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1.
Integr Cancer Ther ; 23: 15347354231226115, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427798

RESUMO

Chemotherapy-induced leukopenia is a common side effect of cytotoxic anticancer drugs. It can deprive patients of treatment opportunities, resulting in the delay, reduction, or discontinuation of chemotherapy or other anticancer drug administration. Two researchers searched English, Chinese, Japanese, and Korean electronic databases, without limiting the time period and language, using search terms such as "Bojungikgi," "WBC," "leuko," and "neutrop." Among the human randomized controlled studies in which Bojungikgi-tang was administered to patients who underwent chemotherapy, studies reporting leukopenia-related outcomes were selected, and data extraction, bias risk assessment, and meta-analysis were performed on the selected papers. Ten studies were selected, and a systematic review with meta-analysis was conducted. Nine papers were published in China and the total number of participants was 715. As a result of administering Bojungikgi-tang to these patients, the number of patients with chemotherapy-induced leukopenia significantly decreased (OR: 0.41, 95% CI: 0.27-0.61, P = .0001, I2 = 35%). Further, white blood cell counts were compared with that of the control group, and it showed an effect on prevention (MD: 0.64, 95% CI: 0.46-0.83, P < .00001, I2 = 90%). A pronounced effect was observed, especially when administered after a diagnosis based on the pattern identification, such as Qi deficiency. (OR: 0.32, 95% CI: 0.18-0.58, P = .0002, I2 = 0%). However, all studies had a high risk of bias due to non-blinding, and most studies had a high or uncertain risk of bias in creating random assignment orders and concealing them. Bojungikgi-tang has an effect on the prevention and treatment of chemotherapy-induced leukopenia. The effect rate can be increased when administered after proper diagnosis, and the possibility of adverse reactions and side effects is lower than that of Granulocyte-Colony Stimulating Factor (G-CSF) injection. Bojungikgi-tang appears to be useful in the treatment and prevention of leukopenia caused by cytotoxic anticancer drugs. However, it is necessary to conduct high-quality clinical studies in the future, considering the possibility of local and language bias, heterogeneity of carcinoma and intervention, and the risk of bias.Registration: PROSPERO CRD4202341054.


Assuntos
Antineoplásicos , Leucopenia , Trombocitopenia , Humanos , Leucopenia/induzido quimicamente , Leucopenia/tratamento farmacológico , Antineoplásicos/efeitos adversos , Trombocitopenia/induzido quimicamente , China
2.
Lancet Haematol ; 11(3): e196-e205, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301670

RESUMO

BACKGROUND: Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression-free survival of up to 16 months. We aimed to investigate an intensified treatment of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL. METHODS: MARTA was a prospective, single-arm, phase 2 study done at 15 research hospitals in Germany. Patients aged 65 years or older with newly diagnosed, untreated PCNSL were enrolled if they had an Eastern Cooperative Oncology Group performance status of 0-2 and were fit for high-dose chemotherapy and autologous HSCT. Induction treatment consisted of two 21-day cycles of high-dose intravenous methotrexate 3·5 g/m2 (day 1), intravenous cytarabine 2 g/m2 twice daily (days 2 and 3), and intravenous rituximab 375 mg/m2 (days 0 and 4) followed by high-dose chemotherapy with intravenous rituximab 375 mg/m2 (day -8), intravenous busulfan 3·2 mg/kg (days -7 and -6), and intravenous thiotepa 5 mg/kg (days -5 and -4) plus autologous HSCT. The primary endpoint was progression-free survival at 12 months in all patients who met eligibility criteria and started treatment. The study was registered with the German clinical trial registry, DRKS00011932, and recruitment is complete. FINDINGS: Between Nov 28, 2017, and Sept 16, 2020, 54 patients started induction treatment and 51 were included in the full analysis set. Median age was 71 years (IQR 68-75); 27 (53%) patients were female and 24 (47%) were male. At a median follow-up of 23·0 months (IQR 16·8-37·4), 23 (45%) of 51 patients progressed, relapsed, or died. 12-month progression-free survival was 58·8% (80% CI 48·9-68·2; 95% CI 44·1-70·9). During induction treatment, the most common grade 3-5 toxicities were thrombocytopenia and leukopenia (each in 52 [96%] of 54 patients). During high-dose chemotherapy and autologous HSCT, the most common grade 3-5 toxicity was leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, all due to infectious complications. INTERPRETATION: Although the primary efficacy threshold was not met, short induction followed by high-dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials. FUNDING: Else Kröner-Fresenius Foundation, Riemser Pharma, and Medical Center-University of Freiburg.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucopenia , Linfoma Difuso de Grandes Células B , Humanos , Feminino , Masculino , Idoso , Estudos Prospectivos , Rituximab , Linfoma Difuso de Grandes Células B/tratamento farmacológico
3.
BMC Cancer ; 24(1): 242, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383340

