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Supportive Care in Cancer : Official... Jun 2024The causal relationship between breast cancer and its estrogen receptor (ER) subtypes and neutropenia and agranulocytosis is unclear.
PURPOSE
The causal relationship between breast cancer and its estrogen receptor (ER) subtypes and neutropenia and agranulocytosis is unclear.
METHODS
In two-sample Mendelian randomization (MR), we used inverse variance weighting (IVW), Bayesian weighted MR (BWMR), MR-Egger, weighted median, simple mode, and weighted mode methods to analyze causality for ER-positive breast cancer, ER-negative breast cancer, overall breast cancer, and drug-induced neutropenia and agranulocytosis. To validate the results, we performed the analysis again using GWAS data on neutropenia from different databases. In multivariable MR (MVMR), we assessed the independent effects of ER-positive and ER-negative breast cancer on causality.
RESULTS
Two-sample MR analysis showed a causal relationship between ER-positive breast cancer (IVW odds ratio (OR) = 1.319, P = 7.580 × 10), ER-negative breast cancer (OR = 1.285, P = 1.263 × 10), overall breast cancer (OR = 1.418, P = 2.123 × 10), and drug-induced neutropenia and a causal relationship between ER-positive breast cancer (OR = 1.349, P = 1.402 × 10), ER-negative breast cancer (OR = 1.235, P = 7.615 × 10), overall breast cancer (OR = 1.429, P = 9.111 × 10), and neutropenia. Similarly, ER-positive breast cancer (OR = 1.213, P = 5.350 × 10), ER-negative breast cancer (OR = 1.179, P = 1.300 × 10), and overall breast cancer (OR = 1.275, P = 8.642 × 10) also had a causal relationship with agranulocytosis. MVMR analysis showed that ER-positive breast cancer remained causally associated with drug-induced neutropenia (OR = 1.233, P = 4.188 × 10), neutropenia (OR = 1.283, P = 6.363 × 10), and agranulocytosis (OR = 1.142, P = 4.549 × 10). Heterogeneity analysis and pleiotropy test showed that our results were reliable.
CONCLUSION
Our study provides genetic evidence for a causal association between breast cancer and its estrogen receptor subtypes and neutropenia. In clinical practice, in addition to focusing on therapeutic factors, additional attention should be given to breast cancer patients to avoid severe neutropenia.
Topics: Humans; Breast Neoplasms; Neutropenia; Mendelian Randomization Analysis; Female; Agranulocytosis; Genetic Predisposition to Disease; Receptors, Estrogen; Genome-Wide Association Study; Bayes Theorem; Polymorphism, Single Nucleotide
PubMed: 38949722
DOI: 10.1007/s00520-024-08682-1 -
Annals of the American Thoracic Society Jul 2024
Topics: Humans; Male; Jaundice; Fever; Neutropenia; Pain; Middle Aged
PubMed: 38949601
DOI: 10.1513/AnnalsATS.202310-902CC -
BMC Cancer Jun 2024To explore the correlation between effective dose to immune cells (EDIC) and vertebral bone marrow dose and hematologic toxicity (HT) for esophageal squamous cell...
Association of effective dose to immune cells and vertebral marrow dose with hematologic toxicity during neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma.
BACKGROUND
To explore the correlation between effective dose to immune cells (EDIC) and vertebral bone marrow dose and hematologic toxicity (HT) for esophageal squamous cell carcinoma (ESCC) during neoadjuvant chemoradiotherapy (nCRT).
METHODS
The study included 106 ESCC patients treated with nCRT. We collected dosimetric parameters, including vertebral body volumes receiving 10-40 Gy (V10, V20, V30, V40) and EDIC and complete blood counts. Associations of the cell nadir and dosimetric parameters were examined by linear and logistic regression analysis. The receiver operating characteristic (ROC) curves were used to determine the cutoff values for the dosimetric parameters.
RESULTS
During nCRT, the incidence of grade 3-4 lymphopenia, leukopenia, and neutropenia was 76.4%, 37.3%, and 37.3%, respectively. Patients with EDIC ≤ 4.63 Gy plus V10 ≤ 140.3 ml were strongly associated with lower risk of grade 3-4 lymphopenia (OR, 0.050; P < 0.001), and patients with EDIC ≤ 4.53 Gy plus V10 ≤ 100.9 ml were strongly associated with lower risk of grade 3-4 leukopenia (OR, 0.177; P = 0.011), and patients with EDIC ≤ 5.79 Gy were strongly associated with lower risk of grade 3-4 neutropenia (OR, 0.401; P = 0.031). Kaplan-Meier analysis showed that there was a significant difference among all groups for grade 3-4 lymphopenia, leukopenia, and neutropenia (P < 0.05).
