Use of inflammatory molecules to predict the occurrence of fever in onco-hematological patients with neutropenia

Febrile neutropenia remains a frequent complication in onco-hematological patients, and changes in the circulating level of inflammatory molecules (IM) may precede the occurrence of fever. The present observational prospective study was carried out to evaluate the behavior of plasma tumor necrosis factor alpha (TNF-α), soluble TNF-α I and II receptors (sTNFRI and sTNFRII), monocyte chemoattractant protein-1 [MCP-1 or chemokine (c-c motif) ligand 2 (CCL2)], macrophage inflammatory protein-1α (MIP-1α or CCL3), eotaxin (CCL11), interleukin-8 (IL-8 or CXCL8), and interferon-inducible protein-10 (IP-10 or CXCL10) in 32 episodes of neutropenia in 26 onco-hematological patients. IM were tested on enrollment and 24-48 h before the onset of fever and within 24 h of the first occurrence of fever. Eight of 32 episodes of neutropenia did not present fever (control group) and the patients underwent IM tests on three different occasions. sTNFRI levels, measured a median of 11 h (1-15) before the onset of fever, were significantly higher in patients presenting fever during follow-up compared to controls (P = 0.02). Similar results were observed for sTNFRI and CCL2 levels (P = 0.04 for both) in non-transplanted patients. A cut-off of 1514 pg/mL for sTNFRI was able to discriminate between neutropenic patients with or without fever during follow-up, with 65% sensitivity, 87% specificity, and 93% positive predictive value. Measurement of the levels of plasma sTNFRI can be used to predict the occurrence of fever in neutropenic patients.

Aerosolised pentamidine for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome

The goal of this study was to evaluate inhaled pentamidine for the treatment of patients with mild and moderate Pneumocystis carinii pneumonitis. Eight adults with AIDS and pneumocystis pneumonia (4 with a first episode and 4 with a repeat pneumocystosis) received daily inhalations of aerosol pentamidine isethionate for 21 days. Six patients were treated with doses of 300 mg of pentamidine and the remaining 2 received 600 mg every day. In the 300 mg treatment group, 2 individuals showed discrete and transient neutropenia. However, both subjects that received 600 mg of aerosol pentamidine daily developed leukopenia. One of them had major toxicity (overall severe intolerance of 12.5%) that required drug discontinuation and did not allow any analysis of the treatment efficacy. Of the 7 evaluable patients, 6 (88%) completed the treatment successfuly. One subject of the 300 mg regimen experienced an early recurrence. In conclusion, inhaled pentamidine is an effective treatment for mild and moderate cases of P. carinii pneumonia. It is less toxic than standard anti-pneumocystis therapy and is suitable for outpatient use.

Fungal infections in neutropenic patients: a 8-year prospective study

In this paper we report a eight-year prospective study designed to further characterize incidence, epidemiology, specific syndromes, treatment and prognosis associated with fungal infections in neutropenic patients. During the study period 30 fungal infections were diagnosed in 30 patients among 313 episodes of fever and neutropenia (10%). There were 15 cases of candidiasis, 5 pulmonary aspergillosis, 3 sinusitis by Aspergillus fumigatus, 5 infections by Fusarium sp., one infection by Trichosporon sp., and one infection due to Rhodotorula rubra. Blood cultures were positive in 18 cases (60%). The predisposing factors for fungal infection in multivariate analysis were the presence of central venous catheter (p<0.001), longer duration of profound (<100/mm³) neutropenia (p<0.001), the use of corticosteroids (p<0.001), gram-positive bacteremia (p=0.002) and younger age (p=0.03). In multivariate analysis only recovery of the neutropenia (p<0.001) was associated with good prognosis whereas the diagnosis of infection by Fusarium sp. (p=0.006) was strongly associated with a poor outcome. The death rate was 43%. There was no statistically significant difference in the death rate between patients who did receive (52%) or did not receive (50%) antifungal treatment. Identifying patients at risk, specific syndromes and prognostic factors may help to reduce the high mortality associated with disseminated fungal infections in neutropenic patients.

