Sweat analysis with a wearable sensing platform based on laser-induced graphene.

The scientific community has shown increasing interest in laser scribing for the direct fabrication of conductive graphene-based tracks on different substrates. This can enable novel routes for the noninvasive analysis of biofluids (such as sweat or other noninvasive matrices), whose results can provide the rapid evaluation of a person's health status. Here, we present a wearable sensing platform based on laser induced graphene (LIG) porous electrodes scribed on a flexible polyimide sheet, which samples sweat through a paper sampler. The device is fully laser manufactured and features a two layer design with LIG-based vertical interconnect accesses. A detailed characterization of the LIG electrodes including pore size, surface groups, surface area in comparison to electroactive surface area, and the reduction behavior of different LIG types was performed. The bare LIG electrodes can detect the electrochemical oxidation of both uric acid and tyrosine. Further modification of the surface of the LIG working electrode with an indoaniline derivative [4-((4-aminophenyl)imino)-2,6-dimethoxycyclohexa-2,5-dien-1-one] enables the voltammetric measurement of pH with an almost ideal sensitivity and without interference from other analytes. Finally, electrochemical impedance spectroscopy was used to measure the concentrations of ions through the analysis of the sweat impedance. The device was successfully tested in a real case scenario, worn on the skin during a sports session. In vitro tests proved the non-cytotoxic effect of the device on the A549 cell line.

Electric conductivity measurements employing 3D printed electrodes and cells.

The electric conductivity is one the most routinely inspected characteristics of aqueous media, being employed in monitoring drinking water quality and determining thermodynamic properties of electrolytes. In this work, we utilize fused deposition modelling 3D printing (3DP) to manufacture a platform composed of supporting cells and sensing electrodes for electric conductivity measurements of aqueous solutions. For the first time, the electric conductivity of liquid electrolytes is sensed by 3DP electrodes, employing a direct electrode/electrolyte contact. Conductivity measurements performed in the presented 3DP platform are controlled by an electronic circuitry developed employing a programmable system on chip prototyping kit. The entire conductometric setup was validated employing commercial conductance standards as well as in-lab prepared aqueous solutions of potassium chloride and formic and acetic acid as representatives of strong and weak electrolytes. Conductivity measurements enabled the correct determination of limiting molar conductivity (for potassium chloride) and dissociation constants (for the two weak acids). Finally, the functionality of the presented platform was confirmed by measuring conductivity of various bottled water samples. Results obtained in this work pave the wave for further development and applications of conductometers based on 3DP electrodes and cells.

A Biosensor for the Detection of Acetylcholine and Diazinon.

Acetylcholine is a neurotransmitter and a neuromodulator found in the autonomic, peripheral and central nervous systems. Diazinon is a pesticide with toxic effects on humans, such as the inhibition of acetylcholine. In this paper, a biosensor is proposed for the detection of acetylcholine (range 70 - 1000 µM) and diazinon (range 0.3 - 20000 ppb). This biosensor combines a pH-sensitive layer of reduced graphene oxide functionalized with 4-aminobenzoic acid and acetylcholinesterase. This enzyme was immobilized on reduced graphene oxide and it catalyzed the conversion of acetylcholine into choline and acetic acid, locally decreasing the pH value and triggering the sensor response. The limit of detection for the acetylcholine and diazinon were 70 µM and 0.3 ppb, respectively.

A graphene-based pH sensor on paper for human plasma and seawater.

The relevance of pH assessment in clinical analysis, environmental and industrial control, has raised the demand for the development of portable, low cost and easy-to-use monitoring systems. This paper proposes a pH sensor printed on a paper support passivated with a solid-ink coating. The sensor exploits the pH sensitivity of a reduced graphene oxide functionalized with 3-(4-aminophenil)propionic acid. The sensor responded in the pH range [4], [10] and had a sensitivity of 46 mV/pH. Tests on human plasma and seawater proved this pH sensor to have similar performances than those of a commercial pH-meter with an uncertainty of 0.1 and 0.2 pH unit in plasma and seawater, respectively.

