RESUMEN
PURPOSE OF REVIEW: In patients with hematological malignancies, high-resolution computed tomography (CT) is the recommended imaging approach for diagnosis, staging and monitoring of invasive fungal disease (IFD) but lacks specificity. We examined the status of current imaging modalities for IFD and possibilities for more effective applications of current technology for improving the specificity of IFD diagnosis. RECENT FINDINGS: Although CT imaging recommendations for IFD are largely unchanged in the last 20âyears, improvements in CT scanner technology and image processing algorithms now allow for technically adequate examinations at much lower radiation doses. CT pulmonary angiography can improve both the sensitivity and specificity of CT imaging for angioinvasive molds in both neutropenic and nonneutropenic patients, through detection of the vessel occlusion sign (VOS). MRI-based approaches also show promise not only for early detection of small nodules and alveolar hemorrhage but can also be used to detect pulmonary vascular occlusion without radiation and iodinated contrast media. 18F-fluorodeoxyglucose (FDG) PET/computed tomography (FDG-PET/CT) is increasingly used to monitor long-term treatment response for IFD, but could become a more powerful diagnostic tool with the development of fungal-specific antibody imaging tracers. SUMMARY: High-risk hematology patients have a considerable medical need for more sensitive and specific imaging approaches for IFD. This need may be addressable, in part, by better exploiting recent progress in CT/MRI imaging technology and algorithms to improve the specificity of radiological diagnosis for IFD.
Asunto(s)
Infecciones Fúngicas Invasoras , Enfermedades Pulmonares Fúngicas , Tecnología Radiológica , Humanos , Neoplasias Hematológicas , Infecciones Fúngicas Invasoras/diagnóstico por imagen , Medición de Riesgo , Sensibilidad y Especificidad , Enfermedades Pulmonares Fúngicas/diagnóstico por imagenRESUMEN
BACKGROUND: Our multicentre study aims to identify baseline factors and provide guidance for therapeutic decisions regarding Magnusiomyces-associated infections, an emerging threat in patients with haematological malignancies. METHODS: HM patients with proven (Magnusiomyces capitatus) M. capitatus or (Magnusiomyces clavatus) M. clavatus (formerly Saprochaete capitata and Saprochaete clavata) infection diagnosed between January 2010 and December 2020 were recorded from the SEIFEM (Sorveglianza Epidemiologica Infezioni nelle Emopatie) group and FungiScope (Global Emerging Fungal Infection Registry). Cases of Magnusiomyces fungemia were compared with candidemia. RESULTS: Among 90 Magnusiomyces cases (60 [66%] M. capitatus and 30 (34%) M. clavatus), median age was 50 years (range 2-78), 46 patients (51%) were female and 67 (74%) had acute leukaemia. Thirty-six (40%) of Magnusiomyces-associated infections occurred during antifungal prophylaxis, mainly with posaconazole (n = 13, 36%) and echinocandins (n = 12, 34%). Instead, the candidemia rarely occurred during prophylaxis (p < .0001). First-line antifungal therapy with azoles, alone or in combination, was associated with improved response compared to other antifungals (p = .001). Overall day-30 mortality rate was 43%. Factors associated with higher mortality rates were septic shock (HR 2.696, 95% CI 1.396-5.204, p = .003), corticosteroid treatment longer than 14 days (HR 2.245, 95% CI 1.151-4.376, p = .018) and lack of neutrophil recovery (HR 3.997, 95% CI 2.102-7.601, p < .001). The latter was independently associated with poor outcome (HR 2.495, 95% CI 1.192-5.222, p = .015). CONCLUSIONS: Magnusiomyces-associated infections are often breakthrough infections. Effective treatment regimens of these infections remain to be determined, but neutrophil recovery appears to play an important role in the favourable outcome.
