[Current situation and prospect of diagnosis and therapy of childhood acute leukemia in China].

Acute leukemia is the most common hematopoietic stem cell malignant tumor in children, which ranks in the top one of the incidence of tumor in children, it is a major disease that affects the growth and survival of children. With the continuous improvement of medical diagnosis and treatment and the extensive development of immunotherapy, the survival rate and quality of life of children with acute leukemia have been significantly improved. In recent years, three cooperative groups of childhood leukemia have been established in China, and a series of high-level research results have been published. In the future, efforts should be made to promote the process of standardization and homogenization in the diagnosis and treatment of children's acute leukemia, explore the monitoring targets of sensitive residual diseases, and find the best treatment for refractory/recurrent cases. Speeding up the clinical research of new drugs will be an urgent problem and development direction in the field of acute leukemia diagnosis and treatment in children.

[The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children].

To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive (CD19+) B-cell acute lymphoblastic leukemia (B-ALL) in children. A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023. Based on their disease status, the patients were divided into refractory/relapsed(RR) group, minimal residual disease clearance (MC) group, and chemotherapy intolerance (IC) group. Clinical data of the children were collected to evaluate the adverse drug reactions, therapeutic efficacy and survival of the children. In total, 35 patients were included, with 20 males and 15 females, aged from 0.6 to 16.4 (9.9±4.2) years old. There were 10 cases in the RR group, 20 cases in the MC group and 5 cases in the IC group. A total of 56 cycles of infusion were completed, with one cycle in 24 cases, two cycles in 5 cases, three cycles in 2 cases and four cycles in 4 cases. The median infusion time [M (Q1, Q3)] from the first to the fourth cycle was 14 (14, 28) days, 28 (28, 28) days, 28 (28, 28) days and 28 (26, 28) days, respectively. In terms of adverse reactions, the incidence of grade 1-2 cytokine release syndrome(CRS) was 57.1% (32/56), with grade 1 CRS accounting for 84.4% (27/32). The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS) (grade 4) was 1.8% (1/56). In the RR group, 6 cases were treated effectively, and minimal residual disease(MRD) turned negative, before treatment, MRD levels were all less than 20%. Among them, 3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab. Four cases were treated ineffectively, with MRD >20% before treatment. All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment. The median follow-up time of RR group was 5.7 (3.8, 9.4) months, and 1 year median survival rate and event-free survival rate were 40.0%±21.9% and 33.3%±19.2%, respectively. The median follow-up time for MC and IC group patients was 6.7 (5.2, 12.5) months and 7.1 (5.1, 7.6) months, respectively, with an event free survival rate of 100%. The safety and efficacy of using belintoumab in partial RR, MRD clearance, and chemotherapy intolerance are good.

[Clinical features and prognostic factors of advanced myelodysplastic syndromes in children].

Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 µg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.

[Clinical features and prognostic analysis of testicular relapse in pediatric acute lymphoblastic leukemia].

Objective: To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis (HR=3.09, 95%CI 1.10-8.72), combined relapse (HR=4.26, 95%CI 1.34-13.52) and CAR-T cell therapy after relapse (HR=0.15,95%CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions: The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

[Clinical and prognostic characteristics of pediatric acute myeloid leukemia with myelodysplasia-related changes under different diagnostic criteria].

Objective: To evaluate the clinical and prognostic differences in acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) children under different diagnostic criteria (World Health Organization (WHO) 2016 and WHO 2022 criteria). Methods: In this retrospective cohort study, clinical characteristics and prognosis information of 260 acute myeloid leukemia (AML) children admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2017 to August 2021 were analyzed retrospectively. According to WHO 2016 and WHO 2022 diagnostic criteria, patients were divided into AML-MRC group and non-AML-MRC group, the prognostic and genetic differences between two groups were compared respectively. Meanwhile, the characteristics of children with 8 MRC-related genes defined in WHO 2022 diagnostic criteria were described. Mann-Whitney U test, chi-square test were used for comparison between groups. Survival curve was plotted by Kaplan-Meier method, and comparison between groups was performed by Log-Rank method. Results: Among the 260 children, there were 148 males and 112 females. The follow-up time was 26 (16, 38) months. A total of 28 children (10.8%) were diagnosed with AML-MRC according to the WHO 2016 diagnostic criteria. Compared with non-AML-MRC children, the frequency of PTPN11, RUNX11, SH2B3, MPL and STAG2 mutations was higher in AML-MRC children (25.0% (7/28) vs. 4.3% (10/232), 14.3% (4/28) vs. 3.9% (9/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 0.9% (2/232), all P<0.05). The 2-year overall survival (OS) and events free survival (EFS) rate of 28 AML-MRC children under WHO 2016 diagnostic criteria were worse than those of 232 non-AML-MRC children ((62.1±10.8)% vs. (94.5±1.6)%, χ2=22.1,P<0.001;(48.0±10.6)% vs. (70.9±3.2)%, χ2=6.33,P=0.012). Twenty-seven children (10.4%) were eventually diagnosed with AML-MRC according to WHO 2022 criteria, their 2-year OS rate were worse than 233 non-AML-MRC children ((60.8±11.1)% vs. (94.5±1.6)%, χ2=24.49,P<0.001), and there was no statistically significant difference in EFS rate between two groups at 2 years ((55.1±10.8)% vs. (70.1±3.2)%, χ2=2.44, P=0.119). Conclusions: Compared with the 2022 WHO diagnostic criteria, the survival rates of children with AML-MRC under the 2016 WHO diagnostic criteria were worse than that of children without MRC.The new version of the AML-MRC diagnostic criteria emphasizes the importance of genes.

