Lack of surgical resection is associated with increased early mortality in hematological patients complicated with rhino-orbital-cerebral mucormycosis.

Rhino-orbital-cerebral mucormycosis (ROCM), which is an acute fatal infectious disease with a high mortality rate, is increasingly being diagnosed in patients with hematological diseases worldwide. We aimed to investigate the clinical characteristics, treatment, and prognosis of hematological diseases complicated by ROCM. Our sample comprised a total of 60 ROCM patients with hematological diseases. The most common primary disease was acute lymphoblastic leukemia (ALL) (n=27, 45.0%), while 36 patients (60.0%) were diagnosed with a clear type of pathogen, all belonging to the Mucorales, most commonly Rhizopus (41.7%). Of the 32 patients (53.3%) who died, 19 (59.3%) died of mucormycosis, and 84.2% (n=16) of those died within 1 month. Forty-eight cases (80.0%) received antifungal treatment combined with surgical therapy, 12 of whom (25.0%) died of mucormycosis, amounting to a mortality rate that was significantly lower than in patients who received antifungal therapy alone (n=7, 58.3%) (P=0.012). The median neutrophil value of patients who underwent surgery was 0.58 (0.11-2.80) 103/µL, the median platelet value was 58.00 (17.00-93.00) 103/µL, and no surgery-related deaths were reported. Multivariate analysis showed that patient's advanced age (P=0.012, OR=1.035 (1.008-1.064)) and lack of surgical treatment (P=0.030, OR=4.971 (1.173-21.074)) were independent prognostic factors.In this study, hematological diseases associated with ROCM have a high mortality rate. Lack of surgical treatment is an independent prognostic factor for death from mucormycosis. Surgery may therefore be considered in patients with hematological disease even if their neutrophil and platelet values are lower than normal.

Discovery of Weyl Nodal Lines in a Single-Layer Ferromagnet.

Two-dimensional (2D) materials have attracted great attention and spurred rapid development in both fundamental research and device applications. The search for exotic physical properties, such as magnetic and topological order, in 2D materials could enable the realization of novel quantum devices and is therefore at the forefront of materials science. Here, we report the discovery of twofold degenerate Weyl nodal lines in a 2D ferromagnetic material, a single-layer gadolinium-silver compound, based on combined angle-resolved photoemission spectroscopy measurements and theoretical calculations. These Weyl nodal lines are symmetry protected and thus robust against external perturbations. The coexistence of magnetic and topological order in a 2D material is likely to inform ongoing efforts study the rich physics in 2D topological ferromagnets.

Superstructure-Induced Splitting of Dirac Cones in Silicene.

Atomic scale engineering of two-dimensional materials could create devices with rich physical and chemical properties. External periodic potentials can enable the manipulation of the electronic band structures of materials. A prototypical system is (3×3)-silicene/Ag(111), which has substrate-induced periodic modulations. Recent angle-resolved photoemission spectroscopy measurements revealed six Dirac cone pairs at the Brillouin zone boundary of Ag(111), but their origin remains unclear [Proc. Natl. Acad. Sci. USA 113, 14656 (2016)]. We used linear dichroism angle-resolved photoemission spectroscopy, the tight-binding model, and first-principles calculations to reveal that these Dirac cones mainly derive from the original cones at the K (K^{'}) points of free-standing silicene. The Dirac cones of free-standing silicene are split by external periodic potentials that originate from the substrate-overlayer interaction. Our results not only confirm the origin of the Dirac cones in the (3×3)-silicene/Ag(111) system, but also provide a powerful route to manipulate the electronic structures of two-dimensional materials.

Direct evidence of interaction-induced Dirac cones in a monolayer silicene/Ag(111) system.