RESUMO

PURPOSE: To explore the association between preoperative WBC count and the long-term survival outcomes and clinical outcomes in different stage patients who underwent surgical resection for colorectal cancer (CRC). PATIENTS AND METHODS: A cohort of 8121 Chinese patients who underwent surgical resection for CRC from January 1, 2008 to December 31, 2014 were enrolled as part of the retrospective cohort were retrospectively analyzed. Based on that the preoperative WBC optimal cut-off value was 7*109/L (7,000/µL), the high preoperative WBC group and the low preoperative WBC group was defined. Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce confounding. The impact of preoperative WBC count on overall survival (OS) and disease-free survival (DFS) was investigated using the Kaplan-Meier method and Univariate Cox proportional hazards models in different stage subgroup respectively. RESULTS: After IPTW, the clinical characters in the high preoperative WBC count group and the low preoperative WBC count group were balanced. Kaplan-Meier analysis showed that the 5-year OS rate were significantly lower in the high preoperative WBC count group overall, in stage II and IV. The 5-year DFS rate was significantly lower overall, in stage II and III in the high preoperative WBC count group. High preoperative WBC count was associated with poorer OS overall in stage II and stage IV. CONCLUSIONS: This study suggests that preoperative WBC count is an independent risk factor for survival in patients undergoing colorectal surgery and may need to consider the stage of cancer when applied to predict long-term adverse outcome prognosis.


Assuntos
Neoplasias Colorretais , Leucopenia , Humanos , Estudos Retrospectivos , Prognóstico , Contagem de Leucócitos , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença
4.
Sci Rep ; 14(1): 3816, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360906

RESUMO

Ramucirumab plus docetaxel (RD) can cause febrile neutropenia (FN), which frequently requires the prophylactic administration of pegfilgrastim. However, the effects of prophylactic pegfilgrastim on FN prevention, therapeutic efficacy, and prognosis after RD have not been fully evaluated in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred and eighty-eight patients with advanced NSCLC who received RD as second-line therapy after platinum-based chemotherapy plus PD-1 blockade were included. Patients were divided into groups with and without prophylactic pegfilgrastim, and adverse events, efficacy, and prognosis were compared between both groups. Of the 288 patients, 247 received prophylactic pegfilgrastim and 41 did not. The frequency of grade 3/4 neutropenia was 62 patients (25.1%) in the pegfilgrastim group and 28 (68.3%) in the control group (p < 0.001). The frequency of FN was 25 patients (10.1%) in the pegfilgrastim group and 10 (24.4%) in the control group (p = 0.018). The objective response rate was 31.2% and 14.6% in the pegfilgrastim and control groups (p = 0.039), respectively. The disease control rate was 72.9% in the pegfilgrastim group and 51.2% in the control group (p = 0.009). Median progression free survival was 4.3 months in the pegfilgrastim group and 2.5 months in the control group (p = 0.002). The median overall survival was 12.8 and 8.1 months in the pegfilgrastim and control groups (p = 0.004), respectively. Prophylactic pegfilgrastim for RD reduced the frequency of grade 3/4 neutropenia and febrile neutropenia and did not appear to be detrimental to patient outcome RD.Clinical Trial Registration Number: UMIN000042333.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neutropenia Febril , Filgrastim , Leucopenia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/etiologia , Docetaxel , Neoplasias Pulmonares/etiologia , Polietilenoglicóis/uso terapêutico , Leucopenia/induzido quimicamente , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/prevenção & controle , Neutropenia Febril/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico
5.
Arch. argent. pediatr ; 122(1): e202202972, feb. 2024. tab, graf
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1524470

RESUMO

Introducción. El dengue es la enfermedad transmitida por mosquitos con mayor propagación mundial en los últimos años. Presenta un amplio espectro de manifestaciones clínicas y, en ocasiones, evoluciona a un estado crítico llamado dengue grave. Su tratamiento es de sostén. La información disponible acerca de las características clínicas, epidemiológicas y de laboratorio de la enfermedad en la población pediátrica es limitada. Objetivo. Describir la epidemiología y las manifestaciones clínicas y de laboratorio de la enfermedad. Población y métodos. Estudio descriptivo, observacional y retrospectivo. Incluyó pacientes entre 1 y 180 meses asistidos por dengue probable o confirmado en un hospital de niños, desde el 01 de enero de 2020 hasta el 31 de mayo de 2020. Resultados. Se incluyeron 85 pacientes por criterios microbiológicos de positividad o clínicoepidemiológicos. Veinticinco (29 %) confirmados por RT-PCR, todos serotipos DENV-1. La mediana de  edad fue de 108 meses (rango intercuartílico: 84-144). Las principales manifestaciones clínicas fueron fiebre, cefalea y mialgias. Los hallazgos de laboratorio más importantes fueron leucopenia, trombocitopenia y elevación de transaminasas. Conclusión. El reconocimiento y la comprensión de las alteraciones clínicas y de laboratorio que se presentan durante la enfermedad pueden permitir un abordaje eficaz y contribuir a la reducción de cuadros clínicos más graves en los niños.


Introduction. Dengue has been the most widespread mosquito-borne disease worldwide in recent years. It develops with a broad spectrum of clinical manifestations and sometimes progresses to a critical condition known as severe dengue. It is managed with supportive treatment. Available information about its clinical, epidemiological, and laboratory characteristics in the pediatric population is limited. Objective. To describe the clinical, epidemiological, and laboratory characteristics of dengue. Population and methods. Descriptive, observational, and retrospective study. It included patients aged 1 to 180 months seen due to probable or confirmed dengue at a children's hospital between 1/1/2020 and 5/31/2020. Results. A total of 85 patients with positive microbiological or clinical-epidemiological criteria were included. Of these, 25 (29%) were confirmed by RT-PCR; all corresponded to DENV-1 serotype. Patients' median age was 108 months (interquartile range: 84­144). The main clinical manifestations were fever, headache, and myalgia. The most important laboratory findings were leukopenia, thrombocytopenia, and high transaminase levels. Conclusion. The recognition and understanding of clinical and laboratory alterations that occur during dengue disease may allow an effective approach and help to reduce the more severe clinical form in children.