Fruit Intake and Alzheimer's Disease: Results from Mendelian Randomization.

Alzheimer's disease (AD) is the leading cause of dementia in old age, recognized as a global health priority. To explore causal effects of fresh fruit intake and dried fruit intake on AD liability, this study utilized GWAS from the UK Biobank and FinnGen to conduct Mendelian randomization (MR) analysis, and used inverse variance weighted (IVW), MR-Egger, and weighted median approaches for MR estimates, and visual inspections judged result stability. Results suggested little evidence of a potential causal relationship between fresh fruit intake and AD (OR=0.97, 95%CI=0.50-1.91, P=0.939), while significant, robust causality was indicated between dried fruit intake and AD (OR=4.09, 95%CI=2.07-8.10, P<0.001). Stability evaluations showed no heterogeneity or pleiotropy affecting interpretability and credibility of primary analyses. In conclusion, we strengthened evidence for positive causality from dried fruit intake to AD liability, with causality from fresh fruit intake on AD risk was not demonstrated.

Red cell distribution width as a predictor of mortality after hip fracture: a systematic review and meta-analysis.

OBJECTIVE: This review examined the association between red cell distribution width (RDW) and mortality after hip fracture. MATERIALS AND METHODS: PubMed, CENTRAL, Scopus, Web of Science, and Embase were searched up to 10th January 2023 for studies comparing mortality after hip fracture based on RDW. All cut-offs of RDW were accepted. Crude and adjusted mortality ratios were pooled separately. RESULTS: Nine studies with 5,274 patients were eligible. Meta-analysis of eight studies reporting crude mortality rates showed that patients with high RDW had a significantly higher risk of mortality than those with low RDW (RR: 2.81 95% CI: 2.05, 3.86 I2=82%). The results did not change in significance on subgroup analyses based on study location, sample size, the cut-off of RDW, and follow-up. Four studies reported adjusted mortality rates. Analysis of the same showed that high RDW was an independent predictor of mortality in hip fracture patients (HR: 3.14 95% CI: 1.38, 7.14 I2=95%). CONCLUSIONS: Within the limitations of the review, RDW was found to be an indicator of mortality in hip fracture patients. High RDW was significantly associated with increased mortality despite different cut-offs among studies. Further research is needed to generate more rigorous evidence.

[Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease].

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

[Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene].

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Steinernema populi n. sp. (Panagrolaimomorpha, Steinernematidae), a new entomopathogenic nematode species from China.

Steinernema populi n. sp. was recovered by baiting from beneath poplar trees in China. Morphological and molecular features provided evidence for placing the new species into the Kushidai clade. The new species is characterized by the following morphological features: third-stage infective juveniles (IJ) with a body length of 1095 (973-1172) µm, a distance from the anterior end to excretory pore of 77 (70-86) µm and a tail length of 64 (55-72) µm. The Body length/Tail length (c) ratio and Anterior end to Excretory pore/ Tail length × 100 (E%) of S. populi n. sp. are substantially greater than those of all other 'Feltiae-Kushidai-Monticolum' group members. The first-generation males can be recognized by a spicule length of 66 (57-77) µm and a gubernaculum length of 46 (38-60) µm. The new species is further characterized by sequences of the internal transcribed spacer and partial 28S regions of the ribosomal DNA. Phylogenetic analyses show that Steinernema akhursti and Steinernema kushidai are the closest relatives to S. populi n. sp.

