group respectively, with statistically significant difference in stenosis rate (P<0.001). The proportion of patients with bleeding disorders in the treatment group was slightly higher than that in the control group (13.7% vs 8.7%), and the proportion of infarct diseases was slightly lower than that in the control group (1.6% vs 4.9%). But there was no significant difference in aspirin-related complications between the two groups (P>0.05). Subgroup analysis showed that there was no significant difference in initially diagnosed and confirmed TRAS and aspirin-related complications between the early group and the delayed group (all P>0.05). Conclusions: Oral low-dose aspirin after kidney transplantation can effectively reduce the incidence of TRAS, without increasing the risk of aspirin-related complications.

[Sternal bone marrow cell morphology evaluation utility for diagnostic categorization in patients with acquired hypocellular bone marrow failure syndromes].

Objective: Diagnostic value assessment of sternal bone marrow cell morphology in patients with acquired hypocellular bone marrow failure syndromes (BMFS) characterized by normal cytogenetics. Methods: A total of 194 eligible patients with an acquired hypocellular BMFS pre-sternum diagnosis in Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College from June 2014 to January 2019 were reviewed. Sternal bone marrow evaluation was performed, and a post-sternum diagnosis was made. Clinical characteristics and overall survival (OS) were then compared among patients with different post-sternum diagnosis. Binary logistic regression was used to develop a predictive scoring system. Results: In 152 patients with pre-sternum AA diagnosis, 29 patients with a pre-sternum idiopathic cytopenia of undetermined significance (ICUS) diagnosis, and 13 patients with a pre-sternum clonal cytopenia of undetermined significance (CCUS) diagnosis, sternal bone marrow evaluation resulted in a change of diagnosis to hypocellular myelodysplastic syndrome (hypo-MDS) in 42.8% (65/152) , 24.1% (7/29) , and 30.8% (4/13) , respectively. Patients with a post-sternum hypo-MDS diagnosis showed a significant difference in OS compared with patients with a post-sternum AA diagnosis (P=0.005) . Patients with ICUS/CCUS showed no difference in OS compared with AA and hypo-MDS (P=0.095 and P=0.480, respectively) . A 4-item predictive scoring system to identify hypocellular BMFS patients that need sternal bone marrow evaluation was developed, including age > 60 years old (OR=6.647, 95% CI 1.954-22.611, P=0.002, 2 points) , neutrophil alkaline phosphatase score ≤ 160 (OR=2.654, 95% CI 1.214-5.804, P=0.014, 1 point) , abnormal erythroid markers evaluated by flow cytometry on iliac bone marrow (OR=6.200, 95% CI 1.165-32.988, P=0.032, 2 points) , and DAT (DNMT3A, ASXL1, TET2) genes mutation (OR=4.809, 95% CI 1.587-14.572, P=0.005, 1 point) . The Akaike information criterin (AIC) was 186.1. Conclusion: Patients with a pre-sternum acquired hypocellular BMFS diagnosis characterized by normal cytogenetics may not reach accurate diagnostic categorization without sternal bone marrow cell morphology evaluation, which could be considered a diagnostic tool for this patient population. A predictive scoring system was developed, and when the total score is ≥ 2 points, sternal bone marrow evaluation should be performed for accurate diagnostic categorization that is critical to optimal patient care.

[Risk factors for leukemia transformation in patients with myelodysplastic syndromes].

Objective: To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) . Methods: From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done. Results: The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age (P<0.001) , bone marrow blast percentage (P<0.001) , bone marrow fibrosis (P=0.046) , WHO classification (P<0.001) , IPSS-R (P<0.001) and IPSS-R karyotype group (P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference (P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation (P=0.034) , DNMT3A mutation (P=0.026) , NRAS mutation (P=0.027) and NPM1 mutation (P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups (HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation (HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation (HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion: Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.

[The relationship between symptom burden and hematologic responses after treatment with interferon/hydroxyurea in patients with polycythemia vera].

