Amphotericin B- and Voriconazole-Echinocandin Combinations against Aspergillus spp.: Effect of Serum on Inhibitory and Fungicidal Interactions

Antifungal combination therapy with voriconazole or amphotericin B and an echinocandin is often employed as primary or salvage therapy for management particularly of refractory aspergillosis. The pharmacodynamic interactions of amphotericin B- and voriconazole-based combinations with the three echinocandins caspofungin, micafungin, and anidulafungin in the presence of serum were tested against 15 Aspergillus fumigatus complex, A. flavus complex, and A. terreus complex isolates to assess both their growth-inhibitory and fungicidal activities. The in vitro activity of each drug alone and in combination at a 1:1 fixed concentration ratio was tested with a broth microdilution colorimetric method, and interactions were assessed by isobolographic analysis. Synergy was found for all amphotericin B- and voriconazole-based combinations, with amphotericin B-based combinations showing strong inhibitory synergistic interactions (interaction indices of 0.20 to 0.52) and with voriconazole-based combinations demonstrating strong fungicidal synergistic interactions (interaction indices of 0.10 to 0.29) (P < 0.001). Drug- and species-specific differences were found, with caspofungin and the A. fumigatus complex exhibiting the weakest synergistic interactions. In the presence of serum, the synergistic interactions were reduced in the order (from largest to smallest decrease) micafungin > anidulafungin > caspofungin, and A. flavus complex > A. fumigatus complex > A. terreus complex, resulting in additive interactions, particularly for inhibitory activities of amphotericin B-echinocandin combinations and fungicidal activities of voriconazole-echinocandin combinations. Drug- and species-specific differences were found in the presence of serum for inhibitory activities of antifungal drugs, with the lowest interaction indices being observed for amphotericin B-caspofungin (median, 0.77) and for the A. terreus complex (median, 0.56). The present in vitro data showed that serum had a major impact on synergistic interactions of amphotericin B-echinocandin and voriconazole-echinocandin combinations, resulting in additive interactions and explaining the indifferent outcomes usually observed in vivo.     

Coronary artery ectasias: imaging, functional assessment and clinical implications.

Coronary artery ectasia is a relatively common entity characterized by inappropriate dilatation of the coronary vasculature. The exact mechanism of its development is unknown, but evidence suggests a combination of genetic predisposition, common risk factors for coronary artery disease and abnormal vessel wall metabolism. It frequently coexists with aneurysms elsewhere, mostly involving the aorta. In this review, the flow disturbances that are associated with this condition and the imaging modalities, which can be used for diagnosis and prospective follow-up are described. The prognosis of coronary ectasias is controversial and prospective studies focusing on conservative or invasive strategies to prevent cardiac complications are needed.     

Macular arteritis associated with concurrent HIV and hepatitis B infections: a case report and evidence for a disease spectrum association with cutaneous polyarteritis nodosa

We report the first case of macular arteritis in a 33‐year‐old Black, African female with concurrent human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Of particular interest in macular arteritis is the striking discordance between the clinical presentation and the histopathological findings, a fact that both dermatologists and dermatopathologists should be aware. Histopathologically, the case showed typical findings of macular arteritis with a perivascular, predominantly lymphocytic, infiltrate and intraluminal thrombosis. Both HIV and HBV have been reported as viral inducers of cutaneous polyarteritis nodosa (PAN). Their association with macular arteritis in this case supports existing evidence that macular arteritis and cutaneous PAN represent a single‐disease spectrum of vasculitides, with macular arteritis representing the chronic, lymphocytic and indolent stage, and cutaneous PAN the neutrophilic, acute stage with a risk for systemic progression. Lymphocytic thrombophilic arteritis (LTA), a third, uncommon disease would be in between macular arteritis and cutaneous PAN on a spectrum. Features of this case and other published cases provide strong evidence that there is a single, mild‐to‐severe disease spectrum of macular arteritis‐LTA‐cutaneous PAN.     

Prognostic potential of body composition indices in detecting risk of musculoskeletal injury in army officer cadet profiles

Objectives: High values in most of the body composition indices have been related to musculoskeletal injuries, but limited data exists on the accuracy of these diagnoses when detecting musculoskeletal injuries in military populations.

Methods: The suitability of body fat percentage, body mass index, fat mass index and fat free mass index to identify injury risk was examined in a group of army officer recruits. All body composition diagnoses were measured in 268 male army officer recruits prior to the commencement of basic combat training. Musculoskeletal injury was identified using codes from the International Classification of Diseases. The area under the curve, in the receiver operating characteristic curve, was used to quantify the overall ability to discriminate between those who were injured and those who were not.

Results: The statistics indicated that all indices, apart from body mass index, had a significant possibility to detect musculoskeletal injury potential (p < 0.05; 61%–63%). The respective cut-off points used to classify individuals as injured were for body fat percentage >22, for fat mass index >6.5 and for fat free mass index <16.5.

Conclusion: Body mass index values can not similarly detect the possibility of occurrence of musculoskeletal injuries in army officer recruits, just as other body composition diagnoses related to fat mass or/and free fat mass. However, the cut off-points related to the overall diagnostic performance of each body composition index should be used with caution and in accordance with the aims of each experimental setting.     

Apoptosis and myofibroblast expression in human glomerular disease: a possible link with transforming growth factor-beta-1

BACKGROUND/AIMS: The pathophysiological pathways involved in the pathogenesis and evolution of renal fibrosis, have not been fully elucidated. Transforming growth factor-beta(1) (TGF-beta(1)) is involved in the development of renal scarring. Apoptosis is responsible for intrinsic cell deletion observed in end-stage kidney disease. Myofibroblasts are involved in the development of renal fibrosis. This study investigates whether there is a potential relationship between apoptosis, myofibroblast infiltration and TGF-beta(1) expression in the kidney of patients with glomerulonephritis (GN). METHODS: Forty patients with various types of GN were included in the study. Myofibroblasts and TGF-beta(1) positive cells were detected in kidney biopsies by immunohistochemistry, while apoptotic cells were detected by the in situ end labelling of fragmented DNA. RESULTS: Myofibroblasts were identified in the glomeruli of some patients with severe mesangioproliferative GN and glomerulosclerosis but a more intensive myofibroblast expression was found in the renal interstitium. TGF-beta(1) was expressed in the cytoplasm of tubular epithelial cells, in the renal interstitium and in the glomeruli of patients with GN. Apoptotic cells were mainly detected in the tubules and interstitium and were present in areas with intense myofibroblast infiltration. Positive correlations were observed between the intensity of myofibroblast expression in the interstitium and apoptosis in the tubulointerstitial area (r = 0.521, p < 0.01) as well as TGF-beta(1) expression (r = 0.462, p < 0.05) and degree of renal impairment (r = 0.430, p < 0.05). CONCLUSIONS: These observations suggest that myofibroblast infiltration and apoptosis along with TGF-beta(1) expression are associated with the development of interstitial fibrosis in patients with glomerular disease.     

Gastrosplenic fistula: A rare complication of splenic abscess

Gastrosplenic fistulas are rare complications of malignant gastric or splenic diseases and, less frequently, are the result of benign diseases such as gastric ulcers and Crohn's disease. Spontaneous gastrosplenic fistula as a result of splenic abcess has not been reported in the literature so far. A 70‐year‐old man presented with a splenic abscess which had spontaneously developed a gastrosplenic fistula. The fistula was diagnosed by computed tomography scan and upper gastrointestinal endoscopy and was successfully managed by splenectomy with en bloc resection of part of the greater curvature of the stomach. Although gastrosplenic fistulas are a relatively rare complication of gastric or splenic diseases, an awareness might lead the clinician to early recognition and surgery can be offered earlier as the treatment of choice.     

Emergence of Equine West Nile Encephalitis in Central Macedonia,Greece, 2010

During the summer of 2010, an outbreak of West Nile virus (WNV) infections attributed to a lineage 2 WNV strain was reported among humans and horses in Central Macedonia, Northern Greece. Here, the clinical and laboratory investigation of horses that showed severe neurological signs due to WNV infection is being described. Specifically, between August and September 2010, 17 horses with neurological signs were detected. WNV infection was confirmed in all 17 clinical cases by applying laboratory testing. The duration of WNV‐specific IgM antibodies in sera obtained from seven of the clinically affected horses was relatively short (10–60 days; mean 44 days). In the regional unit of Thessaloniki, (i) seroprevalence of WNV and fatality rate in horses were high (33% and 30%, respectively), and (ii) the ratio of neurological manifestations‐to‐infections for this virus strain was high (19%). These observations indicate that the strain responsible for the massive human epidemic of 2010 in Greece was also highly pathogenic for horses. This is the first time that WNV infection has been documented in horses with clinical manifestations in Greece. WNV infection should be included in the differential diagnosis of horses with encephalitis in Greece.