Background
The epidemiology of and risk factors for invasive mold disease (IMD) among allogeneic hematopoietic cell transplant (HCT) recipients may vary according to the region. In this study, we ...sought to evaluate risk factors for IMD in our patient population.
Methods
Between May 2007 and July 2009, all HCT recipients from 8 Brazilian centers were followed prospectively until 1 year post transplant. Cases of IMD were classified as early (before day +40) or late (after day +40). Patients with IMD (cases) were compared with controls (patients without IMD) using univariate and multivariate Cox regression analysis.
Results
Among 345 HCT recipients, 28 IMDs were diagnosed. Risk factors for early IMD were acute myeloid leukemia (hazard ratio HR 2.95, 95% confidence interval 95% CI 1.13–7.68, P = 0.03) and transplant with a human leukocyte antigen‐mismatched donor (HR 3.38, 95% CI 1.18–9.68, P = 0.02), and for late IMD risk factors were lymphoma (HR 8.49, 95% CI 2.35–30.68, P = 0.001), cytomegalovirus reactivation (HR 5.51, 95% CI 1.15–26.47, P = 0.03), and neutropenia (HR 3.49, 95% CI 1.01–12.13, P = 0.049).
Conclusion
The variables identified in this study may help to define risk groups, and to tailor special preventive measures to patients at higher risk to develop IMD.
The study presented here was performed in order to create a rule that identifies subjects at high risk for invasive candidiasis in the intensive care setting. Retrospective review and statistical ...modelling were carried out on 2,890 patients who stayed at least 4 days in nine hospitals in the USA and Brazil; the overall incidence of invasive candidiasis in this group was 3% (88 cases). The best performing rule was as follows: Any systemic antibiotic (days 1-3) OR presence of a central venous catheter (days 1-3) AND at least TWO of the following-total parenteral nutrition (days 1-3), any dialysis (days 1-3), any major surgery (days -7-0), pancreatitis (days -7-0), any use of steroids (days -7-3), or use of other immunosuppressive agents (days -7-0). The rate of invasive candidiasis among patients meeting the rule was 9.9%, capturing 34% of cases in the units, with the following performance: relative risk 4.36, sensitivity 0.34, specificity 0.90, positive predictive value 0.01, and negative predictive value 0.97. The rule may identify patients at high risk of invasive candidiasis.
If tn are the heights of the Riemann zeros 1/2 + itn, an old idea, attributed to Hilbert and Polya 6, stated that the Riemann hypothesis would be proved if the tn could be shown to be eigenvalues of ...a self-adjoint operator. In 1986 Berry 1 conjectured that tn could instead be the eigenvalues of a deterministic quantum system with a chaotic classical counterpart and in 1999 Berry and Keating 3 proposed the Hamiltonian H xp, with x and p the position and momentum of a one-dimensional particle, respectively. This was proven not to be the correct Hamiltonian since it yields a continuum spectrum 23 and therefore a more general Hamiltonian H w(x)(p + ℓ2p/p) was proposed 25, 4, 24 and different expressions of the function w(x) were considered 25, 24, 16 although none of them yielding exactly tn. We show that the quantization by means of Lie and Noether symmetries 18, 19, 20, 7 of the Lagrangian equation corresponding to the Hamiltonian H yields straightforwardly the Schrödinger equation and clearly explains why either the continuum or the discrete spectrum is obtained. Therefore we infer that suitable Lie and Noether symmetries of the classical Lagrangian corresponding to H should be searched in order to alleviate one of Berry's quantum obsessions 2.
It is shown that the nonlinear pendulum equation can be transformed into a linear harmonic oscillator in the phase space thanks to Kerner’s method 12. Moreover, as a mathematical divertissement, the ...second-order differential equation determining the phase-space trajectories of the nonlinear pendulum is quantized.
