Nelson Spector

Risk factors for death in patients with candidemia.

OBJECTIVE To analyze possible risk factors for death among patients with nosocomial candidemia. To identify risk factors for death in patients with candidemia, we analyzed demographic, clinical, and microbiological data. SETTING Six tertiary hospitals in Brazil. PATIENTS A cohort of 145 patients with candidemia. DESIGN 26 possible risk factors for death, including age, underlying disease, signs of deep-seated infection, neutropenia, number of positive blood cultures, removal of a central venous catheter, etiologic agent of the candidemia, susceptibility pattern of the isolate to amphotericin B, and antifungal treatment were evaluated by univariate stepwise logistic regression analysis. RESULTS Non-albicans species accounted for 63.4% of the candidemias. Risk factors for death in univariate analysis were older age, catheter retention, poor performance status, candidemia due to species other than Candida parapsilosis, hypotension, candidemia due to species other than Candida parapsilosis, and no antifungal treatment. In multivariate analysis, older age and nonremoval of a central venous catheter were the only factors associated with an increased risk for death. CONCLUSIONS These data suggest that patients with candidemia and a central venous catheter should have the catheter removed.

Prognosis of Critically Ill Patients With Cancer and Acute Renal Dysfunction

PURPOSE To evaluate the outcomes of critically ill patients with cancer and acute renal dysfunction. PATIENTS AND METHODS Prospective cohort study conducted at a 10-bed oncologic medical-surgical intensive care unit (ICU) over a 56-month period. RESULTS Of 975 patients, 309 (32%) had renal dysfunction and were studied. Their mean age was 60.9 +/- 15.9 years; 233 patients (75%) had solid tumors and 76 (25%) had hematologic malignancies. During the ICU stay, 98 patients (32%) received dialysis. Renal dysfunction was multifactorial in 56% of the patients, and the main associated factors were shock/ischemia (72%) and sepsis (63%). Overall hospital and 6-month mortality rates were 64% and 73%, respectively. Among patients who required dialysis, mortality rates were lower in patients who received dialysis on the first day of ICU in comparison with those who required it thereafter. In a multivariable Cox model, age more than 60 years, uncontrolled cancer, impaired performance status, and more than two associated organ failures were associated with increased 6-month mortality. Renal function was completely re-established in 82% and partially re-established in 12%, and only 6% of survivors required chronic dialysis. CONCLUSION Acute renal dysfunction is frequent in critically ill patients with cancer. Although mortality rates are high, selected patients can benefit from ICU care and advanced organ support. When evaluating prognosis and the appropriateness of dialysis in these patients, older age, functional capacity, cancer status and the severity of associated organ failures are important variables to take into consideration.

Characteristics and outcomes of cancer patients requiring mechanical ventilatory support for >24 hrs*

Objectives:To describe the characteristics of a large cohort of cancer patients receiving mechanical ventilation for >24 hrs and to identify clinical features predictive of in-hospital death. Design:Prospective cohort study. Setting:Ten-bed oncologic medical-surgical intensive care unit. Patients:A total of 463 consecutive patients were included over a 45-month period. Interventions:None. Measurements and Main Results:Data were collected on the day of admission to the intensive care unit. The intensive care unit and hospital mortality rates were 50% and 64%, respectively. There were 359 (78%) patients with solid tumors and 104 (22%) with hematologic malignancies; 35 (8%) patients had leukopenia. Sepsis (63%), coma (15%), invasion or compression by tumor (11%), pulmonary embolism (7%), and cardiopulmonary arrest (6%) were the main reasons for mechanical ventilation. The independent unfavorable risk factors for mortality were older age (odds ratio, 3.09; 95% confidence interval, 1.61–5.93, for patients 40–70 yrs old, and odds ratio, 9.26; 95% confidence interval, 4.16–20.58, for patients >70 yrs old); performance status 3–4 (odds ratio, 2.51; 95% confidence interval, 1.40–4.51); cancer recurrence/progression (odds ratio, 3.43; 95% confidence interval, 1.81–6.53); Pao2/Fio2 ratio <150 (odds ratio, 2.64; 95% confidence interval, 1.40–4.99); Sequential Organ Failure Assessment score (excluding respiratory domain, each 4 points; odds ratio, 2.34; 95% confidence interval, 1.70–3.24); and airway/pulmonary invasion or compression by tumor as a reason for mechanical ventilation (odds ratio, 5.73; 95% confidence interval, 1.92–17.08). Conclusions:Severity of acute organ failures, poor performance status, cancer status, and older age were the main determinants of mortality. The appropriate use of such easily available clinical characteristics may avoid forgoing intensive care for patients with a chance of survival.

