Incidence Of IA Research Articles

852. Epidemiology, clinical characteristics and outcomes of invasive pulmonary aspergillosis among critically ill patients in medical intensive care unit: A retrospective study from the tertiary care hospital in Thailand

Abstract Background Invasive pulmonary aspergillosis (IPA) is a serious infection which leads to poor outcomes particularly in immunocompromised patients. Recently, IPA in critically ill patients in intensive care unit (ICU) has been increasingly recognized owing to its substantial morbidity and mortality. However, clinical data of IPA in ICU is scarce especially in Thailand. Methods A single-center, retrospective, observational study was conducted in King Chulalongkorn Memorial Hospital. We collected data on demographic, clinical characteristics, and outcomes of the patients who developed IPA during admission in the medical intensive care unit (MICU) between Jan 2016 to Dec 2021. IPA was identified by using ICD-10 and medication code for voriconazole, amphotericin B or liposomal amphotericin B. Patients met proven, probable IPA according to EORTC/MSG definition or putative IPA were included. The primary outcome was the incidence of IA in the MICU. Clinical characteristics, 12-week all-cause mortality and associated risk factor were the secondary outcomes. Results During the study period, a total of 5,019 patients were admitted in MICU. Fifty-seven met definitions of IPA which represented incidence of 1.14%. Seven patients (12.3%) had proven IPA, while 37 (61.4%) and 13 (22.8%) patients had probable and putative IPA, respectively. Cardiovascular disease (33.3%), chronic liver disease (26.7%), and diabetes (20.0%) were common comorbidities in patients with putative IPA. Diagnosis was made at median of 5 (3-10) days after ICU admission. Organisms were identified in 36 patients (63%) which Aspergillus fumigatus was the most common species (36.8%). All-cause mortality at week 12 was 89.5%. SOFA score (OR 1.494, 95%CI 1.058-2.110) and vasopressor used on admission (OR 16.00, 95%CI 2.209-115.92) had trend toward increase mortality. Median survival in putative and probable IPA group were 4 and 8 days after diagnosis (p= 0.023). Patients who received treatment with voriconazole had median survival 13 days compared to 5 days in other antifungal agents (p= 0.006). Conclusion IPA carried a high mortality among critically ill patients in MICU. High SOFA score and vasopressors used at the MICU admission were associated with mortality. Voriconazole therapy appeared to correlate with longer survival time. Disclosures All Authors: No reported disclosures

Prevalence of bicuspid aortic valve in patients with aneurysmal sub-arachnoid hemorrhage: neurologic features and outcomes