Silicene, analogous to graphene, is a one-atom-thick 2D crystal of silicon, which is expected to share many of the remarkable properties of graphene. The buckled honeycomb structure of silicene, along with enhanced spin-orbit coupling, endows silicene with considerable advantages over graphene in that the spin-split states in silicene are tunable with external fields. Although the low-energy Dirac cone states lie at the heart of all novel quantum phenomena in a pristine sheet of silicene, a hotly debated question is whether these key states can survive when silicene is grown or supported on a substrate. Here we report our direct observation of Dirac cones in monolayer silicene grown on a Ag(111) substrate. By performing angle-resolved photoemission measurements on silicene(3 × 3)/Ag(111), we reveal the presence of six pairs of Dirac cones located on the edges of the first Brillouin zone of Ag(111), which is in sharp contrast to the expected six Dirac cones centered at the K points of the primary silicene(1 × 1) Brillouin zone. Our analysis shows clearly that the unusual Dirac cone structure we have observed is not tied to pristine silicene alone but originates from the combined effects of silicene(3 × 3) and the Ag(111) substrate. Our study thus identifies the case of a unique type of Dirac cone generated through the interaction of two different constituents. The observation of Dirac cones in silicene/Ag(111) opens a unique materials platform for investigating unusual quantum phenomena and for applications based on 2D silicon systems.

New developments in laser-based photoemission spectroscopy and its scientific applications: a key issues review.

The significant progress in angle-resolved photoemission spectroscopy (ARPES) in last three decades has elevated it from a traditional band mapping tool to a precise probe of many-body interactions and dynamics of quasiparticles in complex quantum systems. The recent developments of deep ultraviolet (DUV, including ultraviolet and vacuum ultraviolet) laser-based ARPES have further pushed this technique to a new level. In this paper, we review some latest developments in DUV laser-based photoemission systems, including the super-high energy and momentum resolution ARPES, the spin-resolved ARPES, the time-of-flight ARPES, and the time-resolved ARPES. We also highlight some scientific applications in the study of electronic structure in unconventional superconductors and topological materials using these state-of-the-art DUV laser-based ARPES. Finally we provide our perspectives on the future directions in the development of laser-based photoemission systems.

Electronic evidence of an insulator-superconductor crossover in single-layer FeSe/SrTiO3 films.

In high-temperature cuprate superconductors, it is now generally agreed that superconductivity is realized by doping an antiferromagnetic Mott (charge transfer) insulator. The doping-induced insulator-to-superconductor transition has been widely observed in cuprates, which provides important information for understanding the superconductivity mechanism. In the iron-based superconductors, however, the parent compound is mostly antiferromagnetic bad metal, raising a debate on whether an appropriate starting point should go with an itinerant picture or a localized picture. No evidence of doping-induced insulator-superconductor transition (or crossover) has been reported in the iron-based compounds so far. Here, we report an electronic evidence of an insulator-superconductor crossover observed in the single-layer FeSe film grown on a SrTiO3 substrate. By taking angle-resolved photoemission measurements on the electronic structure and energy gap, we have identified a clear evolution of an insulator to a superconductor with increasing carrier concentration. In particular, the insulator-superconductor crossover in FeSe/SrTiO3 film exhibits similar behaviors to that observed in the cuprate superconductors. Our results suggest that the observed insulator-superconductor crossover may be associated with the two-dimensionality that enhances electron localization or correlation. The reduced dimensionality and the interfacial effect provide a new pathway in searching for new phenomena and novel superconductors with a high transition temperature.

Silymarin-Loaded Nanoparticles Based on Stearic Acid-Modified Bletilla striata Polysaccharide for Hepatic Targeting.

Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products, especially for liver-targeting purposes. In this study, silymarin was encapsulated in self-assembled nanoparticles of Bletilla striata polysaccharide (BSP) conjugates modified with stearic acid and the physicochemical properties of the obtained nanoparticles were characterized. The silymarin-loaded micelles appeared as spherical particles with a mean diameter of 200 nm under TEM. The encapsulation of drug molecules was confirmed by DSC thermograms and XRD diffractograms, respectively. The nanoparticles exhibited a sustained-release profile for nearly 1 week with no obvious initial burst. Compared to drug solutions, the drug-loaded nanoparticles showed a lower viability and higher uptake intensity on HepG2 cell lines. After intravenous administration of nanoparticle formulation for 30 min to mice, the liver became the most significant organ enriched with the fluorescent probe. These results suggest that BSP derivative nanoparticles possess hepatic targeting capability and are promising nanocarriers for delivering silymarin to the liver.

Robustness of topological order and formation of quantum well states in topological insulators exposed to ambient environment.

The physical property investigation (like transport measurements) and ultimate application of the topological insulators usually involve surfaces that are exposed to ambient environment (1 atm and room temperature). One critical issue is how the topological surface state will behave under such ambient conditions. We report high resolution angle-resolved photoemission measurements to directly probe the surface state of the prototypical topological insulators, Bi(2)Se(3) and Bi(2)Te(3), upon exposing to various environments. We find that the topological order is robust even when the surface is exposed to air at room temperature. However, the surface state is strongly modified after such an exposure. Particularly, we have observed the formation of two-dimensional quantum well states near the exposed surface of the topological insulators. These findings provide key information in understanding the surface properties of the topological insulators under ambient environment and in engineering the topological surface state for applications.

Phase diagram and electronic indication of high-temperature superconductivity at 65 K in single-layer FeSe films.

The recent discovery of possible high-temperature superconductivity in single-layer FeSe films has generated significant experimental and theoretical interest. In both the cuprate and the iron-based high-temperature superconductors, superconductivity is induced by doping charge carriers into the parent compound to suppress the antiferromagnetic state. It is therefore important to establish whether the superconductivity observed in the single-layer sheets of FeSe--the essential building blocks of the Fe-based superconductors--is realized by undergoing a similar transition. Here we report the phase diagram for an FeSe monolayer grown on a SrTiO3 substrate, by tuning the charge carrier concentration over a wide range through an extensive annealing procedure. We identify two distinct phases that compete during the annealing process: the electronic structure of the phase at low doping (N phase) bears a clear resemblance to the antiferromagnetic parent compound of the Fe-based superconductors, whereas the superconducting phase (S phase) emerges with the increase in doping and the suppression of the N phase. By optimizing the carrier concentration, we observe strong indications of superconductivity with a transition temperature of 65±5 K. The wide tunability of the system across different phases makes the FeSe monolayer ideal for investigating not only the physics of superconductivity, but also for studying novel quantum phenomena more generally.

Pomalidomide improves the effectiveness of CAR-T treatment in the relapsed and refractory multiple myeloma or B-cell leukemia/lymphoma with extramedullary disease.

Relapsed and refractory multiple myeloma (RRMM) and B-cell leukemia/lymphoma with extramedullary disease (EMD) have poor prognosis and high mortality, lack of effective therapeutic approaches. We reported for the first time that 6 patients with malignant hematological diseases with EMD received chimeric antigen receptor (CAR)-T treatment combined with pomalidomide, and CAR-T cells were treated with pomalidomide in vitro to determine its killing activity and cytokine secretion. Three patients with RRMM were given B cell maturation antigen (BCMA)-CAR-T therapy. All 3 patients with B-cell leukemia/lymphoma received CD19/22-CAR-T sequential infusion. There were no treatment-related deaths. The maximum overall response rate (ORR) was 100%. Median follow-up was 211.5 days (75-407 days). Three patients (50%) experienced cytokine release syndrome, all of which were grade 1, and no neurotoxicity was observed. In vitro experiments showed that the killing activity did not differ significantly between BCMA-CAR-T cells with and without pomalidomide (10, 25, or 50 µg/mL) in 8226/U266 cell cocultures (P > .05). Tumor necrosis factor (TNF)-α and interferon (IFN)-γ secretion was significantly higher from 8226 and Raji cells cocultured with BCMA-CAR-T and cluster of differentiation (CD)19-CAR-T cells (P < .05). Based on the cocultures, adding pomalidomide significantly promoted IFN-γ and TNF-α secretion (P < .05). Based on the above clinical and in vitro studies demonstrating the co-administration of pomalidomide with CAR-T cell treatment demonstrated favorable tolerability and therapeutic effectiveness in RRMM or B-cell leukemia/lymphoma.

