Infective endocarditis: Absence of microbiological diagnosis is an independent predictor of inhospital mortality

Infective endocarditis (IE) is associated with high inhospital mortality. New microbiological diagnostic techniques have reduced the proportion of patients without etiological diagnosis, but in a significant number of patients the cause is still unknown. Our aim was to study the association of the absence of microbiological diagnosis with in-hospital prognosis. Prospective cohort of 2000 consecutive patients with IE. Data were collected in 26 Spanish hospitals. Modified Duke criteria were used to diagnose patients with suspected IE. A total of 290 patients (14.8%) had negative blood cultures. Etiological diagnosis was achieved with other methods (polymerase chain reaction, serology and other cultures) in 121 (6.1%). Finally, there were 175 patients (8.8%) without microbiological diagnosis (Group A) and 1825 with diagnosis (Group B). In-hospital mortality occurred in 58 patients in Group A (33.1%) vs. 487 (26.7%) in Group B, p = 0.07. Patients in Group A had a lower risk profile than those in Group B, with less comorbidity (Charlson index 1.9 ± 2.0 vs. 2.3 ± 2.1, p = 0.03) and lower surgical risk (EuroSCORE 23.6 ± 21.8 vs. 29.6 ± 25.2, p = 0.02). However they presented heart failure more frequently (53% vs. 40%, p = 0.005). Multivariate analysis showed that the absence of microbiological diagnosis was an independent predictor of inhospital mortality (odds ratio 1.8, 95% Confidence Interval 1.1–2.9, p = 0.016). Approximately 9% of patients with IE had no microbiological diagnosis. Absence of microbiological diagnosis was an independent predictor of inhospital mortality.

Taking advantage of an old concept, "illegitimate transcription", for a proposed novel method of genetic diagnosis of McArdle disease

McArdle disease is a metabolic disorder caused by pathogenic mutations in the PYGM gene. Timely diagnosis can sometimes be difficult with direct genomic analysis, which requires additional studies of cDNA from muscle transcripts. Although the "nonsense-mediated mRNA decay" (NMD) eliminates tissue-specific aberrant transcripts, there is some residual transcription of tissue-specific genes in virtually all cells, such as peripheral blood mononuclear cells (PBMCs).We studied a subset of the main types of PYGM mutations (deletions, missense, nonsense, silent, or splicing mutations) in cDNA from easily accessible cells (PBMCs) in 12 McArdle patients.Analysis of cDNA from PBMCs allowed detection of all mutations. Importantly, the effects of mutations with unknown pathogenicity (silent and splicing mutations) were characterized in PBMCs. Because the NMD mechanism does not seem to operate in nonspecific cells, PBMCs were more suitable than muscle biopsies for detecting the pathogenicity of some PYGM mutations, notably the silent mutation c.645G>A (p.K215=), whose effect in the splicing of intron 6 was unnoticed in previous muscle transcriptomic studies.We propose considering the use of PBMCs for detecting mutations that are thought to cause McArdle disease, particularly for studying their actual pathogenicity.