Objective:To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA).Methods:This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People′s Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method.Results:In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days ( n=11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases ( n=26). Most patients ( n=28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions:Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.

Objective:To investigate the types, incidences, and clinical characteristics of shock in polytrauma patients at different stages after polytrauma.Methods:A retrospective study was conducted on polytrauma patients admitted to multiple trauma centers from June 2020 to December 2021. The inclusion criteria were patients >18 years old and treated due to polytrauma. Exclusion criteria included an admission time of more than 48 h after trauma, a history of malignancy, or metabolic, consumptive, and immunological diseases. The early stage was defined as the period of ≤48 h after polytrauma, and the middle stage was defined as the period between 48 h and 14 days. The patient’s medical history, clinical manifestations, laboratory tests, imaging examination, injury severity score (ISS), and Glasgow coma scale (GCS) were collected. The types, incidences, and clinical characteristics of shock in different stages after polytrauma were analyzed, according to the diagnostic criteria of each type of shock. The differences between the groups were compared by Student’s t test, χ2 test or Mann-Whitney U test. Results:The incidence of the early and middle stage shock after polytrauma were 73.1% and 36.4%, respectively, with statistically significant difference between stages ( P<0.01). There were significant differences in the incidence of hypovolemic shock (83.6% vs. 28.4%), distributed shock (13.7% vs. 80.9%) and cardiogenic shock (3.5% vs. 6.6%) between stages (all P<0.05). The incidence of obstructive shock (8.4% vs. 9.7%, P>0.05) was similar between stages. The incidence of undifferentiated shock was 1.6% and 1.2%, respectively. There were 9.5% patients with multifactorial shock in the early stage and 14.4% in the middle stage. Totally 7 combinations of multifactorial shock were found in different stages after polytrauma. In the early stage, the combination of HS and DS accounted the highest ratio (42.3%) and followed by HS and OS for 28.8%. In the middle stage, the combination of HS and DS was the most common (48.6%) and followed by DS and OS (24.3%). Conclusions:The incidence of shock in polytrauma patients is high. Different types of shock can occur simultaneously or sequentially. Therefore a comprehensive resuscitation strategy is significant to improve the success rate of treatment.

Objective:To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG.Methods:This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People′s Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups.Results:In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [ M ( Q1, Q3)] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P>0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day Ⅱ to Ⅳ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), Ⅲ to Ⅳ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P>0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P>0.05). Conclusions:Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.

Objective:To retrospectively assess early risk factor of persistent inflammation, immunosuppression and catabolism syndrome (PICS) in patients with severe polytrauma, in order to deepen the understanding of the pathological changes of chronic critical illness (CCI) after severe polytrauma.Methods:A total of 276 patients with severe polytrauma admitted to Department of Trauma Surgery of Tongji Hospital from March 2019 to December 2020 were enrolled. Inclusion criteria included patients who suffered severe polytrauma, and injury severity score (ISS) ≥27, age ≥18 years old, and had length of hospital stay >15 days. Exclusion criteria included previous medical history of malignancy, or immunological, consumptive, and metabolic diseases. The patient’s clinical characteristics, ISS scores, Glasgow coma scale (GCS), sequential organ failure assessment, APACHEⅡ scores, and nutrition and immune indexes on day 3 after injury were collected. The difference between the PICS group and N-PICS group were performed by Student’s t test, χ2 test or Mann-Whitney U test. The early risk factors were assessed in patients with PICS after severe polytrauma by logistic regression analysis. Results:According to the diagnostic criteria of PICS, all enrolled patients were divided into two groups: PICS group ( n=102) and N-PICS group (without PICS, n=174). Compared with the N-PICS group, patients in the PICS group were older and associated with more brain and chest injuries. On the third day after injury, serum levels of IL-6 and IL-10, and the ratio of Treg cells were significantly higher, the number and ratio of NK cells subset, and the ratio of activated T lymphocyte were significantly lower in the PICS group than in the N-PICS group ( P<0.05). Logistic regression analysis showed that the age>65 years old ( OR=2.375, 95% CI: 1.442-4.531), GCS ≤8 scores ( OR=3.431, 95% CI: 1.843-8.512), IL-10 >10 pg/mL ( OR=2.173, 95% CI: 1.751-5.614), the ratio of Treg cells >7% ( OR=3.871, 95% CI: 1.723-6.312), and the occurrence of traumatic brain and chest injuries ( OR=2.846, 95% CI: 1.522-5.361) were the early risk factors in patients with PICS after severe polytrauma. Conclusions:Age>65 years old, GCS score, IL-10, the ratio of Treg cells, and the occurrence of traumatic brain and chest injuries could be used as the early risk factors in patients with PICS after severe polytrauma. The discovery of early risk factors will help identify patients at high risk of PICS after severe polytrauma, and create the possibility for early intervention.

BACKGROUND: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH. METHODS: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded. RESULTS: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH. CONCLUSIONS: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT02164526.
Coronary Artery Disease/epidemiology* ; Creatinine ; Heart Failure/complications* ; Humans ; Hypertension, Pulmonary/complications* ; Nitrates ; Prevalence ; Prognosis ; Prospective Studies ; Registries ; Risk Factors ; Stroke Volume ; Ventricular Function, Left

Objective:To look into the security of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) using rabbit anti-human thymocyte immunoglobulin (rATG) .Methods:Twenty-seven patients who used rATG in the first and second allo-HSCT at the Institute of Hematology, Peking University were enrolled in the study. Experienced toxicities associated with the conditioning protocol within 10 days (-5 d to +3 d) following the beginning of the rATG application, including fever, diarrhea, arrhythmia, reduced blood pressure, liver damage, seizures, and other problems.Results:The overall incidence of conditioning regimen early adverse reactions during the first transplantation and the second allo-HSCT conditioning regimen was 96.3% and 77.8% ( P=0.043) . Fever rates were 81.5% and 63.0% ( P=0.129) , diarrhea rates were 59.3% and 25.9% ( P=0.013) , liver damage rates were 22.2% and 25.9% ( P=0.75) , and the rates of other events (cardiac arrhythmia, low blood pressure, and epilepsy) were 3.7% and 18.5% ( P=0.083) . Adverse reactions that occurred during both the first and second course of rATG applications have been improved with symptomatic treatment, and no treatment interruptions occurred. Conclusion:Reusing rATG in a second transplant was risk-free and did not result in higher early toxicities.

Objective:To retrospectively assess the relationship between immune disorder and acute gastrointestinal injury (AGI) in patients after severe polytrauma.Methods:Totally 205 patients with severe polytrauma admitted to Tongji Hospital from April 2018 to October 2019 were enrolled as the observation group, and 23 healthy volunteers were served as the control group. According to the diagnostic criteria of AGI, all patients were divided into the AGI group (with AGI) or N-AGI group (without AGI), AGI patients were divided into the S-AGI group or L-AGI group according to the severity. The levels of cytokines and lymphocyte subset were evaluated at day 1, 7, and 14 after severe polytrauma. The differences between groups were statistically analyzed. The independent risk factors of AGI were analyzed by Logistic regression analyzed.Results:Totally 79.5% (163/205) of patients with severe polytrauma were accompanied by AGI. There were significant differences in the ratio of Tc, Th at day 1 after trauma, the levels of IL-6, TNF-α, IL-8, IL-10, the ratio of Ts, Th/Ts, Treg at day 7 after trauma, and the levels of IL-8, IL-10,the ratio of Ts, Th/Ts, Treg at day 14 after trauma between the AGI group and N-AGI group ( P<0.05). There were significant differences in the ratio of Tc, Th, the levels of IL-6, TNF-α at day 1 after trauma and the ratio of Ts, Th/Ts, Treg, the levels of IL-8, IL-10 at day 7 and 14 after trauma between the S-AGI group and L-AGI group ( P<0.05). Logistic regression analysis showed that Ts 7 d ( OR=2.018, 95% CI: 1.105-5.364, P=0.013), Treg 14 d ( OR=3.612, 95% CI: 1.375-8.476, P=0.006), IL-6 7 d ( OR=1.824, 95% CI: 1.011-5.835, P=0.024), IL-10 14 d ( OR=2.847, 95% CI: 1.241-6.216, P=0.014), TNF-α 7 d ( OR=1.754, 95% CI: 1.215-5.441, P=0.018) were independent risk factors in patients with AGI after severe polytrauma. Conclusions:AGI is more easily occurred in patients with the heavier immune disorders after severe polytrauma. AGI can also aggravate pre-existing immune disorders in patients after severe polytrauma.

Objective:To retrospectively assess the occurrence and risk factors in patients with acute gastrointestinal injury (AGI) after polytrauma.Methods:Totally 430 patients with polytrauma admitted to Tongji Hospital from April 2018 to October 2019 were enrolled as the observation group. According to the diagnostic criteria of AGI, all patients were divided into the AGI group (with AGI) or N-AGI group (without AGI). The patients with abdominal injury or previously suffered from gastrointestinal disease were excluded. The patient's clinical characteristics lab tests results, and the first ISS, APACHEⅡ, SOFA and GCS scores were collected. The differences between different groups were statistically analyzed. The independent risk factors of AGI were analyzed by Logistic regression.Results:65.3% of patients with polytrauma were accompanied by AGI (281/430 cases).There were significant differences between the AGI group and N-AGI group in ISS, GCS, APACHE Ⅱ and SOFA score, PCT or IL-6 level, shock index and length of stay in ICU ( P<0.05). Logistic regression analysis showed that shock, ISS≥16, APACHE Ⅱ≥16, SOFA≥5, GCS≤8 and IL-6>50 pg/mL were the early independent risk factors in patients with ACI after polytrauma. Conclusion:The incidence of AGI in patients after polytrauma is higher, which is related to ischemia, hypoxia, abnormal blood coagulation and stress in the early stage after trauma.

Objective To investigate the possibility of P-wave dispersion parameters of 12-lead ECG in predicting paroxysmal atrial fibrillation (PAF) in patients with embolic stroke of undetermined source (ESUS).Methods Patients with ESUS admitted to the Department of Neurology,the Affiliated Hospital of Yangzhou University from January 2017 to December 2018 were enrolled.According to the findings of 24 h dynamic ECG monitoring,they were divided into PAF group and non-PAF group.The maximum P-wave duration (Pmax),minimum P-wave duration (Pmm) and P-wave dispersion (Pd) in the conventional 12-1ead ECG were documented.Multivariate logistic regression analysis was used to determine the independent correlation between different P-wave dispersion parameters and PAF in patients with ESUS.Results A total of 87 patients with ESUS were enrolled,including 40 females and 47 males,with an average age of 68.53 ± 10.68 years.PAF was detected in 17 patients (19.54％).There were significant differences in age,baseline NIHSS score,Pmax,Pd,and left atrial diameter (LAD) between the PAF group and the non-PAF group (all P ＜0.05).Multivariate logistic regression analysis showed that Pd Was the only independent predictor of PAF in patients with ESUS (odds ratio,1.279,95％ confidence interval 1.048-1.561,P =0.015).Conclusion Pd is an independent predictor of PAF in patients with ESUS.

Five patients with Fanconi anemia who received hematopoietic cell transplantation were retrospectively analyzed. The conditioning regimens included fludarabine, cyclophosphamide and anti-thymocyte globulin. Two patients received both bone marrow and peripheral blood stem cells as the source of stem cell grafts from haploidentical matched related donors, while the others received peripheral blood stem cells from unrelated donors.All patients tolerated well and reached hematopoietic reconstitution. One patient died of intracranial infection.During follow-up,4 patients survived independent of transfusion with full donor chimerism.