Abstract Background Intracranial aneurysm (IA) has been associated with bicuspid aortic valve (BAV) with prevalence of 6–10% which has led some to recommend routine surveillance for IA in BAV patients. Higher incidence of IA in BAV could signal towards systemic arteriopathy beyond the thoracic aorta. With CoA as an independent risk factor for IA formation, it is currently uncertain if the association between IA and BAV reflects the association of BAV and CoA, or the result of BAV-related systemic arterial changes. Purpose Despite this association, 2 small studies suggest no increased risk of the most important patient outcome: aneurysmal sub-arachnoid hemorrhage (aSAH). Our primary aim was identifying the prevalence of BAV in aSAH patients and compare it with that of a control group without aSAH. Secondary aims included neurologic outcomes of aSAH and anatomical characteristics of IA in BAV, and final disposition and outcome. Methods Patients (>18 years age) with an accurate diagnosis of aSAH and at least one echocardiogram in the system between January 2000-December 2019 were identified from a prospectively maintained registry of aSAH admissions. Controls, without a diagnosis of SAH ever, were age- and gender-matched (1:2 cases:controls). BAV prevalence was echocardiographically-confirmed in all patients. Severity of aSAH was categorized using the modified Fisher (mFisher) and the World Federation of Neurological Scale (WFNS). Results A total of 488 aSAH cases and 990 controls were included in the final analysis with confirmed aortic valve status. The prevalence of BAV in aSAH patients was 1.2% (6/488) vs 3.5% (35/990) in controls, p=0.01. None of the aSAH cases were noted to have CoA, whereas 3 (0.3%; p=0.12) control patients had presence of both BAV and CoA. Within aSAH patients, BAV+aSAH were noted to be younger than tricuspid aortic valve (TAV)+aSAH (56±11 vs 68±14; p=0.03). Aneurysm size was smaller in the BAV+aSAH group (5±2 vs 7±4 in TAV+aSAH; p=0.31). The severity of the bleed was lesser in BAV+aSAH than TAV+aSAH (mFisher grade >2 50% vs 74%; p=0.19, WFNS grade >3 17% vs 36%; p=0.43) which is clinically significant. The BAV+aSAH group had higher disposition rate to home (67% vs 39%; p=0.21) with no difference in in-hospital mortality rates (17% vs 18%; p=0.93). BAV had lower odds on univariate and multivariate analyses adjusted for age/sex/body mass index (OR 0.33 [CI 0.14–0.81]; p=0.01, OR 0.23 [CI 0.08–0.65]; p=0.01) of presenting with aSAH. Conclusion Within a large prospective registry with accurate aSAH diagnoses, we found 3-times lower prevalence of echocardiographically-confirmed BAV as compared to non-aSAH controls. We observed 3-times higher prevalence of BAV in controls than among aSAH cases. In addition, size of intracranial aneurysms was clinically smaller in BAV patients, and the severity of SAH was significantly lesser in BAV from a clinical standpoint. Our findings argue against routine surveillance for IA in BAV patients without CoA. Funding Acknowledgement Type of funding sources: None.

Association Between Neoadjuvant Chemoradiotherapy and Intractable Serous Ascites After Pancreaticoduodenectomy for Pancreatic Cancer.

Intractable serous (not chylous) ascites (IA) that infrequently develops early following pancreaticoduodenectomy (PD) for pancreatic cancer is a life-threatening problem. The relationship between neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer and the incidence of IA following PD has not been evaluated. This study aims to identify the risk factors associated with IA that develops early after PD for pancreatic cancer. We retrospectively identified 94 patients who underwent PD for pancreatic cancer at the Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Osaka, Japan, from April 2012 to March 2020. Data on 29 parameters were obtained from medical records. Univariate and multivariate analyses were conducted to identify independent risk factors. Levels of serum albumin were compared before and after NACRT to analyze its effect. Survival analysis was also conducted. Of the 92 patients included in this study, 8 (8.70%) were categorized into the IA group. Multivariate analysis identified NACRT [odds ratio (OR) 27, 95% confidence interval (CI) 1.87-394, p = 0.016)] and hypoalbuminemia (≤ 1.6g/dl) just after the operation (OR 50, 95% CI 1.68-1516, p = 0.024) as risk factors. The level of serum albumin was significantly decreased following NACRT. The IA group had poorer prognosis than the control group. IA is a serious problem that aggravates patient's prognosis. Postoperative lymphatic leak might be a trigger of IA. NACRT was a major risk factor, followed by hypoalbuminemia caused by various reasons. These factors may act synergistically and cause IA.

Evaluation of posaconazole antifungal prophylaxis in reducing the incidence of invasive aspergillosis in patients with acute myeloid leukemia

