Investigating infectious diseases at autopsy

Autopsy has a central role in diagnosing severe infectious diseases of all types: virus, prions, bacteria, mycobacteria, fungi, protozoa and helminths. The majority can be identified using histopathology – with special stains and immunohistochemistry - which is an essential part of the autopsy. In addition, cytology, microbiology culture and molecular diagnostics, serology and urine antigen testing are important adjuncts. This review encompasses a general overview of infectious autopsies, recommends working practices, and highlights the scenarios of HIV, post-transplantation and post-vaccine deaths, and rabies.     

Clinical features of three cases with pulmonary alveolar proteinosis secondary to myelodysplastic syndrome developed during the course of Behçet's disease

We have previously reported that myelodysplastic syndrome (MDS) is the most common underlying disease in cases of secondary pulmonary alveolar proteinosis (PAP). Here, we present 3 MDS cases in which PAP developed during the course of Behçet's disease (BD). All patients carried trisomy 8 in the bone marrow. Chest HRCT scans showed variable distribution of ground glass opacities, but none of the scans showed so called “crazy paving appearance”. Two patients with intestinal BD who underwent potent immunosuppressive therapy died of sepsis. These findings demonstrate that PAP secondary to MDS may be occasionally associated with BD.     

Anti-inflammatory effects of benzenediamine derivate FC-98 on sepsis injury in mice via suppression of JNK,NF-κB and IRF3 signaling pathways

FC-98, a synthesized benzenediamine derivate, was reported to regulate Toll-like receptor 9-induced activation of dendritic cells in our previous study. In this study, we evaluated the anti-inflammatory properties of FC-98 both in macrophages and in septic mouse models. By using enzyme-linked immunosorbent assay and real-time quantitative PCR, we found that FC-98 (6.25, 25 and 100 μM) dose-dependently attenuated lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein (MCP-1) productions in RAW264.7 and primary mouse peritoneal macrophages. These inhibitory effects were not due to inducing cell cytotoxicity or altering LPS binding or TLR4 expression. Subsequently, western blot, immunofluorescence and luciferase reporter assays were used to investigate the underlying mechanisms of its anti-inflammatory activities. Results showed that FC-98 blocked activation of the c-Jun N-terminal kinase (JNK), nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) signaling pathways. In vivo, FC-98 (30 or 100 mg/kg) was intraperitoneally administrated into LPS-induced or CLP-induced sepsis mice. It was observed to enhance the survival rate, inhibit pro-inflammatory mediator production, improve organ injuries and suppress bacterial propagation. In conclusion, FC-98 effectively inhibited macrophage inflammatory responses and ameliorated sepsis in mice through down-regulation of both MyD88 and TRIF-dependent pathways. These results suggest that FC-98 could be a promising therapeutic agent for inflammatory diseases.     

A retrospective analysis of deep sternal wound infections after longitudinal median sternotomy

Median sternotomy is the most commonly performed surgical procedure in the treatment of heart conditions in both adults and children. Deep sternal wound infections (DSWI) present a serious complication occurring after surgery, highly demanding both of patients and surgery departments. The present study is a retrospective analysis of 9110 patients who underwent a cardiac surgery at the Center of Cardiovascular Surgery and Transplantations, Brno, Czech Republic, in the years 2005–12, and as its objective it has a definition of risk factors of DSWI after median sternotomy.In this study, a multivariate analysis found sepsis to be the most serious risk factor, in addition to harvesting of the mammary artery (to be used as a graft for revascularisation), haemodynamic instability, reintubation and male sex.     

Can we back off using antibiotics in the NICU?

Antibiotics are extensively and inconsistently prescribed in neonatal ICUs, and usage does not correlate with rates of culture positive sepsis. There is mounting data describing the short and long-term adverse effects associated with antibiotic overuse in neonates, including the increased burden of multi-drug resistant organisms. Currently there is considerable variation in antibiotic prescribing practice among neonatologists. Applying the practice of antibiotic stewardship in the NICU is crucial for standardizing antibiotic use and improving outcomes in this population.Several approaches have been proposed to identify neonatal sepsis, with the hope of reducing antibiotic utilization. These strategies all have their limitations, and often include laboratory testing and treatment of well-appearing, non-septic, infants. A conservative “watch and wait” algorithm is suggested as an alternative method for when to initiate antibiotics. This observational approach relies on availability of trained personnel able to examine infants at specified intervals, without delaying antibiotics, should signs of sepsis arise.