[The Preventive Effect of Levofloxacin Combined with G-CSF or Only G-CSF Supportive Therapy on Infection in Autologous Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor (G-CSF) or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT), and to analyze the length of hospital stay, hospitalization cost and post-transplant survival of the patients. METHODS: A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022, the febrile neutropenia, the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed. The length of hospital stay, total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared. RESULTS: A total of 102 cases were included in this study, including 57 cases of multiple myeloma, 36 cases of acute leukaemia, 7 cases of lymphoma, 3 cases of myelodysplastic syndrome, 1 case of light chain amyloidosis, and 1 case of POEMS syndrome. 47 patients received levofloxacin+ G-CSF antibacterial prophylaxis, and 55 patients received G-CSF supportive therapy. In the levofloxacin+ G-CSF group, 40 cases (85.11%) developed febrile neutropenia, and 13 cases (27.66%) were confirmed as bacterial infection. In the G-CSF group, 44 cases (80.00%) developed febrile neutropenia, and 16 cases (29.09%) were bacterial infection. There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups (χ2=0.46，P =0.50; χ2=0.03，P =0.87). The use rate of intravenous antibiotics in the levofloxacin+ G-CSF group was 85.11% (40/47), which was not statistically different from 85.45% (47/55) in the G-CSF group (χ2=0.04，P =0.84). The detection rates of levofloxacin-resistant bacteria in the levofloxacin+ G-CSF group and G-CSF group were 8.57% (3/35) and 21.43% (6/28), respectively, with no statistical difference (χ2=0.65, P >0.05). The median length and median cost of hospitalization in the levofloxacin+ G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan, with no statistically significant differences ( t =3.00，P =0.09; t =0.94，P =0.09). Within 90 days after transplantation, two cases (4.26%) died in the levofloxacin+ G-CSF group and one case (1.82%) died in the G-CSF group, with no statistically significant difference between the two groups (χ2=0.53，P =0.47). CONCLUSION: Application of levofloxacin+ G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.

Coexistence of two sharp-mode couplings and their unusual momentum dependence in the superconducting state of Bi2Sr2CaCu2O(8+δ) revealed by laser-based angle-resolved photoemission.

High-resolution laser-based angle-resolved photoemission measurements have been carried out on Bi2Sr2CaCu2O(8+δ) (Bi2212) superconductors to investigate momentum dependence of electron coupling with collective excitations (modes). Two coexisting energy scales are clearly revealed over a large momentum space for the first time in the superconducting state of the overdoped Bi2212 superconductor. These two energy scales exhibit distinct momentum dependence: one keeps its energy near 78 meV over a large momentum space while the other changes its energy from ∼40 meV near the antinodal region to ∼70 meV near the nodal region. These observations provide a new picture on momentum evolution of electron-boson coupling in Bi2212 that electrons are coupled with two sharp modes simultaneously over a large momentum space in the superconducting states. Their unusual momentum dependence poses a challenge to our current understanding of electron-mode-coupling and its role for high-temperature superconductivity in cuprate superconductors.

Microenvironmental pH Modification in Buccal/Sublingual Dosage Forms for Systemic Drug Delivery.

Many drug candidates are poorly water-soluble. Microenvironmental pH (pHM) modification in buccal/sublingual dosage forms has attracted increasing interest as a promising pharmaceutical strategy to enhance the oral mucosal absorption of drugs with pH-dependent solubility. Optimizing drug absorption at the oral mucosa using pHM modification is considered to be a compromise between drug solubility and drug lipophilicity (Log D)/permeation. To create a desired pHM around formulations during the dissolution process, a suitable amount of pH modifiers should be added in the formulations, and the appropriate methods of pHM measurement are required. Despite pHM modification having been demonstrated to be effective in enhancing the oral mucosal absorption of drugs, some potential risks, such as oral mucosal irritation and teeth erosion caused by the pH modifiers, should not been neglected during the formulation design process. This review aims to provide a short introduction to the pHM modification concept in buccal/sublingual dosage forms, the properties of saliva related to pHM modification, as well as suitable drug candidates and pH modifiers for pHM modifying buccal/sublingual formulations. Additionally, the methods of pHM measurement, pHM modification methods and the corresponding challenges are summarized in the present review.