Purpose of the studyInvasive aspergillosis (IA) is the most prevalent invasive fungal disease (IFD) in neutropenic patients. Environment is the main source of Aspergillus spores aerosolization especially during building construction. International guidelines recommend mechanical protection during hospital building works; otherwise the use of antifungal prophylaxis is not clearly indicated.Our objective was to determine the efficacy of antifungal prophylaxis by posaconazole on IA incidence in acute myeloid leukemia population and to analyse the benefit of this prophylaxis and HEPA-filters during hospital buildings works. Patients and methodsWe included patients treated for acute myeloid leukemia at Brest teaching hospital from January 2009 to December 2015. We compared incidence of IA in the group treated by posaconazole from 2012 to 2015 to the incidence of IA in the first group who did not receive antifungal prophylaxis (from 2009 to 2011). The one-year overall survival was also analyzed using the Kaplan–Meier method. Results245 patients were enrolled including 151 treated with posaconazole. 23 IA were diagnosed between 2009 and 2011 (without antifungal prophylaxis), then 31 between 2012 and 2015 (with posaconazole) without statistical difference between the incidence densities (0.34 per 100 hospitalization-days vs. 0.30 per 100 hospitalization-days, p = 0.71). Incidence density of IA increased during building works (2.40 per 100 hospitalization-days vs. 0.28 per 100 hospitalization-days, p < 0.0001). The incidence density of IA significantly decreased during construction periods when posaconazole prophylaxis was used (1.59 per 100 hospitalization-days vs. 4.87 per 100 hospitalization-days p < 0.0001). ConclusionOur study suggests, for the first time, the interest of antifungal prophylaxis in addition to HEPA filtration in prevention of IA during hospital building works.

National trends in incidence, prevalence and disability-adjusted life years of invasive aspergillosis in Iran: a systematic review and meta-analysis

ABSTRACTObjectives: We aimed to study the epidemiology, prevalence, incidence, clinical manifestations, underlying diseases, treatments, outcomes, and societal impact through disability-adjusted life years (DALYs) of IA in Iran.Methods: A random-effect meta-analytic model was fitted to estimate the prevalence and incidence of IA in Iran. We also calculated DALYs.Results: Out of 79 published studies during the past 25 years from Iran, 23 met the inclusion criteria. A total of 2947 patients were included, of whom 396 (13.4%) patients were diagnosed with IA according to EORTC/MSG and ICU criteria. The main underlying condition for IA was hematologic disorders (39.4%). A. flavus 86 (43%) was the most common isolate. The pooled prevalence and incidence rates were 20.5 (95% CI 12.5 to 29.9) and 4.8 (95% CI 2.3–8.2) per 100,000 population, respectively. Total DALYs was estimated 164.13 per 100,000 population. YLLs constitute the majority of IA burden compared to YLDs (162.80 YLLs/100,000 population vs 1.33 YLDs per 100,000 population). The highest YLL rates were found in people aged 45–49 (62.9 YLLs/100,000 population) and 30–34 years (45.2 YLLs/100,000 population), respectively.Conclusion: This study indicates an increasing burden of IA in Iran, despite the extensive use of prophylaxis, challenging the public health, especially immunocompromised patients.

Airborne fungal spores and invasive aspergillosis in hematologic units in a tertiary hospital during construction: a prospective cohort study

BackgroundInvasive aspergillosis (IA) is an opportunistic fungal infection that mostly occurs in immunocompromised patients, such as those having hematologic malignancy or receiving hematopoietic stem cell transplantation. Inhalation of Aspergillus spores is the main transmission route of IA in immunocompromised patients. Construction work in hospitals is a risk factor for environmental fungal contamination. We measured airborne fungal contamination and the incidence of IA among immunocompromised patients, and evaluated their correlation with different types of construction works.MethodsOur tertiary hospital in Seoul, Korea underwent facility construction from September 2017 to February 2018. We divided the entire construction period into period 1 (heavier works: demolition and excavation) and period 2 (lighter works: framing, interior designing, plumbing, and finishing). We conducted monthly air sampling for environmental spore surveillance in three hematologic wards. We evaluated the incidence of IA among all immunocompromised patients hospitalized in the three hematologic wards (2 adult wards and 1 pediatric ward) during this period. IA was categorized into proven, probable, and possible aspergillosis based on the revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria.ResultsA total of 15 patients was diagnosed with proven (1 case), probable (8 cases), or possible (6 cases) hospital-acquired IA during period 1. In period 2, 14 patients were diagnosed with either proven (1 case), probable (10 cases), or possible (3 cases) hospital-acquired IA. Total mold and Aspergillus spp. spore levels in the air tended to be higher in period 1 (p = 0.06 and 0.48, respectively). The incidence rate of all IA by the EORTC/MSG criteria was significantly higher in period 1 than in period 2 (1.891 vs. 0.930 per 1000 person-days, p = 0.05).ConclusionsAirborne fungal spore levels tended to be higher during the period with heavier construction works involving demolition and excavation, during which the incidence of IA was significantly higher as well. We recommend monitoring airborne fungal spore levels during construction periods in hospitals with immunocompromised patients. Subsequently, the effect of airborne fungal spore level monitoring in reducing hospital-acquired IA should be evaluated.

