A longitudinal and cross-sectional study of placental circulation between normal and placental insufficiency pregnancies.

INTRODUCTION: To longitudinally and cross-sectionally study the differences in the uterine artery pulsatility index (UTPI), umbilical artery pulsatility index (UAPI) and placental vascularization indices (PVIs, derived from 3-dimensional power Doppler) between normal and placental insufficiency pregnancies throughout gestation. METHODS: UTPI, UAPI and PVI were measured 6 times at 4- to 5- week intervals from 11 to 13+6 weeks-36 weeks. Preeclampsia (PE) and fetal growth restriction (FGR) were defined as placental insufficiency. Comparisons of UTPI, UAPI and PVI between normal and insufficiency groups were performed by one-way repeated measures analysis of variance. RESULTS: A total of 125 women were included: monitored regularly from the first trimester to 36 weeks of gestation: 109 with normal pregnancies and 16 with placental insufficiency. Longitudinal study of the normal pregnancy group showed that UTPI and UAPI decreased significantly every 4 weeks, while PVIs increased significantly every 8 weeks until term. In the placental insufficiency group however, this decrease occurred slower at 8 weeks intervals and UTPI stabilized after 24 weeks. No significant difference was noted in PVIs throughout pregnancy. Cross-sectional study from different stages of gestation showed that UTPI was higher in the insufficiency group from 15 weeks onward and PVIs were lower after 32 weeks. DISCUSSION: Compared to high-risk pregnancies with normal outcome, UTPI and UAPI needed a longer time to reach a significant change in those with clinical confirmation of placental insufficiency pregnancies and no significant change was found in PVI throughout gestation. UTPI was the earliest factor in detecting adverse outcome pregnancies.

[Multicenter evaluation of minimal residual disease monitoring in early induction therapy for treatment of childhood acute lymphoblastic leukemia].

Objective: To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL). Methods: This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children's Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors. Results: Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×109/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively (χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant (χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively (χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%,χ2=4.13,P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%,χ2=4.06,P=0.044;(58.3±18.6)% vs. (85.7±3.2)%,χ2=9.44,P=0.002). Multivariate analysis showed that age (OR=0.58, 95%CI 0.35-0.97) and white blood cell count at first diagnosis (OR=0.43, 95%CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 (OR=0.55,95%CI 0.31-0.97), ETV6-RUNX1 fusion gene (OR=0.13,95%CI 0.03-0.54), MLL gene rearrangement (OR=2.55,95%CI 1.18-5.53) and white blood cell count at initial diagnosis (OR=0.52,95%CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions: The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

[Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma].

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

[Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis].

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

[Safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use in healthy people aged 9-65 years].

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.

[Preliminary exploration of the metabolic profile and metabolic pathways in newly diagnosed multiple myeloma].

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

Association between Cognitive Frailty and Adverse Outcomes among Older Adults: A Meta-Analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to pool the effect size of the association between cognitive frailty and adverse outcomes (e.g., falls, disability, and hospitalization) among older adults. DESIGN: Systematic review and meta-analysis. METHODS: PubMed, ScienceDirect, and Embase were searched from their respective inceptions to June 1, 2022. We extracted prospective cohort studies that reported the association between cognitive frailty and adverse outcomes. Random or fixed-effects models based on heterogeneity were used to pool the effect sizes of independent associations of cognitive frailty, frailty only, and cognitive impairment only with each adverse outcome. RESULTS: Fifteen studies involving 49,122 older adults were included in the meta-analysis. Older adults with cognitive frailty had higher odds ratios (OR) for falls (1.82, 95% confidence interval [CI]: 1.29-2.58), disability (3.17, 95%CI: 2.24-4.48), and hospitalization (1.78, 95%CI: 1.48-2.14) compared with those without frailty and cognitive impairment. Older adults with frailty only demonstrated a high risk for falls (pooled OR 1.76, 95%CI: 1.25-2.48), disability (pooled OR 1.82, 95%CI: 1.43-2.33), and hospitalization (pooled OR 1.64, 95% CI: 1.45-1.85). The influence of cognitive impairment only on adverse outcomes was lower compared with cognitive frailty or frailty. Subgroup analyses showed that those with cognitive frailty (defined by the frailty phenotype plus Mini-Mental State Examination) were at greater risk for developing adverse outcomes. CONCLUSION: Our findings indicate that cognitive frailty is an independent risk factor for adverse outcomes (e.g., falls, disability, and hospitalization). Early screening and comprehensive intervention may improve cognitive frailty and reduce the risk for adverse outcomes among older adults.