Assuntos
Humanos , Animais , Lactente , Pré-Escolar , Criança , Adolescente , Trombocitopenia , Dengue/diagnóstico , Dengue/epidemiologia , Leucopenia , Estudos Retrospectivos , Febre/epidemiologia , Sorogrupo
6.
Front Immunol ; 15: 1260191, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384459

RESUMO

Background: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with a dismal prognosis and few effective therapeutic approaches. This study aimed to investigate the efficacy, safety, and predictive biomarkers of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) in combination with lenvatinib and PD-1 inhibitor for patients with advanced iCCA. Methods: Locally advanced or metastatic iCCA patients receiving the triple combination therapy of lenvatinib, PD-1 inhibitor, and FOLFOX-HAIC were included in this retrospective study. Primary endpoint was the progression-free survival, evaluated using the RECIST criterion. The secondary endpoints included overall survival, objective response rate, and safety. Whole exome and RNA sequencing of tumor biopsy tissues were performed for biomarker exploration. Results: Between May, 2019 and December 2022, a total of 46 patients were included in this study. The primary endpoint showed a median progression-free survival of 9.40 months (95% CI: 5.28-13.52), with a 6-month progression-free survival rate of 76.1%. The median overall survival was 16.77 months (95% CI, 14.20-19.33), with an objective response rate of 47.8% and disease control rate of 91.3% per RECIST. In addition, 4.3% and 8.7% of patients achieved complete response of all lesions and intrahepatic target lesions per mRECIST, respectively. The most common treatment-related adverse events were neutropenia, thrombocytopenia, elevated aspartate aminotransferase and alanine aminotransferase level. Furthermore, integrated analysis of genetic, transcriptomic, and immunohistochemistry data revealed that pre-existing immunity (high expression level of immune-related signatures and intra-tumoral CD8+ T cell density) in baseline tumor tissues was associated with superior clinical benefits. However, the evaluation of tumor mutation burden did not show potential predictive value in this triple combination. Conclusion: FOLFOX-HAIC in combination with lenvatinib and PD-1 inhibitor demonstrated a promising antitumor activity with manageable safety profiles in patients with advanced iCCA. Moreover, our study also revealed new perspectives on potential biomarkers for clinical efficacy.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Leucopenia , Compostos de Fenilureia , Quinolinas , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos
7.
Hum Reprod ; 39(2): 326-334, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38166353

RESUMO

STUDY QUESTION: Do prepregnancy peripheral leukocytes (PPLs) and their subsets influence the risk of spontaneous abortion (SAB)? SUMMARY ANSWER: PPLs and their subsets are associated with the risk of SAB. WHAT IS KNOWN ALREADY: Compelling studies have revealed the crucial role of maternal peripheral leukocytes in embryo implantation and pregnancy maintenance. Adaptive changes are made by PPLs and their subsets after conception. STUDY DESIGN, SIZE, DURATION: This population-based retrospective cohort study was based on data from the National Free Pre-pregnancy Check-up Project (NFPCP) in mainland China. Couples preparing for pregnancy within the next six months were provided with free prepregnancy health examinations and counseling services for reproductive health. The current study was based on 1 310 494 female NFPCP participants aged 20-49 who became pregnant in 2016. After sequentially excluding 235 456 participants lost to follow-up, with multiple births, and who failed to complete blood tests, a total of 1 075 038 participants were included in the primary analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: PPLs and their subset counts and ratios were measured. The main outcome was SAB. A multivariable logistic regression model was used to estimate the odds ratio (OR) and 95% CI of SAB associated with PPLs and their subsets, and restricted cubic spline (RCS) was used to estimate the nonlinear exposure-response relationship. MAIN RESULTS AND ROLE OF CHANCE: Of the included pregnant participants, a total of 35 529 SAB events (3.30%) were recorded. Compared to participants with reference values of PPLs, the ORs (95% CIs) of leukopenia and leukocytosis for SAB were 1.14 (1.09-1.20) and 0.74 (0.69-0.79), respectively. The RCS result revealed a monotonous decreasing trend (Pnonlinear < 0.05). Similar relationships were observed for the neutrophil count and ratio, monocyte count, and middle-sized cell count and ratio. The lymphocyte ratio showed a positive and nonlinear relationship with the risk of SAB (Pnonlinear < 0.05). Both eosinophils and basophils showed positive relationships with the risk of SAB (eosinophil Pnonlinear > 0.05 and basophil Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Chemical abortion events and the cause of SAB were not collected at follow-up. Whether women with abnormal PPLs had recovered during periconception was not determined. WIDER IMPLICATIONS OF THE FINDINGS: PPLs and their subsets are associated with the risk of SAB. Leukopenia and neutropenia screening in women preparing for pregnancy and developing a feasible PPL stimulation approach should be emphasized to utilize the immune window of opportunity to prevent SAB. STUDY FUNDING/COMPETING INTEREST(S): This study was approved by the Institutional Research Review Board of the National Health and Family Planning Commission. This study was supported by the National Key Research and Development Program of China (grants 2021YFC2700705 [Y.Y.] and 2016YFC100307 [X.M.]) and the National Natural Science Foundation of China (grant no. 82003472 [L.W.]). The funding source was not involved in the study design, data collection, analysis and interpretation of the data, writing the report, or the decision to submit this article for publication. No competing interests. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Aborto Induzido , Aborto Espontâneo , Leucopenia , Gravidez , Animais , Feminino , Humanos , Cavalos , Aborto Espontâneo/etiologia , Estudos Retrospectivos , Aborto Induzido/efeitos adversos , Leucócitos , Leucopenia/complicações
8.
Phytomedicine ; 125: 155293, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38295658