[Safety and feasibility of intrathoracic modified overlap esophagojejunostomy in laparoscopic radical resection of Siewert type â ¡ adenocarcinoma of esophagogastric junction].

Objective: The study aimed to investigate the safety and feasibility of intrathoracic modified overlap method in laparoscopic radical resection of Siewert type II adenocarcinoma of the esophagogastric junction (AEG). Methods: A descriptive case series study was conducted. The clinical data of 27 patients with Siewert type II AEG who underwent transthoracic single-port assisted laparoscopic total gastrectomy and intrathoracic modified overlap esophagojejunostomy in Guangdong Provincial Hospital of Chinese Medicine from May 2017 to December 2020 were retrospectively analyzed. The intrathoracic modified overlap esophagojejunostomy was performed as follows: (1) The Roux-en-Y loop was made; (2) The jejunum side was prepared extraperitoneal for overlap anastomosis; (3) The esophagus side was prepared intraperitoneal for overlap anastomosis; (4) The overlap esophagojejunostomy was performed; (5) The common outlet was closed after confirmation of anastomosis integrity without bleeding; (6) A thoracic drainage tube was inserted into the thoracic hole with the diaphragm incision closed. The intraoperative and postoperative results were reviewed. Results: All 27 patients were successfully operated, without mortality or conversion to laparotomy. The operative time, digestive tract reconstruction time and esophageal-jejunal anastomosis time were (327.5±102.0) minute, 50 (28-62) minute and (29.0±7.4) minute, respectively. The blood loss was 100 (20-150) ml. The postoperative time to flatus and postoperative hospital stay were (4.7±3.7) days and 9(6-73) days, respectively. Three patients (11.1%) developed postoperative grade III complications according to the Clavien-Dindo classification, including 1 case of anastomotic fistula with empyema, 1 case of pleural effusion and 1 case of pancreatic fistula, all of whom were cured by puncture drainage and anti-infective therapy. Conclusions: The intrathoracic modified overlap esophagojejunostomy is safe and feasible in laparoscopic radical resection of Siewert type II AEG.

[Efficacy observation of the caudal-medial approach combined with "page-turning" middle lymphadenectomy in the laparoscopic right hemicolectomy].

Objective: To investigate the safety and feasibility of caudal-medial approach combined with "page-turning" middle lymphadenectomy in the laparoscopic right hemicolectomy. Methods: A descriptive cohort study was conducted. Clinical data of 35 patients who underwent laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy at Department of Gastrointestinal Surgery, Guangdong Hospital of Chinese Medicine from April 2018 to May 2020 were retrospectively analyzed. All operations were performed consecutively by the same surgeon. The caudal-medial approach was used to dissect the right Toldt's fascia and the anterior pancreaticoduodenal space in a caudal-to-cranial and medial-to-lateral manner guided by the duodenum. The "page-turning" middle lymphadenectomy was used to dissect the mesocolon along the superior mesenteric vein with ileocolic vein, Henle's trunk and pancreas exposed preferentially. Results: All the 35 patients completed the operation successfully, and there was no damage and bleeding of superior mesenteric vessels and their branches. The operative time was (186.9±46.2) minutes, and the blood loss was 50 (10-200) ml. The first time to flatus was (2.1±0.6) days, and the time to fluid intake was (2.5±0.8) days. The postoperative hospital stay was 6 (3-18) d. The overall morbidity of postoperative complication was 8.6% (3/35), including grade II in 1 cases (2.8%) and grade IIIa in 2 case (5.7%) according to the Clavien-Dindo grading standard. The total number of lymph node dissected was 30.2±5.6, and the positive lymph node was 0 (0-7). Tumor staging revealed 5 cases of stage I, 18 cases of stage II, 11 cases of stage III, and 1 case of stage IVA. In this study, the median follow-up time was 15 (4-29) months. One patient died due to cerebrovascular accident 12 months after surgery, and no tumor recurrence or metastasis was observed in all other patients. Conclusions: Laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy is safe and feasible. The anterior pancreaticoduodenal space is preferentially mobilized, which reduces the difficulty of central vascular dissection.

[Analysis of bloodstream infections in children with acute myeloid leukemia during induction chemotherapies].