The value of placental vascularization indices for predicting preeclampsia and fetal growth restriction in different stages of gestation: A prospective and longitudinal study.

INTRODUCTION: To assess value of placental vascularization indices (PVIs) for predicting preeclampsia (PE) and fetal growth restriction (FGR) in different stages of pregnancy in high-risk women. METHOD: PVIs derived from 3-dimensional power doppler(3DPD) imaging were measured at seven stages of pregnancy: 11-13+6w, 15-19+6w, 20-23+6w, 24-27+6w, 28-31+6w, 32-36+6w, and ≥37w. PE and FGR were used as outcomes in logistic regression models. Area under the receiver operating characteristic (ROC) curve (AUC) of each PVI was calculated, cut-off points were determined to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Finally, AUCs combined with baseline characteristics, uterine artery pulsatility index (UTPI) and PVIs were used to determine whether PVIs could increase the predictive value. RESULTS: Adverse outcomes occurred in 10.9% of pregnancies. Statistical differences appeared in 32-36+6w only. AUCs of vascularization index (VI) and vascularization flow index (VFI) for 32-36+6w were 0.79 (0.70-0.87, p: 0.000), and 0.78 (0.69-0.88, p: 0.000). Sensitivity, specificity, PPV, NPV, PLR, and NLR for VI were 0.91, 0.63, 20%, 98%, 2.39, and 0.15, and those for VFI were 0.62, 0.84, 29%, 95%, 3.75, and 0.45. AUC increased from 0.79 to 0.85 by adding PVIs to baseline characteristics and UTPI model. No statistical significance was found before 32w. DISCUSSION: VI and VFI were valuable for predicting PE and FGR at the 32-36+6w stage, while their values before 32w were poor.

[Intervention effects of drugs on GSH and SOD enzyme activity of rats kidney acutely poisoned by nickel carbonyl].

Objective: To evaluate the intervention effect of various drugs on glutathione (GSH) and superoxide dismutase (SOD) enzyme activity of rats kidney with acute nickel carbonyl poisoning. Methods: In January 2019, The 250 SPF male SD rats were randomly divided into normal control group (n=10) , poisoned group (n=40) and treatment groups (n=200) according to the random number table method. And the treatment groups were divided into methylprednisolone group (20 mg/kg) , DDC group (100 mg/kg) , sodium selenite group (10 µmol/kg) , Shenfu huiyang decoction group (0.25 ml) and methylprednisolone combined with DDC group (100 mg/kg) , with 40 mice in each group. Except for the normal control group, rats in the other groups were exposed to nickel carbonyl for 30 min, at 4 h and 30 h after exposure, the rats in each treatment group were intraperitoneally injected with corresponding drugs, and kidney tissues were collected 3 d and 7 d after administration, with 10 mice in each group. The activities of GSH and SOD in kidney were measured by enzyme-linked immunosorbent assay, and using electron microscopy observe ultrastructure changes. Results: Compared to the control group, the activities of GSH and SOD enzyme of poisoned group were significantly decreased at 3 d or 7 d after 4 h or 30 h exposure, and the difference was statistically significant (P=0.000, 0.031, 0.001, 0.033) , the epithelial nuclei of proximal convoluted tubules were pyknosis and lysosome hyperplasia in the cytoplasm. And compared to poisoned group, the activities of GSH and SOD enzyme of methylprednisolone+DDC group were significantly increased at treatment with 7 d after 4 h exposure, the difference was statistically significant (P=0.022, 0.000) , and the activities of GSH and SOD enzyme of methylprednisolone and enzyme of methylprednisolone+DDC group were significantly higher at 7 days than at 3 days, the difference was statistically significant (P=0.020, 0.017, 0.018, 0.033) . The results of electron microscopy showed that the cell nuclei and cytoplasmic organelles of proximal convolute tubule were almost restored to normal tissue level of both methylprednisolone group and methylprednisolone+DDC group. Conclusion: The methylprednisolone and methylprednisolone+DDC have obvious repair effect on renal enzyme activity level of rats with acute nickel carbonyl poisoning, and the treatment effect is better for a long time of medication.