Plasmacytoid dendritic cell expansion in myeloid neoplasms: A novel distinct subset of myeloid neoplasm?

Plasmacytoid dendritic cells (pDCs) are a specific dendritic cell type stemming from the myeloid lineage. Clinically and pathologically, neoplasms associated with pDCs are classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN), mature plasmacytoid dendritic myeloid neoplasm (MPDMN) and pDC expansion in myeloid neoplasms (MNs). BPDCN was considered a rare and aggressive neoplasm in the 2016 World Health Organization (WHO) classification. MPDMN, known as mature pDC-derived neoplasm, is closely related to MNs and was first recognized in the latest 2022 WHO classification, proposing a new concept that acute myeloid leukemia cases could show clonally expanded pDCs (pDC-AML). With the advances in detection techniques, an increasing number of pDC expansion in MNs have been reported, but whether the pathogenesis is similar to that of MPDMN remains unclear. This review focuses on patient characteristics, diagnosis and treatment of pDC expansion in MNs to gain further insight into this novel and unique provisional subtype.

Eastern Cooperative Oncology Group, ß2-microglobulin, hemoglobin, and lactate dehydrogenase can predict early grade ≥ 3 infection in patients with newly diagnosed multiple myeloma: A real-world multicenter study.

Introduction: This research explored the clinical application of grade ≥ 3 infection predictive models for the newly diagnosed multiple myeloma (NDMM) population. Methods: It evaluated 306 patients with NDMM based on three different predictive models. The relationship between the grade ≥ 3 infection rates in NDMM and the scores was analyzed retrospectively. The cumulative incidence of early grade ≥ 3 infection was estimated using the Kaplan-Meier method and log-rank test to assess the statistical significance of the difference. To compare the predictive performance in the prediction of infection, the Receiver Operating Characteristic Curve (ROC) curve was used to show the area under the curve (AUC), and DeLong's test was used to analyze the difference in AUC. Results: The incidence of grade ≥ 3 infection within the first 4 months of NDMM was 40.20%. Concerning the FIRST score (predictors: ECOG, ß2-microglobulin, hemoglobin, and lactate dehydrogenase), GEM-PETHEMA score (predictors: albumin, male sex, ECOG, and non-IgA type MM), and Infection Risk model of Multiple Myeloma (IRMM) score (predictors: ECOG, serum ß2-microglobulin, globulin, and hemoglobin), the probability of early grade ≥ 3 infection in the different groups showed statistically significant differences (low-risk vs. high-risk: 25.81% vs. 50.00%, p < 0.001; low-risk vs. moderate-risk vs. high-risk: 35.93% vs. 41.28% vs. 60.00%, p= 0.045; low-risk vs. moderate-risk vs. high-risk: 20.00% vs. 43.75% vs. 52.04%, p < 0.001). Statistical differences existed in the probability of early grade ≥ 3 infection among the different groups by the FIRST and IRMM scores but no statistical differences in the GEM-PETHEMA score (p < 0.001, p< 0.001, and p = 0.090, respectively). The FIRST score showed good discrimination and simple calculation with highest AUC. Further subgroup analysis showed that the FIRST score could still apply for patients treated with bortezomib-based regimen and frail patients. Discussion: Our findings indicate that the FIRST score (consisting of ECOG, ß2-microglobulin, hemoglobin, and lactate dehydrogenase) is a simple and robust infection stratification tool for patients with NDMM and could be used in routine clinical work.

[Clinical Characteristics and Nomogram Model of Nosocomial Infection in Patients with Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model. METHODS: The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established. RESULTS: 164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 µmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285). CONCLUSION: Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.