RESUMO

BACKGROUND: In China, Shenqi Fuzheng injection (SFI) has been used as an adjuvant therapy to treat all kinds of cancer for many years. A large number of systematic reviews or meta-analyses (SRs/MAs) were published to assess its efficacy and safety in the past few years. However, the quality of SRs/MAs was unclear and did not generate high-quality clinical evidence. OBJECTIVE: We conducted an overview to integrate relevant SRs/MAs published in the past with the aim of providing new clinical evidence for SFI in combination with chemotherapy in the treatment of cancer. OBJECTIVE: We conducted an overview to integrate relevant SRs/MAs published in the past with the aim of providing new clinical evidence for SFI in combination with chemotherapy in the treatment of cancer. METHODS: A comprehensive search of PubMed, Web of Science, Embase, the Cochrane Library, CNKI, VIP, WanFang, and CBM was performed from the database inception to September 30, 2023. SRs/MAs of randomized controlled trials (RCTs) on SFI combined with chemotherapy for cancer were included. Four reviewers screened the literature and extracted relevant information. Five reviewers assessed the quality of reporting, methodological quality, risk of bias, and quality of evidence for SRs/MAs. We used corrected covered area (CCA) to assess the degree of overlap among the RCTs included in SRs/MAs. We performed a descriptive analysis for the results of the included SRs/MAs. RESULTS: A total of 32 SRs/MAs of SFI combined with chemotherapy for cancer were included. We assessed the reporting quality of SRs/MAs using the PRISMA 2020 statement. 1 SR/MA had relatively complete reports, 20 SRs/MAs had some deficiencies in reporting, and 11 SRs/MAs had serious deficiencies in reporting. We assessed the methodological quality of SRs/MAs using the AMSTAR 2 tool. The methodological quality of all SRs/MAs was very low. We assessed the risk of bias for SRs/MAs using the ROBIS tool. The risk of bias was low for 19 SRs/MAs and unclear for 13 SRs/MAs. We assessed the quality of evidence for SRs/MAs using the GRADE evidence quality evaluation system. 50 items were moderate quality, 46 items were low quality, 27 items were very low quality, and 85 items were unclear. SFI combined with chemotherapy played a role in increasing efficacy and decreasing toxicities in all kinds of cancer, including clinical efficacy (except liver cancer), quality of life, immune function (except CD8+), leukopenia, thrombocytopenia, hemoglobinopenia, nausea and vomiting, liver damage, kidney damage, neurotoxicity, alopecia, and diarrhea. CONCLUSION: The overview showed that SFI combined with chemotherapy may improve clinical efficacy (except for liver cancer), quality of life, and immune (except for CD8+) function in all types of cancer, as well as adverse events (AEs) such as leukopenia, thrombocytopenia, etc. Since most of the clinical evidence was low, higher quality clinical trials will be expected to improve the reliability of the above conclusions in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Medicamentos de Ervas Chinesas , Leucopenia , Neoplasias Hepáticas , Neoplasias Pulmonares , Trombocitopenia , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico
10.
Pathology ; 56(3): 382-390, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38296677

RESUMO

Kikuchi-Fujimoto disease (KFD) is a benign self-limiting condition primarily affecting young females. It usually presents with fever and cervical lymphadenopathy of unknown aetiology with a preponderance of the Asian population. Histopathology is critical in making an accurate diagnosis. While the typical microscopic features include paracortical necrosis with debris, histiocytosis with immunoblasts, and absent neutrophils, rarely, KFD can show atypical features like marked immunoblastic proliferation mimicking lymphoma, demonstrate vasculitis mimicking lupus erythematosus, etc. The diagnosis is extremely challenging if such features occur in cases with generalised lymphadenopathy, which is infrequent in KFD. The study aims to describe the morphological, clinical, and immunohistochemical features of KFD and determine the frequency of the atypical features. We also analysed the subtle histological and immunohistochemical features that aid in the diagnosis of atypical cases. Cases reported as KFD over a period of 6 years were retrieved from the archives of histopathology. The morphological features were categorised as typical and atypical. In the atypical cases, the features that aided in the correct diagnosis of KFD were analysed. Out of the 42 cases evaluated, 23.9% (n=10) had generalised lymphadenopathy; 57.2% (n=24) were women with a median age of 25 years. Leukopenia was observed in 42% (n=13) of patients. Typical features were present in 76.2% (n=32) cases and 23.8% (n=10) presented with atypical features. Eight cases were antinuclear antibody-positive. Atypical features included five (50%) cases with vasculitis and panniculitis, and three (30%) cases with large, atypical cells for which immunohistochemistry (IHC) was performed. In two of these cases, the patent sinuses, absence of neutrophils, and IHC with CD68 aided the diagnosis. There is an overlap of clinical and histopathological features between KFD and malignant lymphomas and systemic lupus erythematosus. Given the fact that the atypical features (23.8%) are not rare occurrences in KFD, correlations with clinical findings and ancillary studies are essential to avoid misdiagnosis and inadvertent therapy.