[A comparison of C+SCAV and SEAM conditioning regimens in efficacy and safety in autologous hematopoietic stem cell transplantation for non-Hodgkin's lymphoma patients].

Objective: This study aimed to compare the efficacy and safety of cladribine, smustine, etoposide, cyclophosphamide, and cytarabine (C+SCAV) and smustine, etoposide, cytarabine, and melphalan (SEAM) conditioning regimens in autologous stem cell transplantation (auto-HSCT) for non-Hodgkin's lymphoma (NHL) . Methods: A retrospective analysis was conducted on 61 NHL patients who received auto-HSCT in the Department of Hematology, the First Affiliated Hospital of Suzhou University, from March 2018 to May 2021. The C + SCAV group and SEAM group had 19 and 42 patients, respectively. Results: ① Among the 61 patients with NHL, 37 were male and 24 were female. The median age was 48 (21-66) years old. There were 19 cases in the C+SCAV group and 42 cases in the SEAM group. There was no significant difference in the baseline characteristics between the two groups (P>0.05) . ② The median time to neutrophil and platelet engraftment in the C+SCAV cohort were 10 (8-15) days and 13 (9-22) days, respectively, which does not differ from the SEAM group (P=0.103, P=0.403) . ③ No differences existed between the two groups in terms of survival. The 1-year progression-free survival (PFS) was (76.5±10.3) % for patients receiving C+SCAV and (78.4±6.8) % for those who received SEAM (P=0.841) . The 1-year overall survival was 100.0% for the C+SCAV group and 95.2±3.3% for the SEAM group (P=0.339) . ④The 1-year PFS of patients with complete remission in the C+SCAV group was similar to those who in the SEAM group [ (92.3±7.4) % vs (82.5±7.2) %, P=0.406]. ⑤ The incidence of non-hematological serious adverse events (≥ grade 3) in the C+SCAV group and SEAM group were 10.5% (2/19) and 40.5% (17/42) (P=0.013) , the incidence of severe mucositis was 5.3% (1/19) and 31.0% (13/42) (P=0.015) , and the incidence of severe infection (≥ grade 3) was 10.5% (2/19) and 19.0% (8/42) (P=0.389) , respectively. Conclusion: C + SCAV conditioning regimen appeared to be no different from the SEAM regimen in terms of survival. It can lower the incidence of SAE and does not increase the risk of severe infection. As a result, it can be used as an alternative conditioning regimen for lymphoma patients undergoing auto-HSCT.

[Clinical analysis of amphotericin B cholesteryl sulfate complex for injection in the treatment of invasive fungal disease for patients with hematological malignancies in 30 cases].

Objective: To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness. Methods: This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives. Results: 30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day. Conclusions: Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.

Cognitive Frailty and Falls in a National Cohort of Older Chinese Inpatients.

Previous studies have investigated the association between cognitive frailty and falls among older adults in community; however, no study investigated this relationship among older patients living in hospital. This study aimed to examine the relationship of cognitive frailty with falls among older inpatients in Chinese hospital. METHODS: This analysis consisted of 9192 older inpatients aged 65 years or over from six hospitals in China. We used FRAIL scale and Mini-Cog to assess frailty and cognitive impairment, respectively. A generalized estimating equation was used to examine the relationship between cognitive frailty and falls at 30-day follow-up. RESULTS: Among 9192 older inpatients enrolled in this present study, the mean (SD) age was 72.40(5.72) years, with 3850(41.88%) women. The cross-sectional analysis found that after controlling for variables (age, gender, education, depression, and hospital ward cluster effect), hospitalized patients with cognitive frailty, frailty only, or cognitive impairment only at baseline were all associated with history of falls (P<0.05). At 30-day follow-up, generalized estimating equation with full-adjustment showed that inpatients with cognitive frailty were at greater risk of falls than those of non-frail and cognitive intact (OR=3.0,95%CI:1.32-6.83). This association was also observed in individuals with frailty only (OR=2.11,95%CI:1.04-4.27) but not for patients with cognitive impairment only((OR=1.11,95%CI:0.43-2.85). CONCLUSION: Our study suggested that hospitalized Chinese older adults with cognitive frailty were independently associated with falls. Early screening frailty and cognitive impairment were significant for older patients by clinicians, and corresponding interventions, exercise training and nutritional programs, should be implemented to prevent falls.