CONCLUSION
The dose of vertebral bone marrow irradiation and EDIC were significantly correlated with grade 3-4 leukopenia and lymphopenia, and EDIC was significantly correlated with grade 3-4 neutropenia. Reducing vertebral bone marrow irradiation and EDIC effectively reduce the incidence of HT.
Topics: Humans; Male; Female; Middle Aged; Esophageal Squamous Cell Carcinoma; Bone Marrow; Neoadjuvant Therapy; Aged; Esophageal Neoplasms; Adult; Chemoradiotherapy; Radiotherapy Dosage; Leukopenia; Neutropenia; Lymphopenia; Retrospective Studies
PubMed: 38943075
DOI: 10.1186/s12885-024-12531-z -
Scientific Reports Jun 2024In contrast to transplant recipients, there is a paucity of data regarding frequency and clinical significance of viraemia in children receiving conventional... (Observational Study)
Observational Study
In contrast to transplant recipients, there is a paucity of data regarding frequency and clinical significance of viraemia in children receiving conventional chemotherapy. In a prospective observational study, we assessed the frequency of and clinical impact of viraemia with cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, human herpesvirus-6 (HHV6) and herpes-simplex virus 1/2 (HSV1/2) in paediatric cancer patients at diagnosis, at a routine examination during intensive chemotherapy, and during febrile neutropenia (FN). Seventy-nine patients (median age 6 years; 66 children with haematological malignancies) were included in the study. Overall, 362 blood samples were analysed, 72 from the time at diagnosis (11.1% with positive PCR result), 118 during a regular control after chemotherapy (11.0% positive), and 159 during FN (8.8% positive). The overall positivity rate was 9.6% (CMV 3.3%, HHV6 2.7%, HSV 2.2%, EBV 0.8% and adenovirus 0.3%). There were no significant differences between FN episodes with and without viraemia in terms of duration of fever or neutropenia/lymphopenia, severity of mucositis (> II), incidence of diarrhea and ICU admission. Our results indicate that viraemia in paediatric cancer patients generally does not have a major clinical impact, and may help in the decision regarding the indication of routine evaluation for viraemia in febrile neutropenic, but otherwise asymptomatic children.
Topics: Humans; Child; Viremia; Female; Male; Child, Preschool; Neoplasms; Adolescent; Prospective Studies; Infant; Febrile Neutropenia; Hematologic Neoplasms
PubMed: 38937530
DOI: 10.1038/s41598-024-65641-w -
Kidney Research and Clinical Practice Jun 2024Continuous kidney replacement therapy (CKRT) is crucial in the management of acute kidney injury in intensive care units (ICUs). Nonetheless, the optimal anticoagulation...
The role of nafamostat mesylate anticoagulation in continuous kidney replacement therapy for critically ill patients with bleeding tendencies: a retrospective study on patient outcomes and safety.
BACKGROUND
Continuous kidney replacement therapy (CKRT) is crucial in the management of acute kidney injury in intensive care units (ICUs). Nonetheless, the optimal anticoagulation strategy for patients with bleeding tendencies remains debated. This study aimed to evaluate patient outcomes and safety of nafamostat mesylate (NM) compared with no anticoagulation (NA) in critically ill patients with bleeding tendencies who were undergoing CKRT.
METHODS
This retrospective study enrolled 2,313 patients who underwent CKRT between March 2013 and December 2022 at the third affiliated hospital in South Korea. After applying the exclusion criteria, 490 patients were included in the final analysis, with 245 patients in the NM and NA groups each, following 1:1 propensity score matching. Subsequently, in-hospital mortality, incidence of bleeding complications, agranulocytosis, hyperkalemia, and length of hospital stay were assessed.
RESULTS
No significant differences were observed between the groups regarding the lengths of hospital and ICU stays or the incidence of agranulocytosis and hyperkalemia. The NM group showed a smaller decrease in hemoglobin levels during CKRT (-1.90 g/dL vs. -2.39 g/dL) and less need for blood product transfusions than the NA group. Furthermore, the NM group exhibited a survival benefit in patients who required transfusion of all three blood products.
CONCLUSION
NM is an effective and safe anticoagulant for CKRT in critically ill patients, especially those requiring transfusion of all three blood products. Although these findings are promising, further multicenter studies are needed to validate them and explore the mechanisms underlying the observed benefits.
PubMed: 38934038
DOI: 10.23876/j.krcp.23.310 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease.
OBJECTIVE
To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease.