Potential Side Effects of the Entomopathogenic Fungus Metarhizium anisopliae on the Egg Parasitoid Trichogramma pretiosum (Hymenoptera: Trichogrammatidae) Under Controlled Conditions.

The purpose was to evaluate the side effects of strains Metarhizium anisopliae (Metsch.) Sorokin sensu lato Unioeste 43 and M. anisopliae sensu stricto ESALQ 1641 on Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae) under controlled conditions. A free-choice test for parasitism was performed, with the confinement of T. pretiosum females mated with cards (1 × 5 cm) containing age-standardized Anagasta kuehniella Zeller eggs, either sprayed with a fungal strain (109 conidia/ml) or 0.01% v/v Tween 80 (control). For the no-choice tests, T. pretiosum females mated were confined with cards sprayed with fungal strains before or after parasitism, and cards with fungal applications at different times. The number of parasitized eggs, percentage of emergence, longevity, egg-to-adult period, sex ratio, total and confirmed mortality by the fungus, and longevity of females that parasitized previously sprayed eggs, were assessed. Histological analysis of immature phases was also performed. The fungus was repellent to T. pretiosum in the free-choice test, while in the no-choice test, fungal applications before and after parasitism did not affect the number of eggs parasitized by T. pretiosum or the sex ratio of emerging adults. However, both strains affected adult emergence rates, the egg-to-adult period, and longevity. Overall, both M. anisopliae strains had minor effects on these biological parameters of T. pretiosum under controlled conditions. Hyphae were not detected in histological observations of immature stages of the parasitoid.

Field Assessments to Control the Lesser Mealworm (Coleoptera: Tenebrionidae) Using Diatomaceous Earth in Poultry Houses.

Control of the lesser mealworm (Alphitobius diaperinus Panzer, 1797 [Coleoptera: Tenebrionidae]) is usually conducted with chemical insecticides, which have limited efficacy as well as environmental and health risks. Diatomaceous earth (DE) is safe and effective in controlling many insects including lesser mealworm. However, little is known of DE efficacy against this pest. Thus, an assessment of DE was conducted for the first time in commercial broiler houses in Brazil, with the aim of developing a strategy for the use of DE in the control of this insect. The efficacy of DE was determinate to a minimum concentration, and the application was directed to the most infested sites. The DE applied to the entire poultry house (280 g/m2) was verified to control the insects. DE was also comparable to chemical treatments, with a reduction of 80% in the insect population. DE controlled the lesser mealworm and is recommended for application at a concentration of 280 g/m2 when applied to the surface of new poultry litter, before the first lot of birds is housed. Thereafter, DE should be reapplied before the housing of each lot of birds, in the same concentration, only in the housing area and under the feeders and near the walls and pillars. In addition to being a control strategy, DE can be an important tool in the management of lesser mealworm insecticide resistance.

The ambiguous role of healthcare providers: a new perspective in Human Resources Management.

BACKGROUND AND AIM: A strategic Human Resources Management approach, that overcomes anadministrative Personnel Management, is becoming crucial for hospital organizations. In this sense, the aimof this work was to examine the figure of healthcare provider using the concept of role, as expected behaviourin term of integration in the organizational culture. METHOD: The instrument used to analyse the healthcareprovider figure was "role mapping". Particularly, semistructured interviews were conducted and involved to36 health professionals of four units in order to examine the behaviour expectations system towards thehealthcare providers. RESULTS: The analysis revealed that the expectations of different professionals relatedto the healthcare provider were dissimilar. Physicians' expectations referred to technical preparation and efficiency,while nurses and nurse coordinators required collaboration in equip work and emotional support forpatients. In all Operating Units, directors were perceived as missing persons with vague expectations of efficiency.Differences concerned also the four Units. For example, in intensive care Unit, the role of healthcareprovider was clearer and this figure was perceived as essential for patients' care and for the equip teamwork.On the contrary, in Recovery Unit the healthcare provider was underestimated, the role was ambiguous andnot integrated in the equip even if there was a clear division of tasks between nurses and healthcare providers. CONCLUSION: The "role mapping" instrument allows to identify healthcare provider profile and find possible roleambiguity and conflicts in order to plan adequate human resources management interventions.