[Etiology of severe community-acquired pneumonia in immunocompromised patients].

Objective: To analyze the etiology of severe community-acquired pneumonia (SCAP) in immunocompromised patients, and to investigate the relationship between underlying diseases and infectious microorganisms. Methods: A retrospective analysis was performed on SCAP in immunocompromised patients admitted to the Fourth Department of Respiratory and Critical Medicine (MICU) of China-Japan Friendship Hospital from January 1, 2017 to December 31, 2019. A total of 119 SCAP patients were finally enrolled, including 65 males (54.6%), with an average age of (59.3±14.5) years. The average of Sequential Organ Failure Assessment (SOFA) score was 6.7±3.6 and the acute physiology and chronic health evaluation (APACHE) Ⅱ score was 19.4±6.8. Sixty (50%) of these patients were finally improved and discharged. Long-term glucocorticoid treatment was the main risk factor for immunocompromise. The difference of pathogenic microorganisms between patients with and without structural lung diseases, and the influence of different pathogenic microorganisms on hospital mortality were calculated, respectively. P<0.05 was considered to be statistically significant. Results: In this study, 99 (83.2%) patients were identified to have positive etiological results, and the incidence of concurrent infection was 54.5%. The top three pathogens were Pneumocystis Jiroveci (55.6%), Cytomegalovirus (47.5%) and Aspergillus (23.2%). Staphylococcus aureus was the most common bacterium, followed by Pseudomonas aeruginosa and Klebsiella pneumoniae. The risk of Pneumocystis Jiroveci infection was significantly higher in patients without underlying lung diseases as compared to those with underlying lung diseases (64.3% vs. 44.2%, P = 0.046). The in-hospital mortality was not different among patients infected with different pathogens(all P>0.05), but was higher in those with mixed infections(56.7% vs. 33.9%, P=0.013). Conclusions: Pneumocystis Jiroveci and Cytomegalovirus were the most common pathogens in immunocompromised patients with severe community-acquired pneumonia, and the incidence of Pneumocystis Jiroveci was significantly higher in patients without underlying lung diseases.

[Adherence to adjuvant with therapy imatinib in patients with gastrointestinal stromal tumor: a national multi-center cross-sectional study].

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.

[Clinical and prognostic values of TP53 mutation in patients with B-lineage acute lymphoblastic leukemia].

Objective: To investigate the survival and prognosis of B-lineage acute lymphoblastic leukemia (B-ALL) patients with TP53 mutation. Methods: The clinical data of 479 newly diagnosed B-ALL patients treated in the First Affiliated Hospital of Soochow University from January 2016 to December 2019 were retrospectively analyzed. Results: Among 479 B-ALL patients, 34 cases (7.1%) were positive for TP53 gene mutation, and a total of 36 TP53 mutations were detected, including 10 frameshift gene mutations (27.8%) , 23 missense mutations (63.9%) and 3 nonsense mutations (8.3%) . A total of 34 (94.4%) mutations were located in the DNA binding domain (exons 5-8) .The average number of mutated genes in patients with TP53 gene mutation (2.3) and the group without TP53 gene mutation (1.1) were statistically different (P<0.001) . The proportion of Ph positive and Ph-like positive patients in the TP53 gene mutation negative group was significantly higher than that of the TP53 mutation positive group, and the difference was statistically significant (P<0.001) . The 3-year OS and EFS rates of the TP53 gene mutation negative group were significantly higher than those of the TP53 gene mutation positive group. The differences in OS and EFS rates between the two groups were statistically significant (χ(2)= 4.694, P = 0.030; χ(2)= 5.080, P= 0.024) . In the multivariate analysis, failure to achieve remission (CR) after one course of induction chemotherapy was an independent adverse prognostic factor affecting OS.Of the 34 patients with TP53 mutation, 16 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the CR(1) state, and 2 patients with recurrence after transplantation obtained CR(2) after infusion of donor-derived anti-CD19 chimeric antigen receptor T (CAR-T) cells. Among the 11 patients with TP53 gene mutation who relapsed during consolidation chemotherapy, 6 received anti-CD19 CAR T cell therapy, 4 patients achieved remission and minimal residual disease (MRD) turned negative, followed by bridging allo-HSCT, and 2 of them sustained CR. Conclusion: Missense mutations are the most common in B-ALL patients with TP53 gene mutation, and the majority of mutations were located in the DNA binding domain. B-ALL patients with TP53 gene mutation should undergo allo-HSCT as soon as possible after CAR-T cell therapy has cleared the MRD after recurrence. B-ALL patients with TP53 gene mutation still have a higher recurrence rate after allo-HSCT, and the infusion of donor-derived CAR-T cells can achieve better sustained remission.

