Clinical and Cancer-Related Predictors for Venous Thromboembolism in Cancer Patients Presenting to the Emergency Department.

BACKGROUND: The accurate detection of cancer-associated venous thromboembolism (VTE) can avoid unnecessary diagnostic imaging or laboratory tests. OBJECTIVE: We sought to determine clinical and cancer-related risk factors of VTE that can be used as predictors for oncology patients presenting to the emergency department (ED) with suspected VTE. METHODS: We retrospectively analyzed all consecutive patients who presented with suspicion of VTE to The University of Texas MD Anderson Cancer Center ED between January 1, 2009, and January 1, 2013. Logistic regression models were used to identify risk factors that were associated with VTE. The ability of these factors to predict VTE was externally validated using a second cohort of patients who presented to King Hussein Cancer Center ED between January 1, 2009, and January 1, 2016. RESULTS: Cancer-related covariates associated with the occurrence of VTE were high-risk cancer type (odds ratio [OR] 3.64 [95% confidence interval {CI} 2.37-5.60], p < 0.001), presentation within 6 months of the cancer diagnosis (OR 1.92 [95% CI 1.62-2.28], p < 0.001), active cancer (OR 1.35 [95% CI 1.10-1.65], p = 0.003), advanced stage (OR 1.40 [95% CI 1.01-1.94], p = 0.044), and the presence of brain metastasis (OR 1.73 [95% CI 1.32-2.27], p < 0.001). When combined, these factors along with other clinical factors showed high prediction performance for VTE in the external validation cohort. CONCLUSIONS: Cancer risk group, presentation within 6 months of cancer diagnosis, active and advanced cancer, and the presence of brain metastases along with other related clinical factors can be used to predict VTE in patients with cancer presenting to the ED.

Adverse Effects of Immune Checkpoint Therapy in Cancer Patients Visiting the Emergency Department of a Comprehensive Cancer Center.

STUDY OBJECTIVE: Cancer immunotherapy is evolving rapidly and is transforming cancer care. During the last decade, immune checkpoint therapies have been developed to enhance the immune response; however, specific adverse effects related to autoimmunity are increasingly apparent. This study aims to fill the knowledge gap related to the spectrum of immune-related adverse effects among cancer patients visiting emergency departments (EDs). METHODS: We performed a retrospective review of patients treated with immune checkpoint therapy who visited the ED of a comprehensive cancer center between March 1, 2011, and February 29, 2016. Immune-related adverse effects from the ED visits were identified and profiled. We analyzed the association of each immune-related adverse effect with overall survival from the ED visit to death. RESULTS: We identified 1,026 visits for 628 unique patients; of these, 257 visits (25.0%) were related to one or more immune-related adverse effects. Diarrhea was the most common one leading to an ED visit. The proportions of ED visits associated with diarrhea, hypophysitis, thyroiditis, pancreatitis, or hepatitis varied significantly by immune checkpoint therapy agent. Colitis was significantly associated with better prognosis, whereas pneumonitis was significantly associated with worse survival. CONCLUSION: Cancer patients treated with ipilimumab, nivolumab, or pembrolizumab may have a spectrum of immune-related adverse effects that require emergency care. Future studies will need to update this profile as further novel immunotherapeutic agents are added.

Efficacy and safety of daptomycin in the treatment of Gram-positive catheter-related bloodstream infections in cancer patients.

Excessive vancomycin usage has contributed to the emergence of vancomycin-resistant enterococci, and a high vancomycin minimal inhibitory concentration (MIC) >1.0 microg/mL has been associated with poor outcome in patients with meticillin-resistant Staphylococcus aureus (MRSA) infection. In view of these limitations, there is a need for an alternative agent. We evaluated the clinical efficacy and safety of daptomycin given as an alternative agent in the treatment of Gram-positive catheter-related bloodstream infections (CRBSIs) in cancer patients. Between June 2006 and March 2008, 40 patients with probable or definite CRBSI caused by Gram-positive organisms were prospectively enrolled to receive daptomycin intravenous 6 mg/kg/day for up to 4 weeks. In addition, 40 historical matched control patients treated with vancomycin were retrospectively identified. The control group was matched based on underlying disease, organism and neutropenic status. The daptomycin group was comparable with the vancomycin group in terms of neutropenia rate, complications, adverse events, length of hospital stay and death. However, more patients in the daptomycin group achieved symptom resolution at 48h compared with the vancomycin group (76% vs. 53%; P=0.04). Similarly, more patients in the daptomycin group achieved microbiological eradication at 48h compared with the vancomycin group (78% vs. 34%; P<0.001). Although not significant, nephrotoxicity was almost three-fold lower in the daptomycin group. The overall response was significantly better for daptomycin compared with vancomycin (68% vs. 32%; P=0.003). In conclusion, compared with vancomycin, daptomycin treatment of Gram-positive CRBSI in cancer patients was significantly associated with earlier clinical and microbiological response as well as improved overall response.

Legionella pneumonia in cancer patients.

