Diana F Florescu

University of Nebraska Medical Center, Omaha, Nebraska, United States

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Publications (55)171.46 Total impact

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    ABSTRACT: Background: The experience with cidofovir in pediatric SOT is limited. The study aimed to assess the impact of cidofovir use on the renal function. Methods: Summary statistics were presented for demographics and outcomes, Wilcoxon signed-rank tests to compare changes in renal function and Wilcoxon rank-sum tests to test association with potential confounding factors. Results: We included 25 patients (mean age 4.2years; SD 4.6): liver-small bowel (15), small bowel (4), liver (3) and kidney (3) transplant recipients. Viral infections: adenovirus (20), BKv (2), HHV6 (1), and EBV (1). 24% of patients while on cidofovir compared with 4% at baseline (p=0.03) were on renal replacement therapy (RRT). For patients not on RRT, there was no difference: 1) in the median creatinine clearance between baseline and one month after (p=0.32) or end of cidofovir treatment (p=0.23); 2) in the creatinine from baseline to end of cidofovir therapy (p=0.2); there was marginal decrease in the median creatinine from baseline to one month post-cidofovir treatment (p=0.06). Less patients had proteinuria (72.2% vs. 27.8%;p=0.02) and hematuria (22.2% vs. 0%) at the end than at the beginning of cidofovir treatment. No evidences of associations were found between changes in creatinine clearance (by univariate analysis) with: exposure to vancomycin (p=0.44), amikacin (p=0.13), dopamine (p=0.66), epinephrine (p=0.99), norepinephrine (p=0.48), intravenous contrast (p=0.41) and surgery (p=0.59). Conclusion: Cidofovir was mainly used to treat adenovirus infections. In our study, cidofovir did not have nephrotoxic effects during the treatment and 1 month after treatment in pediatric transplant recipients, although they required RRT while on cidofovir because of fluid overload.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
  • Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 10/2014;
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    ABSTRACT: Background Severe hypogammaglobulinemia (IgG<400 mg/dL) has adverse impact on mortality during the first year post-transplantation. The aim of the study was to determine whether increasing IgG levels to >400mg/dl improved outcomes.Methods Kaplan-Meier analyses were performed to estimate survival, log-rank test to compare survival distributions between groups and Fisher's exact test to determine the association between hypogammaglobulinemia and rejection or graft loss.Results37 solid organ transplant (SOT) recipients were included. Hypogammaglobulinemia was diagnosed at median of 5.6months (range:0-291.8months) post-transplantation. Types of transplants: liver-small bowel (17); liver-small bowel-kidney (2); liver (5); small bowel (4); liver-kidney (1); kidney/kidney-pancreas (3); heart (3); heart-kidney (1); heart-lung (1). The 3-year survival after the diagnosis of hypogammaglobulinemia was 49.5% (95%CI:32.2-64.6%). Patients were dichotomized based upon IgG level at last follow-up: IgG>400mg/dL (23patients) and IgG<400mg/dL (14patients). There was no evidence of a difference in survival (p=0.44), rejection rate (p=0.44) and graft loss censored for death (p=0.99) at one year between these 2 groups. There was no difference in survival between patients receiving or not immunoglobulin (p=0.99) or cytomegalovirus hyperimmunoglobulin (p=0.14).Conclusion Severe hypogammaglobulinemia after SOT is associated with high mortality rates, but increasing IgG levels to >400mg/dL did not seem to translate in better patient or graft survival in this cohort.This article is protected by copyright. All rights reserved.
    Clinical Transplantation 09/2014; · 1.63 Impact Factor
  • Diana F Florescu, Megan A Keck
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    ABSTRACT: CMX001 (hexadecyloxypropyl-cidofovir, Brincidofovir) is a broad spectrum, lipid conjugate of cidofovir that is converted intracellularly into the active antiviral, cidofovir diphosphate. The lipid conjugation results in oral bioavailability, higher intracellular concentrations of active drug, lower plasma concentrations of cidofovir and increased antiviral potency against dsDNA viruses.