Objective: To explore the relationship between symptom burden and hematologic responses after treatment with interferon and/or hydroxyurea in patients with polycythemia vera (PV) . Methods: Hematologic responses after continuous treatment with interferon and/or hydroxyurea for six months were evaluated in 190 patients with PV using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-10 score) . In all patients, the PV diagnosis was based on the 2016 World Health Organization diagnostic definitions. Results: The study cohort comprised 93 (48.9% ) male and 97 (51.1% ) female patients. The median age at the time of MPN-10 assessment was 60 (32-82) years. The median MPN-10 score of the entire cohort was 9 (range, 0-67) . The median MPN-10 score of patients treated with interferon plus hydroxyurea (n=27) was 11 (0-67) , which was significantly higher than those of patients treated with interferon only (n=64) (6[0-56], P=0.019) or hydroxyurea only (n=99) (9[0-64], P=0.047) , whereas the median MPN-10 score was not significantly different between those treated with interferon only and hydroxyurea only (P=0.421) . The rate of severe symptom burden (i.e., any single symptom burden score ≥ 7 and/or total score ≥ 44) was 28.9% (55/190) in the entire cohort, whereas the rate of severe symptom burden was not significantly different among the interferon only (23.4% ) , hydroxyurea only (29.3% ) , and interferon plus hydroxyurea (40.7% ) groups (P>0.05 for all two-group comparisons) . When evaluating MPN-10 score, 37.4% (71/190) of the patients achieved complete hematologic remission (CHR) . Only 28.9% (55/190) patients had adequate disease control, defined as CHR without severe symptom burden. Reasons for inadequate disease control were evaluating blood counts alone, severe symptom burden alone, and evaluating blood counts accompanied with severe symptom burden in 42.1% (80/190) , 8.4% (16/190) , and 20.5% (39/190) of the patients, respectively. Compared to the patients with a platelet count ≤ 400×10(9)/L, those with a platelet count > 400×10(9)/L had a significantly higher rate of severe symptom burden (40.8% [20/49] vs 24.8% [35/141], P=0.044) and a higher median MPN-10 score (14[0-67] vs 7[0-56], P=0.038) . Platelet count > 400×10(9)/L was associated with an increased risk of severe symptom burden (hazard ratio, 2.089; 95% confidence interval, 1.052-4.147, P=0.035) . Conclusions: Symptoms related to disease after treatment with interferon and/or hydroxyurea were rather universal in patients with PV. Some patients still experienced severe symptom burden despite achieving CHR. Platelet count > 400×10(9)/L was associated with an increased risk of severe symptom burden in patients with PV treated with interferon and/or hydroxyurea.

[Prognostic factors of cyclosporine A combined with danazol with or without thalidomide in myelodysplastic syndrome treatment with low-percentage bone marrow blasts].

Objective: To explore the outcome of cyclosporine A (CsA) combined with danazol with or without thalidomide regimen for myelodysplastic syndrome (MDS) with low-percentage bone marrow blasts and predictive factors for treatment response. Methods: Data of 115 subjects who were newly diagnosed with primary MDS with low-percentage bone marrow blasts and were treated with CsA combined with danazol with or without thalidomide from December 2011 to December 2019 in our center were collected. Their clinical features, efficacy, and predictive factors of efficacy were retrospectively analyzed. A model for predicting this response was developed. Results: A total of 55 subjects responded (47.8%) , including 11 complete responses and 44 hematologic improvements. Fifty-two patients (52/105, 49.5%) achieved erythrocyte response; 35 (35/86, 40.7%) , platelet response; and 14 (14/40, 35%) , neutrophil response. Of 29 subjects (24.1%) , 7 who were red blood cell (RBC) transfusion-dependent became independent of transfusion. The median response duration was 20 months (range, 3-84 months) . In the univariate analysis, patients <0 years had a higher response rate than those ≥60 years (52.5% vs 22.2%, P=0.018) . Contrarily, the response rate was substantially decreased in patients with RBC transfusion dependence compared with those without RBC transfusion dependence (24.1% vs 55.8%, P=0.003) , as well as in patients with the mutated U2AF1 compared with those with the wild-type U2AF1 (26.1% vs 53.2%, P=0.020) . In multivariable analyses, age <0 years (OR=4.302, 95% CI 1.245-14.820, P=0.021) , RBC transfusion dependence (OR=3.774, 95% CI 1.400-10.177, P=0.009) , and U2AF1 mutation (OR=3.414, 95% CI 1.168-9.978, P=0.025) were significantly correlated with response. Variables that independently predicted the response were combined to generate the predictive model. According to the model, the overall response rates of patients with 0, 1, 2, and 3 risk factors were 65%, 30%-35%, 10%-15%, and 3%, respectively. Conclusion: CsA combined with danazol with or without thalidomide regimen could improve cytopenia symptoms in patients with MDS with low-percentage bone marrow blasts. At age <60 years, no transfusion dependence of RBC and wild-type U2AF1 mutation is a favorable prognostic factor.