Asunto(s)
Candidemia , Hematología , Humanos , Femenino , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Masculino , Antifúngicos/uso terapéutico , Candidemia/tratamiento farmacológico , Pronóstico , Equinocandinas/uso terapéuticoRESUMEN
Venetoclax (VEN) and hypomethylating agent (HMAs) regimens are emerging as the standard of care for unfit for chemotherapy acute myeloid leukemia (AML) patients, but the safety and feasibility of a total outpatient management have not been fully investigated. Fifty-nine AML patients with active disease received VEN and HMAs. Nineteen out of 59 (32.2%) patients received the first cycle as inpatients, whereas 40/59 (67.8%) patients were treated in the outpatient setting. No significant differences were observed with regard to incidence of adverse events (AEs), including tumor lysis syndrome (TLS), and the 30-day and 60-day mortality was comparable. Notably, an infectious prophylaxis inspired to that adopted during intensive chemotherapy resulted in a low infection rate with a reduced bacterial infections incidence in out- versus hospitalized patients (p < .0001). The overall time of hospitalization was significantly shorter in patients who received a total outpatient treatment as compared to those who received the first cycle as inpatients (5.9 vs. 39.7 days, p < .0001). Despite the adopted differences in treatment management, the efficacy was similar. These data indicate that a total outpatient management of VEN and HMAs is feasible in AML patients without negatively impacting on treatment efficacy and may yield pharmacoeconomic and quality-of-life benefits.
Asunto(s)
Leucemia Mieloide Aguda , Pacientes Ambulatorios , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes , Comorbilidad , Hospitalización , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/epidemiología , SulfonamidasRESUMEN
Over the past 10 years, the number of targeted therapies for haematological malignancies has substantially increased, and many new drugs have entered the market. Many of these therapies have shown improved disease-free survival and reduced toxicity compared with existing treatments, especially in older patients. However, most of these new drugs undergo extensive hepatic metabolism and exhibit moderate to severe drug-drug interactions with triazole antifungal agents, which are essential for the prophylaxis and long-term treatment of invasive fungal infections. In this Review, we give a comprehensive overview of all known drug-drug interactions between new targeted drugs for haematological malignancies and antifungal drugs, in particular the triazoles. We begin with a general background on drug-drug interactions. Next, we provide a management strategy for the use of each targeted haematological drug, and discuss the possible role of therapeutic drug monitoring for both the triazole and the haematological drugs. This Review aims to provide practical guidance to clinical haematologists on managing the complex interplay between targeted therapies for haematological malignancies and triazole antifungal drugs, to pursue better outcomes for their patients.
Asunto(s)
Neoplasias Hematológicas , Preparaciones Farmacéuticas , Anciano , Antifúngicos/efectos adversos , Interacciones Farmacológicas , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Triazoles/efectos adversosRESUMEN
OBJECTIVE: High-resolution computed tomography (CT) is an essential diagnostic tool for invasive mould disease (IMD) in patients with haematological malignancies but is infrequently performed in the first 72 h of neutropenic fever until after chest X-ray (CXR). We hypothesised that early (< 48 h) low-dose CT (LD-CT; 90% reduction in radiation dose) combined with CT pulmonary angiography (CTPA) to detect the venous occlusion sign (VOS) inside suspected infiltrates could improve IMD diagnosis. METHODS: We prospectively studied 68 consecutive adult patients undergoing treatment for haematological malignancies who developed fever following chemotherapy or haematopoietic stem cell transplantation. Within 48 h of fever, patients underwent a standard CXR followed by LD-CT imaging and CTPA if eligible based on baseline imaging findings; the same protocol was performed in 42/68 (61.7%) of patients at day 7 follow-up. The diagnostic performance of CT signs for EORTC/MSG-defined proven, probable, and possible IMD was analysed at both imaging periods. RESULTS: The baseline LD-CT was positive for abnormalities in 43/68 (63%) of patients within 48 h of fever and 35/42 (83%) of patients at the follow-up exam. Amongst these 43 patients, CTPA was performed in 17/43 (39%) and in 18/35 (51%) at D + 7 follow-up. A positive VOS was associated with the highest estimated positive likelihood ratio for EORTC/MSG-defined proven, probable, or possible IMD at baseline (20.6; 95% CI 1.4-311.2) and at day 7 follow-up (19.0; 95% CI 0.93-300.8) followed by the baseline non-contrast enhanced hypodense sign (18.3; 0.93-361.7), reverse halo (11.0; 0.47-256.5), halo sign (8.68;3.13-24.01) and air-crescent sign at day 7 (16.7; 0.93-301.0). However, a negative VOS was the only CT sign at baseline or day 7 associated with sufficiently low negative likelihood ratio (0.05;0.001-0.8) to possibly support ruling-out IMD in patients with positive CT findings. CONCLUSIONS: Early LD-CT combined with CTPA shows promise for improving the early radiographic diagnosis of IMD.
