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1.
Pediatr Blood Cancer ; : e31200, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39016936

ABSTRACT

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Despite bone metastases being present in 5% of patients at diagnosis, there are limited studies examining these outcomes. We sought to define the prognostic factors, clinical courses, and outcomes of children treated on Children's Oncology Group (COG) clinical trials with RMS metastatic to bone at diagnosis. METHODS: We performed a retrospective analysis of patients diagnosed with bone metastatic RMS enrolled on COG RMS clinical trials (D9802, D9803, ARST0431, or ARST08P1) between 1997 and 2013. RESULTS: RMS metastatic to bone was identified in 154 patients at a median age of 14.9 years at diagnosis. Fifty-eight percent of patients were male, 90% had metastases at additional sites, 74% had alveolar histology, and extremity was the most common primary site (31%). Eighty-six percent of patients (n = 133) received radiation therapy. The 3- and 5-year event-free survival (EFS) was 15.4% and 14.5%, respectively. The 3- and 5-year overall survival (OS) was 30.4% and 18.0%, respectively. We identified alveolar histology, FOXO1 fusion presence, unfavorable primary location, higher Oberlin score, and lack of radiation as poor prognostic characteristics for both EFS and OS in univariate analysis. Lack of radiation was not significant when excluding patients with events prior to 20 weeks. CONCLUSIONS: This study is the largest analysis of patients with bone metastatic RMS, and defines the poor overall outcomes and negative prognostic factors for these patients. They may be eligible for therapy deintensification for improved quality of life or pursuit of novel treatments/approaches, which are desperately needed.

2.
Exp Mol Pathol ; 137: 104898, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729059

ABSTRACT

INTRODUCTION: NK cells are an untapped resource for cancer therapy. Sarcomas transduced with lentiviruses to express human IL-12 are only cleared in mice bearing mature human NK cells. However, systemic inflammation limits IL-12 utilization. Fate control a.k.a. "suicide mechanisms" regulate unchecked systemic inflammation caused by cellular immunotherapies. Despite increasing utilization, there remains limited data on immune consequences or tumor-directed effects of fate control. OBJECTIVES: We sought to engage the mutant thymidylate kinase (mTMPK) metabolic fate control system to regulate systemic inflammation and assess the impact on NK cell effector functions. METHODS: Primary human sarcoma short-passage samples and cell lines were transduced with LV/hu-IL-12_mTMPK engineering expression of IL-12 and an AZT-associated fate control enzyme. We assessed transduced sarcoma responses to AZT engagement and subsequent modulation of NK cell functions as measured by inflammatory cytokine production and cytotoxicity. RESULTS: AZT administration to transduced (LV/hu-IL-12_mTMPK) short-passage primary human sarcomas and human Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma cell lines, abrogated the robust expression of human IL-12. Fate control activation elicited a specific dose-dependent cytotoxic effect measured by metabolic activity (WST-1) and cell death (Incucyte). NK effector functions of IFN-γ and cytotoxic granule release were significantly augmented despite IL-12 abrogation. This correlated with preferentially induced expression of NK cell activation ligands. CONCLUSIONS: mTMPK fate control engagement terminates transduced sarcoma IL-12 production and triggers cell death, but also augments an NK cell-mediated response coinciding with metabolic stress activating surface ligand induction. Fate control engagement could offer a novel immune activation method for NK cell-mediated cancer clearance.


Subject(s)
Interleukin-12 , Killer Cells, Natural , Lentivirus , Sarcoma , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Humans , Interleukin-12/genetics , Interleukin-12/metabolism , Lentivirus/genetics , Sarcoma/immunology , Sarcoma/genetics , Sarcoma/pathology , Cell Line, Tumor , Transduction, Genetic , Animals , Mice
3.
Pediatr Blood Cancer ; 70(12): e30701, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37783659

ABSTRACT

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Metastatic disease occurs in 16% of all RMS cases and has a poor prognosis. There are limited studies examining the outcomes specific to patients with RMS metastatic to bone marrow despite an incidence of 6% at diagnosis. Our study aims to document the outcomes, prognostic factors, and clinical courses of children presenting with RMS metastatic to bone marrow treated on Children's Oncology Group (COG) cooperative trials. METHODS: We performed a retrospective analysis of the patients diagnosed with RMS metastatic to bone marrow between 1997 and 2013 enrolled on one of four COG RMS clinical trials of D9802, D9803, ARST0431, and ARST08P1. RESULTS: We identified 179 cases with RMS metastatic to bone marrow. Patients had a median age of 14.8 years, 58% were male, predominantly alveolar histology (76%), extremity was the most common primary site (32%), and 87% had metastatic disease to additional sites; 83% (n = 149) received radiation as a treatment modality. The 3- and 5-year event-free survival was 9.4% and 8.2%, respectively. The 3- and 5-year overall survival was 26.1% and 12.6%, respectively. Age ≥10 years, alveolar histology, FOXO1 fusion presence, unfavorable primary location, higher Oberlin score, and lack of radiation were identified as poor prognostic/predictive characteristics. CONCLUSIONS: This study represents the largest analysis of RMS metastatic to bone marrow, defining the poor prognostic outcome for these patients. These patients may be eligible for therapy deintensification or early pursuit of novel treatments/approaches that are desperately needed.


Subject(s)
Bone Marrow , Rhabdomyosarcoma , Child , Humans , Male , Young Adult , Infant , Adolescent , Female , Bone Marrow/pathology , Retrospective Studies , Rhabdomyosarcoma/pathology , Prognosis
4.
Front Immunol ; 14: 1225610, 2023.
Article in English | MEDLINE | ID: mdl-37646042

ABSTRACT

CD30 is expressed on Hodgkin lymphomas (HL), many non-Hodgkin lymphomas (NHLs), and non-lymphoid malignancies in children and adults. Tumor expression, combined with restricted expression in healthy tissues, identifies CD30 as a promising immunotherapy target. An anti-CD30 antibody-drug conjugate (ADC) has been approved by the FDA for HL. While anti-CD30 ADCs and chimeric antigen receptors (CARs) have shown promise, their shortcomings and toxicities suggest that alternative treatments are needed. We developed novel anti-CD30 x anti-CD3 bispecific antibodies (biAbs) to coat activated patient T cells (ATCs) ex vivo prior to autologous re-infusions. Our goal is to harness the dual specificity of the biAb, the power of cellular therapy, and the safety of non-genetically modified autologous T cell infusions. We present a comprehensive characterization of the CD30 binding and tumor cell killing properties of these biAbs. Five unique murine monoclonal antibodies (mAbs) were generated against the extracellular domain of human CD30. Resultant anti-CD30 mAbs were purified and screened for binding specificity, affinity, and epitope recognition. Two lead mAb candidates with unique sequences and CD30 binding clusters that differ from the ADC in clinical use were identified. These mAbs were chemically conjugated with OKT3 (an anti-CD3 mAb). ATCs were armed and evaluated in vitro for binding, cytokine production, and cytotoxicity against tumor lines and then in vivo for tumor cell killing. Our lead mAb was subcloned to make a Master Cell Bank (MCB) and screened for binding against a library of human cell surface proteins. Only huCD30 was bound. These studies support a clinical trial in development employing ex vivo-loading of autologous T cells with this novel biAb.


Subject(s)
Antibodies, Bispecific , Ataxia Telangiectasia , Hodgkin Disease , Lymphoma, Non-Hodgkin , Adult , Child , Humans , Animals , Mice , Muromonab-CD3 , Antibodies, Bispecific/pharmacology , Antibodies, Monoclonal
5.
Article in English | MEDLINE | ID: mdl-37463465

ABSTRACT

PURPOSE: The authors describe a case of a Retinal capillary hemangioblastoma (RCH) in a pediatric patient with von Hippel-Lindau (VHL) syndrome that was successfully treated with systemic belzutifan. METHODS: Case report - The Clinical course was documented with serial fundus exams and multimodal imaging, including Optos wide field fundus photography and optical coherence tomography. A literature review was conducted to look for similar cases and/or discussion. RESULTS: A left RCH was noted on a standard VHL surveillance retinal exam of a then 15-year-old male with VHL syndrome. Over the course of 17 months this RCH was treated with focal laser therapy, photodynamic therapy (PDT), cryotherapy, bevacizumab injection, and endo laser ablation. Complications of these treatments included sub retinal fluid (SRF) and vitreomacular traction (VMT) necessitating laser retinopexy, scleral buckle, and pars plana vitrectomy with membrane stripping. After a 6-month interval from the last local therapy (endo laser treatment), there was minimal regression of the lesion and many concerning features persisted. At 22 months from presentation, the patient started belzutifan 120 mg PO daily with subsequent regression in size and less perfusion to the hemangioblastoma within 4 months. The patient is tolerating the systemic belzutifan with only the expected normocytic anemia and has not required transfusion therapy after 12 months of treatment. CONCLUSION: VHL disease is a rare and serious condition associated with multiple types of benign and malignant tumors. Belzutifan is tolerated in the adolescent population and can provide a systemic treatment alternative for VHL associated RCH.