A graphene oxide pH sensor for wound monitoring.

This article describes the fabrication and characterization of a pH sensor for monitoring the wound status. The pH sensitive layer consists of a graphene oxide (GO) layer obtained by drop-casting 5 µÎ of GO dispersion onto the working electrode of a screen-printed substrate. Sensitivity was 31.8 mV/pH with an accuracy of 0.3 unit of pH. Open-circuit potentiometry was carried out to measure pH in an exudate sample. The GO pH sensor proved to be reliable as the comparison with results obtained from a standard glass electrode pH-meter showed negligible differences (<; 0.09 pH units in the worst case) for measurements performed over a period of 4 days.

Multicentre surveillance study on feasibility, safety and efficacy of antifungal combination therapy for proven or probable invasive fungal diseases in haematological patients: the SEIFEM real-life combo study.

UNLABELLED: This multicentre observational study evaluated the feasibility, efficacy and toxicity of antifungal combination therapy (combo) as treatment of proven or probable invasive fungal diseases (IFDs) in patients with haematological malignancies. Between January 2005 and January 2010, 84 cases of IFDs (39 proven and 45 probable) treated with combo were collected in 20 Hematological Italian Centres, in patients who underwent chemotherapy or allogeneic haematopoietic stem cell transplantation for haematological diseases. Median age of patients was 34 years (range 1-73) and 37% had less than 18 years. Acute leukaemia was the most common underlying haematological disease (68/84; 81%). The phase of treatment was as follows: first induction in 21/84 (25%), consolidation phase in 18/84 (21%) and reinduction/salvage in 45/84 (54%). The main site of infection was lung with or without other sites. The principal fungal pathogens were as follows: Aspergillus sp. 68 cases (81%), Candida sp. six cases (8%), Zygomycetes four cases (5%) and Fusarium sp. four cases (5%). The most used combo was caspofungin+voriconazole 35/84 (42%), caspofungin + liposomal amphotericin B (L-AmB) 20/84 (24%) and L-AmB+voriconazole 15/84 (18%). The median duration of combo was 19 days (range 3-180). The overall response rate (ORR) was 73% (61/84 responders) without significant differences between the combo regimens. The most important factor that significantly influenced the response was granulocyte (PMN) recovery (P 0.009). Only one patient discontinued therapy (voriconazole-related neurotoxicity) and 22% experienced mild and reversible adverse events (hypokalaemia, ALT/AST increase and creatinine increase). The IFDs-attributable mortality was 17%. This study indicates that combo was both well tolerated and effective in haematological patients. The most used combo regimens were caspofungin + voriconazole (ORR 80%) and caspofungin + L-AmB (ORR 70%). The ORR was 73% and the mortality IFD related was 17%. PMN recovery during combo predicts a favourable outcome. CLINICAL TRIALS REGISTRATION: NCT00906633.

Hema e-Chart registry of invasive fungal infections in haematological patients: improved outcome in recent years in mould infections.