Asunto(s)
Angiografía , Neoplasias Hematológicas , Diagnóstico Precoz , Neoplasias Hematológicas/complicaciones , Humanos , Proyectos Piloto , Tomografía Computarizada por Rayos XRESUMEN
The effectiveness of ceftolozane/tazobactam for the treatment of infections in neutropenic patients caused by hypervirulent multidrug-resistant (MDR) Pseudomonas aeruginosa has not been previously reported. We identified seven cases of MDR P. aeruginosa infection in neutropenic patients over a four-month period within the same hematology ward. Four cases were associated with rapid progression despite piperacillin-tazobactam or meropenem therapy, and three patients developed sepsis or extensive skin/soft tissue necrosis. In three of the four cases, patients were empirically switched from meropenem to ceftolozane/avibactam before carbapenem susceptibility test results were available, and all four patients underwent extensive surgical debridement or amputation of affected tissues and survived. Further investigation revealed a common bathroom source of MDR P. aeruginosa clonal subtypes ST175 and ST235 that harbored genes for type III secretion system expression and elaboration of ExoU or ExoS exotoxin. We conclude that ceftolozane/tazobactam plus early source control was critical for control of rapidly progressing skin and soft infection in these neutropenic patients caused by highly virulent ST175 and ST235 clones of MDR P. aeruginosa.
RESUMEN
Saprochaete clavata is a rare cause of fungaemia with deep organ involvement in patients with haematological malignancies with reported mortality rates of 60%-80%. We describe four cases of S clavata infection in a haematology unit over several months that were treated with voriconazole-based regimens. We also review the literature on factors that could contribute to earlier recognition and effective treatment of S clavata. We included all cases of culture-positive S clavata from sterile sites with associated signs of infection in patients undergoing treatment for a haematological malignancy. Isolates were identified by MALDI-TOF MS, and spectrum profiles were used to prepare clustering analysis of isolates. Susceptibility testing was performed using a commercial microtitre methods. Saprochaete clavata was isolated from the bloodstream in three cases and bronchial alveolar lavage (BAL) fluid in one case. Clustering analysis suggested strains of S clavata were clonal without evidence of divergence although a common source was not identified. Susceptibility testing yielded elevated MICs to fluconazole (8 mg/L) and echinocandins (>1-8 mg/L). All patients were treated with voriconazole-based regimens resulting in survival of 3/4 patients, who continued chemotherapy for their underlying malignancy without evidence of relapse. Saprochaete clavata is a rare but aggressive cause of breakthrough yeast infection in patients undergoing treatment for haematological malignancies, particularly patients with a prior history of echinocandin treatment. Timely initiation of appropriate treatment, aided by more rapid identification in microbiology laboratory, can reduce the risk of deep organ dissemination and patient death.
Asunto(s)
Fungemia/etiología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/microbiología , Adulto , Anciano , Antifúngicos/uso terapéutico , Brotes de Enfermedades , Femenino , Fungemia/tratamiento farmacológico , Fungemia/microbiología , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/microbiología , Saccharomycetales/efectos de los fármacos , Voriconazol/uso terapéuticoRESUMEN
CT imaging remains an essential diagnostic test for identification, staging and management of invasive mould infection (IMI) in patients with hematological malignancies. Yet the limited specificity of standard CT imaging can drive excessive antifungal use in patients, especially when more definitive diagnosis cannot be established through microbiology or invasive diagnostic procedures. CT pulmonary angiography (CTPA) is a complimentary, non-invasive approach to standard CT that allows for direct visualization of pulmonary arteries inside infiltrates for signs of angioinvasion, vessel destruction and vessel occlusion. Experience from several centers that are using CTPA as part of a standard diagnostic protocol for IMI suggests that a positive vessel occlusion sign (VOS) is the most sensitive and a specific sign of IMI in both neutropenic and non-neutropenic patients. CTPA is particularly useful in patients who develop suspected breakthrough IMI during antifungal prophylaxis because, unlike serum and/or BAL galactomannan and polymerase chain reaction (PCR) testing, the sensitivity is not reduced by antifungal therapy. A negative VOS may also largely rule-out the presence of IMI, supporting earlier discontinuation of empirical therapy. Future imaging protocols for IMI in patients with hematological malignancies will likely replace standard chest X-rays in favor of early low radiation dose CT exams for screening, with characterization of the lesions by CTPA and routine follow-up using functional/metabolic imaging such as 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) to assess treatment response. Hence, enhanced CT imaging techniques can improve the diagnostic-driven management of IMI management in high-risk patients with hematological malignancies.