6.
Sci Rep ; 11(1): 8321, 2021 04 15.
Article in English | MEDLINE | ID: mdl-33859303

ABSTRACT

Interleukin-12 (IL-12) is an inflammatory cytokine that has demonstrated efficacy for cancer immunotherapy, but systemic administration has detrimental toxicities. Lentiviral transduction eliciting IL-12-producing human sarcoma for autologous reintroduction provides localized delivery for both innate and adaptive immune response augmentation. Sarcoma cell lines and primary human sarcoma samples were transduced with recombinant lentivirus engineering expression of human IL-12 (hu-IL-12). IL-12 expressing sarcomas were assessed in vitro and in vivo following implantation into humanized NSG and transgenic human IL-15 expressing (NSG.Tg(Hu-IL-15)) murine models. Lentiviral transduction (LV/hu-IL-12) of human osteosarcoma, Ewing sarcoma and rhabdomyosarcoma cell lines, as well as low-passage primary human sarcomas, engendered high-level expression of hu-IL-12. Hu-IL-12 demonstrated functional viability, eliciting specific NK cell-mediated interferon-γ (IFN-γ) release and cytotoxic growth restriction of spheroids in vitro. In orthotopic xenograft murine models, the LV/hu-IL-12 transduced human sarcoma produced detectable IL-12 and elicited an IFN-γ inflammatory immune response specific to mature human NK reconstitution in the NSG.Tg(Hu-IL-15) model while restricting tumor growth. We conclude that LV/hu-IL-12 transduction of sarcoma elicits a specific immune reaction and the humanized NSG.Tg(Hu-IL-15) xenograft, with mature human NK cells, can define in vivo anti-tumor effects and systemic toxicities. IL-12 immunomodulation through autologous tumor transduction and reintroduction merits exploration for sarcoma treatment.


Subject(s)
Gene Expression/genetics , Immunity , Immunomodulation , Interleukin-12/genetics , Interleukin-12/metabolism , Killer Cells, Natural/immunology , Sarcoma/genetics , Sarcoma/immunology , Animals , Cell Line, Tumor , Disease Models, Animal , Humans , Immunotherapy , Interferon-gamma/metabolism , Interleukin-12/immunology , Interleukin-15 , Lentivirus , Mice , Sarcoma/therapy
7.
Oncotarget ; 11(20): 1799-1815, 2020 May 19.
Article in English | MEDLINE | ID: mdl-32499867

ABSTRACT

Histone deacetylase inhibitors (HDACi) are an emerging cancer therapy; however, their effect on natural killer (NK) cell-mediated anti-tumor responses remain unknown. Here, we evaluated the impact of a benzamide HDACi, entinostat, on human primary NK cells as well as tumor cell lines. Entinostat significantly upregulated the expression of NKG2D, an essential NK cell activating receptor. Independently, entinostat augmented the expression of ULBP1, HLA, and MICA/B on both rhabdomyosarcoma and Ewing sarcoma cell lines. Additionally, entinostat increased both cytotoxicity and IFN-γ production in human NK cells following coculture with these tumor cells. Mechanistically, entinostat treatment resulted in increased chromatin accessibility to the promoter region for interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) gene and thereby increasing the transcript and protein levels of IFIT1 that augmented the IFIT1-mediated IRF1, STAT4, and STING pathways. Corresponding transcriptome analysis revealed enrichment of IRF1 and STAT4 and gene sets responsible for NK cell-mediated IFN-γ production and cytotoxicity, respectively. Our results show a novel mechanism by which entinostat initiates an IFIT1-STING-mediated potentiation of STAT4 via IRF1 to augment NK cell-mediated anti-tumor responses.