Assuntos
Linfadenite Histiocítica Necrosante , Leucopenia , Linfadenopatia , Vasculite , Humanos , Feminino , Adulto , Masculino , Linfadenite Histiocítica Necrosante/patologia , Diagnóstico Diferencial , Linfadenopatia/diagnóstico , Linfadenopatia/complicações , Vasculite/diagnóstico
11.
BMC Cancer ; 24(1): 39, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182995

RESUMO

PURPOSE: This investigation sought to examine the efficacy and safety of low-dose apatinib used alongside chemotherapy in the clinical management of patients with metastatic triple-negative breast cancer (TNBC) within a real-world setting, whilst comparing the outcomes with those treated solely with chemotherapy. METHODS: This case series study analyzed clinical data and treatment outcomes of 163 patients with metastatic TNBC who underwent rescue treatment at the Medical Oncology Department of Clinical Oncology, Fujian Cancer Hospital, School of Fujian Medical University, China, between October 2011 and January 2023. All the patients underwent rescue treatment with either chemotherapy alone or apatinib (250 mg/day) combined with chemotherapy. The study's primary outcome was progression-free survival (PFS), whereas the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles. RESULTS: The study was designed to compare two groups [1]. Out of the 163 TNBC patients who participated in the study, 107 individuals (65.6%) received treatment based on chemotherapy, whereas 56 patients (34.4%) were given treatment based on a combination of low-dose apatinib (250 mg/day) and other treatments, including chemotherapy. After propensity score matching (PSM), the objective response rate (ORR) and disease control rate (DCR) of patients with advanced triple-negative breast cancer (TNBC) who received apatinib-based treatment were 50.0 and 90.0%, respectively, while they were 6.7 and 20.0%, respectively, for the chemotherapy-based group (P < 0.001). The group that received apatinib-based treatment showed superior results in both PFS and OS compared to the group that received chemotherapy. The median PFS and OS for the apatinib-based group were 7.8 and 20.3 months, respectively, while they were only 2.2 months and 9.0 months, respectively, for the chemotherapy-based group (P < 0.001) [2]. Patients who were administered combo therapies, including PD-1 inhibitors, were excluded. In total, 97 patients received chemotherapy alone, while 34 patients were treated with apatinib in combination with chemotherapy. After propensity score matching (PSM), the ORR and DCR for the total group who received combo therapies were 44.4 and 81.5%, respectively, while they were 11.1 and 22.2%, respectively, for the chemotherapy alone group (P < 0.001). The group receiving both apatinib and chemotherapy displayed notable advantages over the group solely receiving chemotherapy in regards to PFS and OS for the entirety of the population. The PFS was found to be 7.8 months in comparison to 2.1 months (P < 0.001) and the OS was 21.1 months in contrast to 9.0 months (P < 0.001). Apatinib combined with chemotherapy induced grade 3/4 hematological toxicities, including neutropenia (8.8%) and thrombocytopenia (2.9%). Additionally, non-hematological toxicities were commonly observed, such as Hand-foot syndrome (35.3%), proteinuria (26.5%), hypertension (61.8%), higher alanine aminotransferase levels (26.5%), and fatigue (35.3%). The most frequent non-hematological grade 3/4 toxicities were Hand-foot syndrome (2.9%) and hypertension (5.9%). The study did not report any fatal adverse effects. CONCLUSIONS: The combination of low-dose apatinib with chemotherapy has proven to be more effective than chemotherapy alone in treating metastatic triple-negative breast cancer (TNBC). Additionally, the occurrence of grade 3/4 non-hematologic toxicities was significantly lower compared to the recommended dose of apatinib.


Assuntos
Síndrome Mão-Pé , Hipertensão , Leucopenia , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Protocolos Clínicos
12.
BMC Pediatr ; 24(1): 17, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183053