Asunto(s)
Infecciones Fúngicas Invasoras/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Neoplasias Hematológicas/complicaciones , Humanos , Infecciones Fúngicas Invasoras/complicaciones , Infecciones Fúngicas Invasoras/tratamiento farmacológicoRESUMEN
OBJECTIVE: Our objective was to develop a model that predicts a patient's risk of developing invasive mould disease (IMD) within 60 days of admission for treatment of a haematological malignancy. METHODS: We analysed 19 risk factors for IMD in a cohort of 1944 adult patients with haematological malignancies over 4127 admissions at a haematology referral centre in Northern Italy (2007-2016). We used a multivariable logistic regression to estimate the 60-day probability of developing probable or proven IMD. The model was internally validated using a bootstrap resampling procedure. RESULTS: The prevalence of IMD was 3.3% (90 probable cases, 43 proven cases). Seven risk factors were retained in the final risk model: (1) uncontrolled malignancy, (2) high-risk chemotherapy regimen, (3) high-dose corticosteroids, (4) severe lymphopenia, (5) CMV reactivation or disease, (6) prolonged neutropenia, and (7) a history of previous IMD within 90 days. The model displayed good calibration and discrimination in both the derivation (aROC 0.85, 95% CI 0.84-0.86) and validation (aROC 0.83 95% CI 0.79-0.89) populations. CONCLUSIONS: Our model differentiated with 85% accuracy whether or not patients developed IMD within 60-days of admission. Individualized risk assessment, aided by validated prognostic models, could assist IMD management and improve antifungal stewardship.
Asunto(s)
Neoplasias Hematológicas/complicaciones , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/microbiología , Modelos Teóricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aspergilosis/sangre , Aspergilosis/diagnóstico , Estudios de Cohortes , Femenino , Humanos , Infecciones Fúngicas Invasoras/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Medición de Riesgo/métodos , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
Prognostic models or risk scores are frequently used to aid individualize risk assessment for diseases with multiple, complex risk factors and diagnostic challenges. However, relatively little attention has been paid to the development of risk models for invasive mold diseases encountered in patients with hematological malignancies, despite a large body of epidemiological research. Herein we review recent studies that have described the development of prognostic models for mold disease, summarize our experience with the development and clinical use of one such model (BOSCORE), and discuss the potential impact of prognostic risk scores for individualized therapy, diagnostic and antifungal stewardship, as well as clinical and epidemiological research.
RESUMEN
Objective The aims of the present study were to evaluate the clinical significance of the delay for surgical treatment and the prognostic value of other clinical, pathologic, and microbiological variables among hematologic patients affected by acute invasive fungal rhinosinusitis (AIFRS). Furthermore, we propose our early diagnosis and treatment protocol, reporting its 10-year results. Study Design Monocentric retrospective analysis. Setting The study was conducted from 2001 to 2017 at the University Hospital of Bologna, Italy. Subjects and Methods The impact of time to treatment and clinical, pathologic, and microbiological variables were analyzed among patients with histologically and microbiologically proven AIFRS. The outcomes of patients treated before the introduction of the early diagnosis protocol were compared with those treated afterward. Results Nineteen patients affected by AIFRS were eligible for the study. Treatment delay >4 days ( P = .002), infection caused by Mucorales ( P = .015), and extension of the disease were negative prognostic variables ( P = .017). The application of our protocol significantly reduced the delay for diagnosis and appropriate treatment by an average of 7.3 days ( P = .02). Conclusion The promptness of the diagnosis and surgical treatment may play a significant role in the management of AIFRS, as it appears to be significantly associated with the disease outcome. Our protocol may help to reduce the time required for diagnosis of high-risk hematologic patients.
