Objectives:To investigate the clinical characteristics and risk factors of invasive fungal disease (IFD) in patients with hematological disorders. Methods:From January 2023 to January 2025, 67 patients with blood diseases hospitalized at the Hematology Department who were suspected of infection with IFD underwent metagenomic next-generation sequencing (mNGS) and fungal pathogen detection. Their clinical characteristics and laboratory examinations were retrospectively analyzed. Results:A cohort of 67 patients was enrolled in the study, among which 32 cases were diagnosed with IFD through mNGS and etiological culture, while no fungal pathogens were detected in the remaining 35 cases. The diagnostic yield of mNGS for fungal infection detection (47.76%) demonstrated superior sensitivity compared to conventional pathogenic microbial culture (14.93%), β-D-glucan assay (11.94%), and galactomannan assay (2.99%). Within the IFD cohort, Candida species constituted the most prevalent etiology (46.88%, n = 15), followed by Aspergillus (18.75%, n = 6), Penumocystis (12.5%, n = 4), and Rhizomucor (12.5%, n = 4), with other fungal species accounting for the remaining cases (9.37%, n = 3). Multivariate logistic regression analysis revealed six independent risk factors associated with IFD in patients with hematological disorders: cluster of differentiation 4+ T cell count <400 cells/µL (odds ratio [OR] = 9.45, P = 8.9×10-5), elevated C-reactive protein (OR = 3.18, P = 0.027), elevated interleukin (IL)-6 (OR = 5.75, P = 0.001), elevated IL-10 (OR = 3.31, P = 0.033), hypoproteinemia (OR = 42.17, P = 0.013), and neutropenia lasting for more than 10 days (OR = 4.11, P = 0.015). Conclusions:mNGS has high sensitivity in detecting IFD in patients with hematological diseases. Cluster of differentiation 4+ cell count below 400/uL, increased level of C-reactive protein, IL-6, and IL-10, hypoproteinemia, and neutropenia lasting for more than 10 days are independent risk factors for IFD in patients with hematological diseases.

Objective To explore the testing performance of metagenomic next-generation sequencing (mNGS) in identifying pathogenic microbes in febrile patients with hematological disease and its significant role in guiding clinical treatment. Methods The data of pathogens from the blood cultures of neutropenic patients with hematological disease and/or febrile patients with bloodstream infection (BSI) were summarized and the features of infection were analyzed, through a retrieval of the WoS, PubMed, CNKI, Wanfang, and VIP databases. A retrospective study was conducted on 96 febrile patients with hematological disease (104 specimens) presented to our hospital between May 2022 and May 2024. These patients underwent both routine and mNGS tests for a comparison of the testing performance, and were assigned to mNGS-positive and mNGS-negative groups according to the mNGS results, respectively. Based on an analysis of the data and indexes of the two groups, the contributing factors of mNGS positivity were determined using the univarient and the logistic regression while a prediction model was developed to assess predictive value and summarize the prognosis information using the Receiver Operating Characteristic Curve (ROC). Results According to the included six papers, among totally 3614 isolates from positive blood cultures, Gram-negative bacteria, Gram-positive bacteria, and fungi accounted for 66.66%, 31.02%, and 2.05%, respectively. In this retrospective study, out of 104 peripheral blood tests using mNGS technology, pathogens were detected in 71 tests, with a positive detection rate of 68.27%, which was substantially higher than that of blood culture (7.69%) and routine test (16.35%). Out of 131 isolated pathogenic microbes, viruses held the maximum ratio (60.74%). The identification rate of combined infections by the mNGS test exceeded those by complete blood count (CBC) and routine test. When clinical diagnosis was employed as the gold standard, mNGS test had greater values of sensitivity, positive prediction and negative prediction than those of routine test. The univariant analysis revealed that the mNGS-positive group had higher incidences of pulmonary infection and neutropenia and lower natural killer (NK) cell levels, compared with the mNGS-negative group. The multivariate analysis result of logistic regression model showed that contributing factors of mNGS positivity in febrile patients with hematological disease included pulmonary infection [Odds ratio (OR): 2.389; 95%confidence level (CI): 1.199–4.763)], neutropenia (OR: 4.092; 95% CI: 1.179–14.209), and low NK cell levels (OR: 1.127; 95% CI: 1.117–1.139). According to the analysis result of the ROC curve, the area under curve (AUC) values used for single and combined predictive values of mNGS positivity in febrile patients with hematological disease ranged from 0.623 to 0.849, with the maximum value of 0.849 for combined prediction. The sensitivity and specificity values were 78.79% and 93.33%, respectively. Following relevant guidelines, physicians modified medication for patients with poor disease management based on mNGS results, achieving a survival rate of 75.0%. Conclusion mNGS allows a more comprehensive and accurate identification of pathogenic microbes in patients with hematological disease. However, the positive rate of mNGS test may be affected by pulmonary infection, neutropenia, and low NK cell levels. Therefore, appropriate timing of the mNGS use can provide critical information for the formulation of clinical protocol and enables individualized and accurate treatment.