Legionella is an important cause of nosocomial and community-acquired pneumonia in both immunocompetent and immunosuppressed patients worldwide; however, the clinical course and optimal antibiotic therapy of Legionella pneumonia (LP) in patients with cancer is uncertain. We studied retrospectively the risk factors, clinical manifestations, and outcome of 49 cancer patients with a positive Legionella culture or direct fluorescent antibody (DFA) over a 13-year period (1991-2003). The majority of patients (82%) had an underlying hematologic malignancy, and 37% were bone marrow transplant recipients; 80% of the patients had active malignancy. Lymphopenia (47%), use of systemic corticosteroids (41%), and chemotherapy (63%) were the most common underlying conditions. The laboratory diagnosis was established by positive Legionella culture (n = 8, 16%), DFA (n = 29, 59%), or both (n = 12, 25%). In 4 patients (8%), a positive DFA was deemed to represent false-positive results. There was no temporal or geographic clustering of cases. The majority of the cases had multilobar (61%) or bilateral (55%) pulmonary involvement. The mean time to response to therapy was 8 days; 18 patients (37%) developed complications requiring prolonged duration of treatment (mean, 25 d). The case-fatality rate was 31%. Two patients had relapse of LP despite appropriate therapy. Improved outcome, especially in those with severe pneumonia, seemed to correlate with the use of a combination of antibiotics. LP is an uncommon infection in our patient population but is associated with significant morbidity and mortality. Treatment of LP in cancer patients may require a prolonged course with a regimen that includes a newer macrolide or quinolone.

Rapidly growing mycobacteria: clinical and microbiologic studies of 115 cases.

We analyzed clinical and microbiologic features of 115 cases involving rapidly growing mycobacteria (RGM) isolated at the University of Texas M.D. Anderson Cancer Center, Houston (2000-2005) and identified by 16S ribosomal RNA gene sequencing analysis. At least 15 RGM species were included: Mycobacterium abscessus (43 strains [37.4%]), Mycobacterium fortuitum complex (33 strains [28.7%]), and Mycobacterium mucogenicum (28 strains [24.3%]) most common, accounting for 90.4%. Most M abscessus (32/43) were isolated from respiratory sources, whereas most M mucogenicum (24/28) were from blood cultures. Antimicrobial susceptibility tests showed that M abscessus was the most resistant species; M mucogenicum was most susceptible. From blood and catheter sources, 46 strains (40.0%) were isolated; 44 represented bacteremia or catheter-related infections. These infections typically manifested high fever (mean temperature, 38.9 degrees C), with a high number of RGM colonies cultured. All infections resolved with catheter removal and antibiotic therapy. Six strains (M abscessus and M fortuitum only) were from skin, soft tissue, and wound infections. There were 59 strains from respiratory sources, and 28 of these represented definitive to probable infections. Prior lung injuries and coisolation of other pathogenic organisms were common. Overall, 78 RGM strains (67.8%) caused true to probable infections without direct deaths.

Extrapulmonary tuberculosis active infection misdiagnosed as cancer: Mycobacterium tuberculosis disease in patients at a Comprehensive Cancer Center (2001-2005).

BACKGROUND: Extrapulmonary tuberculosis is an uncommon disease in the U.S., even in immunosuppressed cancer patients. This study evaluated characteristics and frequency of extrapulmonary tuberculosis in patients at a tertiary care referral cancer center. METHODS: The records of all consecutive patients with Mycobacterium tuberculosis diagnosed during January 2001 through April 2005 at the M. D. Anderson Cancer Center were reviewed after obtaining institutional review board approval. RESULTS: There were 26 patients with active tuberculosis during the period studied; 18 of them were cancer patients and the others had been referred for a presumed cancer but did not have cancer. The overall rate of active tuberculosis during this period was 0.2 in 1000 new cancer diagnoses. There were 18 men (69%), the median age was 54 years (range, 3-84 yrs), and 16 patients (62%) were born in the U.S. Thirteen (72%) of the 18 cancer patients had solid-organ tumors; 3 of the 5 patients with a hematologic malignancy had non-Hodgkin lymphoma. Three patients (12%) had diabetes mellitus, and 2 patients (8%) had received high-dose (>1 mg/kg of prednisone daily) corticosteroids in the previous week. No patient had a recent history (within the past 4 wks) of chemotherapy; 4 patients had neutropenia. Cough was a prominent symptom (31%), followed by bone pain (19%), dyspnea (15%), and fever (12%). Fifteen patients (58%) had extrapulmonary infection, including 5 patients with concurrent pulmonary involvement; 7 noncancer patients (88%) and 8 cancer patients (44%, P = 0.22) had extrapulmonary disease. In 11 patients (42%), the lungs were the only site of active tuberculosis. Cavitary pneumonia was seen radiographically in 3 of 16 patients (19%) with pulmonary tuberculosis. All M. tuberculosis isolates were susceptible to isoniazid, rifampin, ethambutol, and pyrazinamide; streptomycin resistance was noted in 1 of 22 (5%) isolates tested. Twenty-two patients (85%) received appropriate antituberculosis treatment; all had a clinical and radiographic response. In 3 patients (12%) the cause of death was attributed to M. tuberculosis disease; 2 of 18 cancer patients (11%) died of progressive M. tuberculosis, and they had advanced solid-organ cancer, whereas 1 of 8 patients (13%) without cancer died and the tuberculosis diagnosis was made only on postmortem examination. Univariate analysis showed no significant differences in patients or disease characteristics between non-U.S.-born and U.S.-born patients, whereas noncancer patients (age 52 yrs) and those with extrapulmonary tuberculosis (age 53 yrs) were younger compared with cancer patients (63 yrs; P < 0.007) and those with pulmonary disease (age 60 yrs; P = 0.09). CONCLUSIONS: Extrapulmonary tuberculosis was relatively common in younger patients with active M. tuberculosis infection, and was often initially misdiagnosed as cancer.