A Double-Blind, Randomized, Placebo-Controlled Trial of Itraconazole Capsules as Antifungal Prophylaxis for Neutropenic Patients

To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B.

Prognosis of Lung Cancer Patients With Life-Threatening Complications

BACKGROUND The management of patients with lung cancer has improved recently, and many of them will require admission to the ICU. The aims of this study were to determine hospital mortality and to identify risk factors for death in a large cohort of critically ill patients. METHODS Cohort study in two ICUs specialized in the management of patients with cancer, in France and Brazil. RESULTS Of the 143 patients (mean age, 61.6 +/- 9.9 years [+/- SD]), 25 patients (17%) had small cell lung cancer and 118 patients (83%) had non-small cell lung cancer. The main reasons for ICU admission were sepsis (44%) and acute respiratory failure (31%). Mechanical ventilation (MV) was used in 100 patients (70%), including 38 patients in whom lung cancer was considered a reason for MV. Hospital mortality was 59% overall and 69% in patients receiving MV. By multivariate logistic regression, airway infiltration or obstruction by cancer, number of organ failures, cancer recurrence or progression, and severity of comorbidities were associated with increased mortality. CONCLUSIONS The improved survival previously reported in patients with cancer admitted to the ICU seems to extend to patients with lung cancer, including those who need MV. Mortality increased with the number of organ failures, severity of comorbidities, and presence of respiratory failure due to cancer progression. The type of the cancer per se was not associated with mortality and, therefore, should not be factored into ICU triage decisions.

Lack of association of tumor-associated macrophages with clinical outcome in patients with classical Hodgkin's lymphoma

BACKGROUND A recent study demonstrated that an increased number of CD68+ macrophages were correlated with primary treatment failure, shortened progression-free survival (PFS) and disease-specific survival (DSS) in patients with classical Hodgkins lymphoma (cHL). PATIENTS AND METHODS The aim of the present study was to verify the relationship between the number of CD68+ and CD163+ macrophages with clinical outcomes in a cohort of 265 well-characterized patients with cHL treated uniformly with the standard doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy regimen. Two pairs of hematopathologists carried out independent pathological evaluations of tissue microarray slides. RESULTS There were no associations between clinical characteristics and the expression of CD68 or CD163. However, higher levels of CD68 and CD163 expression were correlated with the presence of Epstein-Barr virus-positive Hodgkin tumor cells (P = 0.01 and 0.037, respectively). The expression of CD68 or CD163 was not associated with either the PFS or the DSS. CONCLUSION CD68 and CD163 expression require further evaluation before their use can be recommended for prognostic stratification of patients with cHL.BACKGROUND A recent study demonstrated that an increased number of CD68+ macrophages were correlated with primary treatment failure, shortened progression-free survival (PFS) and disease-specific survival (DSS) in patients with classical Hodgkins lymphoma (cHL). PATIENTS AND METHODS The aim of the present study was to verify the relationship between the number of CD68+ and CD163+ macrophages with clinical outcomes in a cohort of 265 well-characterized patients with cHL treated uniformly with the standard doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy regimen. Two pairs of hematopathologists carried out independent pathological evaluations of tissue microarray slides. RESULTS There were no associations between clinical characteristics and the expression of CD68 or CD163. However, higher levels of CD68 and CD163 expression were correlated with the presence of Epstein-Barr virus-positive Hodgkin tumor cells (P = 0.01 and 0.037, respectively). The expression of CD68 or CD163 was not associated with either the PFS or the DSS. CONCLUSION CD68 and CD163 expression require further evaluation before their use can be recommended for prognostic stratification of patients with cHL.