Comparative efficacy and safety of PD-1/PD-L1 immunotherapies for non-small cell lung cancer: a network meta-analysis.

OBJECTIVE: PD-1/PD-L1 inhibitors are a relatively new class of immunotherapeutic drugs approved for advanced non-small-cell lung cancer. The purpose of this study was to conduct a network meta-analysis to compare the safety and efficacy of these immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: We used Bayesian network meta-analysis methods to evaluate the efficacy and safety of the included treatments. We further analyzed subgroups based on PD-L1 expression level, histology type, and line of the treatment setting. RESULTS: We identified 19 RCTs, including 12,753 patients. In the analysis of all-comers, the pembrolizumab/chemotherapy combination ranked best for overall survival (OS) and progression-free survival (PFS). Durvalumab was the only ICI treatment that showed no benefit over chemotherapy. In the first-line setting only, in terms of OS, atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab ranked as the best treatments for patients with PD-L1 expression levels of ≥50%, 1-49%, and <1%, respectively. Nivolumab, atezolizumab, pembrolizumab, and durvalumab all had lower odds of grade 3 or greater treatment-related adverse events (TRAEs) compared to chemotherapy. With the addition of chemotherapy to any ICI regimen, the odds of TRAEs increased in a considerable and statistically significant way. CONCLUSIONS: While the pembrolizumab/chemotherapy combination was the most effective therapy in the overall cohort of all-comers, treatment preferences varied by treatment-line setting, tumor characteristics, and outcome of interest. In the first-line setting, the most effective treatments for patients with PD-L1 expressions of ≥50%, 1-49%, and <1% were atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab, respectively.

[Evaluation of the prognostic value of MIPSS70-plus in Chinese patients with primary myelofibrosis].

Objective: To evaluate the prognostic value of MIPSS70-plus in Chinese patients with primary myelofibrosis (PMF) . Methods: A total of 113 Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, Log-rank test, and Cox proportional hazard regression model were performed to evaluate the prognostic factors. The likelihood ratio test was used to evaluate the predictive power between MIPSS70-plus and DIPSS systems. Results: The median age of the Chinese patients was 55 (range: 20-70) years, including 71 males and 42 females. According to the standard of MIPSS70-plus system, 99 patients (79.6% ) had a favorable karyotype and 23 patients (20.4% ) had an unfavorable karyotype. JAK2V617F in 55.8% (n=63) , CALR exon9 in 17.7% (including 15 CALR type 1 and 5 CALR type 2, n=20) , MPLW515 in 4.4% (n=5) , and triple negative (no detectable JAK2, MPL, and CALR mutations) in 22.1% of patients in our cohort were found by target-specific next-generation sequencing approach. At least one high-molecular risk mutations were presented in 45.1% (n=51) of patients, with ASXL1 in 38.9% (n=44) , SRSF2 in 7.1% (n=8) , IDH1/2 in 4.4% (n=5) , and EZH2 in 3.5% (n=4) of patients. A total of 28 patients (26.7% ) were in low risk, 20 (19.0% ) in intermediate risk, 41 (39.0% ) in high risk, and 16 (15.3% ) in very-high risk categories, which were delineated for the MIPSS70-plus model. A 2-year OS was 100% in low risk, 89.7% (95% CI 76.2% -100.0% ) in intermediate risk, 64.8% (95% CI 47.0% -82.6% ) in high risk, and 35.0% (95% CI 10.3% -59.7% ) in very-high risk categories, which had a significant difference (P<0.001) . A significantly higher predictive power for survival of the MIPSS70-plus group was observed compared with the DIPSS group (P=0.001, -2 log-likelihood ratios of 86.355 vs 95.990 for the MIPSS70-plus and DIPSS systems, respectively) . Conclusion: The MIPSS70-plus had significantly higher predictive power than the DIPSS.

[Overall survival and prognosis of patients with polycythemia vera: an analysis based on 906 patients from a single center].

