How small modifications in laboratory workflow of blood cultures can have a significant impact on time to results

Rapid identification and antimicrobial susceptibility testing of micro-organisms causing bloodstream infections is crucial in the management of septic patients. In this study, we compared a period of twice-daily and a period of thrice-daily reading of subculture agar plates. In 2016, 10,644 positive blood cultures bottles (bioMérieux) from 2608 patients were analyzed at UZ Leuven. Identification and antimicrobial susceptibility testing were performed by MALDI-TOF MS (Bruker Daltonics) and Vitek 2 (bioMérieux) respectively. In period 1 (January to June), subculture plates were read at 8:30 a.m. and 2:00 p.m. during the weekdays. In period 2 (August until December), reading was performed at 8:30 a.m., 2:00 p.m., and 5:00 p.m. Time to identification and time to AST results after positivity were compared. In period 1, median time to identification of all organisms was 22.8 h compared to 20.2 h in period 2 (p?< 0.01). Moreover, micro-organisms were identified before 12 h in 9% of samples in period 2, a significant increase compared to 2% in period 1 (p?< 0.01). In period 2, AST results were known within 36 h in 39% of samples, compared to 31% in period 1 (p?< 0.01). Optimization of the reading frequency of subcultures of blood cultures significantly decreases time to results. Further optimization can be done by introducing lab automation. We will use the data of this study as a baseline to analyze the impact of introducing WASPLab (Copan Diagnostics) automation on time to results.     

Local Angiopeptin Delivery Using Coated Stents Reduces Neointimal Proliferation in Overstretched Porcine Coronary Arteries

BACKGROUND: Systemic administration of angiopeptin has been shown to inhibit myointimal thickening after arterial injury in several animal species. METHODS AND RESULTS: To explore to what extent high and long-lasting local concentrations of angiopeptin influence the healing process after vascular injury, tantalum balloon-expandable stents were first coated with a polymer loaded with angiopeptin 250 μg. Implantation of these stents in porcine coronary arteries resulted in tissue concentrations of 10.7 pg/ml wet weight in the stented arterial segment 24 hours after stent implantation, gradually declining to 2.0 pg/ml wet weight at day 8. Finally, 20 pigs were randomly treated with either an angiopeptin-loaded or a blank-coated stent. At baseline, the angiographic parameters were similar between both groups but, after 6 weeks, the minimal luminal diameter of the stented arterial segment was larger in the angiopeptin-treated pigs when compared to controls (2.20 +/- 0.57 mm vs 1.57 +/- 0.68 mm, p < 0.01) This angiographic finding was confirmed by post-mortem morphometry where the respective lumen area values were 1.00 +/- 0.54 mm2 and 0.43 +/- 0.28 mm2 (p < 0.01). CONCLUSION: Polymer coated stents can be loaded with angiopeptin, which after implantation in porcine right coronary arteries result in high local tissue concentrations gradually declining over more than 8 days. These high local concentrations inhibit myointimal proliferation induced by poly(organo)phosphazene coated overstretched stents.     

Results of percutaneous coronary intervention of the unprotected left main coronary artery in 143 patients and comparison of 30-day mortality to results of coronary artery bypass grafting

Percutaneous coronary intervention (PCI) of the unprotected left main coronary artery (LMCA) is controversial. In 143 patients who underwent PCI of the unprotected LMCA, 30-day mortality was compared with predicted cumulative risk-adjusted perioperative surgical mortality based on logistic European System for Cardiac Operative Risk Evaluation. One-year clinical follow-up was completed in all patients. The overall major adverse cardiac event rate at 1 year was 34.3%, reflecting the high-risk profile of the patient population. Twelve patients (8%) experienced an acute myocardial infarction and 16 (11%) underwent target lesion revascularization. In 31 patients (22%) who died during the first year, median logistic European System for Cardiac Operative Risk Evaluation was 30%. Calculated RRs showed significantly lower 30-day mortality using PCI compared with predicted surgical mortality (RR 0.54, 95% confidence interval 0.31 to 0.86). Angiographic follow-up in 90 of the 118 patients alive at 6 months showed binary restenosis of 6% in patients treated with drug-eluting stents versus 29% in patients receiving bare-metal stents (p < or =0.01). In conclusion, PCI for unprotected LMCA disease was associated with acceptable short- and medium-term outcomes in patients at low to intermediate risk of bypass surgery. Mortality remains high in very high-risk patients unsuitable for surgery. However, in selected indications, PCI of the LMCA can offer an alternative to surgery, especially when using drug-eluting stents.     

A cytokeratin-immunohistochemical study of focal nodular hyperplasia of the liver: further evidence that ductular metaplasia of hepatocytes contributes to ductular “proliferation”

ABSTRACT— A cytokeratin-immunohistochemical study was performed on eight specimens of focal nodular hyperplasia of the liver in order to determine whether hepatocytes in this lesion can express “bile duct type” cytokeratins. Serially cut cryostat sections were reacted with a panel of six monoclonal antibodies specifically reactive with cytokeratin polypeptides nr. 7, 8, 18 and 19, using a 3-step immunoperoxidase procedure. Hepatocytes were positive for cytokeratins nr. 8 and nr. 18, whereas ductules contained in addition to cytokeratins nr. 8 and nr. 18 also polypeptides nr. 7 and nr. 19. In all cases, a variable number of hepatocytes close to fibrous septa or inside the nodules expressed cytokeratin nr. 7. In four cases, a small number of hepatocytes were also immunoreactive for cytokeratin nr. 19. Our data demonstrate that hepatocytes in focal nodular hyperplasia can express one or even two “bile duct type” cytokeratins, supporting the concept that ductular metaplasia of hepatocytes contributes to the ductular “proliferation” observed in this tumor-like lesion.     

Temporal arteritis: the silent presentation and delay in diagnosis

To determine the frequency of the so-called silent or occult presentation of temporal arteritis (presentation with mere constitutional symptoms) and the resulting delay in diagnosis in this particular group, the medical records of all patients (n = 82) with temporal arteritis or polymyalgia rheumatica, presenting between 1982 and 1988 at the Department of General Internal Medicine of the University Hospital, were retrospectively analysed. Only biopsy-proven cases (n = 34) were studied further. Of the 34 patients with temporal arteritis, 13 (38%) presented with the silent or occult form. In this group the mean delay in diagnosis was 21.5 d (range 2-105) in contrast to a delay of 8.5 d (range 1-40) in the other group (P less than 0.05). Increased awareness of this presentation should lead to earlier diagnosis and treatment of this potentially life-threatening disease, resulting in a shorter hospital stay and fewer technical investigations, with a considerable financial saving.     

Hepatic endoplasmic reticulum storage diseases

ABSTRACT— Endoplasmic Reticulum Storage Diseases (ERSD) represent a novel group of inborn errors of metabolism affecting secretory proteins and resulting in hepatocytic storage and plasma deficiency of the corresponding protein. The hepatocellular storage is due to a molecular abnormality hindering the translocation of the abnormal protein from the rough (RER) to the smooth endoplasmic reticulum (SER). The molecular abnormality is genetically determined; hence it is hereditary, congenital, familial and permanent. The storage is selective and exclusive for the mutant protein and predisposes to the development of chronic cryptogenic liver disease. ERSD include alpha-1-antitrypsin deficiency, fibrinogen storage and alpha-1-antichymotrypsin deficiency. Basically, the diagnosis of ERSD is a morphological one: immunohistochemistry and electron microscopy are essential tools for their identification.     

Oral Administration of the Broad-Spectrum Antibiofilm Compound Toremifene Inhibits Candida albicans and Staphylococcus aureus Biofilm Formation In Vivo

We here report on the in vitro activity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, including Candida albicans, Candida glabrata, Candida dubliniensis, Candida krusei, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. We validated the in vivo efficacy of orally administered toremifene against C. albicans and S. aureus biofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound.