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1.
Support Care Cancer ; 32(4): 220, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467943

RESUMO

PURPOSE: Leukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM). METHODS: Whole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes. RESULTS: In P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response." CONCLUSIONS: We identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia , Mucosite , Estomatite , Humanos , Polimorfismo de Nucleotídeo Único , Projetos Piloto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estomatite/genética , Estomatite/induzido quimicamente , Leucemia/genética , Leucemia/terapia , Leucemia/complicações , Terapia Comportamental
2.
Otol Neurotol ; 45(4): 362-375, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437804

RESUMO

OBJECTIVE: To examine the otologic and neurotologic symptoms, physical examination findings, and imaging features secondary to hematologic malignancies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases, including PubMed, Scopus, and CINAHL, were searched for articles including patients with otologic manifestations of leukemia, lymphoma and multiple myeloma. Data collected included patient and study demographics, specific hematologic malignancy, timing and classification of otologic symptoms, physical examination findings, imaging features and methods of diagnosis. Pooled descriptive analysis was performed. RESULTS: Two hundred seventy-two articles, of which 255 (93.8%) were case reports and 17 (6.2%) were case series, reporting on 553 patients were identified. Otologic manifestations were reported on 307 patients with leukemia, 204 patients with lymphoma and 42 patients with multiple myeloma. Hearing loss and unilateral facial palsy were the most common presenting symptoms for 111 reported subjects with leukemia (n = 46, 41.4%; n = 43, 38.7%) and 90 with lymphoma (n = 38, 42.2%; n = 39, 43.3%). Hearing loss and otalgia were the most common presenting symptoms for 21 subjects with multiple myeloma (n = 10, 47.6%; n = 6, 28.6%). Hearing loss and unilateral facial palsy were the most common otologic symptoms indicative of relapse in subjects with leukemia (n = 14, 43.8%) and lymphoma (n = 5, 50%). CONCLUSION: Hearing loss, facial palsy, and otalgia might be the first indication of a new diagnosis or relapse of leukemia, lymphoma, or multiple myeloma. Clinicians should have a heightened level of suspicion of malignant etiologies of otologic symptoms in patients with current or medical histories of these malignancies.


Assuntos
Paralisia de Bell , Surdez , Paralisia Facial , Perda Auditiva , Neoplasias Hematológicas , Leucemia , Linfoma , Mieloma Múltiplo , Humanos , Dor de Orelha , Paralisia Facial/complicações , Mieloma Múltiplo/complicações , Perda Auditiva/etiologia , Neoplasias Hematológicas/complicações , Surdez/complicações , Leucemia/complicações , Paralisia de Bell/complicações , Linfoma/complicações , Recidiva
3.
Sci Rep ; 14(1): 5947, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467719

RESUMO

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.


Assuntos
Infecções por Clostridium , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Adulto , Humanos , Vancomicina/uso terapêutico , Metronidazol/uso terapêutico , Estudos Retrospectivos , Polônia , Estudos Prospectivos , Doença Enxerto-Hospedeiro/etiologia , Leucemia/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/etiologia
6.
JCO Glob Oncol ; 10: e2300292, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38301183

RESUMO

PURPOSE: Febrile neutropenia (FN) is a serious complication in hematologic malignancies, and lung infiltrates (LIs) remain a significant concern. An accurate microbiological diagnosis is crucial but difficult to establish. To address this, we analyzed the utility of a standardized method for performing bronchoalveolar lavage (BAL) along with a two-step strategy for the analysis of BAL fluid. PATIENTS AND METHODS: This prospective observational study was conducted at a tertiary cancer center from November 2018 to June 2020. Patients age 15 years and older with confirmed leukemia or lymphomas undergoing chemotherapy, with presence of FN, and LIs observed on imaging were enrolled. RESULTS: Among the 122 enrolled patients, successful BAL was performed in 83.6% of cases. The study used a two-step analysis of BAL fluid, resulting in a diagnostic yield of 74.5%. Furthermore, antimicrobial therapy was modified in 63.9% of patients on the basis of BAL reports, and this population demonstrated a higher response rate (63% v 45%; P = .063). CONCLUSION: Our study demonstrates that a two-step BAL fluid analysis is safe and clinically beneficial to establish an accurate microbiological diagnosis. Given the crucial impact of diagnostic delays on mortality in hematologic malignancy patients with FN, early BAL studies should be performed to enable prompt and specific diagnosis, allowing for appropriate treatment modifications.


Assuntos
Neutropenia Febril , Neoplasias Hematológicas , Leucemia , Linfoma , Adolescente , Humanos , Líquido da Lavagem Broncoalveolar/microbiologia , Neutropenia Febril/diagnóstico , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/etiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/microbiologia , Neoplasias Hematológicas/patologia , Leucemia/complicações , Leucemia/patologia , Pulmão/microbiologia , Pulmão/patologia , Linfoma/complicações , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Estudos Prospectivos
7.
Br J Anaesth ; 132(2): 277-284, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38044238

RESUMO

BACKGROUND: Clonal haematopoiesis (CH) is an age-associated clonal expansion of blood cells driven by leukaemia-associated somatic mutations. Although CH has been reported to be a risk factor for leukaemia and a number of non-haematopoietic diseases, its role in perioperative medicine remains unexplored. METHODS: This was a single-centre, prospective, observational study. Patients undergoing radical oesophagectomy were enrolled, and peripheral blood samples were collected for DNA sequencing. Patients with haematopoietic somatic mutations (variant allele frequencies ≥1%) in the DNMT3A gene, TET2 gene, or both were defined as CH carriers. The primary outcome was the incidence of severe postoperative complications (Clavien-Dindo classification ≥3). The secondary outcomes included the major types of postoperative complications, mortality, and other common perioperative variables. RESULTS: Clonal haematopoiesis was found in 21.2% (33/156) of the patients (mean age: 66 yr [range: 26-79 yr]; 83% males). Some 14/33 (42.4%) patients with CH had severe postoperative complications, compared with patients without CH carriers (28/123 [22.8%]; P=0.024). Multivariable logistic regression analysis showed that CH was associated with an increased risk of developing severe postoperative complications (odds ratio, 3.63; 95% confidence interval, 1.37-9.66; P=0.010). Among the major postoperative complications, the incidence of pulmonary complications was significantly higher in the patients with CH than in those without CH (15 in 33 [45.5%] vs 30 in 123 [24.4%], P=0.018). CONCLUSIONS: Clonal haematopoiesis was associated with a higher incidence of severe postoperative complications in patients undergoing radical oesophagectomy, suggesting that clonal haematopoiesis can play an important role in perioperative medicine. CLINICAL TRIAL REGISTRATION: ChiCTR2100044175 (Chinese Clinical Trial Registry, http://www.chictr.org.cn/showproj.aspx?proj=123193).


Assuntos
Hematopoiese Clonal , Leucemia , Masculino , Humanos , Idoso , Feminino , Estudos Prospectivos , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Leucemia/complicações , Mutação
8.
Thromb Res ; 233: 109-118, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039723

RESUMO

BACKGROUND: Viscoelastic testing has been used in adult hematologic malignancies in conjunction with conventional coagulation tests (CCTs) to predict coagulopathies and tailor blood product replacement. However, there is a paucity of similar pediatric studies. OBJECTIVES: Analyze and correlate leukemia-associated coagulopathy in newly diagnosed pediatric leukemia patients using CCT's and Rotational Thromboelastometry (ROTEM). METHODS: Pediatric patients with newly diagnosed acute leukemia underwent testing with ROTEM and CCTs on days 0, 15 and 29 of induction chemotherapy. RESULTS: Sixty-two patients were enrolled. At presentation, 54.8 % of patients had platelets <50 K/µL, 73 % had prolonged PT, 1.6 % had fibrinogen <150 mg/dL. Fifteen patients (24.2 %) had WHO grade 1 bleeding and two patients (3 %) had WHO grade 4 bleeding. EXTEM/INTEM values at presentation (day 0) reflected hypocoagulability, however FIBTEM revealed hypercoagulability. Patients showed a progressive hypocoagulability in all ROTEM assays by day 15 (day 0 vs day 15, p < 0.001), with improvement by day 29 (day 15 vs day 29, p < 0.001). Day 0 ROTEM parameters were comparable to day 29. Fibrinogen strongly correlated with ROTEM at all three time points (p < 0.0001), along with platelet count with moderate correlations (p < 0.001). CONCLUSION: Fibrinogen and platelets appear to be the drivers of leukemia associated coagulopathy in the pediatric population, suggesting the utility of using CCTs and ROTEM in this population to better evaluate hemostatic function and guide blood product replacement.


Assuntos
Transtornos da Coagulação Sanguínea , Leucemia , Adulto , Humanos , Criança , Tromboelastografia , Testes de Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/diagnóstico , Fibrinogênio/análise , Leucemia/complicações
9.
Am J Infect Control ; 52(3): 320-323, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37726054

RESUMO

BACKGROUND: SARS-CoV-2, a respiratory viral disease, is thought to have a more severe course in patients with malignancy and low immune systems. METHODS: This prospective single-center study was conducted at the University of Health Sciences Dr Behçet Uz Children's Hospital from September 22 to December 31, 2021. Asymptomatic COVID-19 transmission rates were assessed using SARS-CoV-2 serology in patients with leukemia who had no history of COVID-19 infection. RESULTS: Among the 54 patients, 19 (35.2%) were females and 35 (64.8%) were males. The median age was 5.5 years (min 6 months, max 17 years). Forty-nine (90.5%) of the leukemia patients had acute lymphoblastic leukemia, while 5 (9.5%) had acute myeloid leukemia. Five of the 54 patients had a history of COVID-19 or contact with a positive person. SARS-CoV-2 IgG positivity was detected in 18 (36.7%) of 49 patients with no history of COVID-19 infection. DISCUSSION: Leukemia patients have a high seroconversion for SARS-CoV-2 without showing any symptoms supporting the asymptomatic course of COVID-19 infection in this risk group. CONCLUSION: As a result, patients with leukemia may have a high rate of COVID-19 seroconversion without showing symptoms.


Assuntos
COVID-19 , Leucemia , Masculino , Feminino , Humanos , Criança , Pré-Escolar , SARS-CoV-2 , Soroconversão , Estudos Prospectivos , Anticorpos Antivirais , Leucemia/complicações , Efeitos Psicossociais da Doença
10.
J Antimicrob Chemother ; 79(2): 297-306, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38073151

RESUMO

OBJECTIVES: Historically, patients with leukaemia and invasive fusariosis (IF) have experienced poor outcomes in the setting of persistent immunosuppression. Herein, we retrospectively reviewed the incidence, presentation and outcomes of IF that are scarcely studied in contemporary cohorts of leukaemia patients. METHODS: We identified adult leukaemia patients with proven or probable IF at MD Anderson Cancer Center during 2009-21. Independent risk factors for 42 day mortality after IF diagnosis were determined using a multivariable logistic regression model. Combined with historical data, the annual IF incidence density over the past 23 years was estimated using Poisson regression analysis. RESULTS: Among 140 leukaemia patients with IF (114 proven), 118 patients (84%) had relapsed/refractory leukaemia and 124 (89%) had neutropenia at IF diagnosis. One hundred patients (71%) had pulmonary IF, 88 (63%) had disseminated IF and 48 (34%) had fungaemia. Coinfections were common (55%). Eighty-nine patients (64%) had breakthrough IF to mould-active triazoles. Most patients (84%) received combination antifungal therapy. Neutrophil recovery [adjusted OR (aOR), 0.04; 95% CI, 0.01-0.14; P < 0.0001], pulmonary IF (aOR, 3.28; 95% CI, 1.11-9.70; P = 0.032) and high SOFA score (aOR, 1.91 per 1-point increase; 95% CI, 1.47-2.50; P < 0.0001) were independent predictors of 42 day mortality outcomes. From 1998 to 2021, IF incidence density increased significantly at an annual ratio of 1.03 (95% CI, 1.01-1.06; P = 0.04). CONCLUSIONS: IF is predominantly seen in patients with relapsed/refractory leukaemia and increasingly seen as a breakthrough infection to mould-active triazoles. Despite frequent combination antifungal therapy, high mortality rates have persisted in patients with lasting neutropenia.


Assuntos
Fusariose , Leucemia , Neutropenia , Adulto , Humanos , Fusariose/tratamento farmacológico , Fusariose/epidemiologia , Antifúngicos/uso terapêutico , Infecções Irruptivas , Azóis , Incidência , Estudos Retrospectivos , Triazóis , Fungos , Leucemia/complicações , Leucemia/epidemiologia , Leucemia/tratamento farmacológico , Neutropenia/complicações , Neutropenia/tratamento farmacológico
11.
Ultrasound Med Biol ; 50(2): 224-228, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37968188

RESUMO

OBJECTIVE: A hypo-enhancement of the liver in contrast-enhanced ultrasound (CEUS), pathologic one-minute hepatic enhancement (pOMHE), was recently observed in 70% of allogeneic hematopoietic stem cell transplantation patients with a high-risk profile for veno-occlusive disease (VOD). Whether pOMHE was a pre-clinical sign of VOD or an unspecific feature of liver damage secondary to intensive chemotherapy is unclear. METHODS: To investigate this, we studied CEUS patterns in patients receiving high-dose chemotherapy prior to autologous hematopoietic stem cell transplantation (auto-HSCT) or intensive induction therapy (IT) for the treatment of acute leukemia. From April 2020 to May 2021, patients undergoing auto-HSCT (n = 20) or acute leukemia patients prior to IT (n = 20) were included. All patients underwent a B-mode ultrasound and CEUS of the liver and spleen before treatment (d0) and on day 10 (d10) after therapy start. The one-minute hepatic enhancement was quantified. An optical density of liver enhancement less than 90% compared with the spleen was considered pathologic (pOMHE). Clinical and laboratory parameters used to assess a drug-induced liver injury (DILI) were documented. RESULTS: The OMHE was normal (d0 and d10) in 36 (90%) patients. After IT, 2 of 20 patients had a pOMHE. A DILI grade IV was diagnosed in one case and hyperfibrinolysis in the second case. In 2 of 20 (5%) auto-HSCT patients a pOMHE was observed at d10 without clinical symptoms. CONCLUSION: Chemotherapy-induced effects are not the cause of a pathologic liver enhancement. In contrast, severe DILI or hyperfibrinolysis can be associated with pOMHE.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Hepatopatia Veno-Oclusiva , Leucemia , Doenças Vasculares , Humanos , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/diagnóstico por imagem , Estudos Prospectivos , Doença Hepática Crônica Induzida por Substâncias e Drogas/complicações , Leucemia/complicações
12.
BMC Infect Dis ; 23(1): 811, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978456

RESUMO

The central nervous system is one of the most common sites of aspergillosis involvement in immunocompromised people, just after sinopulmonary infections. Neuroimaging modalities are crucial for the diagnosis of cerebral aspergillosis (CA). Here, we describe a rare case of concurrent mixed aspergillosis infection with Aspergillus fumigatus and Aspergillus niger in a 2-year-old leukemic boy. The first neuroimaging finding, which was followed by focal seizures, was recognized as extensive cerebral hemorrhage in the absence of thrombocytopenia and coagulopathy. As the patient survived for more than 4 months after diagnosis, we were able to perform a neuroimaging evaluation during long-term observation. In serial neuroimaging studies, a secondary fungal abscess was observed at the site of hemorrhagic infarctions. Finally, the patient died from bacterial sepsis. In this case study, we try to categorize the neuroimaging findings of CA into distinct phases to better understand how CA changes over time.