The electronic surveillance system Hema e-Chart allowed us to prospectively collect data and to perform an analysis of invasive fungal infections (IFI) diagnosed in febrile patients as well as the procedures allowing their diagnosis and outcome according to the treatment given. Every patient admitted to 26 Italian Haematology Units with a new diagnosis of haematological malignancy and who was a candidate for chemotherapy was consecutively registered between March 2007 and March 2009. In all, 147 haematological patients with mycoses were identified. Yeasts were found in 23 infections; moulds were diagnosed in 17 proven, 35 probable and 72 possible mycoses. Galactomannan (GM) antigen was the most important test to diagnose probable mould infection; it was positive (cut-off >0.5) in 27 (77%) probable and in nine (53%) proven mould infections. Among patients with probable/proven mould infection who received no prophylaxis or non-mould-active prophylaxis with fluconazole, more patients (n = 26, 78.8%) had GM antigen positivity compared with patients (n = 10, 52.6%) given prophylaxis with mould-active drugs (p <0.05). First-line antifungal therapy was effective in 11/23 (48%) yeast infections and in 37/52 (71.2%) proven/probable mould infections. Twenty patients (14%) died within 12 weeks. The fungal attributable mortality was 30.4% and 17.3% in yeast and proven/probable mould infections, respectively. Among risk factors only age was independently associated (p 0.013) with mortality; sex, underlying haematological malignancy, previous prophylaxis and presence of neutropenia at diagnosis were not significant. A diagnosis of mould infection seemed to have a trend for a better outcome than the diagnosis of yeast infection (p 0.064).

Optical transition radiation used in the diagnostic of low energy and low current electron beams in particle accelerators.

Optical transition radiation (OTR) plays an important role in beam diagnostics for high energy particle accelerators. Its linear intensity with beam current is a great advantage as compared to fluorescent screens, which are subject to saturation. Moreover, the measurement of the angular distribution of the emitted radiation enables the determination of many beam parameters in a single observation point. However, few works deals with the application of OTR to monitor low energy beams. In this work we describe the design of an OTR based beam monitor used to measure the transverse beam charge distribution of the 1.9-MeV electron beam of the linac injector of the IFUSP microtron using a standard vision machine camera. The average beam current in pulsed operation mode is of the order of tens of nano-Amps. Low energy and low beam current make OTR observation difficult. To improve sensitivity, the beam incidence angle on the target was chosen to maximize the photon flux in the camera field-of-view. Measurements that assess OTR observation (linearity with beam current, polarization, and spectrum shape) are presented, as well as a typical 1.9-MeV electron beam charge distribution obtained from OTR. Some aspects of emittance measurement using this device are also discussed.

A prospective survey of febrile events in hematological malignancies.

The Hema e-Chart prospectively collected data on febrile events (FEs) in hematological malignancy patients (HMs). The aim of the study was to assess the number, causes and outcome of HM-related FEs. Data were collected in a computerized registry that systematically approached the study and the evolution of FEs developing in a cohort of adult HMs who were admitted to 19 hematology departments in Italy from March 2007 to December 2008. A total of 869 FEs in 3,197 patients with newly diagnosed HMs were recorded. Fever of unidentified origin (FUO) was observed in 386 cases (44.4%). The other causes of FE were identified as noninfectious in 48 cases (5.5%) and infectious in 435 cases (50.1%). Bacteria were the most common cause of infectious FEs (301 cases), followed by fungi (95 cases), and viruses (7 cases). Mixed agents were isolated in 32 episodes. The attributable mortality rate was 6.7% (58 FEs). No deaths were observed in viral infection or in the noninfectious groups, while 25 deaths were due to FUO, 16 to bacterial infections, 14 to fungal infections, and three to mixed infections. The Hema e-Chart provided a complete system for the epidemiological study of infectious complications in HMs.

BU/melphalan and auto-SCT in AML patients in first CR: a 'Gruppo Italiano Trapianto di Midollo Osseo (GITMO)' retrospective study.

AML patients (total 129; median age =50 years; range 16-72) in first CR received BU and melphalan (BU/Mel) as conditioning regimen before auto-SCT. In all, 82 patients (63.6%) received PBSCs and 47 patients (36.4%) received BM cells. The distribution of cytogenetic categories was conventionally defined as favorable (15.5%), intermediate (60.1%) and unfavorable (24.3%). With a median follow-up of 31 months, the 8-year projected OS and disease-free survival (DFS) was 62 and 56% for the whole population, respectively. The relapse rate was 46% and the non-relapse mortality was 4.65%. Although PBSC transplantation led to a faster hematological recovery than BM transplantation, in univariate analysis the stem cell source, cytogenetics and different BU formulations did not significantly affect OS and DFS, whereas age and the number of post-remission chemotherapy cycles did have a significant effect on the clinical outcome. Multivariate analysis identified age <55 years as the only important independent predictor for OS and DFS. Our data suggest that BU/Mel, being associated with a low toxicity profile (mainly mucositis) and mortality, is an effective conditioning regimen even for high-risk AML patients in first CR undergoing auto-SCT.