    Expert Review of Anti-infective Therapy 08/2014; · 3.06 Impact Factor
  • Uriel Sandkovsky, Luciano Vargas, Diana F Florescu
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    ABSTRACT: Infections caused by adenoviruses are associated with significant morbidity and mortality in both hematopoietic stem cell and solid organ transplant recipients. The risk seems to be highest in allogeneic hematopoietic stem cell transplant recipients as well as heart, lung and small-bowel transplant recipients. Management of these infections may be difficult and includes reduction of immunosuppression whenever possible combined sometimes with antiviral therapy (mainly cidofovir). The currently available antiviral therapy is limited by the need for intravenous administration, potentially significant renal and hematologic toxicities. New emerging therapies such as brincidofovir and transfusion of adenovirus-specific T-lymphocytes may increase the available armamentarium for these potentially life-threatening infections.
    Current Infectious Disease Reports 08/2014; 16(8):416.
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    ABSTRACT: We conducted a randomized and unblinded 2×2 sequential-factorial trial, composed of an induction arm (part 1) comparing single-dose (SD) versus divided-dose rabbit antithymocyte globulin (rATG), and a maintenance arm (part 2) comparing tacrolimus minimization versus withdrawal. We report the long-term safety and efficacy of SD-rATG induction in the context of early steroid withdrawal and tacrolimus minimization or withdrawal.
    Transplantation 07/2014; · 3.78 Impact Factor
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    ABSTRACT: Clinical experience with cidofovir in pediatric solid organ transplantation is limited. We assessed the effect of cidofovir use on renal function.
    The Pediatric Infectious Disease Journal 07/2014; · 3.57 Impact Factor
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    ABSTRACT: Background: We aimed to evaluate and quantify the risk of serious opportunistic infections after induction with polyclonal antibodies versus IL-2 receptor antagonists (IL-2RAs) in randomized clinical trials. Methods: PRISMA guidelines were followed and random-effects models were performed. Results: 70 randomized clinical trials (10,106 patients) were selected: 36 polyclonal antibodies (n = 3377), and 34 IL-2RAs (n = 6729). Compared to controls, polyclonal antibodies showed higher risk of serious opportunistic infections (OR: 1.93, 95% CI: 1.34-2.80; p < 0.0001); IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.80, 95% CI: 0.68-0.94; p = 0.009). Polyclonal antibodies were associated with higher risk of bacterial (OR: 1.58, 95% CI: 1.00-2.50; p = 0.049) and viral infections (OR: 2.37, 95% CI: 1.60-3.49; p < 0.0001), while IL-2RAs were associated with lower risk of cytomegalovirus (CMV) disease (OR: 0.73, 95% CI: 0.56-0.97; p = 0.032). Adjusted indirect comparison: compared to polyclonal antibodies, IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.41, 95% CI: 0.34-0.49; p < 0.0001), bacterial infections (OR: 0.51, 95% CI: 0.39-0.67; p < 0.0001) and CMV disease (OR: 0.58, 95% CI: 0.34-0.98; p = 0.043). Results remained consistent across allografts.Conclusion The risk of serious opportunistic infections, bacterial infections and CMV disease were all significantly decreased with IL-2RAs compared to polyclonal antibodies.
    Expert Review of Anti-infective Therapy 05/2014; · 3.06 Impact Factor
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    ABSTRACT: Background. Prophylactic and preemptive strategies are used to prevent cytomegalovirus infections after solid organ transplantation. We assessed the safety and efficacy of both strategies for CMV prevention. Methods. DerSimonian and Laird random-effects model was used for pooling the data and Q statistic and I-squared methods were used to assess statistical heterogeneity. Results. Twenty studies (2744 patients) were selected for the direct analysis and 20 studies (2544 patients) for the indirect analysis. The odds of CMV syndrome (OR=1.10;95%CI:0.60-2.03;p=0.757;Q=18.55;I(2)=51.49%) and disease (OR=0.77;95%CI:0.41-1.47;p=0.432;Q=32.71;I(2)=44.97%.) were not significantly different between strategies. The odds of developing late-onset CMV infections were higher for the prophylactic compared to the preemptive strategy (OR=6.21;95%CI:2.55-15.20;p<0.0001;Q=9.66;I(2)=37.9%). The odds of CMV viremia were lower for prophylaxis (OR=0.42;95%CI:0.24-0.74;p=0.003;Q=48.10;I(2)=75.1%) than preemptive therapy. No differences between strategies were noted for: graft loss (OR=0.88;95%CI:0.37-2.13;p=0.779;Q=13.03,I(2)=38.62%), graft loss censored for death (OR=0.73;95%CI:0.17-3.21;p=0.679;Q=4.48;I(2)=55.32%), acute rejection (OR=0.93;95%CI:0.70-1.24;p=0.637;Q=12.99;I(2)=7.61%) and mortality (OR=0.80;95%CI:0.56-1.14;p=0.220;Q=8.76;I(2)=0%). Other infections (HSV, VZV, bacterial and fungal infections) were not significantly different between strategies. Leukopenia (OR=1.97;95%CI:1.39-2.79;p=0.0001;Q=7.10;I(2)=0%) and neutropenia (OR=2.07;95%CI:1.13-3.78;p=0.018;Q=6.77;I(2)=11.40%) were more frequent with prophylaxis than preemptive strategy. The results of direct and indirect comparisons were consistent. Conclusions. Prophylaxis was associated with less early post-transplant viremia, but with significantly more late-onset CMV infections and side effects - leukopenia and neutropenia, than the preemptive strategy. Both preventive strategies showed similar efficacy in preventing CMV syndrome and disease, with no differences regarding rejection, graft loss, death and opportunistic infections.