RESUMO

BACKGROUND: Hypertensive disorders in pregnancy can cause prenatal placental perfusion with insufficient blood supply to the fetus, resulting in fetal exposure to hypoxia and leading to disturbance of neonatal hematopoietic stem cells. This study aimed to compare the hematological profiles of newborns from mothers with hypertensive disorders and normotensive delivered at the University of Gondar comprehensive specialized hospital. METHODS: A comparative cross-sectional study was conducted from March to May 2022 among 308 newborns from hypertensive and normotensive mothers in equal proportions. A systematic random sampling technique was used to select study participants. Three milliliters of cord blood were collected to perform a complete blood count by Beckman coulter. The results were presented using tables and graphs. Independent t-test and Mann-Whitney U test were done to compare the hematological profiles of the two groups. P-value < 0.05were considered statistically significant. RESULTS: The majority of hypertensive and normotensive mothers' ages were between 20 and 34 years (83.77% and 90.91%, respectively). The hematocrit levels were significantly higher in neonates of hypertensive mothers than the neonates of normotensive mothers (49.10 ± 5.19% and 46.09 ± 7.63% respectively) (P < 0.001) while neutrophil counts were significantly lower in neonates of hypertensive mothers than the neonates of normotensive mothers (6.62 ± 3.30 and 7.55 ± 3.31 × 103 /ul respectively) (P = 0.007). Also, platelets counts were significantly lower in neonates of hypertensive mothers than neonates of normotensive mothers (221.25 ± 83.56 and 260.24 ± 83.01 × 103/ul respectively) (P < 0.001). The platelet and nucleated red blood cell count showed a statistically significant difference among newborns from mothers with superimposed preeclampsia and gestational hypertension. CONCLUSION: Newborns delivered from hypertensive disorders of pregnancy had low white blood cell parameters, low platelet count and high red blood cell parameters compared to controls. As result, newborns may develop leukopenia, thrombocytopenia and polycythemia, respectively. Therefore, newborns should be monitored for early detection and follow-up of hematological abnormalities before complications occurred.


Assuntos
Hipertensão Induzida pela Gravidez , Leucopenia , Trombocitopenia , Recém-Nascido , Gravidez , Feminino , Humanos , Estudos Transversais , Placenta , Hospitais
13.
Pharmacol Res ; 200: 107068, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38232908

RESUMO

Leukopenia is the most common side effect of chemotherapy and radiotherapy. It potentially deteriorates into a life-threatening complication in cancer patients. Despite several agents being approved for clinical administration, there are still high incidences of pathogen-related disease due to a lack of functional immune cells. ADP-ribosyl cyclase of CD38 displays a regulatory effect on leukopoiesis and the immune system. To explore whether the ADP-ribosyl cyclase was a potential therapeutic target of leukopenia. We established a drug screening model based on an ADP-ribosyl cyclase-based pharmacophore generation algorithm and discovered three novel ADP-ribosyl cyclase agonists: ziyuglycoside II (ZGSII), brevifolincarboxylic acid (BA), and 3,4-dihydroxy-5-methoxybenzoic acid (DMA). Then, in vitro experiments demonstrated that these three natural compounds significantly promoted myeloid differentiation and antibacterial activity in NB4 cells. In vivo, experiments confirmed that the compounds also stimulated the recovery of leukocytes in irradiation-induced mice and zebrafish. The mechanism was investigated by network pharmacology, and the top 12 biological processes and the top 20 signaling pathways were obtained by intersecting target genes among ZGSII, BA, DMA, and leukopenia. The potential signaling molecules involved were further explored through experiments. Finally, the ADP-ribosyl cyclase agonists (ZGSII, BA, and DMA) has been found to regenerate microbicidal myeloid cells to effectively ameliorate leukopenia-associated infection by activating CD38/ADP-ribosyl cyclase-Ca2+-NFAT. In summary, this study constructs a drug screening model to discover active compounds against leukopenia, reveals the critical roles of ADP-ribosyl cyclase in promoting myeloid differentiation and the immune response, and provides a promising strategy for the treatment of radiation-induced leukopenia.


Assuntos
Antígenos CD , Leucopenia , Humanos , Camundongos , Animais , ADP-Ribosil Ciclase/metabolismo , ADP-Ribosil Ciclase 1 , Antígenos CD/genética , Antígenos de Diferenciação/genética , Glicoproteínas de Membrana , Peixe-Zebra/metabolismo , Leucopenia/induzido quimicamente , Leucopenia/tratamento farmacológico
14.
Int J Lab Hematol ; 46(1): 72-82, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37746889

RESUMO

INTRODUCTION: Mindray MC-80 is an automated system for digital imaging of white blood cells (WBCs) and their pre-classification. The objective of this work is to analyse its performance comparing it with the CellaVision® DM9600. METHODS: A total of 445 samples were used, 194 normal and 251 abnormal: acute leukaemia (100), myelodysplastic syndromes/myeloproliferative neoplasms (33), lymphoid neoplasms (50), plasma cell neoplasms (14), infections (49) and thrombocytopenia (5). WBC pre-classification values with the MC-80 and DM9600 were compared with (1) the microscope, (2) Mindray BC-6800Plus differentials in only normal samples, and (3) confirmed or reclassified images (post-classification). Pearson's correlation, Lin's concordance, Passing-Bablok regression, and Bland-Altman plots were used. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for abnormal cells using the MC-80 were calculated. RESULTS: The PPV and NPV were above 98% and 99%, for normal samples. For immature granulocytes (IG), NPV and PPV were 100% and 74.2%. When comparing the WBC differentials using the MC-80, the microscope and the BC-6800Plus, no differences were found except for basophils and IG. Our results showed good agreement between the pre- and post-classification of normal WBC, including IG, quantified by high correlation and concordance values (0.91-1). Sensitivity and specificity for blasts were 0.984 and 0.640. The MC-80 detected abnormal lymphocytes in 30% of the smears from patients with lymphoid neoplasm. Plasma cell identification was better using the DM9600. The sensitivity and specificity for erythroblast detection were 1 and 0.890. CONCLUSION: We found that the MC-80 shows high performance for WBC differentials for both normal samples and patients with haematological diseases.