Assuntos
Aspergilose , Leucemia , Masculino , Humanos , Criança , Pré-Escolar , Aspergilose/diagnóstico por imagem , Aspergilose/complicações , Aspergillus fumigatus , Aspergillus niger , Leucemia/complicações , Leucemia/tratamento farmacológico , Neuroimagem , Antifúngicos/uso terapêutico
14.
Medicine (Baltimore) ; 102(43): e35776, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37904468

RESUMO

RATIONALE: The manuscript aimed to show that an unmeasurable capillary C-reactive protein (CRP) should be a red flag that can indicate a possible severe hematological pathology. PATIENTS CONCERNS AND DIAGNOSES: The authors present 3 case reports of children with fever examined at the pediatric emergency department. Fever is among the most frequently exhibited symptoms of acute pediatric infectious diseases. However, sometimes fever can be the manifestation of other serious noninfectious diseases. CRP is a marker widely used in clinical pediatric practice to help us evaluate inflammation and possible bacterial infection. All mentioned patients had unmeasurable CRP from capillary blood, even though venous CRP ranged from 14 to 21 mg/L. All of the patients were consequently diagnosed with severe hemato-oncological disease. Possible explanations are that a change in blood viscosity or an elevation of circulating immune complexes in the blood of patients with leukemia leads to malfunctioning immunoturbidimetry measurement. LESSON: Although these findings are very interesting and could lead to faster recognition of acute leukemia in pediatric clinical practice, further prospective study is needed for their confirmation.


Assuntos
Infecções Bacterianas , Leucemia , Criança , Humanos , Proteína C-Reativa/análise , Infecções Bacterianas/diagnóstico , Febre/etiologia , Leucemia/complicações , Estudos Prospectivos
15.
Cir Cir ; 91(5): 698-702, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37844902

RESUMO

BACKGROUND: Testicular infiltration is infrequent in pediatric patients with leukemia and can be confused with other testicular conditions. OBJECTIVE: To analyze the presence of clinical and radiological features suggestive of testicular disease and its histological association with leukemia infiltration. METHOD: Retrospective and analytical observational study that included patients with diagnosis of leukemia who underwent biopsy for suspected testicular infiltration. The relationship with the variables analyzed were diagnosis, reason for taking the biopsy, ultrasound findings, stage of treatment, induration, increased volume and pain, with testicular infiltration. RESULTS: Eighteen patients were included; 11 of them with microlithiasis, of which one 1 reported infiltration (odds ratio: 0.075; p = 0.026), no association was found between ultrasound findings and the presence of infiltration. Clinical findings were significantly associated with positive biopsies. CONCLUSIONS: No risk association was found with the ultrasound findings such as microlithiasis and hypoechoic imaging. The clinically evident testicular disease (testicular enlargement and testicular induration) has a significant statistic association with the presence of leukemia infiltration.


ANTECEDENTES: La infiltración testicular en pacientes pediátricos con leucemia es infrecuente y puede ser confundida con otros padecimientos testiculares. OBJETIVO: Analizar la presencia de características clínicas y radiológicas sugestivas de enfermedad testicular y su asociación histológica con infiltración por leucemia. MÉTODO: Estudio observacional retrospectivo y analítico que incluyó a los pacientes con diagnóstico de leucemia sometidos a biopsia por sospecha de infiltración testicular. Se analizó la relación con las variables diagnóstico de base, motivo de toma de biopsia, hallazgos ultrasonográficos, etapa del tratamiento, induración, aumento de volumen y dolor, con infiltración a testículo. RESULTADOS: Se incluyeron 18 pacientes; de ellos, 11 con microlitiasis, de los cuales solo uno reportado con infiltración (odds ratio: 0.075; p = 0.026). No se encontró una asociación entre los hallazgos ultrasonográficos y la presencia de infiltración. Los hallazgos clínicos se asociaron significativamente con biopsias positivas. CONCLUSIONES: No se encontró una asociación de riesgo con los hallazgos por ultrasonido, como microlitiasis e imágenes hipoecogénicas. La enfermedad testicular clínicamente evidente (incremento de volumen e induración testicular) tiene una asociación estadísticamente significativa con la presencia de infiltración por leucemia.