    Clinical Infectious Diseases 01/2014; · 9.37 Impact Factor
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    Diana F Florescu, Andre C Kalil
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    ABSTRACT: Severe sepsis is traditionally associated with bacterial diseases. While fungi and parasites can also cause sepsis, they are significantly less common than bacterial causes. However, viruses are becoming a growing cause of severe sepsis worldwide. Among these viruses, influenza is crossing all geographic boundaries and is causing larger epidemics and pandemics. As a consequence, more critically ill patients with severe sepsis caused directly by influenza viruses, or indirectly by influenza-induced secondary bacterial infections are being admitted to hospitals worldwide. This manuscript aims to provide a pathophysiological and clinical update on the link between influenza and severe sepsis.
    Virulence 11/2013; 5(1). · 2.79 Impact Factor
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    ABSTRACT: Practice variation regarding cytomegalovirus (CMV) prevention and treatment across intestinal transplantation (IT) programs is unknown. An electronic survey was sent to IT programs registered with the Intestinal Transplant Association. Proportions were analyzed for categorical variables; means and SDs were analyzed for continuous variables. Seventy-seven percent of IT programs responded to the survey. For CMV D+/R- recipients, 39.1% programs used universal prophylaxis (UP), 8.7% preemptive strategy (PE), and 52.2% hybrid strategy. For CMV R+ recipients, 45.8% programs used UP, 12.5% PE, 37.1% hybrid strategy, and 4.2% none. For CMV D-/R- recipients, 39.1% programs used UP, 21.7% PE, 26.1% hybrid strategy, and 13% none. Frequency of monitoring for PE was weekly 71.4% of programs, every 2 weeks 21.4%, and monthly 7.1%. For CMV viremia, syndrome and disease, the most common first-line agents used were ganciclovir (100% and 96.2%) and valganciclovir (23.1%) and the second-line agent was foscarnet (73.1% and 84.6%). Immunoglobulins were administered in 65.4% of the programs for pneumonia (69.2%), meningoencephalitis (50%), enteritis (46.2%), colitis (38.5%), syndrome (42.3%), viremia (30.8%), and resistant/refractory infections (11.5%). Prophylaxis and hybrid strategy were the most commonly used. Treatment practices were consistent and mainly involved ganciclovir as first-line agent and foscarnet as second-line agent. The use of immunoglobulins appeared to be more common than in other allografts.