Assuntos
Leucemia , Leucopenia , Humanos , Contagem de Leucócitos , Leucócitos , Plasmócitos
15.
Int J Rheum Dis ; 27(1): e14999, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38063858

RESUMO

OBJECTIVES: To elucidate the efficacy and safety of aggressive multi-combination therapy with mycophenolate mofetil, rituximab, and plasma exchange or polymyxin B immobilized fiber column direct hemoperfusion followed by conventional therapy with corticosteroids, calcineurin inhibitors, and intravenous pulse cyclophosphamide in patients with rapidly progressive interstitial lung disease (RPILD) with anti-melanoma differentiation-associated gene 5 (MDA5)-antibody-positive dermatomyositis (DM). METHODS: A total of 23 patients with anti-MDA5 antibody-positive DM-RPILD were enrolled, with nine patients in Group A (treated conventionally before March 2015) and 14 patients in Group B (received aggressive treatment after April 2015). RESULTS: Pretreatment severity of interstitial lung disease (ILD) did not differ between the two groups. However, Group B exhibited a higher cumulative survival rate at 48 weeks than Group A (64.3% vs. 33.3%). The corticosteroid dose, divided by the initial dose at 3 months and 12 months, was significantly lower in Group B than in Group A (p = .046 and .026, respectively). Among the ILD-related deaths in Group B, there was a tendency toward a higher proportion of males and more severe ILD. The incidence of infection did not differ between the groups, but leukopenia was more common in Group B. CONCLUSION: This aggressive multi-combination therapy may improve the survival outcome of patients with anti-MDA5 antibody-positive DM-RPILD. However, careful management of complications, such as opportunistic infections and leukopenia, is essential. Future refinement through longitudinal investigations tracking the long-term efficacy, safety, and cost-effectiveness of this treatment strategy is needed.


Assuntos
Dermatomiosite , Leucopenia , Doenças Pulmonares Intersticiais , Trombocitopenia , Masculino , Humanos , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Dermatomiosite/complicações , Helicase IFIH1 Induzida por Interferon , Autoanticorpos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/complicações , Corticosteroides/efeitos adversos , Leucopenia/complicações , Progressão da Doença , Estudos Retrospectivos
16.
Int J Clin Pharmacol Ther ; 62(1): 48-55, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37942926

RESUMO

Adverse lamotrigine effects are more likely with concomitant use of antiepileptic drugs, rapid dose titration, and multiple drug use, highlighting the importance of measuring its concentration. Here, lamotrigine was administered the day after the third mRNA vaccination to a 20-year-old bipolar woman with these risk factors. Leukopenia occurred on day 12 without rapid concentration increase, but leukocytes gradually recovered after 22 weeks without discontinuation of lamotrigine. The second mRNA vaccination did not induce leukopenia. Possibly, a synergetic immune response to simultaneous vaccination and lamotrigine caused leukopenia, which recovered as the response weakened. Lamotrigine initiation immediately after mRNA vaccination may be a leukopenia risk factor.


Assuntos
COVID-19 , Leucopenia , Trombocitopenia , Feminino , Humanos , Adulto Jovem , Adulto , Lamotrigina/efeitos adversos , Anticonvulsivantes/efeitos adversos , Triazinas/efeitos adversos , COVID-19/prevenção & controle , Leucopenia/induzido quimicamente , Leucopenia/diagnóstico , Leucopenia/tratamento farmacológico , Trombocitopenia/tratamento farmacológico , RNA Mensageiro
17.
Mult Scler Relat Disord ; 81: 105135, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38006850

RESUMO

INTRODUCTION: Fingolimod is a disease-modifying therapy for multiple sclerosis (MS) that modulates sphingosine 1-phospate receptors, impeding the egress of lymphocytes from lymphnodes and thus causing lymphopenia. Severe lymphopenia should lead to fingolimod discontinuation. We aim to evaluate whether switching from fingolimod to ozanimod can adjust fingolimod-related lymphopenia while maintaining clinical efficacy. METHODS: In this real-world observational study, we included 18 people with MS (47.7 ± 7.6 years of age, 77.8 % of women, 13.9 ± 6.9 years of disease duration, median EDSS 3.0) at the time of fingolimod discontinuation due to lymphopenia. We collected laboratory (lymphocyte absolute count on the same hematological counter) and clinical variables at fingolimod discontinuation, at ozanimod prescription, and 6 months after ozanimod prescription. RESULTS: From 13 cases of grade 3 and 4 lymphopenia at the time of fingolimod discontinuation, we observed only 2 cases of grade 3 and no cases of grade 4 lymphopenia after 6 months of ozanimod treatment. On paired t-tests, absolute lymphocyte count at fingolimod discontinuation were lower than ozanimod prescription (p<0.001), and after 6 months (p<0.001). We observed no clinical changes. DISCUSSION: People with MS who have severe fingolimod-related lymphopenia and are clinically stable, can exhibit increased absolute lymphocyte counts when switched to ozanimod, while preserving clinical stability.