Short- and Long-term Outcomes of Critically Ill Patients With Cancer and Prolonged ICU Length of Stay

BACKGROUND Data on patients with cancer who have a prolonged length of stay (LOS) in the ICU are scarce. The aim of the present study was to evaluate the characteristics and the outcomes of cancer patients with life-threatening complications with an ICU stay > or = 21 days. METHODS A cohort study performed at a 10-bed oncology medical-surgical ICU from May 2000 to December 2005. Prolonged ICU LOS was defined as an ICU stay > or = 21 days. RESULTS During the period, 1,090 patients were admitted to the ICU and 163 patients (15%) had a prolonged ICU LOS. These patients, however, accounted for 48% (5,828/12,224) of the total ICU bed-days. The hospital and 6-month mortality rates were 50% and 60%, respectively, and similar to patients with ICU LOS < 21 days (51% and 61%, respectively). ICU-acquired events and complications were common, and the most frequent were infections (90%), mechanical ventilation (99%), and need for vasopressors (88%). The number of organ failures, older age, and poor performance status were the main outcome predictors. The median long-term follow-up after hospital discharge was 537 days (range, 193 to 1,119 days), and 29 patients (18%) were alive. CONCLUSIONS Fifteen percent of critically ill patients with cancer had a prolonged ICU LOS. Short- and long-term survival rates were reasonable, and the prognosis was better than expected a priori. In our opinion, the length of ICU admission per se should not be used in the clinical decisions regarding the continuation of treatment in these patients.

Risk Factors for Death Among Cancer Patients with Fungemia

In order to identify prognostic factors for death among cancer patients with fungemia, an 18-month survey of fungemia in patients with cancer was undertaken in three hospitals in Rio de Janeiro. For the assessment of risk factors for death, the following variables were analyzed: age; gender; underlying cancer; last treatment for the underlying disease; previous surgery; use of antibiotics, antifungal agents, steroids, or total parenteral nutrition; use of a central venous catheter; chemotherapy; radiotherapy; presence and duration of neutropenia; etiologic agent of the fungemia; treatment of the fungemia; clinical manifestations; and performance status (Karnofsky score) on the day of the positive blood culture. In multivariate analysis, the variables associated with an increased risk for death were older age, persistent neutropenia, and low performance status. Identifying risk factors for death may help to define a group-risk patients for whom new therapeutic options should be tried.

CD10 and Bcl-2 expression combined with the International Prognostic Index can identify subgroups of patients with diffuse large-cell lymphoma with very good or very poor prognoses

Aims : Diffuse large B‐cell lymphoma (DLBCL) is characterized by marked biological heterogeneity. The identification of reproducible parameters that can be combined with the International Prognostic Index (IPI) to better predict outcome could lead to the development of effective risk‐adaptive strategies.

Granulocytic sarcoma of the small intestine with CBFβ/MYH11 fusion gene: report of an aleukaemic case and review of the literature

Granulocytic sarcomas (GS) are rare extramedullary tumours composed of immature myeloid cells. Inversion of chromosome 16 [inv(16)] is a cytogenetic marker for M4Eo subtype of acute myeloid leukaemia (AML). The possibility of an association between the development of granulocytic sarcoma of the small intestine (GSSI) and the M4Eo subtype of AML was suggested in nine previous case reports. Here we report an aleukaemic case of GSSI with inv(16) and its molecular equivalent, the CBFbeta/MYH11 fusion gene, detected by reverse transcriptase-polymerase chain reaction (RT-PCR), that after treatment with conventional AML chemotherapy followed by autologous bone marrow transplantation, achieved complete haematological and molecular remission on bone marrow examination. After chemotherapy, a thickened ileum wall positive for CBFbeta/MYH11 on tumour mass samples was still observed on computed tomography (CT) studies, raising the question of residual GS representing a reservoir of malignant cells. This case demonstrates the critical need of multidisciplinary diagnosis and follow-up of this entity combining immunopathologic, cytogenetic and molecular studies, reinforcing the potentiality of risk-adapted therapy strategies, as it is increasingly claimed for patients with overt AML.