CRYPTOSPORIDIOSIS IN PEDIATRIC PATIENTS

Cryptosporidium was detected in 21 (3.8%) individual stool samples collected from 553 pediatric patients hospitalized in our center employing a Telemann concentration technique (formalinethercentrifugation) and stained with the modified Kinyoun method. The mean age of populations with Cryptosporidiosis (16 boys and 5 girls) was 11 months; 15 months for girls and 6.5 for boys. Ages of 81% of them were less than 19 months. Seventysix per cent of patients lived on the outskirts of Buenos Aires and 71% lacked pretreated running water at home. In 62% of the cases parasitological diagnoses coincided with warm seasons. At diagnosis mucous (63%) or watery (36%) diarrhea was presented in 90% of the patients with a median of 5 (38) bowel movements per day. Fever was presented in 66% of patients while abdominal pain and vomits in 60% and 52%, respectively. The median time from hospitalization up to parasitologic diagnosis was 20 days. Concomitant diseases observed were malnutrition, acute leukemia, bronchiolitis, HIV infection, anemia, celiac disease, myelofibrosis, vitelline sac tumor, neutropenia, osteosarcoma and dehydration. Cryptosporidiosis in our environment seems to occur more frequently in children younger than 18 months of age; who present diarrhea; are immunodeficient; come from a low socioeconomical background; and who live in poor sanitary conditions with no potable running water.

Primary aspergilloma and subacute invasive aspergillosis in two AIDS patients

Although uncommon, invasive aspergillosis in the setting of AIDS is important because of its peculiar clinical presentation and high lethality. This report examines two AIDS patients with a history of severe cellular immunosuppression and previous neutropenia, who developed subacute invasive aspergillosis. One female patient developed primary lung aspergilloma, with dissemination to the mediastinum, vertebrae, and spine, which was fatal despite antifungal treatment. The second patient, who had multiple cavitary brain lesions, and eye and lung involvement, recovered following voriconazole and itraconazole, and drugs for increasing neutrophil and CD4+ lymphocyte levels. These cases demonstrate the importance of Aspergillus infections following neutropenia in AIDS patients, and emphasize the need for early and effective antifungal therapy.

INCIDENCE OF DIARRHEA BY Clostridium difficile IN HEMATOLOGIC PATIENTS AND HEMATOPOIETIC STEM CELL TRANSPLANTATION PATIENTS: RISK FACTORS FOR SEVERE FORMS AND DEATH

We describe the rate of incidence of Clostridium difficile-associated diarrhea (CDAD) in hematologic and patients undergone stem cell transplant (HSCT) at HC-FMUSP, from January 2007 to June 2011, using two denominators 1,000 patient and 1,000 days of neutropenia and the risk factors associated with the severe form of the disease and death. The ELISA method (Ridascreen-Biopharm, Germany) for the detections of toxins A/B was used to identify C. difficile. A multivariate analysis was performed to evaluate potential factors associated with severe CDAD and death within 14 days after the diagnosis of CDAD, using multiple logistic regression. Sixty-six episodes were identified in 64 patients among 439 patients with diarrhea during the study period. CDA rate of incidence varied from 0.78 to 5.45 per 1,000 days of neutropenia and from 0.65 to 5.45 per 1,000 patient-days. The most common underlying disease was acute myeloid leukemia 30/64 (44%), 32/64 (46%) patients were neutropenic, 31/64 (45%) undergone allogeneic HSCT, 61/64 (88%) had previously used antibiotics and 9/64 (13%) have severe CDAD. Most of the patients (89%) received treatment with oral metronidazole and 19/64 (26%) died. The independent risk factors associated with death were the severe form of CDAD, and use of linezolid.

Febre de origem indeterminada em adultos

A febre de origem indeterminada clássica é definida pela presença de temperatura axilar maior do que 37,8ºC, em várias ocasiões, pelo tempo mínimo de três semanas e que se mantém sem causa aparente após uma semana de investigação hospitalar. Tal conceito vem sofrendo alterações com o tempo e em decorrência das inovações médicas. Em resposta à evolução do conhecimento e às pressões ambientais, os casos de febre de origem indeterminada são atualmente classificados em quatro síndromes: clássica, nosocomial, no neutropênico, e no paciente infectado pelo vírus da imunodeficiência humana. No presente artigo procuramos definir e atualizar as informações sobre o assunto.