Peripheral Blood Smears Distinguish Infective Fever after CAR-T Therapy.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy carries the risk of inducing severe and life-threatening toxicities such as cytokine release syndrome (CRS), neurotoxicity, and infection. Although CRS and infections have similar symptoms, their treatment strategies differ, and early diagnosis is very important. For CRS and infections, the fastest detection time currently takes more than 24 h, so a quick and simple method to identify a fever after CAR T-cell infusion is urgently needed. METHODS: We enrolled 27 patients with recurrent fever treated with different types of CAR T-cells, including cluster of differentiation (CD) 7, CD19, CD22, and CD19-CD22 bicistronic CAR T-cells, and evaluated the infection events occurring in these patients. We detailed the morphology of CAR T-cells in peripheral blood smears (PBS) and reported the infection events, CAR transgene copy number, and inflammatory indicators within the first month after treatment. RESULTS: Similar morphological characteristics were observed in the PBS of different CAR T-cells, namely, enlarged cell bodies, deep outside and shallow inside basophilic blue cytoplasm, and natural killer (NK) cell-like purplish red granules. There were ten infections in nine of the twenty-seven patients (33%). The percentage of atypical lymphocytes in PBS was significantly associated with CAR transgene copy number and absolute lymphocyte count in all patients. The atypical lymphocyte percentage was significantly higher in the non-infection group. CONCLUSIONS: In conclusion, the unique morphology of CAR T-cells in PBS can be used to evaluate CAR T-cell kinetics and provide reliable evidence for the rapid early identification of fever after CAR T-cell infusion. CLINICAL TRIAL REGISTRATIONS: ChiCTR-OPN-16008526; ChiCTR-OPN-16009847; ChiCTR2000038641; NCT05618041; NCT05388695.

[Analysis of Pathogenic Bacterial Spectrum, Drug Resistance and Risk Factors for Mortality of Bloodstream Infection in Patients with Hematologic Diseases].

OBJECTIVE: To analyze the pathogenic bacterial spectrum, drug resistance, and risk factors associated with multidrug-resistant bacterial infection and mortality in patients with hematologic diseases complicated by bloodstream infections, so as to provide reference for rational drug use and improving prognosis. METHODS: Positive blood culture specimens of patients with hematologic diseases in two Class A tertiary hospitals of Shanxi province from January 2019 to December 2021 were retrospectively analyzed. Pathogen distribution, drug resistance and outcomes of patients with bloodstream infection were investigated, then the multivariate logistic analysis was performed to analyze the risk factors of multidrug-resistant bacterial infection and factors affecting prognosis. RESULTS: 203 strains of pathogens were identified, mainly Gram-negative bacteria (GNB) (69.46%, 141/203), of which Escherichia coli (E.coli) had the highest incidence (41.13%, 58/141), followed by Klebsiella pneumoniae (20.57%, 29/141) and Pseudomonas aeruginosa (12.77%, 18/141). Extended-spectrum beta-lactamase (ESBL)-producing E.coli and Klebsiella pneumoniae were 46.55% (27/58) and 37.93% (11/29), respectively. Carbapenem-resistant Gram-negative bacteria accounted for 10.64% (15/141). And Gram-positive bacteria accounted for 27.59% (56/203), Staphylococcus epidermidis, Streptococcus pneumoniae, and Staphylococcus aureus were the most frequently isolated pathogen among Gram-positive bacteria (14.29%, 12.50% and 10.71%, respectively), of which methicillin-resistant Staphylococcus aureus accounted for 33.33% (2/6), coagulase-negative staphylococci accounted for 87.50% (7/8), without vancomycin- or linezolid-resistant strain. Additionally, fungi accounted for 2.95% (6/203), all of which were Candida. Multidrug-resistant Gram-negative bacteria (MDR-GNB) accounted for 53.90% (76/141). Duration of neutropenia >14 days was a risk factor for developing MDR-GNB infection. The 30-day all-cause mortality was 10.84%. Multivariate logistic regression analysis showed that the significant independent risk factors for mortality were age≥60 years (P <0.01, OR =5.85, 95% CI: 1.80-19.07) and use of vasopressor drugs (P <0.01, OR =5.89, 95% CI: 1.83-18.94). CONCLUSION: The pathogenic bacteria of bloodstream infection in patients with hematological diseases are widely distributed, and the detection rate of multidrug-resistant bacteria is high. The clinicians should choose suitable antibiotics according to the results of bacterial culture and antibiotic susceptibility test.

