Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a clinical non-trial setting, the efficacy and safety of caspofungin was compared with liposomal amphotericin B for the management of febrile neutropenia or invasive fungal infections in 73 episodes in patients with haematological malignancy. There were fewer episodes of drug toxicity with caspofungin than liposomal amphotericin B (58.3 vs 83.7 %, P=0.02). The favourable response rate for episodes of febrile neutropenia treated with caspofungin or liposomal amphotericin B was similar at 37.5 and 53.8 %, respectively, but more breakthrough fungal infections occurred with caspofungin than with liposomal amphotericin B (33.3 vs 0 %, P<0.05) in these patients who did not receive antifungal prophylaxis. None of four episodes of candidaemia or hepatosplenic candidiasis responded to caspofungin compared with three of four episodes treated with liposomal amphotericin B. Mortality was significantly higher with caspofungin treatment compared with liposomal amphotericin B (6/24 vs 2/49, P=0.01), mainly due to an excess of fungal infections (P=0.04). Caspofungin treatment was a significant independent predictor of mortality [odds ratio=7.6 (95 % confidence interval 1.2-45.5)] when sepsis severity, prolonged neutropenia and length of antifungal therapy were considered in a multiple logistic regression model. In clinical practice, there is a suggestion that caspofungin may not be as effective as liposomal amphotericin B in preventing breakthrough invasive fungal infections in febrile neutropenia or in preventing fungus-related deaths. Because of the potential biases in this observational study, these preliminary findings should be interpreted with caution and clarified with a larger cohort of patients.
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PMID:An open study of the comparative efficacy and safety of caspofungin and liposomal amphotericin B in treating invasive fungal infections or febrile neutropenia in patients with haematological malignancy. 1700 84

We investigated the feasibility of reduced-intensity conditioning with 4 Gy total body irradiation, fludarabine (30 mg/m2 for 6 days), and busulfan (4 mg/kg for 2 days) for bone marrow transplantation from a serologically HLA-matched unrelated donor. Seventeen adult patients (median age, 55 years; range, 27-67 years) with various hematologic malignancies (6 in remission, 11 not in remission) were treated. Successful engraftment was achieved in all patients at a median of day 18 (range, day 14-35) after transplantation, although subsequent secondary graft failure was observed in 2 patients. The cumulative incidence of acute graft-versus-host disease (GVHD) of grades II to IV at day 100 was 48%. With a median follow-up of 286 days (range, 56-687 days), the rates of 1-year overall survival, 100-day nonrelapse mortality, and 1-year nonrelapse mortality were 41%, 14%, and 46%, respectively. Eleven patients died, and the causes of death were relapse (n = 4), pulmonary complications (n = 4), acute GVHD (n = 2), and sepsis (n = 1). The remaining 6 patients (at transplantation, 2 were in remission, and 4 were not in remission) are currently still in remission. These results suggest that this regimen reduces the risk of graft failure, but further studies are needed to ameliorate transplantation-related toxicities, primarily GVHD and/or pulmonary complications.
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PMID:Unrelated-donor bone marrow transplantation with a conditioning regimen including fludarabine, busulfan, and 4 Gy total body irradiation. 1748 64

The cytokines interleukin-1 (IL-1alpha and IL-1beta) and the tumor necrosis factor-alpha (TNF-alpha) both play a major role in the initiation and regulation of inflammation and immunity responses. Polymorphisms within the gene sequences of these cytokines IL-1 and TNF-alpha have been proposed to play an important role in the pathogenesis of certain diseases. Affecting nearly every organ, various diseases, including some cancers, are described to be associated with an increased level of IL-1 and TNF-alpha proteins, for example, solid tumors, hematologic malignancies, malignant histiocytosis, autoimmune disorders, Alzheimer's disease, Parkinson's disease, sepsis, and rheumatoid arthritis. Regarding genetic backgrounds and pathways, numerous canine diseases show close similarities to their human counterparts. As a genetic model, the dog could be used to unravel the genetic mechanisms, for example, in particular the predispositions, the development, and progression of cancer and metabolic diseases. The identity comparison of gene and protein sequences of different species could be used to elucidate the structure and function of the genes and proteins by identifying the evolutionary conserved regions and domains. Herein we analyzed in detail the mRNA and protein structures and identities of the present known mammalian (human, canine, murine, rat, ovine, equine, feline, porcine, and bovine) TNF-alpha, IL-1alpha, and IL-1beta mRNAs and proteins. Additionally, based on the canine genome sequence, we derived in silico the complete mRNA structures of the IL-1alpha and IL-1beta mRNAs.
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PMID:Comparison of the human and canine cytokines IL-1(alpha/beta) and TNF-alpha to orthologous other mammalians. 1757 84