To characterize the epidemiology and prognostic factors of invasive fusariosis in hematopoietic stem cell transplant (HSCT) recipients, the records of HSCT recipients from 9 hospitals (7 in Brazil ...and 2 in the United States) were retrospectively reviewed. Sixty-one cases were identified: 54 in allogeneic HSCT recipients and 7 in autologous HSCT recipients. The incidence of fusariosis among allogeneic HSCT recipients varied between a range of 4.21-5.0 cases per 1000 in human leukocyte antigen (HLA)-matched related transplant recipients to 20.19 cases per 1000 in HLA-mismatched transplant recipients. The median time period between transplantation and diagnosis of fusariosis was 48 days. Among allogeneic HSCT recipients, a trimodal distribution was observed: a first peak before engraftment, a second peak at a median of 62 days after transplantation, and a third peak >1 year after transplantation. The actuarial survival was 13% (median, 13 days). Persistent neutropenia was the single prognostic factor for death identified by multivariate analysis.
Invasive fungal disease (IFD) shows distinct regional incidence patterns and epidemiological features depending on the geographic region. We conducted a prospective survey in eight centres in Brazil ...from May 2007 to July 2009. All haematopoietic cell transplant (HCT) recipients and patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) were followed from admission until 1 year (HCT) or end of consolidation therapy (AML/MDS). The 12-month cumulative incidence (CI) of proven or probable IFD was calculated, and curves were compared using the Grey test. Among 237 AML/MDS patients and 700 HCT recipients (378 allogeneic, 322 autologous), the 1-year CI of IFD in AML/MDS, allogeneic HCT and autologous HCT was 18.7%, 11.3% and 1.9% (p <0.001), respectively. Fusariosis (23 episodes), aspergillosis (20 episodes) and candidiasis (11 episodes) were the most frequent IFD. The 1-year CI of aspergillosis and fusariosis in AML/MDS, allogeneic HCT and autologous HCT were 13.4%, 2.3% and 0% (p <0.001), and 5.2%, 3.8% and 0.6% (p 0.01), respectively. The 6-week probability of survival was 53%, and was lower in cases of fusariosis (41%). We observed a high burden of IFD and a high incidence and mortality for fusariosis in this first multicentre epidemiological study of IFD in haematological patients in Brazil.
We aimed to assess the characteristics, treatment, risk factors and outcome of patients with breakthrough candidaemia (BrC) in the era of broad-spectrum antifungal therapies. We carried out a ...multicentre study of hospitalized adults with candidaemia at six hospitals in three countries. BrC episodes were compared with the remaining episodes (non-BrC). Of 409 episodes of candidaemia, 37 (9%) were BrC. Among them, antifungal treatment was administered as prophylaxis in 26 severely immunosuppressed patients (70%) and as a fever-driven approach in 11 (30%). Candida albicans was significantly less common in patients with BrC (24% versus 46%, p 0.010) whereas Candida krusei was more frequent (16% versus 2.4%, p < 0.001). BrC was associated with infections caused by fluconazole non-susceptible isolates (50% versus 18%, p < 0.001). Candida albicans BrC was associated with previous fluconazole treatment whereas Candida parapsilosis candidaemia was mostly catheter-related and/or associated with previous echinocandin therapy. The empirical antifungal therapy was more often appropriate in the non-BrC group (57% versus 74%, p 0.055). No significant differences were found in outcomes (early and overall mortality: 11% versus 13% p 0.802 and 40% versus 40% p 0.954, respectively). Fluconazole non-susceptibility was independently associated with the risk of BrC (adjusted OR 5.57; 95% CI 1.45–21.37). In conclusion, BrC accounted for 9% of the episodes in our multicentre cohort. The Candida spp. isolated were different depending on the previous antifungal therapy: previous azole treatment was associated with fluconazole non-susceptible strains and previous echinocandin treatment was associated with BrC caused by C. parapsilosis. These results should be taken into account to improve the empirical treatment of BrC.
The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study ...112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six‐ and 12‐week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio HR: 2.29; p‐value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p‐value = 0.017) were independent predictors for 6‐week all‐cause mortality, whereas the initial use of a voriconazole‐based regimen showed a protective effect (HR: 0.34; p‐value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.
Invasive pulmonary aspergillosis presents a high mortality rate in kidney transplant recipients, with diagnosis within the first 6 months posttransplantation and bilateral lung involvement as independent risk factors for mortality.
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