Identifying optimal virtual water management strategy for Kazakhstan: A factorial ecologically-extended input-output model.

Virtual water is an important indicator measuring the amount of water needed from the perspective of consumption, which can help decision makers to identify desired system design and optimal management strategy against water resources shortage. In this study, a novel model named as factorial ecologically-extended input-output model (abbreviated as FEIOM) is developed for virtual water management. FEIOM integrates techniques of input-output model (IOM), ecological network analysis (ENA) and factorial analysis (FA) into a general framework. It is effective to evaluate the virtual water flows, reveal ecological inter-connections in virtual water system (VWS), and identify key water consumption sectors that have significant individual and interactive effects on VWS's performance. FEIOM is then applied to identifying optimal virtual water management strategies for Kazakhstan in Central Asia. The main findings are: (i) Kazakhstan is a net importer of virtual water (reaching up to 46.0 × 109 m3), demonstrating that the national economic structure is reasonable, which can abate the national water scarcity and improve its eco-environmental protection; (ii) the virtual water of agricultural sector is net exporter, where vegetables, fruits and nuts occupy 86% of the total agricultural exports; the massive export of water-intensive products further squeezes the water for other users; (iii) the key factors affecting the national VWS are agriculture > primary manufacturing > advanced manufacturing > services. Therefore, from solving water resources shortage and facilitating sustainable development perspectives, Kazakhstan should stimulate the domestic primary manufacturing productions and improve agriculture and advanced manufacturing water-use efficiencies.

[Risk factors of peritoneal metastasis in primary appendiceal tumor].

Objective: To investigate the risk factors of peritoneal metastasis in primary appendiceal tumor. Methods: The clinic data of 71 patients with primary appendiceal tumor admitted in the Sixth Affiliated Hospital of Sun Yat-sen University between Dec 2012 and Jan 2019 were enrolled retrospectively. Multivariate logistic regression analysis were carried out to evaluate the risk factors of appendiceal tumor with peritoneal metastasis. Results: Of the 71 patients, 33 were peritoneal metastasis (peritoneal metastasis group) and 38 were non-peritoneal metastasis (no peritoneal metastasis group). Twenty-one patients in the peritoneal metastasis group had increased preoperative cancer embryo antigen (CEA), while 3 cases in the non-peritoneal metastasis group, with statistically significant difference (P<0.001). Sixteen cases in peritoneal metastasis group had increased preoperative carbohydrate antigen 199, while only 2 cases in the non-peritoneal metastasis group, the difference was statistically significant (P<0.001). The pathological type of 30 cases in the peritoneal metastasis group was adenocarcinoma (including mucus adenocarcinoma and colon adenocarcinoma), while 12 cases of adenocarcinoma in the non-peritoneal metastasis group, with statistically significant difference (P<0.001). Twelve cases in the peritoneal metastasis group had lymph node metastasis, while 3 cases in the non-peritoneal metastasis group, the difference is statistically significant (P=0.003). Preoperative CEA elevation and pathological type is adenocarinoma were independent risk factors for peritoneal metastasis of appendiceal cancer (P<0.05). Conclusions: The propensity of peritoneal metastasis in primary appendiceal tumor is high and the outcome is poor. Patients with increased preoperative CEA, adenocarcinoma histopathology are more inclined to have peritoneal metastasis.