METHODS
7 cases of acute leukemia (AL) patients diagnosed with mucormycosis by metagenomic next generation sequencing (mNGS) after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected, and their clinical data, including clinical characteristics, diagnosis, treatment, and prognosis, were retrospectively analyzed.
RESULTS
Among the 7 patients with AL complicated with mucormycosis, there were 3 males and 4 females, with a median age of 52(20-59) years. There were 6 cases of acute myeloid leukemia (AML) and 1 case of acute lymphocytic leukemia (ALL). Extrapulmonary involvement in 4 cases, including 1 case suspected of central nervous system involvement. The median time for the occurrence of mucor infection was 16(6-69) days after chemotherapy and 19(14-154) days after agranulocytosis. The main clinical manifestations of mucormycosis were fever (7/7), cough (3/7), chest pain (3/7) and dyspnea (1/7). The most common chest CT imaging findings were nodules, patchy or mass consolidation (6/7). All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase. 5 patients died within 8 months, and the median time from diagnosis to death was 1 month.
CONCLUSION
Although prophylactic antifungal therapy is adopted, patients with acute leukemia still have a risk of mucor infection during the neutropenia phase. Fever is the main manifestation in the early stage of mucor infection. The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.
Topics: Humans; Mucormycosis; Male; Female; Adult; Middle Aged; Prognosis; Retrospective Studies; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antifungal Agents; Young Adult; Leukemia
PubMed: 38926954
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.006 -
Journal of Medical Microbiology Jun 2024Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have...
Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have the highest likelihood of benefiting from prophylactic antimicrobials is important for antimicrobial stewardship (AMS). We aimed to identify groups of HCT recipients that have the highest likelihood of benefiting from prophylactic fluroquinolones. All admissions for HCT in a tertiary centre between January 2020 and December 2022 ( = 400) were retrospectively studied. Allogeneic HCT (allo-HCT) recipients had prophylaxis with ciprofloxacin during the chemotherapy-induced neutropenia, while autologous HCT (auto-HCT) recipients did not. Bacteraemias were recorded when non-contaminant bacterial pathogens were isolated in blood cultures. Allo-HCT was performed for 43.3 % (173/400) of patients and auto-HCT was performed for 56.7 % (227/400). A bacteraemia was documented in 28.3 % (113/400) of cases. Allo-HCT recipients were more likely to have a Gram-positive bacteraemia (20.8%, 36/173, vs 10.1%, 23/227, = 0.03), while a difference was not observed for Gram-negative bacteraemias (18.5%, 32/173 vs 18.1%, 41/227, = 0.91). Among auto-HCT recipients not receiving ciprofloxacin prophylaxis, patients with germ cell tumours had the highest probability ( for trend 0.09) of recording any bacteraemia (43.5%, 10/23) followed by patients with lymphomas (32.5%, 13/40), other auto-HCT indications (22.2%, 2/9), multiple myeloma (22.1%, 29/131) and multiple sclerosis (12.5%, 3/24). The higher number of bacteraemias in patients with germ cell tumours was primarily driven by Gram-negative pathogens. Ciprofloxacin prophylaxis was associated with a reduced incidence of Gram-negative bacteraemias in allo-HCT recipients. Auto-HCT recipients due to germ cell tumours, not receiving ciprofloxacin prophylaxis, recorded the highest incidence of bacteraemias and represent a possible target group for this intervention.
Topics: Humans; Ciprofloxacin; Hematopoietic Stem Cell Transplantation; Male; Retrospective Studies; Neoplasms, Germ Cell and Embryonal; Middle Aged; Female; Adult; Antibiotic Prophylaxis; Anti-Bacterial Agents; Bacteremia; Aged; Young Adult; Neutropenia; Antimicrobial Stewardship; Adolescent
PubMed: 38922673
DOI: 10.1099/jmm.0.001847 -
Pharmacy (Basel, Switzerland) Jun 2024Agranulocytosis represents a severe complication associated with the administration of clozapine. Clozapine is an antipsychotic medication that has demonstrated...
Agranulocytosis represents a severe complication associated with the administration of clozapine. Clozapine is an antipsychotic medication that has demonstrated substantial efficacy in remediating refractory schizophrenia and various other psychiatric disorders. Nonetheless, it is crucial to monitor patients for neutropenia regularly during clozapine therapy. Therefore, this article aimed to delve into the prevalence of agranulocytosis during clozapine treatment by scrutinizing the extant literature to discern trends and correlations. This review endeavored to explore factors such as drug interactions, dose-related factors, duration of treatment, and genetic predispositions that could potentially influence the likelihood of patients developing agranulocytosis while undergoing clozapine therapy. Moreover, this review enunciates the ramifications of agranulocytosis on both patients and healthcare providers and meticulously evaluates the strategies to mitigate this risk and ensure optimal patient outcomes.