Abstract Objective To evaluate the efficacy and safety of aerosol inhalation of amphotericin B (AmB) in preventing invasive fungal disease (IFD) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy (IST). Methods The efficacy and safety of aerosol inhalation of amphotericin B or gargling with sodium bicarbonate/nystatin to prevent IFD in SAA patients within 28 days were compared. Thirty-three cases were assigned to the Am AmB nebulization group and 65 cases to the mouthwash group. Breakthrough fungal infection and related mortality were evaluated. Results Five cases of breakthrough fungal infection occurred in the AmB nebulization group, compared to 34 cases in the mouthwash group (15.2% vs 52.3%, p = 0.00083). In the 3 months after IST, no patient died of fungal infection in the AmB nebulization group, as compared to two cases in the mouthwash group (0% vs 28.5%, p = 0.021). No grade III or above AmB-related toxicity events occurred in the aerosol inhalation group. Conclusion Aerosol inhalation of AmBB could effectively prevent IFD and related mortality in SAA patients during IST, and the treatment was well-tolerated.

Addition of eltrombopag (E-PAG) to intensive immunosuppressive therapy (IST) contributes to restoring hematopoiesis in patients with severe aplastic anemia (SAA). Used at relatively low doses in the East Asian population, the efficacies of E-PAG and the predictors for efficacy are not clear. We conducted a retrospective, multicenter study to analyze the efficacy and the possible predicting factors at 6 months in 58 adult SAA patients with rabbit ATG-based IST and E-PAG. The response rate and complete response rate at 6 months were 76% and 21%, respectively. The baseline reticulocyte percentage [area under a curve (AUC)=0.798, 95% confidence interval (CI) 0.640-0.956, P=0.006], absolute reticulocyte count (ARC) (AUC =0.808, 95%CI 0.647-0.970, P=0.004), red cell distribution width – coefficient of variation (RDW-CV) (AUC=0.722, 95%CI 0.494-0.950, P=0.040), and absolute lymphocyte count (ALC) (AUC=0.706, 95%CI 0.522-0.890, P=0.057) were highly predictive of response at 6 months. The tipping values of reticulocyte percentage, ARC, RDW-CV, and ALC were 0.45%, 7.36×109/L, 11.75%, and 1.06×109/L, respectively. The sensitivity and specificity of reticulocyte percentages were 81.6% and 66.7%; ARC were 86.8% and 66.7%, RDW-CV were 94.7% and 55.6%; ALC were 55.3% and 88.9%. At a median follow-up of 15.5 months, the 2-year cumulative overall survival was 92%. The baseline reticulocyte percentage, ARC, RDW-CV, and ALC were potential factors in predicting a favorable effect of rabbit-ATG based IST plus E-PAG in SAA patients of East Asia (ChiCTR2100045895).Clinical Trial Registrationhttp://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.

Abstract Background: Female breast cancer is the most common cancer nowadays, and its treatment has a significant impact on patients both physically and psychologically. Many randomized trials have proved that case management (CM) can effectively care for patients. However, there is a lack of systematic scientific evaluation, so this systematic evaluation aims to explore the impact of CM on breast cancer patients. Methods: PubMed, Embase, Cochrane Library, Scopus, CINAHL were searched. Chinese repositories included China National Knowledge, Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database. We will also search unpublished literature at ClinicalTrials.gov. Randomized controlled trials were collected from them. The literature will be screened according to inclusion and exclusion criteria, and 2 researchers will extract the literature independently. The primary outcome indicator for this study will be patient satisfaction. Statistics were performed using RevMan 5.4 software. The quality of each outcome will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. Results: This study will provide the most recent evidence for evaluating the impact of CM on breast cancer patients. Conclusion: To evaluate the impact of CM on patients with breast cancer. Registration number: DOI:10.17605/OSF.IO/ZJKHX.

目的:评估环磷酰胺联合泼尼松(CP)方案治疗环孢菌素(CsA)难治/复发的大颗粒淋巴细胞白血病(LGLL)相关纯红细胞再生障碍(PRCA)的疗效及耐受性.方法:回顾性分析登记于中国东部贫血协作组(CEC-GA)数据库的21例CsA治疗无效或复发的LGLL相关PRCA患者临床资料及接受CP方案治疗结果,评估疗效及耐受性.结果:CsA难治/复发患者共21例,其中难治性16例、复发性5例,经CP方案治疗后,15例达完全缓解(CR),3例达部分缓解(PR),3例治疗无效,治疗总有效率为85.7％(18/21),CR率为71.4％(15/21),中位达PR时间为2.2(0.5～6.6)个月,中位达CR时间为2.3(1.3～6.8)个月,中位疗效维持时间17.0(5.0～32.0)个月.8例STAT3突变阳性患者中7例达CR.13例(61.9％)患者在CP方案治疗期间出现不良反应,主要为粒细胞减少和肝功能异常,2例患者因4级粒细胞减少停药.随访期内,无治疗相关死亡事件.3例(14.3％)患者因药物减停出现复发.中位随访20.0(4.0～34.0)个月,15例仍有效,中位无复发生存时间为16.0(3.0～32.0)个月.结论:对于CsA难治/复发的LGLL相关PRCA患者,CP方案疗效确切,且对STAT3突变阳性患者也效果良好.CP方案主要不良反应为骨髓毒性.

BACKGROUND:Female breast cancer is the most common cancer nowadays, and its treatment has a significant impact on patients both physically and psychologically. Many randomized trials have proved that case management (CM) can effectively care for patients. However, there is a lack of systematic scientific evaluation, so this systematic evaluation aims to explore the impact of CM on breast cancer patients.METHODS:PubMed, Embase, Cochrane Library, Scopus, CINAHL were searched. Chinese repositories included China National Knowledge, Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database. We will also search unpublished literature at ClinicalTrials.gov. Randomized controlled trials were collected from them. The literature will be screened according to inclusion and exclusion criteria, and 2 researchers will extract the literature independently. The primary outcome indicator for this study will be patient satisfaction. Statistics were performed using RevMan 5.4 software. The quality of each outcome will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation.RESULTS:This study will provide the most recent evidence for evaluating the impact of CM on breast cancer patients.CONCLUSION:To evaluate the impact of CM on patients with breast cancer.REGISTRATION NUMBER:DOI:10.17605/OSF.IO/ZJKHX.

目的:分析常见髓系肿瘤基因突变在再生障碍性贫血(AA)中的发生率和特点,与AA患者的临床特征和免疫抑制治疗(IST)结果的相关性.方法:收集213例AA患者初诊及IST后第6、12、24个月的外周血标本,使用二代基因测序法对34种常见髓系肿瘤基因进行检测,分析基因突变特点与AA患者的临床特征、IST疗效及疾病转化之间的相关性.结果:初诊时32例患者检测到基因突变,突变频率为15.02％,18个基因发生总计34次突变.突变次数最多的前3位基因分别为PIGA 35.29％(12/34)、TET2 14.71％(5/34)、ASXL1 11.76％(4/34);儿童组(0～18岁)、青中年组(18～59岁)及老年组(≥60岁)突变率分别为12.50％(4/32)、13.99％(20/143)和21.05％(8/38);重型AA患者突变发生率显著高于非重型AA患者(20.20％ vs 10.53％,P=0.048 7).环孢菌素治疗组突变发生率低于抗人胸腺细胞免疫球蛋白联合环孢菌素治疗组(0 vs 6.9％,P=0.018).治疗新出现预后不良基因突变2例,均无效.结论:AA患者的髓系肿瘤基因突变发生与疾病严重程度和治疗措施可能有关,新出现髓系肿瘤相关基因突变可能与疗效不良有关.

Prospective trials showed the clinical efficacy of eltrombopag in refractory/relapsed aplastic anemia (AA), with up to 40% hematologic improvement [1]. Moreover, eltrombopag was combined with frontline immunosupressive therapy (IST) consisited of antithymocyte immunoglobulin (ATG) and cyclosporin (CsA), with an overall response rate exceeding 80% [2]. The metabolism of eltrodopag is different in disparate population. Currently, the recommended dose is 75 mg/d for East Asian populations [2], Pretreatment clinical and laboratory characteristics predicting eltrombopag response are still unclear in severe AA (SAA) patients of real-world in East Asian.

Objective: To explore the current situation of the out-of-hospital management of patients with cancer and evaluate the feasibility of Internet medical intervention outside the hospital in China.Methods: The questionnaire was designed based on the investigators' clinical experience, literature data, and the Anderson Symptom Scale, and adopted a cross sectional survey method.Results: Totally 1,171 qualified questionnaires were analyzed. The results showed that 92.7% of patients with cancer experienced varying degrees of out-of-hospital symptoms after treatment, and a third of them needed clinical intervention. Abnormal blood test results outside the hospital were basically consistent with the events that occurred during the hospitalization. One third of patients with cancer could not identify abnormal results. The primary approaches to solve these abnormalities were to seek guidance from the physician in charge or from nearby hospitals, but only 6.75% patients sought help online. More than half of the life or work of patients with cancer are still greatly affected under the current management model. 92% of respondents required medical help outside the hospital, and 65% ones were willing to pay for the out-of-hospital management.Conclusions: Out-of-hospital management model needs to be improved. Most users are willing to accept Internet cancer management with fees. The survey has a positive effect on guiding future Internet cancer management practices in China to a certain extent.

目的:评估卡泊芬净在预防重型再生障碍性贫血(SAA)患者强化免疫抑制治疗(IST)中侵袭性真菌病(IFD)的效果和安全性.方法:同期对照比较IST后28 d内SAA患者静脉使用卡泊芬净或碳酸氢钠/制霉菌素交替漱口预防IFD的疗效和安全性,未脱离粒细胞缺乏者延长至恢复期,或最多60 d;评估真菌突破感染率、生存率、死亡率等指标.结果:卡泊芬净组纳入45例患者,对照组纳入65例患者.卡泊芬净组真菌感染突破6例(13.3％),明显低于对照组34例(52.3％)(P＜0.001);卡泊芬净组中死于真菌感染0例,对照组中死于真菌感染4例(6.2％)(P=0.009).卡泊芬净组生存率明显优于对照组(95.6％ vs 78.5％,P=0.027).COX回归分析显示,年龄、初诊粒细胞缺乏程度及持续时间是影响生存的不利因素(P＜0.05).卡泊芬净组未见3级及以上卡泊芬净相关毒性.结论:预防性使用卡泊芬净能够降低SAA患者在IST期间IFD的发生率及相关死亡率,且耐受性良好.