Asunto(s)
Diagnóstico Precoz , Huésped Inmunocomprometido , Micosis/diagnóstico , Micosis/microbiología , Rinitis/diagnóstico , Rinitis/microbiología , Sinusitis/diagnóstico , Sinusitis/microbiología , Enfermedad Aguda , Adulto , Anciano , Biomarcadores/análisis , Diagnóstico por Imagen , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Micosis/cirugía , Pronóstico , Estudios Retrospectivos , Rinitis/cirugía , Sinusitis/cirugía , Tiempo de TratamientoRESUMEN
OBJECTIVE: The hypodense sign (HyS) on CT imaging is highly suggestive of pulmonary invasive mould disease (IMD) in patients with haematological malignancies, but its diagnostic utility has not been systematically evaluated on contrast-enhanced CT. The objective of this study was to compare the diagnostic performance of the HyS to other common CT findings in a cohort of haematology patients with proven, probable or possible IMD based on European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. METHODS: We analysed the diagnostic performance of the HyS to other common CT signs among 127 neutropenic patients with haematological malignancies submitted to both non-contrast-enhanced and contrast-enhanced CT scans of the lungs, including CT pulmonary angiography. RESULTS: The HyS was detected in 15.7% of patients imaged without contrast, and 44.1% after contrast administration. A contrast-aided HyS was detected in 86.6, 78.0 and 15.5% of patients with European Organization for Research and Treatment of Cancer/Mycoses Study Group proven, probable and possible IMD, respectively. When analysed per clinical diagnosis (proven, probable and highly possible IMD-i.e. no alternative diagnosis to mould disease reached), the contrast-enhanced HyS was as sensitive as the halo sign but significantly more specific [halo sign 0.56, 95% CI (0.39-0.71) vs HyS 0.98, 95% CI (0.87-1.00)]. Only the vessel occlusion sign was more sensitive [0.97, 95% CI (0.91-0.99)] and specific [0.97, 95% CI (0.86-0.99)] than the HyS for IMD diagnosis. CONCLUSION: The high specificity of the HyS strongly supports the diagnosis of pulmonary IMD in neutropenic patients, and is highly suggestive breakthrough fungal disease in patients on mould-active antifungal prophylaxis. Advances in knowledge: This is the first systematic analysis of the hypodense sign on contrast-enhanced CT; the sign can support the diagnosis of IMD when other CT signs are uncertain.
Asunto(s)
Neoplasias Hematológicas/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Medios de Contraste , Femenino , Humanos , Huésped Inmunocomprometido , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Radiografía Torácica , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Fusarium spp. are an uncommon cause of fungaemia in immunocompromised and neutropenic patients that may hematogenously disseminate to the eyes. Herein, we describe a patient with acute lymphoblastic leukaemia and a prior history of extensive corticosteroid exposure who developed disseminated Fusarium solani infection following chemotherapy despite posaconazole prophylaxis. She was successfully treated with combination liposomal amphotericin B and voriconazole, intraocular injections of voriconazole, topical amphotericin B and bilateral vitrectomy. We also review published literature describing the management of endogenous Fusarium endophthalmitis in immunocompromised hosts.
Asunto(s)
Antifúngicos/uso terapéutico , Endoftalmitis/tratamiento farmacológico , Fusariosis/tratamiento farmacológico , Fusarium/efectos de los fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Anfotericina B/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Endoftalmitis/microbiología , Femenino , Fungemia/tratamiento farmacológico , Fungemia/microbiología , Fusariosis/sangre , Fusariosis/microbiología , Fusarium/aislamiento & purificación , Humanos , Huésped Inmunocomprometido , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiología , Pirimidinas/uso terapéutico , Resultado del Tratamiento , Triazoles/administración & dosificación , Voriconazol/uso terapéuticoRESUMEN
We retrospectively examined the incidence, onset, risk factors, and outcomes of renal injury during 103 treatment courses of liposomal amphotericin B (L-AMB) in 97 adult patients with hematological malignancies. All the patients were analyzed before, during, and after the administration of L-AMB, and renal injury was graded according to the RIFLE criteria (risk, injury, failure, loss of function, end-stage renal disease). Most patients (87.3%) received L-AMB at 3 mg/kg of body weight/day. Nearly two-thirds (61.7%) of the treatment courses did not meet any RIFLE category for renal injury, while 19.4% of patients were classified at risk, 13.6% met an injury classification, and 5.8% were categorized as developing renal failure. However, 15% of the patients developed renal injury within 48 h of the onset of multiorgan failure associated with sepsis, bleeding, or progressing malignancy. When these patients were analyzed as a competing risk for L-AMB-associated renal injury (RIFLE category I or above) in a multivariate Cox regression model, receipt of cyclosporine (subhazard ratio [SHR], 2.62; 95% confidence interval [CI], 1.10 to 6.27; P = 0.03), cyclosporine plus furosemide at ≥40 mg/day (SHR, 5.46; 95% CI, 1.89 to 15.74; P = 0.002), or cyclosporine plus foscarnet (SHR, 9.03; 95% CI, 3.68 to 22.14; P < 0.0001) were the only comedications significantly associated with increased rates of renal injury. The cumulative incidence of L-AMB renal injury during the first 10 days of therapy was 7% overall but only 3% in patients who were not receiving cyclosporine. Hence, the renal risk of L-AMB therapy may be lessened if patients are switched to alternative agents after 7 to 10 days or if aggressive diuresis and/or foscarnet is avoided, especially among patients receiving calcineurin inhibitors.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Anfotericina B/efectos adversos , Anfotericina B/uso terapéutico , Antifúngicos/efectos adversos , Antifúngicos/uso terapéutico , Micosis/prevención & control , Adulto , Femenino , Humanos , Riñón/efectos de los fármacos , Riñón/fisiología , Leucemia/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
In neutropenic patients, lungs are involved in 50%-80% of cases of fusariosis, but imaging of pulmonary fusariosis has been previously described as indistinguishable from other invasive mould diseases. Our attempt was to identify a radiological pattern that may distinguish pulmonary fusariosis from other mould diseases. We examined the CT findings of nine neutropenic haematology patients with invasive fusariosis. As control group for comparison, we examined 14 invasive mould diseases (11 aspergillosis, 3 mucormycosis) in haematology patients with similar underlying disease and timing of CT imaging. Chest-CT in invasive fusariosis showed small airways (7/9) or peribronchial (5/9) infiltrates, less frequently macronodular consolidations (4/9) with hypodense sign, but without halo sign or occluded-vessel sign. The control group presented macronodular consolidations with occluded-vessel sign in all of the cases; the halo and the hypodense signs were observed, respectively, in 100% and 82% of aspergillosis, and in 67% and 100% of mucormycosis. Sinusitis was documented by CT in 7/7 fusariosis, 2/2 mucormycosis and 5/7 aspergillosis; maxillary and ethmoid sinuses were involved in 7/7 fusariosis, in most of the cases with hyperdense opacification (rarely observed in the controls). We concluded that no radiological findings can discriminate between different mould infections, but invasive fusariosis should be suspected if chest-CT demonstrates pulmonary infiltrates with the hypodense sign, but without the halo or the occluded-vessel signs. Suspicion is greater in the presence of hyperdense maxillary and ethmoid sinusitis.