    Transplantation 10/2013; · 3.78 Impact Factor
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    ABSTRACT: Hypogammaglobulinemia has been described after solid organ transplantation and has been associated with increased risk of infections. The aim of the study was to evaluate the rate of severe hypogammaglobulinemia and its relationship with the risk of infections during the first year posttransplantation. Eighteen studies (1756 patients) that evaluated hypogammaglobulinemia and posttransplant infections were included. The data were pooled using the DerSimonian and Laird random-effects model. Q statistic method was used to assess statistical heterogeneity. Within the first year posttransplantation, the rate of hypogammaglobulinemia (IgG < 700 mg/dL) was 45% (95% CI: 0.34-0.55; Q = 330.1, p < 0.0001), the rate of mild hypogammaglobulinemia (IgG = 400-700 mg/dL) was 39% (95% CI: 0.22-0.56; Q = 210.09, p < 0.0001) and the rate of severe hypogammaglobulinemia (IgG < 400 mg/dL) was 15% (95% CI: 0.08-0.22; Q = 50.15, p < 0.0001). The rate of hypogammaglobulinemia by allograft type: heart 49% (21%-78%; Q = 131.16, p < 0.0001); kidney 40% (30%-49%; Q = 24.55, p = 0.0002); liver 16% (0.001%-35%; Q = 14.31, p = 0.0002) and lung 63% (53%-74%; Q = 6.85, p = 0.08). The odds of respiratory infection (OR = 4.83; 95% CI: 1.66-14.05; p = 0.004; I(2) = 0%), CMV (OR = 2.40; 95% CI: 1.16-4.96; p = 0.02; I(2) = 26.66%), Aspergillus (OR = 8.19; 95% CI: 2.38-28.21; p = 0.0009; I(2) = 17.02%) and other fungal infections (OR = 3.69; 95% CI: 1.11-12.33; p = 0.03; I(2) = 0%) for patients with IgG <400 mg/dL were higher than the odds for patients with IgG >400 mg/dL. The odds for 1-year all-cause mortality for severe hypogammaglobulinemia group was 21.91 times higher than those for IgG >400 mg/dL group (95% CI: 2.49-192.55; p = 0.005; I(2) = 0%). Severe hypogammaglobulinemia during the first year posttransplantation significantly increased the risk of CMV, fungal and respiratory infections, and was associated with higher 1-year all-cause mortality.
    American Journal of Transplantation 08/2013; · 6.19 Impact Factor
  • Source
    Andre C Kalil, Diana F Florescu
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    ABSTRACT: Despite the same manufacturer, the same drotrecogin alfa activated dose, and the same placebo-controlled design, the negative result from the PROWESS-SHOCK trial contradicted the survival benefit observed in the PROWESS trial. We hypothesize that the different results were due to factors other than the experimental therapy and performed an analysis of the clinical heterogeneity (differences related to the trials' clinical aspects) and the statistical heterogeneity (differences related to the trials' statistical aspects) between these trials. Baseline characteristics and co-interventions were analyzed by chi-square testing and mortality was analyzed by random-effects modeling and I2. Our findings show that clinical variables presented significant heterogeneity, and that up to 90% of the mortality differences between both trials were not due to chance. These results demonstrate that PROWESS and PROWESS-SHOCK are not comparable trials due to the highly significant clinical and statistical heterogeneity. We propose a new and pragmatic solution.
    Critical care (London, England) 07/2013; 17(4):167. · 4.72 Impact Factor
  • Diana F Florescu, Alan N Langnas, Uriel Sandkovsky
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    ABSTRACT: Intestinal transplantation (IT) has become a standard treatment for patients with intestinal failure and complications of parenteral nutrition. The pool of intestinal transplant recipients has been slowly growing over the last two decades. Of the 2191 ITs performed between 1 January 1990 and 31 March 2012, 50.5% were children less than 10 years of age. Survival rates at 1, 5 and 10 years have been reported to be 78.5, 58.2 and 47%, respectively. IT restores organ functions, but it is associated with complications, with infections representing the major cause of morbidity and mortality in this population.
    Expert Review of Anticancer Therapy 04/2013; 11(4):367-81. · 3.22 Impact Factor
  • Diana F Florescu, Joong Y Kwon, Ioana Dumitru
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    ABSTRACT: Adenovirus infections have been associated with significant morbidity and mortality in immunocompromised hosts. The clinical significance of adenoviral disease in heart transplantation is not well defined; in particular, the significance of adenovirus identification in myocardium remains unclear. Although severe adenovirus disease has been described in heart transplant recipients, adenovirus infections seem to be more frequently associated with increased risk of adverse cardiac events such as rejection, ventricular dysfunction, coronary vasculopathy, need for re-transplantation and graft loss because of death. Cidofovir is currently considered the standard of treatment for adenovirus disease not responding to reduction of immunosuppression.
    Cardiology in review 03/2013;
  • Marius C Florescu, Clifford D Miles, Diana F Florescu
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    ABSTRACT: Adenoviruses are common pathogens that have the potential to cause opportunistic infections with significant morbidity and mortality in immunocompromised hosts. The significance of adenoviral infection and disease is incompletely known in the setting of kidney transplantation. Reported adenovirus infections in renal transplant recipients have typically manifested as hemorrhagic cystitis and tubulointerstitial nephritis, less severe diseases than often seen in other solid organ transplant recipients (i.e. pneumonia, hepatitis and enteritis). The prevalent adenovirus subgroups associated with cystitis and nephritis are B1 and B2 with the serotypes 7, 11, 34, 35. However, disseminated or severe adenovirus infections, including fatal cases, have been described in renal transplant recipients. There is uncertainty regarding monitoring of and treatment of this virus. Although not supported by randomized clinical trials, cidofovir is used for the treatment of adenovirus disease not responding to reduction of immunosuppression.
    Nephrology Dialysis Transplantation 03/2013; · 3.37 Impact Factor
  • D F Florescu, J A Hoffman
    American Journal of Transplantation 03/2013; 13(s4):206-211. · 6.19 Impact Factor
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    ABSTRACT: We describe two patients who developed gastrointestinal bleeding due to cytomegalovirus (CMV) colitis after placement of a HeartMate II left ventricular assist device (LVAD). We aim to raise awareness of CMV colitis as a possible cause of gastrointestinal bleeding after LVAD placement and discuss potential mechanisms for CMV reactivation and areas for future research.
    International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 01/2013; · 2.17 Impact Factor
  • Diana F Florescu, Andre C Kalil
    Critical care medicine 12/2012; 40(12):3313-4. · 6.37 Impact Factor
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    ABSTRACT: Background: Solid organ transplant recipients require lifetime immunosuppression and are highly susceptible to opportunist and non-opportunistic infections. Sepsis is a serious post-transplant complication and physicians commonly assume that survival from sepsis in transplant recipients is worse than survival in non-transplant patients, but evidence is lacking. We aimed to evaluate if survival outcomes differ between these two populations. Methods: Propensity-adjusted, matched, case-control study. Conditional logistic regression was performed for risk factors analyses, and Cox proportional hazards regression was performed for survival analyses. Results: A total of 369 patients, 123 solid organ transplant recipients and 246 non-transplant patients diagnosed with sepsis, (presence of SIRS plus bacteremia or fungemia), were matched 1:2 by age, gender, and hospital location. The distribution of allografts was: 36.6% kidney, 34.1% liver, 13% kidney-pancreas, 7.3% small bowel/liver, 5.7% heart/lung, and 3.3% multivisceral. In patients with sepsis, the conditional logistic regression analysis showed that the following factors were significantly associated with transplantation: higher number of comorbidities OR=8.2 [95%CI 1.48-45.44] (p=0.016); higher SOFA score OR=1.2 [95%CI 1.07-1.32] (p=0.001); presence of nosocomial infection OR=36.3 [95%CI 9.71-135.96] (p<0.0001); less appropriate initial antibiotics OR=0.04 [95%CI 0.006-0.23] (p<0.0001); and lower white blood cells OR=0.93 [95%CI 0.89-0.97] (p<0.0001). Cox proportional hazards regression analysis showed that after all adjustments for clinical presentation, severity of illness and types of infection, solid organ transplant recipients with sepsis had a significantly lower risk of death compared to non-transplant patients at 28 days (HR=0.22 [95%CI 0.09-0.54];p=0.001) and at 90 days (HR=0.43 [95%CI 0.20-0.90];p=0.025). Conclusion: The 28-day and 90-day survival were significantly better for transplant recipients compared with non-transplant patients. This finding suggests that the immunosuppression associated with transplantation may provide a survival advantage to transplant recipients with sepsis through modulation of the inflammatory response.
    IDWeek 2012 Meeting of the Infectious Diseases Society of America; 10/2012

Publication Stats

300 Citations
171.46 Total Impact Points

Institutions

  • 2008–2014
    • University of Nebraska Medical Center
      • Division of Infectious Diseases
      Omaha, Nebraska, United States
  • 2008–2013
    • University of Nebraska at Omaha
      • • Department of Biostatistics
      • • Department of Internal Medicine
      Omaha, Nebraska, United States
  • 2011–2012
    • The Nebraska Medical Center
      Omaha, Nebraska, United States