Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality.

Blood stream infection (BSI) is a serious complication of hematopoietic stem cell transplantation (HSCT). The aim of this retrospective cohort analysis was to describe BSI after HSCT, and to assess the predictors and outcomes of BSI after HSCT using multivariable modeling. Of the 243 subjects transplanted, 56% received allogeneic HSCT and 106 (43.6%) developed BSI. Of the 185 isolates, 68% were Gram-positive cocci, 21% were Gram-negative bacilli (GNR) and 11% were fungi. Type of allogeneic HSCT was an independent risk factor for BSI (hazard ratio (HR) 3.26, 95% confidence interval (CI) 1.50, 7.07, P = 0.01), as was the degree of HLA matching (HR 1.84, 95% CI 1.00, 3.37, P = 0.05). BSI was a significant independent predictor of mortality after HSCT (HR 1.79, 95% CI 1.18, 2.73, P = 0.007), after adjusting for acute graft-versus-host disease (GVHD) and allogeneic HSCT (both predicting death < or = 3 months after HSCT). In contrast to the effects of acute GVHD and allogeneic HSCT, the effect of BSI was evident throughout the post-HSCT period. GNR BSI and vancomycin-resistant enterococcal BSI also were significantly associated with death. We concluded that BSI is a common complication of HSCT associated with increased mortality throughout the post-HSCT period.

A comparison of necrotising fasciitis in diabetics and non-diabetics: a review of 127 patients.

AIMS: Diabetes mellitus is the most common co-morbidity associated with necrotising fasciitis. This study aims to compare the clinical presentation, investigations, Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score, microbiology and outcome of management of this condition in diabetic and non-diabetic patients. PATIENTS AND METHODS: The medical records of all patients with surgically proven necrotising fasciitis treated at our institution between 2005 and 2014 were reviewed. Diagnosis of necrotising fasciitis was made on findings of 'dishwater' fluid, presence of greyish necrotic deep fascia and lack of bleeding on muscle dissection found intra-operatively. Information on patients' demographics, presenting symptoms, clinical signs, investigations, treatment and outcome were recorded and analysed. RESULTS: A total of 127 patients with surgically proven necrotising fasciitis were included in this study. In all, 78 (61.4%) were diabetic and 49 (38.6%) were non-diabetic. Diabetics tended to have polymicrobial infections (p = 0.03), renal impairment (p < 0.001), end-stage renal disease (p = 0.001) and multiple co-morbidities (p < 0.001). They presented atypically, with less tenderness (p = 0.042) and less hypotension (p = 0.034). This resulted in higher rates of misdiagnosis (p = 0.038) and a longer time to surgery (p = 0.05) leading to longer hospital stays (p = 0.043) and higher rates of amputation (p = 0.045). However, the rate of mortality is comparable (p = 0.525). A LRINEC score of > 8 appears to be more sensitive in diabetic patients (p < 0.001). However, the increased sensitivity in diabetic patients may be related to hyperglycemia and electrolyte abnormalities associated with renal impairment in these patients. CONCLUSION: The LRINEC score must be used with caution in diagnosing necrotising fasciitis in diabetic patients. A high index of suspicion is key to the early diagnosis and subsequent management of these patients. Cite this article: Bone Joint J 2016;98-B:1563-8.

Antagonism of TGF-alpha receptor binding and TGF-alpha induced stimulation of cell proliferation by methyl pheophorbides.

Over 4,500 natural product extracts were screened for their abilities to inhibit binding of radiolabeled TGF-alpha to A431 cells; several plant extracts were identified as potential leads with IC50 values of less than 30 micrograms/mL. The active components of one extract were purified to homogeneity and identified as the porphyrin structures, methyl pheophorbides a and b. These compounds inhibited both TGF-alpha receptor binding and the TGF-alpha induced proliferation of NRK-49F cells in soft agar. To construct a structure-function relationship, a series of commercially available porphyrin derivatives was evaluated. The most potent compound, hematoporphyrin IX, inhibited TGF-alpha functions in a dose-dependent fashion with IC50 values slightly lower than the methyl pheophorbides. Further studies revealed that inhibition of TGF-alpha binding was light dependent and that inhibition did not involve direct competition of porphyrins for the TGF-alpha binding site. To determine the specificity of inhibition, the porphyrins were tested in a number of other receptor-ligand assays. TNF-alpha and beta-adrenoceptor bindings were unaffected, whereas IL-1 beta binding to EL-4 membranes and platelet-derived growth factor induced thymidine incorporation in NIH-3T3 cells were both antagonized by the most active porphyrins. Inhibition of TGF-beta binding to NRK-49F cells and TGF-beta-induced growth of AKR-2B cells was also observed. In summary, we report that methyl pheophorbides are naturally occurring, photodynamic antagonists of TGF-alpha, and although the inhibitory properties of these molecules were not confined to TGF-alpha alone, some level of receptor selectivity was observed.

Aridicins, novel glycopeptide antibiotics. III. Preparation, characterization, and biological activities of aglycone derivatives.

The aglycone and two pseudoaglycones of aridicin A were prepared by selective hydrolysis and characterized, chemically and biologically. These new analogs demonstrate improved activities in vitro over the parent antibiotics against methicillin sensitive and resistant staphylococci. The major determinant of activity is the mannose substituent, the presence of which results in less potent compounds. The analogs have potent activity against enterococci.

Aridicins, novel glycopeptide antibiotics. II. Isolation and characterization.

A new antibacterial antibiotic complex, aridicin, was produced by a new genus, Kibdelosporangium aridum (SK&F-AAD-216). The individual factors, aridicins A, B and C, were isolated from the fermentation broth by an Amberlite XAD-7 resin extraction and purified by preparative reversed phase HPLC. The aridicins were found to be novel members of the glycopeptide class of antibiotics as exemplified by ristocetin and vancomycin, based on chemical and spectroscopic data, their molecular weights as determined by FAB mass spectrometry (1,786, 1,800 and 1,814), the detection of actinoidinic acid in their acid hydrolysates, and detailed TLC and HPLC comparisons with representative members of this class.

Blood stream infection (BSI) and acute GVHD after hematopoietic SCT (HSCT) are associated.

Blood stream infection (BSI) and acute GVHD (aGVHD) are serious complications of hematopoietic SCT (HSCT). We hypothesized that the two events were not independent of one another. We studied (1) associations between BSI and aGVHD; and (2) the impact of BSI and/or aGVHD on death within 100 days after HSCT, using a retrospective cohort analysis. Risk factor analysis was carried out using multivariable Cox proportional hazards analyses. Of 211 patients who underwent allogeneic HSCT from January 2000 to December 2005 (58% of whom underwent reduced intensity transplantation), 82 (39%) developed BSI. In 49 patients (23%), grade (gr) 2-4 aGVHD occurred. Early BSI was independently associated with an increased occurrence of subsequent aGVHD gr 2-4. CMV seropositivity was independently associated with decreased occurrence of aGVHD. aGVHD gr 2-4 independently predicted subsequent first BSI. Both BSI and aGVHD gr 2-4 were significant independent predictors of death within 100 days after HSCT. There is a strong, independent association between BSI and aGVHD. Potential explanations include the elaboration of cytokines during BSI favoring the development of aGVHD and/or the immunosuppressive treatment of aGVHD favoring the development of BSI. Future studies should be directed at the mechanistic investigations of this association.

Isolation of bioactive and other oxoaporphine alkaloids from two annonaceous plants, Xylopia aethiopica and Miliusa cf. banacea.

The oxoaporphine alkaloids oxophoebine [1] and liriodenine [2] have been isolated from Xylopia aethiopica (Annonaceae). Both showed selective toxicity against DNA repair and recombination deficient mutants of the yeast Saccharomyces cerevisae. Three related but inactive compounds, oxoglaucine [3], O-methylmoschatoline [4], and lysicamine [5], were also isolated from this plant. Selective toxicity was also observed for 10-methoxyliriodenine (lauterine) [6] and 10-hydroxyliriodenine [7], two oxoaporphine alkaloids isolated from Miliusa cf. banacea (Annonaceae). The structure of 10-hydroxyliriodenine [7], a novel oxoaporphine, was determined by spectroscopic methods and chemical conversion to compound 6. The role of the bioactive oxoaporphine alkaloids as DNA topoisomerase inhibitors is discussed.

Conioidines A and B, novel DNA-interacting pyrrolidines from Chamaesaracha conioides.

Two novel pyrrolidine compounds, conioidines A [1] and B [2], have been isolated from the Texas plant, Chamaesaracha conioides (Solanaceae). Their structures were determined by spectroscopic methods and hydrolysis studies. Both natural products, like doxorubicin, showed DNA-specific KB cell cytotoxicity. Dose-response data indicated a Kd value of 2.8 microM for binding of conioidine A [1] to calf thymus DNA.

New leukotriene B4 receptor antagonist: leucettamine A and related imidazole alkaloids from the marine sponge Leucetta microraphis.

Three new imidazole alkaloids, leucettamines A [1] and B [2] and leucettamidine [3], have been isolated from the Palauan sponge Leucetta microraphis. Their structures were established on the basis of extensive spectral analyses. Leucettamine A showed potent leukotriene B4 receptor binding activity (K(i) = 1.3 microM), while leucettamine B was essentially inactive (K(i) = 100 microM) and leucettamidine showed significant activity (K(i) = 5.3 microM). With leucettamine A identified as a pure LTB4 receptor antagonist, a new structure lead is presented to inflammation therapy.