[Clinical Characteristics and Risk Factors for 30-Day Mortality in Patients with Hematologic Diseases Infected by Carbapenem-Resistant Organisms].

OBJECTIVE: To explore the clinical characteristics of hospitalized patients with hematologic diseases complicated with carbapenem-resistant organisms (CRO) infection and analyze the risk factors of 30-day all-cause mortality. METHODS: The clinical data and laboratory test data of 77 hospitalized patients with hematologic diseases complicated with CRO infection in department of hematology of the Third Hospital of Shanxi Medical University from January 2015 to December 2020 were retrospectively analysed, the risk factors of 30-day all-cause mortality after CRO infection were analyzed by multivariate logistic regression. RESULTS: Among the total of 77 patients with hematologic diseases complicated with CRO infection, 29 died and 48 survived within 30 days of infection, with a case fatality rate of 37.66%. A total of 93 strains of CRO were isolated from these patients, of which Acinetobacter baumannii had the highest detection rate (25.81%, 24/93), followed by Pseudomonas aeruginosa (18.28%, 17/93). The lung was the most common site of CRO infection. The detected pathogens were highly resistant to carbapenems, and 64.52% (60/93) of the pathogens were resistant to imipenem with minimum inhibitory concentration (MIC)≥16 µg/ml. The results of the univariate analysis showed that albumin concentration <25 g/L (P =0.048), serum creatinine concentration≥120 µmol/L (P =0.023), age-adjusted Charlson comorbidity index (ACCI) (P =0.037) and primary treatments (supportive treatment, immunosuppressive therapy, chemotherapy, HSCT) (P =0.048) were significantly associated with 30-day all-cause mortality after infection. The results of multivariate logistic regression analysis showed that when CRO infection confirmed, albumin concentration <25 g/L (P =0.014, OR=6.171), serum creatinine concentration≥120 µmol/L (P =0.009, OR=10.867) were independent risk factors for 30-day mortality of patients with hematologic diseases complicated with CRO infection. CONCLUSION: The mortality rate of CRO-infected patients with hematologic diseases is high. The detected pathogenic bacteria are highly resistant to imipenem. The albumin concentration <25 g/L and the serum creatinine concentration≥ 120 µmol/L at diagnosis of CRO infection were independent risk factors for 30-day mortality of the patients with hematologic diseases.

Simultaneous quantification of pirarubicin, doxorubicin, cyclophosphamide, and vincristine in human plasma of patients with non-Hodgkin's lymphoma by LC-MS/MS method.

Pirarubicin (THP), doxorubicin (DOX), cyclophosphamide (CTX), and vincristine (VCR) are widely used in the treatment of patients with non-Hodgkin's Lymphoma. Herein, a precise and sensitive method was developed for the determination of THP, DOX, CTX and VCR in human plasma by high-performance liquid-chromatography-tandem mass spectrometry (LC-MS/MS). Liquid-liquid extraction was applied to extract THP, DOX, CTX, VCR, and the internal standard (IS, Pioglitazone) in plasma. Agilent Eclipse XDB-C18 (3.0 mm × 100 mm) was utilized and chromatographic separation was obtained in eight minutes. Mobile phases were composed of methanol and buffer (10 mM ammonium formate containing 0.1% formic acid). The method was linear within the concentration range of 1-500 ng/mL for THP, 2-1000 ng/mL for DOX, 2.5-1250 ng/mL for CTX, and 3-1500 ng/mL for VCR. The intra- and inter-day precisions of QC samples were found to be below 9.31 and 13.66%, and accuracy ranged from -0.2 to 9.07%, respectively. THP, DOX, CTX, VCR and the internal standard were stable in several conditions. Finally, this method was successfully utilized to simultaneously determine THP, DOX, CTX and VCR in human plasma of 15 patients with non-Hodgkin's Lymphoma after intravenous administration. Finally, the method was successfully employed in the clinical determination of THP, DOX, CTX, and VCR in patients with non-Hodgkin lymphoma after administration of RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens.