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Nevin Manimala Statistics

Clinical Features and Outcomes of the Patients with B-Cell Chronic Lymphoproliferative Disease in the New Drug Era

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):722-729. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.016.

ABSTRACT

OBJECTIVE: To analyze the clinical characteristics of the patients with B-cell chronic lymphoproliferative disease(B-CLPD) in the new drug era and the effect of new drug treatment on efficacy and survival.

METHODS: The clinical and laboratory data of 200 cases B-CLPD patients diagnosed between April 2015 and August 2021 were analyzed retrospectively. The clinical efficacy and survival of the patients under different treatments including Bruton tyrosine kinase(BTK) inhibitors, rituximab, and chemotherapy alone were analyzed. The prognostic factors affecting the survival of patients were analyzed by univarite analysis and multivariate analysis.

RESULTS: There were 119 male(59.5%) and 81 female(40.5%) in 200 cases B-CLPD patients, the sex ratio(male/female) was 1.5∶1 with median age of 61(30- 91) years old. The distribution of subtypes were as fallows: 51 cases (25.5%) of chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SLL), 64(32.0%) cases of follicular lymphoma(FL), 40(20.0%) cases mantle cell lymphoma(MCL), 30(15.0%) cases of marginal zone lymphoma(MZL), 10(5%) cases of lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia(LPL/WM), 5(2.5%) cases of B cell chronic lymphoproliferative disorders unclassified(B-CLPD-U) . The main clinical manifestation of 102 patients was lymph node enlargement, 32 cases were complicated with B symptoms. Among CLL/SLL patients, there were 12(23.5%) cases in Binet A and 39(76.5%) cases in Binet B/C. There were 29 patients(20.9%) in Ann Arbor or Lugano stage I-II and 110 cases(79.1%) in stage III-IV of other subtypes. The complete remission(CR) rate was 43.1%(25/58), 40.2%(39/97), 7.1%(1/14), and overaIl response rate(ORR) was 87.9%(51/58), 62.9%(61/97), 28.6%(4/14) in the groups of BTK inhibitors, rituximab-based therapy, and chemotherapy alone. The 3-year OS rate and PFS rate in all patients was 79.2% and 72.4% respectively. The 3-year OS rate of patient with MZL, CLL/SLL, FL,WM was 94.7%, 87.7%, 86.8% and 83.3% respectively, while the 3-year OS rate of MCL was only 40.6%, which was significantly lower than other subtypes. The median OS of patients treated with BTK inhibitors and rituximab-based therapy was 20.5 and 18.5 months respectively, and the 3-year OS rate was 97.4% and 90.7%. However, the median PFS of patients receiving chemotherapy alone was 4 months, and the 1-year OS rate was 52.7%, which was statistically significant compared with the other two groups(P<0.05). Univarite analysis showed that anemia, elevated lactate dehydrogenase, elevated β2-microglobulin, and splenomegaly were the poor prognostic factors for OS(P<0.05), elevated lactate dehydrogenase was also poor prognostic factors for PFS(P<0.05). Multifactor analysis showed that anemia and elevated lactate dehydrogenase were the independent poor prognostic factors for survival(P<0.05).

CONCLUSION: The clinical features of B-CLPD was various, anemia and elevated lactate dehydrogenase are the prognostic factors for poor survival. BTK inhibitors and new immunotherapy can improve the survival and prognosis of patients in the new drug era.

PMID:37356932 | DOI:10.19746/j.cnki.issn.1009-2137.2023.03.016

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Nevin Manimala Statistics

Clinical Characteristics and Survival Analysis of Patients with Plasma Cell Leukemia

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):693-698. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.012.

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease.

METHODS: The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis.

RESULTS: There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031).

CONCLUSION: PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.

PMID:37356928 | DOI:10.19746/j.cnki.issn.1009-2137.2023.03.012

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Nevin Manimala Statistics

Treg Cells, FoxP3 and TGF-β Expression and Significance in Chronic Myeloid Leukemia

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):666-670. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.008.

ABSTRACT

OBJECTIVE: To investigate the expression and significance of regulatory T cells (Tregs), FoxP3 and transforming growth factor-β (TGF-β) in different phase of chronic myeloid leukemia (CML).

METHODS: Peripheral blood of 73 CML patients in Department of Hematology, Heze Municipal Hospital from March 2018 to March 2021 were collected. According to patient’s period in CML, they were divided into ND CML group (newly diagnosed), CP CML group (chronic period), and BP CML group (blast phase). The percentage of Tregs, expression level of FoxP3 mRNA and TGF-β were detected by flow cytometry, RT-qPCR, and ELISA, respecitively. The roles of above indices in clinical pathogenesis of patients with CML were analyzed.

RESULTS: The proportion of Treg in the ND CML group was slightly higher than the CP CML group, but the difference was not statistically significant (P =0.695), while the BP CML group was significantly higher than the other two groups (P =0.008, P <0.001). The expression levels of FoxP3 mRNA in ND CML group, CP CML group and BP CML group were 11.61±2.21, 6.46±1.35 and 8.54±2.13, respectively. Significant difference in FoxP3 mRNA levels was observed among patients in different phases of CML (F =55.199, P <0.001). The expression levels of FoxP3 mRNA both in ND CML group and BP CML group were significantly higher than that in CP CML group (P <0.001), and the ND CML group was the highest (P <0.001). However, the expression levels of TGF-β in different phases of CML showed no statistical differences (H =0.634, P =0.728).

CONCLUSION: The abnormal distribution of Treg subset in different phases of CML and the significant increase of the expression level of FoxP3 mRNA in the new onset and blast phase of CML suggest that Tregs may promote the occurrence and progression of CML through immune regulation.

PMID:37356924 | DOI:10.19746/j.cnki.issn.1009-2137.2023.03.008

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Nevin Manimala Statistics

Correlation Analysis between Cerebrospinal Fluid Status and Prognosis in Childhood with Acute Lymphoblastic Leukemia by Flow Cytometry

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):654-658. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.006.

ABSTRACT

OBJECTIVE: To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM).

METHODS: The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed.

RESULTS: Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status.

CONCLUSION: Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.

PMID:37356922 | DOI:10.19746/j.cnki.issn.1009-2137.2023.03.006

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Nevin Manimala Statistics

Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):633-642. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.003.

ABSTRACT

OBJECTIVE: To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML).

METHODS: The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed.

RESULTS: Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified).

CONCLUSION: D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

PMID:37356919 | DOI:10.19746/j.cnki.issn.1009-2137.2023.03.003

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Nevin Manimala Statistics

SISPRO: Signature Identification for Spatial Proteomics

J Mol Biol. 2023 Jul 15;435(14):167944. doi: 10.1016/j.jmb.2022.167944. Epub 2023 Jan 10.

ABSTRACT

Spatial proteomics aims for a global description of organelle-specific protein distribution and dynamics, which is essential for understanding the molecular functions and cellular processes in health and disease. However, the application of this technique is seriously restricted by the neglect of robustness among proteomic signatures identified using standard statistical frameworks. Moreover, it is still a major bottleneck to automatically interpretate the identified proteomic signatures due to lack of integration of subcellular information. Herein, an online-tool SISPRO was constructed to (a) identify proteomic signatures with good robustness and accuracy via collectively evaluating relative weighted consistency (CWrel) & area under the curve (AUC) and (b) interpretate the identified signature based on comprehensive subcellular information from 9 organelles and 22 subcellular structures. All in all, SISPRO provides the endeavor to realize the simultaneous improvement of robustness and accuracy in signature identification and the unique capacity in biological annotation lies in its wide coverage of proteins and comprehensive spatial information. SISPRO is expected to be critical in spatial proteomic studies, which can be freely accessed without any login requirement at https://idrblab.org/sispro/.

PMID:37356911 | DOI:10.1016/j.jmb.2022.167944

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Nevin Manimala Statistics

cgNA+web : A Visual Interface to the cgNA+ Sequence-dependent Statistical Mechanics Model of Double-stranded Nucleic Acids

J Mol Biol. 2023 Jul 15;435(14):167978. doi: 10.1016/j.jmb.2023.167978. Epub 2023 Jan 25.

ABSTRACT

The sequence-dependent statistical mechanics of double-stranded nucleic acid, or dsNA, is believed to be essential in its biological functions. In turn, the equilibrium statistical mechanics behaviour of dsNA depends strongly both on sequence-dependent perturbations in its ground state shape away from an idealised, uniform, double-helical configuration, and on its fluctuations as governed by its sequence-dependent stiffness. We here describe the cgNA+web browser-based interactive tool for visualising the sequence-dependent ground states of dsNA fragments of arbitrary sequences, as predicted by the underlying cgNA+ coarse-grain model. Parameter sets are provided to model dsDNA, including the possibility of epigenetically modified CpG dinucleotide steps, dsRNA, and DNA:RNA Hybrid double helical fragments. The cgNA+web interface is specifically designed to compare ground state shapes of different sequences of the same dsNA, or analogous sequences of different dsNAs. The cgNA+web server is freely available at cgDNAweb.epfl.ch without any login requirement.

PMID:37356908 | DOI:10.1016/j.jmb.2023.167978

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Nevin Manimala Statistics

nASAP: A Nascent RNA Profiling Data Analysis Platform

J Mol Biol. 2023 Jul 15;435(14):168142. doi: 10.1016/j.jmb.2023.168142. Epub 2023 May 5.