Predicting Invasive Aspergillosis in Hematology Patients by Combining Clinical and Genetic Risk Factors with Early Diagnostic Biomarkers.

Personalized medicine provides a strategic approach to the management of IA. The incidence of IA in high-risk hematology populations is relatively low (<10%), despite unavoidable Aspergillus exposure in patients with a potentially similar clinical risk. Nonclinical variables, including genetic mutations that increase susceptibility to IA, could explain why only certain patients develop the disease. This study screened for mutations in 322 hematology patients classified according to IA status and developed a predictive model based on genetic risk, established clinical risk factors, and diagnostic biomarkers. Genetic markers were determined by real-time PCR and, with clinical risk factors and Aspergillus PCR results, subjected to multilogistic regression analysis to identify a best-fit model for predicting IA. The probability of IA was calculated, and an optimal threshold was determined. Mutations in dectin-1 (rs7309123) and DC-SIGN (rs11465384 and rs7248637), allogeneic stem cell transplantation, respiratory virus infection, and Aspergillus PCR positivity were all significant risk factors for developing IA and were combined in a predictive model. An optimal threshold requiring three positive factors generated a mean sensitivity/specificity of 70.4%/89.2% and a probability of developing IA of 56.7%. In patients with no risk factors, the probability of developing IA was 2.4%, compared to >79.1% in patients with four or more factors. Using a risk threshold of 50%, preemptive therapy would have been prescribed for 8.4% of the population. This pilot study shows that patients can be stratified according to risk of IA, providing personalized medicine based on strategic evidence for the management of IA. Further studies are required to confirm this approach.

Domestic mould exposure and invasive aspergillosis-air sampling of Aspergillus spp. spores in homes of hematological patients, a pilot study.

Aspergillus spp.-related morbidity and mortality remains a major challenge in the management of neutropenic patients. Little is known about the impact of domestic Aspergillus spp. In this controlled prospective study, fungal spores were collected from homes of neutropenic patients. Cases were defined as patients with probable or proven controls as patients with no invasive pulmonary aspergillosis, while patients with possible disease were evaluated as a third group. Forty patients were enrolled and returned questionnaires on high-risk activities and mould exposure. A. fumigatus was detected in concentrations of 0 to 76 cfu/m(3) in every home. A. terreus was detected in nine (18%) homes. Mean Aspergillus spp. cfu/m(3) according to EORTC criteria were: proven/probable IA (15 patients) - 36; possible IA (12 patients) - 42; no IA (13 patients) - 42. Of the seven patients with self-reported moulded walls at home, four had probable and three had possible aspergillosis; the risk ratio of developing IA was 1.65 (95% CI: 1.25-2.17). In conclusion self-reported domestic mould exposure was associated with a high incidence of IA and may be a feasible tool for identifying high-risk patients. There was no correlation between domestic ambient-air spore counts and IA.

Effect of the implosion and demolition of a hospital building on the concentration of fungi in the air.

Building renovations increase the concentration of Aspergillus conidia in the air. In 2010, one wing of the hospital building was imploded due to structural problems. To evaluate the impact of building implosion on the concentration of fungi in the air, the demolition was performed in two phases: mechanical demolition of 30 m of the building, followed by implosion of the wing. Patients at high risk for aspergillosis were placed in protected wards. Air sampling was performed during mechanical demolition, on the day of implosion and after implosion. Total and specific fungal concentrations were compared in the different areas and periods of sampling, using the anova test. The incidence of IA in the year before and after implosion was calculated. The mean concentration of Aspergillus increased during mechanical demolition and on the day of implosion. However, in the most protected areas, there was no significant difference in the concentration of fungi. The incidence of invasive aspergillosis (cases per 1000 admissions) was 0.9 in the 12 months before, 0.4 during, and 0.5 in the 12 months after mechanical demolition (P > 0.05). Continuous monitoring of the quality of air and effective infection control measures are important to minimize the impact of building demolition.