Asunto(s)
Fusariosis/diagnóstico por imagen , Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Adulto , Anciano , Aspergilosis/diagnóstico , Diagnóstico Diferencial , Femenino , Fusariosis/tratamiento farmacológico , Fusariosis/microbiología , Fusarium/aislamiento & purificación , Humanos , Huésped Inmunocomprometido , Infecciones Fúngicas Invasoras/diagnóstico por imagen , Pulmón/microbiología , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mucormicosis/diagnóstico , Neutropenia/complicaciones , Neumonía/tratamiento farmacológico , Neumonía/microbiología , Tomografía Computarizada por Rayos XRESUMEN
Mitochondrial neuro-gastro-intestinal encephalomyopathy (MNGIE) is a rare and unavoidably fatal disease due to mutations in thymidine phosphorylase (TP). Clinically it is characterized by gastrointestinal dysfunction, malnutrition/cachexia and neurological manifestations. MNGIE diagnosis remains a challenge mainly because of the complexity and rarity of the disease. Thus, our purposes were to promote a better knowledge of the disease in Emilia-Romagna region (ERR) by creating an accurate and dedicated network; to establish the minimal prevalence of MNGIE in Italy starting from ERR. Blood TP activity level was used as screening test to direct candidates to complete diagnostic work-up. During the study period of 1 year, only 10/71 units of ERR recruited 14 candidates. Their screening did not show TP activity changes. An Italian patient not resident in ERR was actually proved to have MNGIE. At the end of study in Italy there were nine cases of MNGIE; thus, the Italian prevalence of the disease is ~0.15/1,000,000 as a gross estimation. Our study confirms that MNGIE diagnosis is a difficult process which reflects the rarity of the disease and, as a result, a low level of awareness among specialists and physicians. Having available novel therapeutic options (e.g., allogenic hematopoietic stem cell transplantation and, more recently, liver transplantation) and an easy screening test, an early diagnosis should be sought before tissue damage occurs irreversibly.
Asunto(s)
Encefalomiopatías Mitocondriales/epidemiología , Mutación/genética , Adulto , Femenino , Humanos , Italia/epidemiología , Lenguaje , Masculino , Persona de Mediana Edad , Encefalomiopatías Mitocondriales/genética , Timidina Fosforilasa/genética , Adulto JovenRESUMEN
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic diseases, mainly affecting the elderly, characterized by unilinear or multilinear peripheral cytopenia, bone marrow ineffective haemopoiesis, and a varying risk of progression to acute myeloid leukemia (AML). On the basis of the prognostic score systems currently used, MDS patients are generally classified as having higher risk (HR) or lower risk (LR) MDS. Two drugs, azacitidine (AZA) and decitabine (DAC), defined, because of their proven mechanism of action, as DNA methyltransferase inhibitors (DNMTIs), or hypomethylating agents (HMAs), have proven effective in improving peripheral cytopenias and quality of life, reducing or eliminating transfusion need, delaying leukemic evolution, and (only for AZA) prolonging overall survival (OS). HMAs are currently the first therapeutic choice for MDS patients who are not candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT). HMAs have also been used before and after allo-HSCT, but their role in this setting needs to be confirmed by larger studies. Although data from several clinical and biological studies might help to identify patients with a higher probability to respond to HMAs, to date this treatment should not be denied to any HR MDS patient. Several attempts have been made to combine HMAs with other therapeutic agents, and these results await confirmation by further studies.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/análogos & derivados , Azacitidina/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológico , Decitabina , HumanosRESUMEN
This study tested the hypothesis that PI-PLCß1 is associated with myeloid differentiation and that its expression could be useful for predicting the response of MDS patients to azacitidine, as the clinical effect of epigenetic treatments is often detectable only after several cycles of therapy. To this end, PI-PLCß1 was quantified on 70 MDS patients (IPSS risk: 13 Low, 20 Int-1, 31 Int-2, 6 High) at baseline and during the first 3 cycles of azacitidine. Results were then compared with the hematologic response, as assessed after the sixth cycle of azacitidine therapy. Overall, 60 patients completed 6 cycles of azacitidine, and for them, a clinical and molecular evaluation was possible: 37 of these patients (62%) showed a specific increase of PI-PLCß1 mRNA within the first 3 cycles, which was associated with a longer duration of response and with an increased myeloid differentiation, as evidenced by PI-PLCγ2 induction and the recruitment of specific myeloid-associated transcription factors to the PI-PLCß1 promoter during azacitidine response. Moreover, the increase of cyclin D3 gene expression throughout all of the therapy showed that PI-PLCß1-dependent signaling is indeed activated in azacitidine responder patients. Taken together, our results show that PI-PLCß1 quantification in MDS predicts the response to azacitidine and is associated with an increased myeloid differentiation.