Clinical significance and epidemiologic analyses of Mycobacterium avium and Mycobacterium intracellulare among patients without AIDS.

The clinical significance and prevalence of Mycobacterium avium and Mycobacterium intracellulare were analyzed in a cohort of 7,472 patients who, from 1999 to 2003, sought care at the University of Texas M.D. Anderson Cancer Center, Houston, and had cultures performed for mycobacteria. Patients were stratified for age, sex, and underlying diseases, and bacteria were identified by 16S rRNA gene sequencing. M. avium was isolated in 62 (0.83%) of 7,472 patients and M. intracellulare in 65 (0.87%). Clinically, only 10 of the 62 (16.2%) patients with M. avium had probable to definite evidence of infection, whereas the majority (83.8%) had weak evidence of infection. Sex and age did not affect the isolation or infection of M. avium. Hematological tumors predisposed to M. avium colonization but not infection. In contrast, 41 of the 65 (63.1%) patients with M. intracellulare had probable to definite infection, a level much higher than those with M. avium (P < 0.001). M. intracellulare was more prevalent in women (1.33% of 3,311) than in men (0.50% of 4,161) (P < 0.001), and underlying diseases had no effect in women. Men with lung cancer had a higher prevalence (1.37%) than men without (0.34%) (4.0-fold; P < 0.001), but it was similar to that in women. A marked age trend for the isolation of M. intracellulare among women was noted: 0.27% (1-fold) for ages of <50 years, 0.85% (3.1-fold) for ages 50 to 59 years, 1.50% (5.6-fold) for ages 60 to 69 years, and 3.74% (13.9-fold) for ages >/=70 years (trend, P < 0.001). The combined rate for women >/=50 was 1.86% (95% confidence interval [1.30 to 2.42%]) (6.9-fold). Together, these results suggest that, among non-AIDS patients, M. intracellulare is more pathogenic and tends to infect women increasingly beyond menopause (age >/=50 years) regardless of underlying disease. The prevalence rate of 1.86% in postmenopausal women suggests the need to further investigate the public health significance of M. intracellulare.

West Nile encephalitis in 2 hematopoietic stem cell transplant recipients: case series and literature review.

Most human cases of West Nile virus infection are acquired via bites from an infected mosquito. In some cases, infection may also be transmitted by infected blood products or transplanted organs. There have been recent publications suggesting that chemotherapy and immunosuppression may increase a person's risks of developing central nervous system disease if the person is infected with the West Nile virus. Because patients undergoing hematopoietic stem cell transplantation not only are immunocompromised, but also receive multiple blood products, they are at a particularly high risk for acquiring symptomatic disease if exposed to the West Nile Virus. We describe here 2 patients who underwent hematopoietic transplantation at our institution and subsequently developed fatal West Nile virus infections.

Treatment of febrile neutropenic patients with cancer who require hospitalization: a prospective randomized study comparing imipenem and cefepime.

BACKGROUND: The objective of the current study was to compare the efficacy and safety of imipenem and cefepime in the treatment of adult patients with cancer who had fever and neutropenia requiring hospitalization according to Infectious Disease Society of America criteria. METHODS: In the current prospective randomized clinical trial at a university-affiliated tertiary cancer center, adult patients with cancer who had fever (> or = 38.3 degrees C or > or = 38.0 degrees C for > 2 hours) and neutropenia (< or = 500/mm(3) or < 1000/mm(3) but declining) requiring hospitalization were randomized to receive either cefepime or imipenem. Vancomycin or amikacin was added on suspicion of gram-positive or gram-negative bacterial infection, respectively. RESULTS: Patients who received an imipenem regimen or a cefepime regimen were comparable in terms of age, gender, underlying malignancy, prior transplantation, degree and trend of neutropenia, and presence of central venous catheters (P > or = 0.3). An intent-to-treat analysis showed a 68% response rate to the imipenem regimen, compared with a 75% response rate to the cefepime regimen (P = 0.2). The rates of antibiotic-related adverse events and superinfections also were comparable (P = 0.6). There was no difference in response among patients who received imipenem or cefepime alone compared with patients who also received vancomycin or amikacin (P = 1.0). Leukemia was the only independent risk factor associated with a poor outcome (odds ratio, 4.6; 95% confidence interval, 1.9-10.7; P < 0.0001). CONCLUSIONS: Imipenem and cefepime had similar efficacy and safety profiles in the treatment of adult cancer patients with fever and neutropenia who required hospitalization. The addition of either vancomycin or amikacin may not be necessary.