PubMed: 38921968
DOI: 10.3390/pharmacy12030092 -
Clinics and Practice May 2024In recent years, a series of recommendations have been issued regarding the administration of drugs because of awareness of the serious side effects associated with... (Review)
Review
In recent years, a series of recommendations have been issued regarding the administration of drugs because of awareness of the serious side effects associated with certain classes of drugs, especially in vulnerable patients. Taking into account the obligation of the continuous improvement of professionals in the medical fields and the fact that we are in the midst of a "malpractice accusations pandemic", through this work, we propose to carry out a "radiography" of the scientific literature regarding adverse effects that may occur as a result of the interaction of drugs with the physiopathological particularities of patients. The literature reports various cases regarding different classes of drugs administration associated with adverse effects in the elderly people, such as fluoroquinolones, which can cause torsade de pointes or tendinopathy, or diuretics, which can cause hypokalemia followed by torsade de pointes and cardiorespiratory arrest. Also, children are more prone to the development of adverse reactions due to their physiological particularities, while for pregnant women, some drugs can interfere with the normal development of the fetus, and for psychiatric patients, the use of neuroleptics can cause agranulocytosis. Considering the physiopathological particularities of each patient, the drug doses must be adjusted or even completely removed from the treatment scheme, thus requiring the mandatory active participation both of clinician pharmacists and specialists in the activity of medical-pharmaceutical analysis laboratories within the structure of hospitals.
PubMed: 38921258
DOI: 10.3390/clinpract14030080 -
Frontiers in Cellular and Infection... 2024Bloodstream infection (BSI) represent a prevalent complication in haematological malignancies (HMs). Typically, Patients with BSI usually undergo empirical treatment...
BACKGROUND
Bloodstream infection (BSI) represent a prevalent complication in haematological malignancies (HMs). Typically, Patients with BSI usually undergo empirical treatment pending pathogen identification. The timely and effective management of BSIs significantly influences patient prognosis. However, pathogen distribution in BSIs exhibits regional variation. In this study, we investigated the clinical characteristics, pathogen spectrum, drug resistance, risk factors of short-term prognosis and long-term prognostic factors of acute myeloid leukemia (AML) patients with BSI at Zhejiang Provincal People's Hospital.
METHODS
From 2019 to 2021, a total of 56 AML patients with BSI were treated in the Department of Haematology at Zhejiang Province People's Hospital. Data regarding pathogen spectrum and drug resistance were collected for analysis. The patients were stratified into non-survivor cohort and survivor cohort within 30 days after BSI, and the predictors of 30-days mortality were identified through both univariate and multivariate Logistic regression analyses. Furthermore, Kaplan-Meier survival analysis and Cox regression analysis were employed to ascertain the risk factors associated with poor prognosis in AML patients complicated by BSI.
RESULTS
A total of 70 strains of pathogenic bacteria were isolated from 56 AML patients with BSI. Gram-negative bacteria constituted the predominant pathogens (71.4%), with being the most prevalent (22.9%). Gram-positive bacteria and fungi accounted for 22.9% and 5.7%, respectively. Univariate and multivariate analyses revealed significant differences in total protein, albumin levels, and the presence of septic shock between the non-survivor cohort and the survior cohort 30 days post-BSI. COX regression analysis showed that agranulocytosis duration exceeding 20 days (HR:3.854; 95% CI: 1.451-10.242) and septic shock (HR:3.788; 95% CI: 1.729-8.299) were independent risk factors for poor prognosis in AML patients complicated by BSI. Notably, the mortality rate within 30 days after infection was up to 71.4%.
CONCLUSIONS
In this study, Gram-negative bacteria, predominantly Klebsiella pneumoniae, constituted the primary pathogens among AML patients with BSIs. Serum albumin levels and the presence of septic shock emerged as independent risk factors for mortality within 30 days among AML patients with BSI. In terms of long-term prognosis, extended agranulocytosis duration exceeding 20 days and septic shock were associated with elevated mortality rates in AML patients with BSI. Additionally, in our centre, infection was found to be associated with a poor prognosis. Early intervention for infection in our centre could potentially improve patient outcomes.
Topics: Humans; Leukemia, Myeloid, Acute; Male; Female; Middle Aged; Retrospective Studies; Adult; Risk Factors; Aged; Bacteremia; Prognosis; Anti-Bacterial Agents; China; Drug Resistance, Bacterial; Young Adult; Bacteria; Gram-Negative Bacteria
PubMed: 38912203
DOI: 10.3389/fcimb.2024.1390053