Assuntos
Leucemia , Doenças Testiculares , Neoplasias Testiculares , Masculino , Humanos , Criança , Neoplasias Testiculares/diagnóstico por imagem , Estudos Retrospectivos , Doenças Testiculares/diagnóstico por imagem , Doenças Testiculares/complicações , Biópsia , Leucemia/diagnóstico por imagem , Leucemia/complicações , Ultrassonografia
16.
Ann Hematol ; 102(12): 3593-3601, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37831153

RESUMO

Hepatitis B virus (HBV)has a high, chronic infection rate in Asian populations, but only few studies have analyzed the effect of Epstein-Barr virus (EBV) or Cytomegalovirus (CMV) reactivation in patients exposed to HBV after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This study aimed to assess the clinical outcomes of these patients. We conducted a retrospective research including 61 patients exposed to HBV after undergoing haplo-HSCT. The patients were classified into two groups: the CMV reactivation group and no CMV reactivation group. The results were compared between the two groups using the K-W test for continuous variables, Pearson's chi-square test for categorical variables, Kaplan-Meier curves to estimate overall survival (OS) and leukemia-free survival (LFS), and a Cox proportional hazards model to analyze multivariable influences. The 3-year cumulative HBV reactivation rate was 8.2%. The median duration of HBV reactivation was 16 months (16-22 months) after haplo-HSCT. The CMV reactivation group had a higher cumulative incidence of HBV reactivation than the group without CMV reactivation. The EBV reactivation was substantially higher in the CMV reactivation group compared to that in the no CMV reactivation group (37.0% vs.5.9% respectively; P = 0.002). Furthermore, EBV reactivation was a risk factor for 1-year LFS and 1-year OS. Based on our data, EBV reactivation was related to worse outcomes in patients exposed to HBV after haplo-HSCT, whereas CMV reactivation was not.


Assuntos
Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Humanos , Herpesvirus Humano 4 , Vírus da Hepatite B , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/etiologia , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Citomegalovirus , Leucemia/complicações , Ativação Viral , Doença Enxerto-Hospedeiro/etiologia
17.
Am J Physiol Renal Physiol ; 325(5): F669-F680, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37733875

RESUMO

Mixed lineage leukemia 1 (MLL1) is a methyltransferase that induces histone H3 lysine 4 trimethylation (H3K4me3) and partially exerts its untoward functional effects by interacting with multiple subunits including menin and WD repeat-containing protein 5 (WDR5). In this study, we investigated the role and mechanisms of MLL1 in murine models of acute kidney injury induced by folic acid (FA) and ischemia-reperfusion. Injury to the kidney elevated the expression of MLL1, menin, WDR5, and H3K4Me3, which was accompanied by increased serum creatinine and blood urea nitrogen, renal tubular injury, and apoptosis. Pharmacological inhibition of MLL1 activity with MI503 to disrupt the interaction between MLL1 with menin further increased serum creatinine and blood urea nitrogen levels, enhanced expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, and induced more apoptosis in the kidney following FA and ischemia-reperfusion injury. In contrast, MI503 treatment decreased the expression of vimentin and proliferating cell nuclear antigens. Similarly, treatment with MM102 to disrupt the interaction between MLL1 and WDR5 also worsened renal dysfunction, aggravated tubular cell injury, increased apoptosis, and inhibited cellular dedifferentiation and proliferation in mice following FA injection. Moreover, MI503 inhibited FA-induced phosphorylation of epidermal growth factor receptor, signal transducer and activator of transcription 3, and extracellular signal-regulated kinase-1/2 in injured kidneys. Collectively, these data suggest that MLL1 contributes to renal protection and functional recovery and promotes renal regeneration through a mechanism associated with activation of the epidermal growth factor receptor signaling pathway.NEW & NOTEWORTHY Mixed lineage leukemia 1 (MLL1) is a methyltransferase that induces histone H3 lysine 4 trimethylation and exerts its functional roles by interacting with multiple subunits. In this study, we demonstrated that inhibition of MLL1 activity by MI503 or MM102 aggravated renal injury and apoptosis and suppressed renal tubular cell dedifferentiation and proliferation, suggesting that MLL1 activation during acute kidney injury acts as an intrinsic protective mechanism to mediate renal tubular cell survival and regeneration.