ABSTRACT

Although nascent RNA profiling data are widely used in transcriptional regulation studies, the development and standardization of data processing pipeline lags far behind RNA-seq. We are filling this gap by establishing the nASAP web server (https://grobase.top/nasap/) to provide practical quality evaluation and comprehensive analysis of nascent RNA datasets. In nASAP, four customized analysis modules are provided, including i) quality assessment, which summarizes the sequencing statistics, mapping ratio, and evaluates RNA integrity and mRNA contamination; ii) quantification analysis for mRNAs, lncRNAs and eRNAs; iii) pausing analysis across the whole genome based on sequencing reads distribution; and iv) network analysis to better understand the gene regulatory mechanism by obtaining annotated enhancer-promoter interactomes. The nASAP is user-friendly and outperforms the existing pipeline for quality control of nascent RNA profiling data. We anticipate that nASAP, which eases both basic and advanced analysis of nascent RNA data, will be extremely useful in various fields.

PMID:37356907 | DOI:10.1016/j.jmb.2023.168142

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The 2022 Certified Flight Registered Nurse Pulse Survey

Air Med J. 2023 Jul-Aug;42(4):263-267. doi: 10.1016/j.amj.2023.04.004. Epub 2023 Apr 28.

ABSTRACT

OBJECTIVE: The Certified Flight Registered Nurse (CFRN) credential independently validates a registered nurse’s advanced knowledge, skills, and abilities in the unique specialty of flight nursing. Introduced in 1993 and celebrating its 30th anniversary in July 2023, the CFRN is held by over 5,500 registered nurses. The purpose of the 2022 CFRN pulse survey was to better understand the ways CFRN-certified registered nurses value this national flight nursing specialty credential. The CFRN survey is a companion to the 2022 Certified Transport Registered Nurse pulse survey, which focused on the Certified Transport Registered Nurse critical care ground transport nursing credential.

METHODS: The Board of Certification for Emergency Nursing e-mailed individuals in its database of CFRN credential holders and asked them to respond to a 14-question online survey between October 17, 2022, and November 8, 2022. Participation in the survey was voluntary. Of the 5,275 verified CFRN holders who received the survey, 992 responded, for a response rate of 18.8%. The survey instrument included discrete field and open-ended questions. Data were deidentified for analysis, and institutional review board exemption was received. Counts and percentages were reported, and descriptive statistics were used.

RESULTS: The highest percentage of flight nurses who responded have more than 10 years of experience in flight nursing (35.3%) and are employed by a stand-alone transport program (42.7%). Flight nurses reported they spent a mean of 70% of their work hours transporting via rotor wing aircraft, with a predominantly adult patient population. The top perceived benefits of being a CFRN-certified nurse were a sense of accomplishment and pride (90.7%) followed by flight physiology knowledge (85.4%), flight nursing clinical knowledge (83.4%), and confidence as a flight nurse (80.6%).

CONCLUSION: The 2022 CFRN pulse survey identified current CFRN demographics, practice environments including transport percentage by mode and patient population types, and perceived benefits of the CFRN credential. The findings suggest CFRNs are very experienced, provide care for patients across the age continuum, and perceive multiple intrinsic and extrinsic benefits of CFRN certification, all of which are essential to safe, evidence-based advanced nursing practice in the unique, complex, autonomous, and dynamic flight environment.

PMID:37356887 | DOI:10.1016/j.amj.2023.04.004

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Nevin Manimala Statistics

The Transport of Respiratory Distress Syndrome Twin Newborns: The 27-Year-Long Experience of Gaslini Neonatal Emergency Transport Service Using Both Single and Double Ventilators

Air Med J. 2023 Jul-Aug;42(4):246-251. doi: 10.1016/j.amj.2023.03.003. Epub 2023 Mar 28.

ABSTRACT

OBJECTIVE: Twin pregnancy rates have increased in the past 30 years. We describe the experience of the Neonatal Emergency Transport Service of the Gaslini Hospital, Genoa, Italy, in the transport of twin newborns.

METHODS: This was a retrospective study (1996-2021); 7,852 medical charts from the Neonatal Emergency Transport Service were reviewed. We included all twin newborns who were transported with respiratory distress syndrome in the study. We split the included patients into 2 groups (group A and group B) based on if they were simultaneously ventilated by a single ventilator or by 2 different ventilators, and then each group was split by the different types of ventilation (nasal continuous positive airway pressure or intermittent positive pressure ventilation). The pH level, base excess, O2 saturation, Pco2, body temperature, plasma glucose, and Transport Risk Index of Physiologic Stability score were recorded at departure and arrival.

RESULTS: One hundred thirty-six patients were included (68 pairs of twins); group A consisted of 92 newborns and group B 44 newborns. Although some significant differences were observed (statistic), none of these had real clinical significance.

CONCLUSION: Transporting respiratory distress syndrome twin newborns is challenging. Our study provided a 27-year experience in the field. Transporting twins by a single ventilator is possible, but, in our opinion, using 2 ventilators mounted on the same transport module is the best possible choice in terms of clinical performance, logistics, and cost.

PMID:37356884 | DOI:10.1016/j.amj.2023.03.003