Infective endocarditis in intravenous drug abusers: patterns of presentation and long-term outcomes of surgical treatment

BACKGROUND AND AIM OF THE STUDY: Few data exist on infective endocarditis (IE) in intravenous drug abuse (IVDA) patients. In particular, clinical features, site of involvement and bacteriologic findings are controversial. Little is also known on the results of surgical treatment and on the long-term prognosis. METHODS: The clinical and microbiological characteristics of IE in a series of 39 IVDA patients were retrospectively assessed and compared to those in 85 non-IVDA patients with a likely similar life expectancy. The total follow up of patients was 717.6 patient-years (119.9 pt-yr for IVDA, 597.7 pt-yr for non-IVDA). RESULTS: Although tricuspid involvement was significantly more frequent in IVDA cases than in non-IVDA cases (p = 0.001), left-sided endocarditis prevailed in both groups. In addition to Staphylococcus aureus (51.3%), Staph. epidermidis (15.4%) and streptococcal spp. (23.1%) were emerging pathogens in IVDA cases. A worse cardiac function (p < 0.002) and a higher rate of embolism (p = 0.04) characterized the preoperative status of IVDA patients. No difference was observed as to indications, emergency procedures and pathologic findings. Hospital and long-term survival did not significantly differ between the two groups. The rate of recurrence was higher in IVDA cases; this difference was mostly accounted for by early postoperative events. CONCLUSION: A new pattern of IE in IVDA is emerging, characterized by more frequent left heart involvement (61.5%), a severe clinical course, and a need for surgery in the active phase. Staph. epidermidis and streptococci are emerging pathogens. Drug abuse does not affect postoperative prognosis when an aggressive surgical attitude is combined with prolonged medical therapy. Higher rates of early recurrence are expected during the follow up period.     

Spatial patterns of matrix protein expression in dilated ascending aorta with aortic regurgitation: congenital bicuspid valve versus Marfan's syndrome

BACKGROUND AND AIM OF THE STUDY: Aortic wall stress has been shown to increase locally at the convex aspect of the ascending tract when axial root motion is increased, as occurs in aortic valve regurgitation. The study aim was to assess the expression of extracellular matrix (ECM) proteins involved in stress-induced vascular remodeling in the convexity and the concavity of dilated ascending aortas with aortic valve regurgitation. METHODS: Aortic wall specimens, harvested at the convexity and concavity of eight dilated ascending aortas with severe aortic valve regurgitation underwent morphometry, Western blot, RT-PCR and confocal immunohistochemistry. Five patients (group A) had congenital bicuspid aortic valve (BAV), and three (group B) had Marfan's syndrome. Specimens from the aorta of three multi-organ donors served as controls. RESULTS: At morphometry, medial degeneration was more severe in the convexity than in the concavity, especially in group A. Western blot, RT-PCR and immunohistochemistry disclosed an asymmetric pattern in the expression of some ECM proteins (laminin, tenascin, fibronectin). Fibronectin was increased in the convexity of both groups compared to controls at Western blot. Immunohistochemistry confirmed this pattern only in BAV. Higher levels of tenascin were found in the convexity in group A. The laminin content was greater in the concavity than in the convexity of both groups, but in group B the type of laminin was different, with the beta2 chain particularly expressed, and almost absent in non-Marfan patients. Type I and type III collagens were more markedly reduced in the convexity than in the concavity in BAV. In group B, type I collagen was decreased and type III increased, but without any significant difference between the two aspects of the aorta. CONCLUSION: A tissue remodeling response to valve disease-related wall stress may underlie aortic dilatation with BAV regurgitation. Although morphometry showed similar changes in Marfan aortas, molecular investigations differentiated this condition, qualitatively, from BAV.     

Microbiologically documented nosocomial infections after cardiac surgery: an 18-month prospective tertiary care centre report.