Assuntos
Injúria Renal Aguda , Leucemia , Traumatismo por Reperfusão , Camundongos , Animais , Histonas/metabolismo , Ácido Fólico/farmacologia , Creatinina , Lisina/uso terapêutico , Proteína de Leucina Linfoide-Mieloide/efeitos adversos , Proteína de Leucina Linfoide-Mieloide/metabolismo , Injúria Renal Aguda/metabolismo , Receptores ErbB/metabolismo , Fatores de Transcrição/metabolismo , Leucemia/complicações , Leucemia/tratamento farmacológico , Traumatismo por Reperfusão/complicações , Isquemia/complicações , Reperfusão , Metiltransferases/metabolismo
19.
J Infect Public Health ; 16(10): 1525-1530, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37557008

RESUMO

BACKGROUND: Patients with neutropenic cancers are at high risk of acquiring infections, especially if on chemotherapy. Gram-negative bacterial infections are associated with high mortality. This study aimed to assess clinical characteristics, outcomes, and epidemiology of gram-negative bacterial (GNB) bloodstream infections (BSI) in adult patients with leukemia. METHODS: This single-center, retrospective study included 102 adult patients diagnosed with leukemia between 2017 and 2019. The patients' demographics, infection diagnosis, leukemia diagnosis, comorbidities, and infection outcomes were collected from electronic medical records. RESULTS: The most common GNB were Klebsiella pneumoniae (33.3 %), Pseudomonas aeruginosa (23.5 %), and Escherichia coli (17.6 %). Additionally, 36.7 % of infections were multidrug resistant. The most common comorbidities were cardiovascular diseases (36.7 %), diabetes mellitus (33.3 %), and liver diseases (24.1 %). GNB-infected patients had a higher mortality than noninfected patients (35.3 % and 11.8 %, respectively, p = 0.005). In a multivariable analysis, patients with acute myeloid leukemia and acute lymphoid leukemia were significantly more likely to acquire GNB BSI (p = 0.01), while patients with chronic myelogenous leukemia and chronic lymphocytic leukemia had a lower likelihood of developing GNB BSI. In addition, low hemoglobin level was an independent risk factor of GNB BSI (p = 0.001). Chemotherapeutic agents showed an association with increased risk of GNB BSI. CONCLUSIONS: Patients with acute leukemia and low hemoglobin levels have increased risk of GNB BSI, which was associated with increased mortality. Prospective studies are needed to further assess the effect of co-morbidities and chemotherapy medications on the occurrence of GNB BSI according to the type of leukemia.


Assuntos
Bacteriemia , Infecções por Bactérias Gram-Negativas , Leucemia , Humanos , Adulto , Estudos Retrospectivos , Bactérias Gram-Negativas , Centros de Atenção Terciária , Arábia Saudita/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Fatores de Risco , Leucemia/complicações , Leucemia/epidemiologia , Leucemia/tratamento farmacológico , Registros Médicos , Hemoglobinas , Bacteriemia/microbiologia , Antibacterianos/farmacologia
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