There are reports of patients with sickle cell disease who developed hematological malignancies but the relationship between these malignancies and sickle cell disease (SCD) is not yet defined. The co-existence of a hematological malignancy with SCD poses certain challenges for the management of each condition. We describe a 7-year-old boy with sickle cell anemia who developed Hodgkin's lymphoma and the challenges of management. He presented with a 4-year history of bilateral neck swelling and a 2-month history of weight loss and high-grade fever. Histology of a lymph node biopsy was consistent with mixed cellularity Hodgkin's lymphoma. He was treated with five cycles of Cyclophosphamide, Vincristine, Procarbazine and Prednisolone (COPP) and had complete clinical response. Chemotherapy was associated with an increase in frequency of painful crises and complicated by septicaemia. Blood transfusion needs were minimal; apart from the transfusion preceding the first cycle of chemotherapy, there was no need for further transfusion. Myelosuppression was not a problem in the patient; he responded well to antibiotics during the two episodes of septicemia without the use of hemopoetic growth factor. Patients with sickle cell anaemia who develop Hodgkin's lymphoma can be successfully treated with chemotherapy along with supportive management for crises and infections.
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PMID:Hodgkin lymphoma in a child with sickle cell anemia. 1778 89

Nucleosomes, complexes of DNA and histone proteins, are released during cell death into the blood circulation. Elevated serum and plasma levels have been found in various forms of cancer, but also in autoimmune diseases and acute situations such as stroke, trauma, and during sepsis. Here, the clinical relevance of circulating nucleosomes for diagnosis, staging, prognosis, and therapeutic monitoring of cancer is reviewed. Several studies have shown that levels of nucleosomes are significantly higher in serum and plasma of cancer patients in comparison to healthy controls. However, because of elevations of nucleosome levels in patients with benign diseases relevant for differential diagnosis, they are not suitable for cancer diagnosis. Concerning tumor staging, nucleosome levels correlate with tumor stage and presence of metastases in gastrointestinal cancer, but not in other tumor types. Prognostic value of circulating nucleosomes is found in lung cancer in univariate analyses, but not in multivariate analyses. Circulating nucleosomes are most informative for the monitoring of cytotoxic therapy. Strongly decreasing levels are mainly found in patients with remission of disease, whereas constantly high or increasing values are associated with progressive disease during chemo- and radiotherapy. In addition, therapy outcome is already indicated by the nucleosomal course during the first week of chemo- and radiotherapy in patients with lung, pancreatic, and colorectal cancer as well as in hematologic malignancies. Despite their non-tumor-specificity, kinetics of nucleosomes are valuable markers for the early estimation of therapeutic efficacy and may be helpful to adapting early cancer therapy in the future.
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PMID:Clinical relevance of circulating nucleosomes in cancer. 1883 45

This study investigated the clinical characteristics of, and outcomes and risk factors for hospital mortality of 390 patients admitted with severe sepsis or septic shock in an intensive care unit (ICU). Prospectively collected data from patients collected between 1 July 2004 and 30 June 2006 were analysed. Overall hospital mortality was 49.7% and comorbidities were found in 40.3% of patients, the most common of which was haematological malignancy. The respiratory tract was the most common site of infection (50%). Hospital-acquired infections accounted for 55.6% of patients with Gram-negative bacteria predominant (68%). Multivariate analysis showed that acute respiratory distress syndrome, pulmonary artery catheter placement, comorbidities, hospital-acquired infection, APACHE II score and maximum LOD score, were independent risk factors for hospital mortality. In conclusion, severe sepsis and septic shock are common causes of ICU admission. Patients with risk factors for increased mortality should be carefully monitored and aggressive treatment administered.
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PMID:The epidemiology of, and risk factors for, mortality from severe sepsis and septic shock in a tertiary-care university hospital setting. 1919 20

Universal empirical antifungal therapy (EAT) in patients with unexplained persistent febrile neutropenia (PFN) is the standard of care, but EAT could be applied in selected patients on the basis of clinical criteria and risk factors. A prospective interventional study was carried out to analyse the incidence and related mortality of invasive fungal infection (IFI) in patients with PFN according to whether or not EAT was indicated. EAT was indicated according to the following criteria: (a) severe sepsis or septic shock; (b) focused infection: lung, central nervous system, sinus, abdominal or skin; (c) individualized clinical decision in patients at high risk. Sixty-six (19%) of 347 episodes of febrile neutropenia fulfilled PFN criteria, 97% with a haematological malignancy. Just 26 (39.4%) were treated with EAT. The overall IFI incidence was 4.5%. In the group that received EAT, three patients developed IFI (11.5%), in comparison with none in the group that did not receive it (P=0.04, RR 2.7:1.9-3.8). IFI-related mortality was null in the group that did not receive EAT and 8% (two of 26 patients) in the group that received EAT. These data suggest that in patients with PFN, EAT in selected patients may be safe and avoid unnecessary antifungal therapy.
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PMID:Empirical antifungal therapy in selected patients with persistent febrile neutropenia. 1952 83