Objective: To explore the clinical features of bloodstream infections (BSI) in children with acute myeloid leukemia (AML) during the first induction chemotherapy. Methods: The clinical data, pathogen of BSI, antibiotic susceptibility in vitro, complications and prognosis of 204 newly diagnosed AML children admitted to Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2009 to December 2015 were analyzed retrospectively. χ2 test was used for the comparison between groups and Logistic regression was used for BSI risk factor analysis. Results: Among 204 patients, 116 were males and 88 were females. The age was 8 (ranged from 1 to 14) years. Among them, 170 patients received MAE chemotherapies (etoposide, mitoxantrone and cytarabine) and 25 received IAE chemotherapies (etoposide, idarubicin and cytarabine). The other 9 patients used granulocyte colony stimulating factor (G-CSF)-priming regimen (aclacinomycin or homoharringtonine, cytarabine and G-CSF) for induction treatments. A total of 28 patients experienced BSI and the incidence rate was 13.7% (28/204), 26 of them developed BSI once and 2 patients developed twice. Gram-positive bacteria were predominant pathogens accounting for 53.3% (16/30) while gram-negative bacteria accounting for 40.0% (12/30) and fungal accounted for 6.7% (2/30). The most common detected pathogens were Coagulase negative Staphylococcus (CoNS, 26.7% (8/30)), followed by Streptococcus spp. (13.3% (4/30)) and Escherichia coli (13.3% (4/30)). Among Gram-negative bacteria (GNB), 3 cases showed carbapenem resistance and 2 cases were Stenotrophomonas maltophilia. BSI-related mortality was 28.6% (8/28). Infections caused by drug-resistant GNB or fungi resulted in 6 fatal cases. The incidence rate of BSI in group with severe neutropenia was higher than in group without it (16.6% (25/151) vs. 5.7% (3/53), χ²=3.933, P=0.047). Multivariable analysis showed severe neutropenia at the onset of fever was independent risk factor of BSI (OR=4.258,95%CI 1.097-16.524,P=0.036). Conclusions: During the first induction chemotherapy courses, Gram-positive bacteria cause most of the BSI. Drug-resistant bacteria related infection often result in fatal outcomes. Severe neutropenia is a significant risk factor.

[Familial platelet disorder with predisposition to myeloid leukemia (FPD/AML): a case report and literature review].

Objective: To analyze the clinical features, bone marrow features, and gene mutations of children with familial platelet disorder with predisposition to myeloid leukemia (FPD/AML) caused by a RUNX1 germline mutation as well as their family members. Methods: The clinical data and gene mutations of a child with FPD/AML hospitalized in the Pediatric Blood Disease Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and some family members were extracted and analyzed. The literature was searched using "RUNX1 germline mutation" and "FPD/AML" as keywords in the Chinese databases; also PubMed was reviewed until September 2020. Results: A male patient aged 5 with dermatorrhagia was admitted due to thrombocytopenia for more than 3 years. The laboratory tests revealed a peripheral blood routine (WBC 6.38×10(9)/L, HGB 113 g/L, PLT 54×10(9)/L, NEUT 4.03×10(9)/L, and MPV 9.1 fl) . Bone marrow smear revealed dysplasia of megakaryocytes. The immunohistochemistry for CD42b and CD41 highlighted small mononuclear megakaryocytes. Second generation sequencing revealed RUNX1 (exon3:c.520delC: p.R174Efs*10, NM_001001890) frameshift mutations, and its germline mutation was verified via genetic detection of oral epithelial cells. Five members of the family had blood diseases and successively died. The child's mother and maternal grandfather were sequenced for the second generation, and RUNX1 frameshift mutation was detected in the same locus as the child. However, the clinical features among them were different. A total of 37 English literatures were retrieved, and more than 70 FPD/AML families were reported. No relevant Chinese literature was retrieved. Conclusion: Runx1 germline mutations cause FPD/AML with a high risk of progression to myeloid malignancy. Family members carrying the same mutations may exhibit different clinical features and severity.

[Safety and feasibility of laparoscopic double-flap technique in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction tumors larger than 5 cm].