OBJECTIVE: The aim of this study was to prospectively evaluate frequency, characteristics, and predictors of nosocomial infections (NI) in a tertiary care centre. METHODS: Study population included 925 patients (mean age 62.3+/-12.5, 32.3% females, 22.9% diabetics, 6.8% with previous cardiac procedures) operated on between June 2005 and December 2006 (CABG 48.72%, valvular procedures 30.05%, thoracic aortic 10.9%, heart transplantations 3.78% and miscellanea 6.55%, procedure status: elective 72.9%, urgent 15.9% and emergent 11.2%). The study population was divided in two groups according to development of NI. Primary endpoints were multiorgan failure (MOF) and hospital mortality in the two groups. Secondary endpoints were length of intubation, intensive care unit (ICU) stay and overall hospitalisation. Univariate and multivariate analysis of NI predictors was conducted between 115 perioperative variables. RESULTS: Eighty-three patients (9%) developed a NI. Infections affected respiratory tract in 51.8%, blood stream in 20.5 and wound infection in 27.7 (13.3% deep wound). Staphylococcal species (60.6%) predominated in blood stream and surgical wound infections while Gram-negative species predominated in respiratory infections. Patients affected by NI experienced significantly higher incidence of MOF (12% vs 0.8%) and hospital mortality (24.1 vs 6.9%). Development of NI significantly lengthened all the steps of postoperative process of care (length of intubation: 49.9+/-73 h vs 19.1+/-35.2; ICU stay: 10.4+/-12.8 days vs 3.4+/-4.6 and hospitalisation 20.7+/-15.3 vs 10.6+/-7). Independent predictors of NI were immunosuppressive therapy [OR 12.9 (CI 5.07-31.2)], reintubation [OR 10.3 (CI 4.6-2.3)], stroke [OR 9.5 (CI 1.8-49)], resternotomy for bleeding [OR 6.7 (CI 1.9-23.6)], emergent/urgent status [OR 3.6 (CI 1.5-8.4)], CVVH [OR 3.2 (CI 1.4-7.5)] and length of intubation [OR 1.03 (CI 1.01-1.1)]. CONCLUSIONS: NI still represents a serious complication. Presence of identified determinants of NI should prompt modification of management algorithms.     

Bilateral striatal necrosis,dystonia and multiple mitochondrial DNA deletions: Case study and effect of deep brain stimulation

Bilateral striatal necrosis (BSN) is relatively rare and has been related to a wide array of causes, including nuclear and mitochondrial DNA mutations. We report the clinical vignette of a patient with a 37 years‐history of generalized dystonia secondary to BSN associated with multiple mitochondrial DNA deletions of undefined origin. Globus pallidus interna deep brain stimulation produced sustained benefit, with predominant improvements in disability. © 2007 Movement Disorder Society     

Tolerability and improved protective action of idebenone-loaded pegylated liposomes on ethanol-induced injury in primary cortical astrocytes

The potential therapeutic advantages of the encapsulation of idebenone within pegylated liposomes were investigated in vitro on primary cortical astrocytes of rats. In particular, both the concentration-dependent effects and the therapeutic effectiveness toward excitotoxic injury, elicited by chronic treatment with ethanol (100 microM) for 12 days, were evaluated. The following parameters were taken into consideration to assay free or liposomally entrapped idebenone: lactic dehydrogenase release, respiratory capacity measured by tetrazolium salt conversion, glutamine synthetase, and the levels of constitutive and inducible 70-kDa heat shock proteins. To evaluate the effects on astrocytes, three different drug concentrations were used (0.5 microM, 5 microM, and 50 microM). At the highest concentration used (50 microM), a toxic effect of the free and liposomally entrapped drug was observed. Toxic effects seem to be due to a cellular membrane perturbation, as demonstrated by (45)Ca(2+) permeation. The therapeutic effect of free or liposomally entrapped idebenone on ethanol-induced injury of primary cortical astrocytes was evaluated as a function of the drug concentration. The drug liposome formulation was much more effective than the free drug in counteracting the ethanol-induced damage in astrocytes, i.e., 10-times-lower doses of liposomally entrapped idebenone are able to provide a greater protective action than the free drug. The improved action of idebenone-loaded liposomes is probably due to the greater drug bioavailability at the cellular level.     

Mitochondrial DNA depletion and dGK gene mutations

Mitochondrial DNA depletion syndrome is a clinically heterogeneous group of disorders characterized by a reduction in mitochondrial DNA copy number. The recent discovery of mutations in the deoxyguanosine kinase (dGK) gene in patients with the hepatocerebral form of mitochondrial DNA depletion syndrome prompted us to screen 21 patients to determine the frequency of dGK mutations, further characterize the clinical spectrum, and correlate genotypes with phenotypes. We detected mutations in three patients (14%). One patient had a homozygous GATT duplication (nucleotides 763-766), and another had a homozygous GT deletion (nucleotides 609-610); both mutations lead to truncated proteins. The third patient was a compound heterozygote for two missense mutations (R142K and E227K) that affect critical residues of the protein. These mutations were associated with variable phenotypes, and their low frequencies suggests that dGK is not the only gene responsible for mitochondrial DNA depletion in liver. The patient with the missense mutations had isolated liver failure and responded well to liver transplantation, which may be a therapeutic option in selected cases.