Is severe visceral leishmaniasis a systemic inflammatory response syndrome? A case control study

INTRODUCTION: The objective of the study is to identify the main risk factors for death by New World visceral leishmaniasis and establish a coherent pathogenic substrate of severe disease based on clinical findings. METHODS: Seventy-six deceased inpatients and 320 successfully treated inpatients with VL were studied in a case control study. RESULTS: Bacterial infection and bleeding were mutually exclusive events leading to death. Five risk factors were unique for death by bacterial infection (malnutrition, pulmonary rales, severe anemia, severe absolute neutropenia and higher neutrophil count), while another six were unique for death by bleeding (jaundice, severe relative neutropenia, severe thrombocytopenia, liver injury, kidney failure, higher bone marrow parasite load). Bacterial infection, bleeding, severe anemia, diarrhea, dyspnea, edema, jaundice and bone marrow parasite load were the main syndromes of visceral leishmaniasis among successfully treated patients. CONCLUSIONS: The data support the idea that bacterial infections are due to immune paralysis. Broad organ and system involvement is plausibly due to the high production of proinflammatory cytokines, whose actions fit well with visceral leishmaniasis. The syndromes and causative mediators are typical of a slowly developing systemic inflammatory response syndrome.

Clinical and laboratory alterations in dogs naturally infected by Leishmania chagasi

INTRODUCTION: Canine visceral leishmaniasis (CVL) is a zoonotic disease with different clinical manifestations. Parasitism often occurs in bone marrow, but changes have been observed in peripheral blood and serum biochemical parameters. The aim of this study was to evaluate the hematological and biochemical parameters in dogs naturally infected by Leishmania chagasi. METHODS: Eighty-five adult dogs of both sexes and various weights and ages from the Zoonosis Control Center of Fortaleza (CCZ) were used, selected by immunofluorescence assay (IFA) and considered positive with IFA titers greater than 1:40 and by visualizing amastigotes of Leishmania chagasi in smears obtained by bone marrow aspiration. The dogs (n = 85) were grouped according to clinical signs: negative (CN = 7), subclinical (CS = 10), and clinical (CC = 68). Blood samples were collected for determination of hematological and biochemical serum values. The experimental protocol was approved by the CEUA/UECE. RESULTS: The most frequent clinical signs were cachexia (77.9%), keratitis (61.8%), and lymphadenopathy (55.9%), and 86.8% of the animals showed more than one clinical sign characteristic of CVL. In CC were observed reductions in red blood cells (63%), hematocrit (72%), and hemoglobin (62%), as well as leukocytosis (33%), neutropenia (28%), thrombocytopenia (50%), uremia (45%), hyperproteinemia (53%, p<0.05), hypergammaglobulinemia (62%, p<0.01), and hypoalbuminemia (58%). CONCLUSIONS: Animals with the clinical form of the disease demonstrate hematological and biochemical changes consistent with anemia, uremia, hyperproteinemia, and hyperglobulinemia, which present themselves as strong clinical markers of visceral leishmaniasis associated with the signs previously reported.

Factors of poor prognosis of visceral leishmaniasis among children under 12 years of age. A retrospective monocentric study in Belo Horizonte, State of Minas Gerais, Brazil, 2001-2005

INTRODUTION: A major concern with the visceral leishmaniasis (VL) is its high lethality rate, even with proper treatment. Low age, prior malnutrition, disease duration prior to diagnosis, severe anemia, fever for more than 60 days, diarrhea and jaundice are known poor prognostic factors. The goals of this study are to describe the clinical and laboratory characteristics of VL among children under 12 years of age and to identify the factors associated with VL poor outcome. METHODS: Two hundred and fifty children under 12 years of age with confirmed VL admitted to Hospital João Paulo II (FHEMIG), Belo Horizonte, Brazil, between January 2001 and December 2005 were evaluated retrospectively. The primary outcome was the poor clinical evolution: sepsis, and/or pneumonia, and/or urinary tract infection, and/or of bleeding (expect epistaxis), and/or severe neutropenia (neutrophil < 500 cells/mm3). Odds ratio (crude and adjusted) and its 95% confidence interval for each variable were calculated. Values less than 0.05 were considered significant. RESULTS: Average age was 3.3 years (3.6 months-11.6 years), 71.2% were younger than 5 years and 47.2% lived in Metropolitan Area of Belo Horizonte. The mean fatality rate was 3.6%. Sixty-six (26.4%) patients presented poor evolution. After a multivariate analysis, age <18 months, abnormal respiratory physical examination on hospital admission, and platelets <85,000/mm3 remained associated with increased chance of poor evolution. CONCLUSIONS: The results suggest that patients aged between 12 and 18 months, with platelet counts bellow 85,000/mm3, and respiratory abnormalities at admission should be considered potentially severe.

Case report of vancomycin-induced pancytopenia

Abstract: Vancomycin is the first-line agent for the treatment of bacteremia, endocarditis, pneumonia, cellulitis, and osteomyelitis. Pancytopenia is an uncommon adverse effect of vancomycin therapy, with only a few cases of vancomycin-related neutropenia and pancytopenia described in the literature. We describe a case of a 56-year-old man who was diagnosed with chronic paraspinal abscess and started on intravenous vancomycin. He was re-admitted two weeks later with new-onset pancytopenia. Discontinuation of vancomycin resulted in improved cell counts. Physicians should monitor cell counts in patients who are on long-term intravenous vancomycin.

Chemotherapy versus best supportive care in stage IV non-small cell lung cancer, non metastatic to the brain

Stage IV non-small cell lung cancer is a fatal disease, with a median survival of 14 months. Systemic chemotherapy is the most common approach. However the impact in overall survival and quality of life still a controversy. OBJECTIVES: To determine differences in overall survival and quality of life among patients with stage IV non-small cell lung cancer non-metastatic to the brain treated with best supportive care versus systemic chemotherapy. PATIENTS: From February 1990 through December 1995, 78 eligible patients were admitted with the diagnosis of stage IV non-small cell lung cancer . Patients were divided in 2 groups: Group A (n=31 -- treated with best supportive care ), and Group B (n=47 -- treated with systemic chemotherapy). RESULTS: The median survival time was 23 weeks (range 5 -- 153 weeks) in Group A and 55 weeks (range 7.4 -- 213 weeks) in Group B (p=0.0018). In both groups, the incidence of admission for IV antibiotics and need of blood transfusions were similar. Patients receiving systemic chemotherapy were also stratified into those receiving mytomycin, vinblastin, and cisplatinum, n=25 and those receiving other combination regimens (platinum derivatives associated with other drugs, n=22). Patients receiving mytomycin, vinblastin, and cisplatinum, n=25 had a higher incidence of febrile neutropenia and had their cycles delayed for longer periods of time than the other group. These patients also had a shorter median survival time (51 versus 66 weeks, p=0.005). CONCLUSION: In patients with stage IV non-small cell lung cancer, non-metastatic to the brain, chemotherapy significantly increases survival compared with best supportive care.

Fibroelastoma of the mitral valve as a cause of transient ischemic stroke

A 44-year-old woman had a transient ischemic stroke, fibroelastoma of the mitral valve being the source of the embolus. The patient evolved with neutropenia induced by ticlopidine after 10 days of treatment. We report the major clinical features, therapeutical options, and medicamentous toxicity resulting from the use of antiplatelet drugs.

Comprometimento pulmonar nas leucemias: avaliação por tomografia computadorizada de alta resolução

OBJETIVO: Avaliar o papel da tomografia computadorizada de alta resolução (TCAR) no estudo de pacientes com leucemia e sintomas pulmonares, analisar os principais padrões encontrados e definir sua etiologia. MATERIAIS E MÉTODOS: Foi feito estudo retrospectivo das TCAR de 15 pacientes com diagnóstico confirmado de leucemia, em vigência de sintomas respiratórios. Os exames foram feitos com protocolo de alta resolução espacial, sendo avaliados por dois radiologistas, de forma independente. RESULTADOS: Os principais padrões observados foram: atenuação em vidro fosco (n = 11), consolidação (n = 9), nódulos do espaço aéreo (n = 3), espessamento de septos interlobulares (n = 3), padrão de árvore em brotamento (n = 3) e derrame pleural (n = 3). A infecção pulmonar foi o achado mais comum, observado em 12 pacientes, com a seguinte freqüência: pneumonia bacteriana (n = 6), infecção fúngica (n = 4), tuberculose pulmonar (n = 1) e infecção viral (n = 1). Os outros três pacientes mostraram infiltração leucêmica pleural (n = 1), linfoma (n = 1) e hemorragia pulmonar (n = 1). CONCLUSÃO: Concluiu-se que a TCAR é de grande importância na avaliação de pacientes com leucemia e neutropenia, com o objetivo de sugerir a causa do quadro pulmonar, avaliar a sua extensão e, em alguns casos, orientar procedimentos invasivos.

Resultados maternos e perinatais em gestantes portadoras de leucemia

RESUMO OBJETIVO: Descrever as complicações maternas e os resultados perinatais entre as gestantes com diagnóstico de leucemia que foram acompanhadas no pré-natal e no parto em hospital universitário. MÉTODOS: Estudo retrospectivo do período de 2001 a 2011, que incluiu 16 gestantes portadoras de leucemia acompanhadas pela equipe de pré-natal especializado em hemopatias e gestação. Nas leucoses agudas, diagnosticadas após o primeiro trimestre, a recomendação foi realizar a quimioterapia apesar da gestação em curso. Nas gestantes com leucoses crônicas, quando controladas do ponto de vista hematológico, foram mantidas sem medicação durante a gravidez, ou, foi introduzida terapêutica antineoplásica após o primeiro trimestre. Foram analisadas as complicações maternas e os resultados perinatais. RESULTADOS: A leucemia linfoide aguda (LLA) foi diagnosticada em cinco casos (31,3%), a leucemia mieloide aguda (LMA) em dois casos (12,5%) e a leucemia mieloide crônica (LMC) em nove casos (56,3%). Nos casos de leucemias agudas, dois (28,6%) casos foram diagnosticados no primeiro trimestre, dois (28,6%) no segundo e três (42,9%) no terceiro. Duas gestantes com LLA diagnosticada no primeiro trimestre optaram pelo aborto terapêutico. Quatro casos de leucemia aguda receberam tratamento quimioterápico na gestação, com diagnóstico estabelecido após a 20ª semana. Em um caso de LLA com diagnóstico tardio (30ª semana) a quimioterapia foi iniciada após o parto. Todas as gestantes com leucemia aguda evoluíram com anemia e plaquetopenia, quatro casos (57,1%) evoluíram com neutropenia febril. Das gestantes com LMC, quatro utilizavam mesilato de imatinibe quando engravidaram, três delas suspenderam no primeiro trimestre e uma no segundo. Durante a gravidez, três (33,3%) não necessitaram de terapêutica antineoplásica após suspensão do imatinibe; e em seis (66,7%) foram utilizadas as seguintes drogas: interferon (n=5) e/ou hidroxiureia (n=3). No grupo de gestantes com LMC, verificou-se a ocorrência de anemia em quatro casos (44,4%) e plaquetopenia em um (11,1%). Quanto aos resultados perinatais, nas gestações complicadas pela leucemia aguda, a média da idade gestacional no parto foi de 32 semanas (desvio padrão - DP=4,4) e a média do peso do recém-nascido foi 1476 g (DP=657 g). Houve 2 (40,0%) óbitos perinatais (um fetal e um neonatal). Nas gestações complicadas pela LMC, a média da idade gestacional no parto foi de 37,6 semanas (DP=1,1) e a média do peso do recém-nascido foi 2870 g (DP=516 g); não houve morte perinatal e nenhuma anomalia fetal foi detectada. CONCLUSÕES: É elevada a morbidade materna e fetal nas gestações complicadas pela leucemia aguda; enquanto que, nas complicadas pela LMC, o prognóstico materno e fetal parece ser mais favorável, com maior facilidade no manejo das complicações.