8.
Methods Mol Biol ; 2097: 115-123, 2020.
Article in English | MEDLINE | ID: mdl-31776923

ABSTRACT

NK cells are innate lymphocytes that are vital to clearance of virally infected or malignantly transformed cells. Assessment of the cytotoxic response is an important component of NK cell research and investigation of human disease. Standard assays of NK cell-mediated cytotoxicity of CD107a degranulation or 51Cr release assay utilize cultured or freshly isolated NK cell populations in vitro. In addition to requirements to maintain multiple target cell lines and radioactivity precautions in the case of 51Cr, these are in vitro evaluations of a complex in vivo function. Here, we describe the in vivo assessment of NK cell-mediated cytotoxicity through the adoptive transfer of splenocytes and their subsequent rejection. This protocol offers rapid, quantitative, and concurrent assessment of NK cell-mediated cytotoxicity against the prototypic NK stimulations of "missing-self" and "nonself."


Subject(s)
Adoptive Transfer/methods , Cytotoxicity, Immunologic , Killer Cells, Natural/immunology , Spleen/cytology , Animals , Antibodies/metabolism , Data Analysis , Lymphocyte Depletion , Mice, Inbred BALB C , Mice, Inbred C57BL
9.
Front Immunol ; 9: 1168, 2018.
Article in English | MEDLINE | ID: mdl-29892299

ABSTRACT

Natural killer (NK) cells are innate lymphocytes that play essential roles in mediating antitumor immunity. NK cells respond to various inflammatory stimuli including cytokines and stress-induced cellular ligands which activate germline-encoded activation receptors (NKRs), such as NKG2D. The signaling molecules activated downstream of NKRs are well defined; however, the mechanisms that regulate these pathways are not fully understood. IQ domain-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffold protein. It regulates diverse cellular signaling programs in various physiological contexts, including immune cell activation and function. Therefore, we sought to investigate the role of IQGAP1 in NK cells. Development and maturation of NK cells from mice lacking IQGAP1 (Iqgap1-/- ) were mostly intact; however, the absolute number of splenic NK cells was significantly reduced. Phenotypic and functional characterization revealed a significant reduction in the egression of NK cells from the bone marrow of Iqagp1-/- mice altering their peripheral homeostasis. Lack of IQGAP1 resulted in reduced NK cell motility and their ability to mediate antitumor immunity in vivo. Activation of Iqgap1-/- NK cells via NKRs, including NKG2D, resulted in significantly reduced levels of inflammatory cytokines compared with wild-type (WT). This reduction in Iqgap1-/- NK cells is neither due to an impaired membrane proximal signaling nor a defect in gene transcription. The levels of Ifng transcripts were comparable between WT and Iqgap1-/- , suggesting that IQGAP1-dependent regulation of cytokine production is regulated by a post-transcriptional mechanism. To this end, Iqgap1-/- NK cells failed to fully induce S6 phosphorylation and showed significantly reduced protein translation following NKG2D-mediated activation, revealing a previously undefined regulatory function of IQGAP1 via the mechanistic target of rapamycin complex 1. Together, these results implicate IQGAP1 as an essential scaffold for NK cell homeostasis and function and provide novel mechanistic insights to the post-transcriptional regulation of inflammatory cytokine production.


Subject(s)
Cytokines/immunology , Cytoskeleton/immunology , Killer Cells, Natural/immunology , Mechanistic Target of Rapamycin Complex 1/immunology , NK Cell Lectin-Like Receptor Subfamily K/immunology , Protein Biosynthesis/immunology , ras GTPase-Activating Proteins/immunology , Animals , Cytokines/genetics , Cytoskeleton/genetics , Killer Cells, Natural/cytology , Mechanistic Target of Rapamycin Complex 1/genetics , Mice , Mice, Knockout , NK Cell Lectin-Like Receptor Subfamily K/genetics , Protein Biosynthesis/genetics , ras GTPase-Activating Proteins/genetics
10.
J Pediatr Hematol Oncol ; 39(5): e254-e258, 2017 07.
Article in English | MEDLINE | ID: mdl-28452856

ABSTRACT

Anthracycline-induced cardiotoxicity remains a significant contributor to late morbidity/mortality in children and young adults with acute myeloid leukemia (AML). The cardioprotectant dexrazoxane can be used as prophylaxis to diminish risk for cardiomyopathy but whether it affects risk of relapse in pediatric AML is unclear. Our institution adopted the use of dexrazoxane before anthracyclines administration for all oncology patients in 2011. We compared patients with AML (ages, 0 to 21 y) who received or did not receive dexrazoxane during the years 2008 to 2013. In total, 44 patients with AML (ages, 4.5 mo to 21.7 y) were included. We identified no statistical difference in 2-year event rate (62% vs. 50%, P=0.41) or 2-year overall survival (69% vs. 69%, P=0.53) between patients receiving (n=28) or not receiving (n=16) dexrazoxane. Ejection fraction (P=0.0262) and shortening fraction (P=0.0381) trended significantly higher in patients that received dexrazoxane compared with those that did not receive dexrazoxane. Utilization of the cardioprotectant dexrazoxane before anthracycline chemotherapy in pediatric patients with AML demonstrated no significant difference in either event rate or overall survival relative to institutional controls and seems to improve cardiac function indices. Further studies in this patient population are needed to confirm these findings.


Subject(s)
Dexrazoxane/administration & dosage , Heart Function Tests/drug effects , Leukemia, Myeloid, Acute/drug therapy , Adolescent , Anthracyclines/therapeutic use , Cardiomyopathies/drug therapy , Cardiomyopathies/etiology , Cardiotonic Agents , Child , Child, Preschool , Dexrazoxane/pharmacology , Humans , Infant , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/mortality , Survival Rate , Young Adult
11.
Pediatr Crit Care Med ; 15(7): e294-9, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24901803

ABSTRACT

OBJECTIVES: To demonstrate that low-molecular-weight heparin (enoxaparin) can be used in critically ill pediatric patients to achieve target anti-factor Xa concentrations and determine appropriate dosing corrected for age and illness severity. DESIGN: Retrospective cohort study. SETTING: Single tertiary level PICU. PATIENTS: One hundred ninety-two children age 1 day through 18 years admitted to PICU undergoing every 12-hour enoxaparin therapy with at least one anti-factor Xa concentration obtained. Patients receiving renal replacement therapy or infants with corrected gestational age less than 37 weeks were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected patient characteristics including age, weight, height/length, gender, corrected gestational age, illness severity markers, diagnosis, creatinine, enoxaparin dose and times of administration, anti-factor Xa concentrations, and collection times. Only 42% of critically ill children (80 of 192) and only 29% of children (9 of 31) on inotropes achieved recommended target range of anti-factor Xa concentrations on initial recommended enoxaparin dosing (1.5 mg/kg/dose < 2 mo; 1 mg/kg/dose > 2 mo), but 81% were ultimately within target range with dose titration. Increased enoxaparin dose was required to reach target concentrations in younger patients and those with worse illness severity as evidenced by concurrent use of inotropes, previous ICU admission, mechanical ventilation, cardiac surgery, and increased risk of mortality defined by severity-of-illness scores. CONCLUSIONS: Enoxaparin can be used to reach recommended target range of anti-factor Xa concentrations in the PICU patient. However, younger patients and patients with higher illness severity are less likely to achieve target concentrations using currently recommended dosing and may require higher doses of enoxaparin to reach target anti-factor Xa concentrations. Starting enoxaparin dose at least 1.3 mg/kg dosed every 12 hours for treatment of thromboembolic disease in critically ill patients aged 61 days to 1 year or those requiring inotropic support should be confirmed in prospective study.


Subject(s)
Critical Care , Enoxaparin/administration & dosage , Factor Xa Inhibitors/blood , Fibrinolytic Agents/administration & dosage , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Adolescent , Age Factors , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies , Venous Thromboembolism/blood
13.
Iran J Kidney Dis ; 6(4): 284-90, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22797098

ABSTRACT

INTRODUCTION: The management of neonates with congenital hydronephrosis (CHN) diagnosed antenatally is still controversial. MATERIALS AND METHODS: A prospective study was performed in all newborn infants with CHN born over a 2-year period in order to identify which neonates require a full radiologic investigation including investigation with invasive tests such as voiding cystoureterography (VCUG) and diuretic-enhanced renography. Data on kidney ultrasonography, VCUG, and diuretic renography were collected. The ultrasound grading of hydronephrosis was determined according to Society of Fetal Urology criteria. RESULTS: Sixty-one neonates (47 boys and 14 girls) with CHN were enrolled. All underwent kidney ultrasonography within 72 to 96 hours after birth. Four (7%) had no residual CHN, 34 (56%) had and 23 (38%) unilateral CHN. Of the 41 newborns exposed to diuretic renography, 18 (44%) had ureteropelvic junction obstruction (UPJO). Of the 34 infants that underwent VCUG, 8 (24%) had vesicoureteral reflux (7 bilateral grade 2 or higher, 1 unilateral grade 1 CHN SFU classification). None of the unilateral grade 1 or 2 CHN due to UPJO had vesicoureteral reflux and none with vesicoureteral reflux had UPJO. Twelve patients required surgery (7 had UPJO and 3 high-grade vesicoureteral reflux). CONCLUSIONS: These data suggest that mild to moderate unilateral or bilateral CHN rarely coexists with severe obstruction or vesicoureteral reflux. Therefore, systemic VCUG and renography in such patients do not seem justified. Postnatal ultrasonography in combination with renography and VCUG is warranted in the routine examination of neonates presenting with severe unilateral or bilateral CHN.


Subject(s)
Algorithms , Hydronephrosis/congenital , Early Diagnosis , Female , Humans , Hydronephrosis/diagnostic imaging , Infant, Newborn , Male , Prospective Studies , Radiography , Radionuclide Imaging , Ultrasonography, Prenatal , Ureteral Obstruction/diagnosis , Urethra/diagnostic imaging , Urethral Obstruction/diagnosis , Urinary Bladder/diagnostic imaging , Vesico-Ureteral Reflux/diagnosis
15.
Pediatr Infect Dis J ; 29(4): 352-6, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19934791

ABSTRACT

BACKGROUND: Invasive fungal infections (IFI) are an important cause of late-onset disease in extremely low birth weight (ELBW) infants. Despite prior trials of fluconazole prophylaxis in neonates, application of this regimen remains controversial. Review of our neonatal intensive care unit aggregate annual number of fungal isolates from sterile sites in ELBW infants from 1997 to 2006 suggested a significant decrease following the institution of routine prophylactic fluconazole in February 2002. We undertook a retrospective study to document the efficacy and adverse effects of routine fluconazole prophylaxis. METHODS: ELBW infants admitted during 2000 to 2006 were divided into 2 groups: Control group-admitted before the institution of fluconazole prophylaxis, and Fluconazole group-admitted after institution of fluconazole prophylaxis. Primary outcome was the frequency of IFI. Secondary outcome was the frequency of cholestasis, which has been rarely reported with fluconazole use. RESULTS: Data were extracted from 262 infant records: control 99, fluconazole 163. Baseline demographics and potentially confounding variables differed between the 2 groups with greater birth weight, greater gestational age, shorter durations of ventilation and central catheter use, and earlier start of feeding in the control group, reflecting healthier control infants. Frequency of IFI was 7.1% in the control group versus 1.8% in the fluconazole group, P = 0.045. Logistic regression revealed that fluconazole prophylaxis was independently associated with a lower risk of IFI. There was no difference in the frequency of cholestasis between the control and fluconazole groups. CONCLUSIONS: Prophylactic administration of fluconazole to all ELBW infants was associated with significantly decreased rates of IFI without associated adverse effects.


Subject(s)
Antibiotic Prophylaxis , Antifungal Agents , Fluconazole , Infant, Extremely Low Birth Weight , Mycoses/prevention & control , Antifungal Agents/adverse effects , Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Candidiasis/epidemiology , Candidiasis/microbiology , Candidiasis/prevention & control , Cholestasis/epidemiology , Female , Fluconazole/adverse effects , Fluconazole/therapeutic use , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/drug therapy , Infant, Premature, Diseases/epidemiology , Infant, Premature, Diseases/microbiology , Infant, Premature, Diseases/prevention & control , Intensive Care Units, Neonatal/statistics & numerical data , Male , Mycoses/drug therapy , Mycoses/epidemiology , Mycoses/microbiology , Treatment Outcome
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