Zygomycosis in Italy: a survey of FIMUA-ECMM (Federazione Italiana di Micopatologia Umana ed Animale and European Confederation of Medical Mycology).

The aims of the study were to analyze the clinical and epidemiological characteristics and treatments for patients who developed zygomycosis enrolled in Italy during the European Confederation of Medical Mycology of medical mycology survey. This prospective multicenter study was performed between 2004 and 2007 at 49 italian Departments. 60 cases of zygomycosis were enrolled: the median age was 59.5 years (range 1-87), with a prevalence of males (70%). The majority of cases were immunocompromised patients (42 cases, 70%), mainly hematological malignancies (37). Among non-immunocompromised (18 cases, 30%), the main category was represented by patients with penetrating trauma (7/18, 39%). The most common sites of infection were sinus (35%) with/without CNS involvement, lung alone (25%), skin (20%), but in 11 cases (18%) dissemination was observed. According to EORTC criteria, the diagnosis of zygomycosis was proven in 46 patients (77%) and in most of them it was made in vivo (40/46 patients, 87%); in the remaining 14 cases (23%) the diagnosis was probable. 51 patients received antifungal therapy and in 30 of them surgical debridement was also performed. The most commonly used antifungal drug was liposomal amphotericin B (L-AmB), administered in 44 patients: 36 of these patients (82%) responded to therapy. Altogether an attributable mortality rate of 32% (19/60) was registered, which was reduced to 18% in patients treated with L-AmB (8/44). Zygomycosis is a rare and aggressive filamentous fungal infection, still associated with a high mortality rate. This study indicates an inversion of this trend, with a better prognosis and significantly lower mortality than that reported in the literature. It is possible that new extensive, aggressive diagnostic and therapeutic procedures, such as the use of L-AmB and surgery, have improved the prognosis of these patients.

Gastric fundus tension before and after division of the short gastric vessels in a cadaveric model of fundoplication.

Short gastric vessels (SGV) division is a controversial topic in antireflux surgery. Some surgeons do not divide the SGV routinely to perform a fundoplication; however, excessive tension of the gastric fundus (GF) forces this procedure necessary in some cases. This study aims to evaluate in a cadaveric model of Nissen fundoplication: (i) the correlation of GF tension with anatomic parameters; and (ii) the effect of SGV division on GF tension. In total, 23 fresh cadavers (18 men, mean age 62 years) were studied. The abdominal esophagus was dissected, and the GF transposed to a limit of 3 cm to the right border of the esophagus. A dynamometer was attached to the GF and the tension recorded. Cadavers were grouped according to the presence or absence of tension. SGV were divided and GF tension measured again. The presence or absence of initial GF tension was correlated to: (i) number of SGV; (ii) length of the GF; (iii) distance between His angle and the first SGV; and (iv) size of the spleen. The mean GF pressure was 0.5 N +/- 1.0 (0-2.5) before SGV division and 0.1 N +/- 0.3 (0-1.5) after SGV division (P= 0.002). Initial tension was absent in 12 (52.2%) cases. GF tension did not correlate with any of the anatomic parameters. Our results show that: (i) GF tension does not correlate with anatomic parameters; and (ii) SGV division affects GF tension significantly.

Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne.

BACKGROUND: The purpose of our study was to evaluate the incidence and outcome of invasive fungal infection (IFI) among patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers. METHODS: This cohort-retrospective study, conducted during 1999-2003, involved HSCT patients admitted to 11 tertiary care centers or university hospitals in Italy, who developed IFIs (proven or probable). RESULTS: Among 3228 patients who underwent HSCT (1249 allogeneic HSCT recipients and 1979 autologous HSCT recipients), IFI occurred in 121 patients (overall incidence, 3.7%). Ninety-one episodes (2.8% of all patients) were due to molds, and 30 (0.9%) were due to yeasts. Ninety-eight episodes (7.8%) occurred among the 1249 allogeneic HSCT recipients, and 23 (1.2%) occurred among the 1979 autologous HSCT recipients. The most frequent etiological agents were Aspergillus species (86 episodes) and Candida species (30 episodes). The overall mortality rate was 5.7% among allogeneic HSCT recipients and 0.4% among autologous HSCT recipients, whereas the attributable mortality rate registered in our population was 65.3% (72.4% for allogeneic HSCT recipients and 34.7% for autologous HSCT recipients). Etiology influenced the patients' outcomes: the attributable mortality rate for aspergillosis was 72.1% (77.2% and 14.3% for allogeneic and autologous HSCT recipients, respectively), and the rate for Candida IFI was 50% (57.1% and 43.8% for allogeneic and autologous HSCT recipients, respectively). CONCLUSIONS: IFI represents a common complication for allogeneic HSCT recipients. Aspergillus species is the most frequently detected agent in these patients, and aspergillosis is characterized by a high mortality rate. Conversely, autologous HSCT recipients rarely develop aspergillosis, and the attributable mortality rate is markedly lower. Candidemia was observed less often than aspergillosis among both allogeneic and autologous HSCT recipients; furthermore, there was no difference in either the incidence of or the attributable mortality rate for candidemia among recipients of the 2 transplant types.

Efficacy of caspofungin as secondary prophylaxis in patients undergoing allogeneic stem cell transplantation with prior pulmonary and/or systemic fungal infection.

Transplanted patients with a history of invasive fungal infection (IFI) are at high risk of developing relapse and fatal complications. Eighteen patients affected by hematological malignancies and a previous IFI were submitted to allogeneic stem cell transplantation, using Caspofungin as a secondary prophylaxis. Patients had a probable or proven fungal infection and 16 had a pulmonary localization. No side effects were recorded during treatment with Caspofungin. Compared to pre-transplant evaluation, stability or improvement of the previous IFI was observed in 16 of the 18 patients at day 30, in 13 of the 15 evaluable patients at day 180 and in 11 of the 11 evaluable patients at day 360 post transplant. In particular, all the six patients with a proven fungal infection were alive, with a stable or improved IFI after 1 year from transplant. At a maximum follow-up of 31 months, eight patients died for disease progression or transplant-related complications, but only two had evidence of fungal progression. Secondary prophylaxis with Caspofungin may represent a suitable approach to limit IFI relapse or progression, allowing patients with hematological malignancies to adhere to the planned therapeutic program.

Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database.

Over the last decade, hematopoietic stem cells transplantation (HSCT) has been increasingly used in the treatment of severe progressive autoimmune diseases. We report a retrospective survey of 183 multiple sclerosis (MS) patients, recorded in the database of the European Blood and Marrow Transplantation Group (EBMT). Transplant data were available from 178 patients who received an autologous graft. Overall, transplant related mortality (TRM) was 5.3% and was restricted to the period 1995-2000, with no further TRM reported since then. Busulphan-based regimens were significantly associated with TRM. Clinical status at the time of transplant and transplant techniques showed some correlations with toxicity. No toxic deaths were reported among the 53 patients treated with the BEAM (carmustine, etoposide, cytosine-arabinoside, melphalan)/antithymocyte globulin (ATG) regimen without graft manipulation, irrespective of their clinical condition at the time of the transplant. Improvement or stabilization of neurological conditions occurred in 63% of patients at a median follow-up of 41.7 months, and was not associated with the intensity of the conditioning regimen. In this large series, HSCT was shown as a promising procedure to slow down progression in a subset of patients affected by severe, progressive MS; the safety and feasibility of the procedure can be significantly improved by appropriate patient selection and choice of transplant regimen.

Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia.

Toxicity limits the use of anthracyclines in elderly sick patients and in heavily pretreated patients. Since the liposomal preparation of daunorubicin (DNR) (DaunoXome, or DNX) is expected to be less toxic than conventional DNR, we tested DNX combined with high-dose arabinosyl cytosine (HDAC) in 42 adult poor-risk acute leukemia patients. Thirty-one patients had acute non-lymphocytic leukemia (ANLL). Of these, 12 patients were newly diagnosed but were not eligible for standard induction treatment, 13 were in first relapse, and 6 were in second or subsequent relapse. Eleven patients had acute lymphocytic leukemia (ALL), in first (eight cases) or second (three cases) relapse. DNX was given i.v. in three doses of 80 or 100 mg/m(2) each (days 1-3) by a 60-min infusion in glucose 5%, followed by a 4-h infusion of HDAC 2 g/m(2) (days 1-5). Among 31 ANLL patients there were 16 (51%) complete remissions (CR), 5 deaths during induction, and 10 failures. Among 11 ALL patients there were 10 CRs and 1 failure. The response rate was not affected by the overexpression of MDR-related proteins (PgP, MRP-1, and LRP). Non-hemopoietic toxicity was negligible, with no intestinal toxicity and only one case of gram-negative bacteremia. We conclude that DNX, in combination with HDAC, is an effective treatment for poor-risk adult AL. Because of the low non-hematologic toxicity, it can be used to reinduce remission in poor-risk patients who are candidates for allogeneic bone marrow transplantation. The high CR rate observed in ALL requires confirmation.

Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program.

BACKGROUND AND OBJECTIVES: To evaluate the clinical characteristics of patients with hematologic malignancies developing a filamentous fungi infection (FFI) and to define the prognostic factors for their outcome. DESIGN AND METHODS: A retrospective study, conducted on patients admitted to 14 Hematology divisions of tertiary care or university hospitals, participating in the GIMEMA Infection Program, over a ten-year period (1988-1997). The study included patients with hematological malignancies and a histologically and/or microbiologically proven or probable FFI. RESULTS: We included 391 patients (male/female: 262/129, median age 49 years) with hematologic malignancies (225 acute myeloid leukemia, 67 acute lymphocytic leukemia, 30 chronic myeloid leukemia, 22 non-Hodgkin's lymphoma, 12 myelodysplastic syndrome, 10 aplastic anemia, 7 Hodgkin's disease, 8 chronic lymphocytic leukemia, 5 multiple myeloma, and 5 hairy cell leukemia) who developed a proven FFI. Eighty percent of the patients had been neutropenic for an average of 14 days before the infection, and 71% had an absolute neutrophil count lower than 0.5 x 10(9)/L at the time of FFI diagnosis. The primary sites of infection were: lungs (85%), nose and paranasal sinus (10%), and other sites (5%). The diagnosis was made while still alive in 310 patients (79%), and at autopsy in the remaining 81 patients (21%). Chest X-ray was diagnostic in 77% of patients with pulmonary FFI, while computed tomography (CT) scan of the thorax was positive in 95% of cases. A significant diagnostic advantage for CT scan was observed in 145 patients who had both a chest X-ray and CT scan. Aspergillus was identified as the cause of FFI in 296 patients, Mucorales in 45 patients, Fusarium in 6 patients and other filamentous fungi species in 4 patients, while in a further 40 patients no agent was identifiable. The overall mortality rate three months after the diagnosis of FFI was 74%, and fungal infection had been the cause of death in 51% of patients. INTERPRETATION AND CONCLUSIONS: Our retrospective study shows that FFI still remains a life-threatening complication in neutropenic patients. Despite appropriate treatment, half of the patients die due to this complication. The use of glucocorticoids and recovery from neutropenia are the most important prognostic factors. Mucorales infections are associated with a significantly poorer prognosis than those due to Aspergillus spp.