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Item Epidemiology and source of infection in patients with febrile neutropenia: A ten-year longitudinal study(Elsevier, 2019-05-01) Al-Tawfiq, Jaffar A.; Hinedi, Kareem; Khairallah, Hanan; Saadeh, Bassam; Abbasi, Suhail; Noureen, Madeeha; Raza, Safia; Alkhatti, Adil; Medicine, School of MedicineObjectives No recent studies are available from Saudi Arabia on the etiology of febrile neutropenia. The objective of this study was to describe the characteristics of patients with febrile neutropenia and to calculate the rate of occurrence of bacteremia in these patients. Methods This is a hospital-based study of patients admitted with febrile neutropenia from 2006 to 2015. Results A total of 372 distinct episodes of febrile neutropenia representing 231 patients were included. Hematologic malignancies constituted 56.6% of the episodes. Positive blood cultures were reported in 13.5% with equal frequency of Gram-negative bacilli and gram positive cocci. The most commonly suspected sites of infection were blood 10.8% and pulmonary 9.2%, and the majority (72.5%) was thought to have no identifiable source of infection. Of all the episode, 32% had central venous catheters. The most frequently used single antimicrobial agents were imipenem (38%) and ceftazidime (7.5%). The mortality rate was 11.2% and it was significantly associated with the presence of bacteremia 24.4% versus 12.4% (P=0.016). Mortality was not significantly association with age, type of malignancy, presence of central venous catheter, or the severity of neutropenia. Compared to patients with hematological malignancy, patients with solid organ malignancy were more likely to be female 62% versus 14.9% (P<0.001) and were less likely to have bacteremia 8.7% versus 17.1%, P=0.042, respectively. Conclusion We had shown that febrile neutropenia in this study has a low rate of bacteremia and that about 45% received the recommended initial empiric therapy.Item Evaluation of neutropenia and neutrophilia in preterm infants(Informa UK (Informa Healthcare), 2012-10) Nittala, Solomon; Subbarao, Girish C.; Maheshwari, Akhil; Department of Pediatrics, IU School of MedicineOBJECTIVE: Neutrophil counts are used routinely as part of the sepsis evaluation in newborn infants. In this article, we review the normal blood neutrophil concentrations and the clinical approach to neutropenia and neutrophilia in the neonatal period. METHODS: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RESULTS: Neutropenia and neutrophilia are documented frequently in premature infants. Neutropenia can be seen in up to 8% of all infants admitted to neonatal intensive care. Neutrophilia is even more common, reported in up to 40% of all preterm infants. CONCLUSIONS: Neutrophil counts should be carefully evaluated in premature neonates. Maternal and perinatal history, physical examination, and a limited laboratory assessment is usually adequate for making a diagnosis in most infants.Item Prostaglandin E₂ promotes recovery of hematopoietic stem and progenitor cells after radiation exposure(2014-07-11) Stilger, Kayla N.; Broxmeyer, Hal E.; Kacena, Melissa A.; Srour, Edward F.; Pelus, LouisThe hematopoietic system is highly proliferative, making hematopoietic stem and progenitor cells (HSPC) sensitive to radiation damage. Total body irradiation and chemotherapy, as well as the risk of radiation accident, create a need for countermeasures that promote recovery of hematopoiesis. Substantive damage to the bone marrow from radiation exposure results in the hematopoietic syndrome of the acute radiation syndrome (HS-ARS), which includes life-threatening neutropenia, lymphocytopenia, thrombocytopenia, and possible death due to infection and/or hemorrhage. Given adequate time to recover, expand, and appropriately differentiate, bone marrow HSPC may overcome HS-ARS and restore homeostasis of the hematopoietic system. Prostaglandin E2 (PGE2) is known to have pleiotropic effects on hematopoiesis, inhibiting apoptosis and promoting self-renewal of hematopoietic stem cells (HSC), while inhibiting hematopoietic progenitor cell (HPC) proliferation. We assessed the radiomitigation potential of modulating PGE2 signaling in a mouse model of HS-ARS. Treatment with the PGE2 analog 16,16 dimethyl PGE2 (dmPGE2) at 24 hours post-irradiation resulted in increased survival of irradiated mice compared to vehicle control, with greater recovery in HPC number and colony-forming potential measured at 30 days post-irradiation. In a sublethal mouse model of irradiation, dmPGE2-treatment at 24 hours post-irradiation is associated with enhanced recovery of HSPC populations compared to vehicle-treated mice. Furthermore, dmPGE2-treatment may also act to promote recovery of the HSC niche through enhancement of osteoblast-supporting megakaryocyte (MK) migration to the endosteal surface of bone. A 2-fold increase in MKs within 40 um of the endosteum of cortical bone was seen at 48 hours post-irradiation in mice treated with dmPGE2 compared to mice treated with vehicle control. Treatment with the non-steroidal anti-inflammatory drug (NSAID) meloxicam abrogated this effect, suggesting an important role for PGE2 signaling in MK migration. In vitro assays support this data, showing that treatment with dmPGE2 increases MK expression of the chemokine receptor CXCR4 and enhances migration to its ligand SDF-1, which is produced by osteoblasts. Our results demonstrate the ability of dmPGE2 to act as an effective radiomitigative agent, promoting recovery of HSPC number and enhancing migration of MKs to the endosteum where they play a valuable role in niche restoration.Item Substantial effect of efavirenz monotherapy on bilirubin levels in healthy volunteers(Elsevier, 2014-09-27) Metzger, Ingrid F.; Quigg, Troy C.; Epstein, Noam; Aregbe, Abdulateef O.; Thong, Nancy; Callaghan, John T.; Flockhart, David A.; Nguyen, Anne T.; Stevens, Colleen K.; Gupta, Samir K.; Desta, Zeruesenay; Department of Medicine, School of MedicineBACKGROUND: Efavirenz exhibits multiple interactions with drug-metabolizing enzymes and transporters, and for this reason efavirenz-based HIV therapy is associated with altered pharmacokinetics of coadministered drugs. Probably by the same mechanism, efavirenz-based HIV therapy affects the disposition of endogenous compounds, but this effect is difficult to directly link with efavirenz because it is used in combination with other drugs. OBJECTIVES: To explore the effect of efavirenz monotherapy on biochemical laboratory values in a clinical trial of healthy volunteers. METHODS: Men and women (aged 18-49 years) with body mass index ≤32 who were assessed to be healthy based on medical history, physical examination, and standard laboratory screening received a single (600 mg) and multiple doses (600 mg/d for 17 days) of efavirenz orally. This trial was designed to determine the pharmacokinetics and drug interactions of efavirenz. As part of this study, analysis of serum chemistries that were measured at study entry (screening) and 1 week after completion of the multiple dose study (exit) is reported. RESULTS: Data from 60 subjects who fully completed and 13 subjects who partially completed the study are presented. Total bilirubin was substantially reduced at exit (by ~30%, with large intersubject variability) compared with screening values (P < 0.0001). The percent changes were in part explained by the intersubject differences in baseline total bilirubin because there was a significant correlation between baseline (screening) values and percent change at exit (r = 0.50; P < 0.0001). Hemoglobin and absolute neutropenia were also substantially decreased at exit compared with screening, but this may be due to intensive blood sampling rather than direct effect of efavirenz on these parameters. No significant correlation was found between percent change in hemoglobin versus percent change in bilirubin, indicating the effect of efavirenz on bilirubin is independent of its effects on hemoglobin. CONCLUSIONS: Efavirenz monotherapy significantly lowers plasma total bilirubin concentration in healthy volunteers independent of its effect on hemoglobin, probably through its effects on bilirubin metabolism and transport (uptake and efflux). These findings help explain reversal by efavirenz of hyperbilirubinemia induction observed by some protease inhibitor antiretroviral drugs (eg, atazanavir). Besides its well-documented role on drug interactions, efavirenz may alter the disposition of endogenous compounds relevant in physiologic homeostasis through its interaction with drug metabolizing enzymes and/or drug transporters. ClinicalTrials.gov identifier: NCT00668395.