Epidemiology Of Invasive Aspergillosis (IA) During Induction Therapy In Adults With Acute Lymphoblastic Leukemia (ALL): A Graall-2005 Study

BackgroundIA is a major cause of morbidity and mortality for patients with hematological malignancies and has been mainly reported in patients with acute myeloblastic leukemia (AML) and stem cell transplantation. Much less is known about the role of IA during the treatment of lymphoproliferative diseases like ALL. Here, we retrospectively evaluated the characteristics of patients and the incidence of IA occurring during the induction course in adult ALL patients enrolled in the GRAALL-2005 trial. MethodsWe collected the data of 36 patients with IA during induction chemotherapy. All were included between May 2006 and October 2012 in the multicentric GRAALL-2005 phase III trial. According to ALL characteristics, these patients were treated in 3 different substudies: GRAALL, GRAALL-Rituximab (GRAALL-R) for CD20+ ALL, GRAAPH for Philadelphia (Ph) chromosome-positive ALL. IA was defined retrospectively using the EORTC modified criteria (De Pauw, CID 2008). ResultsAmong the 969 patients enrolled, 36 (3.7%) developed IA during induction therapy. The median age was 30 years for all patients receiving induction and 47 years (range, 18 to 59) for patients with IA. We observed 18 IA (3%) by the GRAALL protocol (593 patients enrolled), 16 (8.3%) by the GRAALL-R protocol (191 patients enrolled), and 2 (0.7%) by the GRAAPH protocol (270 patients enrolled). In the GRAALL-R protocol, IA was diagnosed in 6 patients randomly assigned to receive rituximab and in 10 patients treated in the control group. The median time between first day of induction therapy and IA diagnosis was 20 days (range, -2 to 71). The median time between the first day of neutropenia and IA diagnosis was 18 days (range, 0 to 76). At the time of IA diagnosis, 13 patients were hospitalized in laminar airflow rooms, 10 patients in rooms with overpressure, 1 patient in a room with high-efficiency particulate filter, 5 patients in conventional rooms, 1 patient received home care and the type of hospitalization was unknown for the 6 remaining patients. Four patients with IA (11%) had received antifungal drug for invasive fungal infection (IFI) prophylaxis: one patient received fluconazole, one received caspofungin, and two received liposomal amphotericin B. All patients with IA presented pulmonary symptoms associated with a sinusal or cutaneous localization in 1 and 2 patients respectively. The diagnosis of IA was classified as possible in 7 episodes (19 %), probable in 22 episodes (61%), proven in 4 episodes (11%), and indeterminate in the remaining 3 episodes. Detection of Aspergillus antigen in serum by latex agglutination was positive in 24 cases (67%). Chest CT scans were taken for 33 patients (92%): nodules were found in 19 patients, halo sign in 20 patients, and “air crescent sign” in 1 patient. Bronchoalveolar lavage was performed in 11 patients (31%): culture was positive in 7 of them and Aspergillus antigen was positive in 2 of them. Biopsies where positive in 4 cases: in pulmonary biopsy in 3 patients and in cutaneous biopsy in 1 patient. Of all the Aspergillus isolates identified to the species level, Aspergillus fumigatus was isolated from 4 patients and Aspergillus flavus from 1 patient. Overall and IA-attributable 12-week mortality was 8 (0.8%) and 6 (16.7%) patients respectively. ConclusionIA is less frequently observed during induction therapy in adult ALL as compared to adult AML patients. However, the attributable mortality appears to be high in these patients. They are as at risk patients for IA and should be included in prophylactic and empirical antifungal clinical trials. Disclosures:No relevant conflicts of interest to declare.

AB1370 Case mix of new patients seen in northumberland-results from a local survey

BackgroundThere is a paucity of data regarding the case mix in Rheumatology new patient clinics in the United Kingdom. In addition, the prevalence of inflammatory rheumatic diseases is known to...

Culture-positive invasive aspergillosis in a medical center in Taiwan, 2000–2009

We reviewed 776 patients who were culture positive for Aspergillus species at the hospital from 2000 to 2009. The isolates were collected for species identification by oligonucleotide hybridization and sequence analysis. A total of 96 cases of proven or probable IA were identified according to published criteria. The incidence of IA has increased significantly during the study period. Aspergillus fumigatus and A. flavus (41.7% each) were equally prevalent causative species. IA due to unusual species including A. nidulans (n=2), A. versicolor (n=2), and A. tubingensis (n=1) were also found. Among patients with IA, 55.2% had hematological disorder, 19.8% had underlying lung disorder, and 10.4% had autoimmune disease. The isolates species (P<0.001) and underlying disease (P<0.001) significantly affect the association of a positive culture with invasive disease. The overall mortality at three months was 62.5%, which remained stable throughout the study period. Multivariate analysis identified prior steroid use (P=0.007) as a significant risk factor for death, while surgery (P=0.030) and voriconazole (P=0.012) had protective effects. In conclusion, autoimmune disorders and underlying pulmonary diseases should also be considered as important predisposing factors of IA. Further emphasis on surgery and voriconazole in the management of IA might be beneficial.

Validation of Positive Effect of Posaconazole Prophylaxis During Induction Chemotherapy in AML: Study of Invasive Aspergillosis Incidence and of Risk Factors On Short and Long-Term Survival.

Abstract 4124We reported our experience on the antifungal prophylaxis by posaconazole in patients with acute myeloblastic leukaemia (AML) who were exposed to induction chemotherapy. To validate the benefit of an antifungal prophylaxis in this kind of population, we conducted a prospective study giving posaconazole (200mg per os x 3/24h) to all AML patients hospitalized for induction in the period 2007-2008 (group I) and to compare the observed results (incidence of severe invasive aspergillosis and overall survival) with a control group (group II) which was represented by all AML patients hospitalized for induction during the period 2006-2007 and who did not received any antifungal prophylaxis. There was in total 143 AML patients and after matching on age, gender, FAB classification and molecular markers, we got 121 patients (59 males and 62 females with a median age of 55 years): 55 patients in group I and 66 patients in group II. There were 91 AML de novo and 30 secondary AML, 18 patients had good cytogenetic markers, 43 intermediate and 58 poor (2 non evaluated). According to cytogenetics plus molecular markers, we distinguished 2 groups: a good prognostic group (n=29) associating favourable cytogenetics and intermediate 1 (normal cytogenetics+ Flt3 ITD, CEBPA,NMP1) and a poor prognosis group (n=75) with unfavourable cytogenetics and intermediate 2 (17 patients were not determined). As induction chemotherapy, patients received different combinations according to protocols, age and AML characteristics. The median interval between AML diagnosis and hospitalization was 0 day (-41 – +7), 92 patients (76%) were placed in laminar air flow rooms. After induction, 100 patients achieved a CR and 2 patients died during induction period. The median duration of aplasia and of hospitalization were 28 days (7 – 91) and 37 days (22 – 101) respectively. There was no significant difference for all the above characteristics between group I and group II. Concerning posaconazole prophylaxis, the treatment was started the 1st day of chemotherapy with a median duration of 27 days (8-94): 35 patients (64%) received their prophylaxis until their discharge, 7 (13%) discontinued due to toxicity [hepatic (n=3), renal (n=1), transfer to intensive care unit (n=3)] and 13 (23%) switched to another fungal treatment because of IA suspicion (n=5), probable IA (n=2) and invasive candidosis (n=5). ResultsAt Day32 post induction, we observed 2 probable IA (3.6%) in group I and 8 IA [possible (n=4) + probable IA (n=4)] (12%) in group II (p = 0.085). The cumulative incidence of IA in group I and II was: at day 100, 7.27% vs 15.5%, at 1 year 12.72% vs 22.72% and at 18 months 14.54% vs 24.24% respectively. The Kaplan-Myer analysis on time to death from any cause at Day 100, showed a significant survival benefit in favour of the Pozaconazole group (group I) over the control group (group II) (p=0.0023) (figure1), this difference was also significant when we adjusted the analysis only on deaths caused by IA (figure2). After a median follow-up of 8.6 months, the probability of overall survival was 92.3% at day 100, 83.5% at 6 months, 70% at 1 year, 58% at 18 months and 36% at 2 years with a significant difference between groups I and II(p=0.02). At the last follow-up, 39 patients died in the group II and 10 in the group I. Concerning the other risk factors, the multivariate analysis showed a significant impact on long term OS of age [HR= 0.103 (0.02 – 0.5) (p= 0.00029) ], cytogenetics [HR=2.524 (1.172-5.44) (p=0.0018)] and response to induction [HR=7.73 (3.579-16.7) (p=1.9e-7)]. ConclusionWe showed a very important impact of anti-fungal prophylaxis in patients undergoing chemotherapy for AML especially for invasive aspergillosis, which is a risk factor to take into account in addition to age, cytogenetics and response to treatment. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Incidence of Invasive Aspergillosis in Allogeneic Stem Cell Transplantation Patients: An Italian Prospectic Multicenter Study.

Between January 2003 and June 2004, every consecutive patient admitted for HSCT in three institutions was monitored for circulating galactomannan (GM) with Platelia Aspergillus assay (Bio-Rad) twice weekly from admittance until day 100, and then once weekly until day 365. Following fever occurence or GM optical density index increase (+ve cut-off value was >0.7), screening with weekly chest HR CT scan was started. Diagnosis of IA was made according to the EORTC/MSG criteria. 74 patients were analyzed, and 100 entered by now in the present study. Clinical characteristics of the patients are reported in table 1. We observed 10 cases of probable IA and 2 cases of possible IA. IA occurred before day 40 in 3 patients (median, day 13 after HSCT), between day 40 and day 180 in 8 cases (median, day 109 after HSCT), and after day 180 in 1 patient. Among the probable IA group of patients, 7/10 had GVHD, 6/10 were given steroids, and 3/10 had fever. Two consecutive positive GM test results were observed in the sera of 6/10 patients, GM was detected in BAL only in 3/10 cases and 1 patient had GM detected only in a SNC fluid. Chest CT scan was diagnostic in 8/10 cases, and in another patient CNS RMN scan shown lesions consistent with IA. All patients were lymphopenic at the time of IA diagnosis with an absolute count <450 mm^3, and only 1 patient was neutropenic. 3/10 patients had CMV reactivation during the IA episode and 4/10 had CMV reactivation in the 100 days following IA diagnosis. Cumulative incidence of IA after day 60 was 8,1%, overall incidence of IA was 16.2%, and probability of developing IA reached 24% at 1year after HSCT. Cumulative incidence of IA in the RIC group was 12.3%.6/12 patients died of IA, with a median survival of 24 days (range 1–83). IA accounted for 37.5% (6/16) of all deaths and for 55% of non-relapse deaths. 1-year survival in the IA group was 22% and 80% in non-IA group. Bimodal incidence distribution of IA after HSCT was confirmed, 25% of IA cases were diagnosed early (< day 40) after HSCT, 67% were diagnosed between day 40 and day 180, and an additional 8% developed after day 180. We confirm the role of GVHD and lymphopenia as important risk factors during the late post-transplantation periods. The relatively high incidence of IA could be a consequence of the increase of IA in recent years and of diagnostic improvement (GM+HR CT scan). We recommend the use of serial screening for GM after day 100 in patients lymphopenic or with GVHD. We need new diagnostic and therapeutic strategies for HSCT patients as IA accounts still for an unacceptable high portion of non-relapse deaths.Clinical characteristics of patientsPatients71DiseaseMultiple myeloma27 (38%)Myelodisplastic syndrome8 (11.3%)Acute myeloid leukemia9 (12.7%)Chronic myeloid leukemia6 (8.5%)Hodgkin's disease5 (7%)Non Hodgkin's lymphoma8 (11.3%)Acute lymphoblastic leukemia4 (5.6%)Chronic lymphatic leukemia2 (2.8%)Aplastic anemia1 (1.4%)Renal cell carcinoma1 (1.4%)Mean age years (range)48.8% (20–70)HSCT74*HLA id RIC52 (70.3%)MUD RIC5 (6.8%)HLA id conventional10 (13.5%)Syngeneic conventional1 (1.3%)MUD conventional5 (6.8%)MUD conventional UCB1 (1.3%)Stem cell sourcePBSC64 (86.5%)BM9 (12.2%)UCB1 (1.3%)Follow up daysMedian214Min48Max595GVHDAcute53/74 (71%)Chronic36/51 (70%)Chronic extensive14/36 (39%)*Second transplant3 patients

Epidemiology of invasive aspergillosis in France: a six-year multicentric survey in the Greater Paris area

Invasive aspergillosis is the most prevalent mould infection. An epidemiological surveillance network was set up in 18 teaching hospitals in Paris and the Greater Paris area. Prospective surveillance was conducted between 1994 and 1999. Between 1994 and 1997 cases were categorized as proven or probable aspergillosis and then the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria were used. The authors analysed 621 cases (115 proven, 506 probable). No seasonal variation was found. Haematological disorders (73%) including stem-cell transplantation (36%), solid-organ transplantations (10%) and AIDS (9%) were the main underlying conditions. The crude mortality was 63%. Incidence of IA was 8% (CI95: 6.5–9.5) in acute myelocytic leukaemia and 6.3% (CI95: 4.3–8.3) in acute lymphocytic leukaemia. Incidence was 12.8% (CI95: 10.8–14.8) following allogeneic stem-cell transplantation and 1.1% (CI95: 0.7–1.5) following autologous stem-cell transplantation. In solid-organ recipients incidence ranged from 11% following heart–lung transplantation and small bowel to 0.4% following kidney transplantation. Incidence in HIV infected patients ranged from 0.02 to 0.13% per annum. This large series confirmed that patients with haematologic disorders and transplantations are the most at risk for IA.

The effects of MHC chromosome dosage on bursal B-cell subpopulations in embryonic and neonatal chickens

The effect of MHC dosage on the population structure of developing bursal lymphocytes was studied in the Trisomic strain of chickens. These chickens contain either 2 (disomic), 3 (trisomic), or 4 (tetrasomic) copies of the MHC-encoding chromosome. To assess the developmental profile of bursal cell populations, bursal cells were characterized in the older embryo (18 days of incubation) and at two neonatal ages (1 day and 1 week post hatch) by a number of cellular parameters. Both transient and persistent alterations in cellular composition were revealed in the bursal subpopulations of trisomics and tetrasomics (aneuploids). Aneuploid bursal cells showed increased cell surface expression of MHC class II Ia antigen, at each age, compared to normal disomic cells. Aneuploid cell populations showed an increased incidence of small cells, at each age, a decreased incidence of Ia+ and IgM+ cells during late embryogenesis, and an increased incidence of IgG+ cells in the late embryo and 1-day-old chick. Significantly fewer proliferating cells were observed in the aneuploids, as compared to disomics, in the late embryo and 1-week-old chick. Three subpopulations were observed to be persistently altered in the MHC-aneuploids: an increased pool of Ia+++, small, IgM+ cells; a decreased pool of Ia+, large, IgM+ cells; and a decreased pool of Ia+, large, IgM- cells. Thus, increasing MHC-chromosome dosage is accompanied by specific alterations in B-cell differentiation. The elevated surface Ia antigen expression found on developing aneuploid B cells may play a role in these alterations.