Objective: To investigate the safety and feasibility of laparoscopic double-flap technique (Kamikawa) in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction (EGJ) leiomyoma and gastrointestinal stromal tumor (GIST) with the maximum diameter >5 cm. Methods: A descriptive case-series study was used to retrospectively analyze the data of patients with EGJ leiomyoma and GIST undergoing laparoscopic-assisted proximal gastrectomy and double-flap technique (Kamikawa) at the Department of Gastrointestinal Surgery, Guangdong Hospital of Traditional Chinese Medicine from September 2017 to March 2019. All the tumors invaded the cardia dentate line, and the maximum diameter was >5 cm. After the exclusion of patients requiring emergency surgery and complicating with severe cardiopulmonary diseases, a total of 4 patients, including 3 males and 1 female with age of 29-49 years, were included in this study. After laparoscopic-assisted proximal gastrectomy, the residual stomach was pulled out of the abdominal cavity and marked with methylene blue at the proximal end 3~4 cm from the anterior wall of the residual stomach in the shape of "H". The gastric wall plasma muscular layer was cut along the "H" shape, and the space between the submucosa and the muscular layer was separated to both sides along the longitudinal incision line to make the seromuscular flap. The residual stomach was put back into the abdominal cavity. Under laparoscopy, 4 stitches were intermittently sutured at the upside of "H" shape and 4-5 cm from the posterior wall of the esophageal stump. The stump of the esophagus was cut open, and the submucosa and mucosa were cut under the "H" shape to enter the gastric cavity. The posterior wall of the esophageal stump was sutured continuously with the gastric stump mucosa and submucosa under laparoscopy. The anterior wall of the esophageal stump was sutured continuously with the whole layer of the residual stomach. The anterior wall of the stomach was sutured to cover the esophagus. The anterior gastric muscle flap was sutured and embedded in the esophagus to complete the reconstruction of digestive tract. The morbidity of intraoperative complications and postoperative reflux esophagitis and anastomosis-related complications were observed. Results: All the 4 patients completed the operation successfully, and there was no conversion to laparotomy. The median operative time was 239 (192-261) minutes, the median Kamikawa anastomosis time was 149 (102-163) minutes, and the median intraoperative blood loss was 35 (20-200) ml. The abdominal drainage tube and gastric tube were removed, and the fluid diet was resumed on the first day after surgery in all the 4 patients. The median postoperative hospitalization time was 6 (6-8) days. Postoperative pathology revealed 3 leiomyomas and 1 GIST. There were no postoperative complications such as anastomotic leakage or stenosis, and no reflux symptoms were observed. The median follow-up time was 22 (11-29) months after the operation, and no reflux esophagitis occurred in any of the 4 patients by gastroscopy. Conclusion: For >5 cm EGJ leiomyoma or GIST, double-flap technique (Kamikawa) used for digestive tract reconstruction after proximal gastrectomy is safe and feasible.

[Efficacy and prognostic factors of the chemotherapy regimen of CCLG-ALL-2008 on pediatric acute lymphoblastic leukemia with ETV6-RUNX1 rearrangement].

Objective: To evaluate the predictive role of ETV6-RUNX1 fusion gene in protocol CCLG-ALL-2008 as well as identify the prognostic factors that influence the outcome of ALL with ETV6-RUNX1 fusion gene. Methods: One hundred and seventy-eight patients newly diagnosed with pediatric acute lymphoblastic leukemia with ETV6-RUNX1 rearrangement from April 2008 to April 2015 were enrolled in CCLG-ALL-2008. The follow up period ended in July 2018; we performed retrospective analyses of their data to determine the efficacy of the regimen and the prognostic factors. Results: The median age of the study population (178 pediatric patients) , including 100 boys and 78 girls was 4 (1-13) y, and the median white blood cell count at diagnosis was 9.46 (1.25-239.83) ×10(9)/L. Three patients died, and 1 was lost to follow up by the end of the first induction chemotherapy, resulting in an induced remission rate of 97.8% (174/178) . The cumulative incidence of relapse was 15.9% with a median follow up of 73.5 mon. Total 83.3% of the relapse cases were those of isolated bone marrow relapse, while 79.2% of the cases were those of late relapse. The median interval time between relapse and first complete remission was 35.5 mon (range, 1-62 months) . One of the 5 patients with early recurrence and 7 of the 19 with late recurrence cases survived. The 5-year-OS and 5-year-EFS of ETV6-RUNX1 positive children was (89.4±2.4) % and (82.1±6.9) %, respectively. The estimated 10-year-OS and 10-year-EFS of ETV6-RUNX1 positive children was (88.6±2.5) % and (77.3±4.0) %, respectively. The Kaplan-Meier method and Log-rank test were used to estimate and compare the survival. Univariate statistical analysis showed that poor prognostic factors that influenced survival included central nervous system state 2 at diagnosis, poor prednisone response, high risk, gene positivity after induction chemotherapy, as well as MRD positivity and gene positivity at the 12(th) week. In the multivariate analysis, only the central nervous system state 2 at diagnosis and MRD positivity at the 12(th) week were associated with the outcome. Conclusion: ETV6-RUNX1-positive ALL is a subgroup with a favorable prognosis as per the CCLG-ALL-2008 protocol. Patients with ETV6-RUNX1 should be given more intensive therapy, including hematopoietic stem cell transplantation when they are CNS2 at diagnosis or have high level of MRD at the 12(th) week after treatment.