The risk factors for and clinical features of bloodstream infection with uncommon Candida spp. (species other than C. albicans, C. glabrata, C. parapsilosis, C. tropicals and C. krusei) are incompletely defined. To identify clinical variables associated with these species that might guide management, 57 cases of candidaemia resulting from uncommon Candida spp. were analysed in comparison with 517 episodes of Candida albicans candidaemia (2001-2004). Infection with uncommon Candida spp. (5.3% of candidaemia cases), as compared with C. albicans candidaemia, was significantly more likely to be outpatient-acquired than inpatient-acquired (15 of 57 vs. 65 of 517 episodes, p 0.01). Prior exposure to fluconazole was uncommon (n=1). Candida dubliniensis was the commonest species (n=22, 39%), followed by Candida guilliermondii (n=11, 19%) and Candida lusitaniae (n=7, 12%).C. dubliniensis candidaemia was independently associated with recent intravenous drug use (p 0.01) and chronic liver disease (p 0.03), and infection with species other than C. dubliniensis was independently associated with age<65 years (p 0.02), male sex (p 0.03) and human immunodeficiency virus infection (p 0.05). Presence of sepsis at diagnosis and crude 30-day mortality rates were similar for C. dubliniensis-related, non-C. dubliniensis-related and C. albicans-related candidaemia. Haematological malignancy was the commonest predisposing factor in C. guilliermondii (n=3, 27%) and C. lusitaniae (n=3, 43%) candidaemia. The 30-day mortality rate of C. lusitaniae candidaemia was higher than the overall death rate for all uncommon Candida spp. (42.9% vs. 25%, p not significant). All isolates were susceptible to amphotericin B, voriconazole, posaconazole, and caspofungin; five strains (9%) had fluconazole MIC values of 16-32 mg/L. Candidaemia due to uncommon Candida spp. is emerging among hospital outpatients; certain clinical variables may assist in recognition of this entity.
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PMID:Candidaemia with uncommon Candida species: predisposing factors, outcome, antifungal susceptibility, and implications for management. 1961 18

Recent studies suggest that patients with common variable immunodeficiency (CVID) and low numbers of switched memory B cells have lower IgG levels and higher rates of autoimmune disease, splenomegaly, and granulomatous disease; however, no prior literature has focused exclusively on pediatric cases. We examined the relationship between switched memory B cells and clinical and immunologic manifestations of CVID in a pediatric population. Forty-five patients were evaluated. Patients were categorized as Group I (<5 switched memory B cells/ml, n = 24) or Group II (> or =5 switched memory B cells/mL, n = 21). CD3(+) T-cell counts and CD19(+) B-cell levels were lower among Group I patients. Only those in Group I had meningitis, sepsis, bronchiectasis, granulomatous lung disease, autoimmune cytopenias, or hematologic malignancies. Segregation of pediatric patients into high risk (Group I) and average risk (Group II) may assist in targeting surveillance appropriately.
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PMID:Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells. 2145 41

Bacillus cereus is a growing concern as a cause of life-threatening infections in patients with hematologic malignancies. However, the risk factors for patients with unfavorable outcomes have not been fully elucidated. At our institution, we observed the growth of B. cereus in blood culture in 68 patients with (23) or without (45) hematologic malignancies treated from September 2002 to November 2009. We defined a case as having sepsis when more than two blood culture sets were positive for B. cereus or only a single set was positive in the absence of other microorganisms in patients who had definite infectious lesions. We determined 12 of 23 patients with hematologic malignancies as having sepsis, as well as 10 of 45 patients without hematologic malignancies (p = 0.012). Of the 12 patients with hematologic malignancies, four patients with acute leukemia died of B. cereus sepsis within a few days. In our cohort, risk factor analysis demonstrated that a neutrophil count of 0/mm(3), central venous (CV) catheter insertion, and the presence of central nervous system (CNS) symptoms were significantly associated with a fatal prognosis (p = 0.010, 0.010, and 0.010, respectively). Analysis of data from our cohort in conjunction with those from 46 previously reported patients with B. cereus sepsis identified similar risk factors, that is, acute leukemia, extremely low neutrophil count, and CNS symptoms (p = 0.044, 0.004, and 0.002, respectively). These results indicate that appropriate prophylaxis and early therapeutic intervention against possible B. cereus sepsis are crucially important in the treatment of hematologic malignancies.
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PMID:Fulminant sepsis caused by Bacillus cereus in patients with hematologic malignancies: analysis of its prognosis and risk factors. 2036 71


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