Objective: To explore predictors of overall survival (OS) in Chinese patients with polycythemia vera (PV) . Methods: A total of 906 consecutive newly diagnosed patients with PV seen at the Blood Diseases Hospital, Chinese Academy of Medical Sciences, from June 2007 to February 2020 were included, and their data were collected. PV was diagnosed according to 2016 World Health Organization (WHO) diagnostic definitions. OS and prognostic factors were retrospectively analyzed. Results: Among the 906 patients, 439 were male (48.5%) and 467 were female (51.5%) . The median age was 57 years (range: 18-91 years) . 31.6% (276/874) of the patients had a thrombosis history at diagnosis, and 4.6% (25/541) of the patients had abnormal cytogenetics. The median follow-up was 54 months (95% confidence interval [CI] 8-130 months) . The 5- and 10-year cumulative deaths were 5.8% (95% CI 4.8%-6.7%) and 11.1% (95% CI 9.3%-12.9%) , respectively. Univariate analysis showed that age ≥60 years, thrombosis history, white blood cells (WBC) ≥15×10(9)/L, platelet (PLT) ≥450×10(9)/L, and platelet distribution width (PDW) ≥15 fl significantly correlated with worse OS, and palpable spleen correlated with better OS. Multivariate analysis showed that age ≥60 years (HR=4.3, 95% CI 2.1-9.2, P<0.001) and PDW ≥15 fl (HR=2.1, 95% CI 1.1-4.0, P=0.023) were independent prognostic factors for worse OS. The 5-year cumulative death for patients with PDW ≥15 fl or PDW<15 fl was 8.6% (95% CI 5.9%-11.3%) or 4.4% (95% CI 3.4%-5.4%) , respectively. The 5-year cumulative death for patients defined as low-, intermediate-, and high-risk patients by international working group score system for PV (IWG-PV) were 0.8% (95 CI 0.2%-1.4%) , 4.0% (95% CI 2.7%-5.3%) , and 12% (95% CI 9.6%-14.4%) , respectively, with a significant difference among the three cohorts (P<0.05) . PDW ≥ 15 fl significantly affected OS for intermediate- and high-risk patients (HR=2.3, 95% CI 1.2-4.2, P=0.009) defined by IWG-PV score system, but not for low-risk patients (HR=3.1, 95% CI 0.2-52.0, P=0.405) . Conclusions: Age ≥60 years and PDW ≥15 fl were independent prognostic factors for worse OS in PV. IWG-PV score system effectively predicted OS for Chinese patients with PV.

[Clinical analysis of 30 cases of traumatic aortic injury].

Objective: To examine the clinical treatment methods and short- and mid-term results of traumatic aortic injury (TAI). Methods: The clinical data of 30 patients suffering from TAI who were admitted to Department of Cardiothoracic Surgery, General Hospital of Eastern Theater Command from January 2010 to December 2018 were summarized and analyzed retrospectively. All patients were diagnosed as TAI by aortic CT angiography. There were 20 males and 10 females, aging (46.4±15.2) years (range: 17 to 76 years). One patient was diagnosed as extensive intramural hematoma (IMH). The other 29 cases had aortic intimal injury, and the primary intimal tear of all these patients was located in the isthmus of descending aorta. There were 2 cases of ulcer-like changes combined with IMH, and 27 cases of traumatic aortic dissection (TAD) including 23 cases of localized TAD and 4 cases of extensive TAD. Endovascular repair, artificial vascular replacement or conservative treatment were performed according to the patient's specific condition. The patients were followed up in outpatient or by telephone. The clinical data of all the patients of the in-hospital treatment and during follow-up period was analyzed retrospectively. Results: One patient with IMH was treated conservatively. Surgical intervention was performed in 29 cases with intimal injury, of which 14 cases underwent emergency surgery on the day of admission or the next day, and 15 cases underwent elective surgery. Twenty-seven cases underwent thoracic endovascular aortic repair (TEVAR), and 2 cases underwent artificial vascular replacement. Nine cases suffered combined operations in early or late stage. All patients were cured and discharged with in-hospital stay of (13.2±5.4) days (range: 7 to 30 days). There was no in-hospital death. Two patients underwent tracheotomy, and the rest had no serious complications. Up to the last follow-up in June 2019, 4 patients were lost to follow-up, and the remaining 26 patients were followed up for (50.6±34.1) months (range: 6 to 112 months) and survived healthily without new aortic events. Conclusions: Most of TAD cases are ascribed to Stanford type B aortic dissection, and a satisfactory short-term and mid-term result can be achieved by emergency TEVAR in most patients. Some patients can achieve good long-term results by open surgery with artificial vascular replacement.