Assuntos
Anemia , Indanos , Leucopenia , Linfopenia , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Oxidiazóis , Humanos , Feminino , Idoso , Cloridrato de Fingolimode/efeitos adversos , Imunossupressores/efeitos adversos , Linfopenia/induzido quimicamente , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
18.
Pediatr Transplant ; 28(1): e14628, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37877312

RESUMO

BACKGROUND: Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients. METHODS: Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post-transplant. RESULTS: The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p = .02), increased number of hospitalizations (82% vs. 67%, p = .01), and viral replications (79% vs. 47%, p < .0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow-up (-7 vs. -1 mL/min/1.73 m2 , p = .05). CONCLUSIONS: Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post-transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post-transplant outcomes.


Assuntos
Transplante de Rim , Leucopenia , Nefrologia , Humanos , Criança , Ácido Micofenólico , Estudos Retrospectivos , Prevalência , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/epidemiologia , Imunossupressores/efeitos adversos , Diarreia/epidemiologia , Diarreia/etiologia , Leucopenia/etiologia , Leucopenia/induzido quimicamente
19.
Leuk Lymphoma ; 65(1): 118-122, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37871127

RESUMO

Epstein-Barr virus (EBV) associated T-cell and NK-cell lymphoproliferative diseases are lethal and extremely rare in Caucasians. We expand on the clinical, immunological and histogenetic characteristics associated with this second European case (19 years old, previously healthy, Caucasian boy) of systemic EBV positive T-cell lymphoma of childhood. We report, as novel findings, severe lympho-depletion and abrogation of thymopoiesis secondary to severe EBV activation and excessive immune activation. Similar to the first European case, we also detected a somatic missense variant in the proto-oncogene FYN. In the first European patient however, the FYN variant allele frequency (VAF) was 10% and the patient only experienced moderate leukopenia, whereas in our case, the VAF was 48% and the patient experienced severe leukopenia and lymphopenia. This could suggest a pathogenic role of these FYN variants in driving excessive T cell activation. If confirmed, FYN might become target in future treatments of this fatal disorder.


Assuntos
Infecções por Vírus Epstein-Barr , Leucopenia , Linfoma de Células T Periférico , Linfoma de Células T , Transtornos Linfoproliferativos , Masculino , Humanos , Adulto Jovem , Adulto , Herpesvirus Humano 4 , Infecções por Vírus Epstein-Barr/complicações , Linfócitos T/patologia , Linfoma de Células T/etiologia , Linfoma de Células T/genética , Linfoma de Células T Periférico/patologia , Transtornos Linfoproliferativos/terapia
20.
Arch Argent Pediatr ; 122(1): e202202972, 2024 02 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37639337

RESUMO

Introduction. Dengue has been the most widespread mosquito-borne disease worldwide in recent years. It develops with a broad spectrum of clinical manifestations and sometimes progresses to a critical condition known as severe dengue. It is managed with supportive treatment. Available information about its clinical, epidemiological, and laboratory characteristics in the pediatric population is limited. Objective. To describe the clinical, epidemiological, and laboratory characteristics of dengue. Population and methods. Descriptive, observational, and retrospective study. It included patients aged 1 to 180 months seen due to probable or confirmed dengue at a children's hospital between 1/1/2020 and 5/31/2020. Results. A total of 85 patients with positive microbiological or clinical-epidemiological criteria were included. Of these, 25 (29%) were confirmed by RT-PCR; all corresponded to DENV-1 serotype. Patients' median age was 108 months (interquartile range: 84-144). The main clinical manifestations were fever, headache, and myalgia. The most important laboratory findings were leukopenia, thrombocytopenia, and high transaminase levels. Conclusion. The recognition and understanding of clinical and laboratory alterations that occur during dengue disease may allow an effective approach and help to reduce the more severe clinical form in children.


Introducción. El dengue es la enfermedad transmitida por mosquitos con mayor propagación mundial en los últimos años. Presenta un amplio espectro de manifestaciones clínicas y, en ocasiones, evoluciona a un estado crítico llamado dengue grave. Su tratamiento es de sostén. La información disponible acerca de las características clínicas, epidemiológicas y de laboratorio de la enfermedad en la población pediátrica es limitada. Objetivo. Describir la epidemiología y las manifestaciones clínicas y de laboratorio de la enfermedad. Población y métodos. Estudio descriptivo, observacional y retrospectivo. Incluyó pacientes entre 1 y 180 meses asistidos por dengue probable o confirmado en un hospital de niños, desde el 01 de enero de 2020 hasta el 31 de mayo de 2020.  Resultados. Se incluyeron 85 pacientes por criterios microbiológicos de positividad o clínico-epidemiológicos. Veinticinco (29 %) confirmados por RT-PCR, todos serotipos DENV-1. La mediana de edad fue de 108 meses (rango intercuartílico: 84-144). Las principales manifestaciones clínicas fueron fiebre, cefalea y mialgias. Los hallazgos de laboratorio más importantes fueron leucopenia, trombocitopenia y elevación de transaminasas. Conclusión. El reconocimiento y la comprensión de las alteraciones clínicas y de laboratorio que se presentan durante la enfermedad pueden permitir un abordaje eficaz y contribuir a la reducción de cuadros clínicos más graves en los niños.


Assuntos
Dengue , Leucopenia , Trombocitopenia , Animais , Humanos , Criança , Dengue/diagnóstico , Dengue/epidemiologia , Estudos Retrospectivos , Sorogrupo , Febre/epidemiologia
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