PET/TC con 18F-FDG en la sospecha de infección asociada a dispositivos intracardiacos: rendimiento y utilidad diagnóstica

Introduction and objectivesCardiac device-related infections (CDRI) may be life-threatening and require early and accurate diagnosis. The aims of this study were to analyze the performance of positron emission tomography-computed tomography (PET/CT) in suspected CDRI, to assess changes to the initial diagnosis, and to identify a clinical subgroup deriving the greatest benefit from this imaging modality.MethodsRetrospective study including patients evaluated by PET/CT for suspected CDRI from 2011 to 2018. We assessed PET/CT performance and the agreement between the initial, post-PET and definitive diagnoses. We also assessed changes in the diagnosis, depending on initial clinical suspicion, to identify patients deriving the greatest benefit from PET/CT.ResultsWe included 44 patients. The prevalence of endocarditis was 57%. The sensitivity and specificity of PET/CT for the diagnosis of infective endocarditis were 0.84 and 0.95, respectively. Post-PET diagnosis improved the initial diagnosis by 45%. PET/CT correctly reclassified 57% of patients with initial suspicion of generator pocket infection by detecting lead infection.ConclusionsPET/CT showed high diagnostic performance in suspected of CDRI and significantly improved the conventional diagnostic approach, especially in patients with initial suspicion of focal infection.     

Amoxicillin for acute lower respiratory tract infection in primary care: subgroup analysis of potential high-risk groups

Background

Antibiotics are of limited overall clinical benefit for uncomplicated lower respiratory tract infection (LRTI) but there is uncertainty about their effectiveness for patients with features associated with higher levels of antibiotic prescribing.

Aim

To estimate the benefits and harms of antibiotics for acute LRTI among those producing coloured sputum, smokers, those with fever or prior comorbidities, and longer duration of prior illness.

Design and setting

Secondary analysis of a randomised controlled trial of antibiotic placebo for acute LRTI in primary care.

Method

Two thousand and sixty-one adults with acute LRTI, where pneumonia was not suspected clinically, were given amoxicillin or matching placebo. The duration of symptoms, rated moderately bad or worse (primary outcome), symptom severity on days 2–4 (0–6 scale), and the development of new or worsening symptoms were analysed in pre-specified subgroups of interest. Evidence of differential treatment effectiveness was assessed in prespecified subgroups by interaction terms.

Results

No subgroups were identified that were significantly more likely to benefit from antibiotics in terms of symptom duration or the development of new or worsening symptoms. Those with a history of significant comorbidities experienced a significantly greater reduction in symptom severity between days 2 and 4 (interaction term −0.28, P = 0.003; estimated effect of antibiotics among those with a past history −0.28 [95% confidence interval = −0.44 to −0.11], P = 0.001), equivalent to three people in 10 rating symptoms as a slight rather than a moderately bad problem. For subgroups not specified in advance antibiotics provided a modest reduction in symptom severity for non-smokers and for those with short prior illness duration (<7 days), and a modest reduction in symptom duration for those with short prior illness duration.

Conclusion

There is no clear evidence of clinically meaningful benefit from antibiotics in the studied high-risk groups of patients presenting in general practice with uncomplicated LRTIs where prescribing is highest. Any possible benefit must be balanced against the side-effects and longer-term effects on antibiotic resistance.     

New thiazolyl-pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents

A new series of N-substituted pyrazoline derivatives 6a–g , 7a–g , 8a–g , and 9a–g was synthetized by reaction of hydrazine derivatives and chalcone–thiazole hybrids bearing nitrogen mustard 5a–g . The chalcones 5a–g were obtained by Claisen–Schmidt condensation of thiazole-2-nitrogen mustard 3 and selected acetophenones 4a–g . These new compounds 6/7/8/9a–g were screened for their antifungal activity against Cryptococcus neoformans, with IC₅₀ values of 3.9–7.8 µg/ml for the N-3,5-dichlorophenyl pyrazolines 9e – g . Interestingly, those compounds show low cytotoxic effects toward erythrocytes (RBC). In addition, N-acetyl ( 6a,b ) and N-formyl pyrazolines ( 7a , 7b , 7c , and 7g ) showed inhibitory activity against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, and vancomycin-intermediate S. aureus, with the most important minimum inhibitory concentration values ranging from 31.25 to 125 µg/ml. Regarding the antiprotozoal activity, thiazolyl-pyrazolines 9g , 8f , and 7c display high activity against Plasmodium falciparum, Leishmania (V) panamensis, and Trypanosoma cruzi, with EC₅₀ values of 11.80, 6.46, and 4.98 μM, respectively, and with 7c being approximately 2.6-fold more potent than benznidazole with a selectivity index of 1.61 on U-937 human cells, showing promising potential as a novel antitrypanosomal agent.     

DNA methylation changes in human lung epithelia cells exposed to multi-walled carbon nanotubes

Humans are increasingly exposed to nanoparticles and, although many of their physiological effects have been described, the molecular mechanisms underlying them are still largely unknown. The present study aimed to determine the possible role of certain epigenetic mechanisms in the cellular response of human lung epithelial cells that are triggered by long-term exposure to titanium dioxide nanoparticles (TiO₂NPs) and multi-walled carbon nanotubes (MWCNTs). The results showed that exposure to TiO₂NPs had only minor effects on genome-wide DNA methylation. However, we identified 755 CpG sites showing consistent DNA hypomethylation in cells exposed to MWCNTs. These sites were mainly located at low density CpG regions and enhancers, and very frequently on the X chromosome. Our results thus suggest that long-term MWCNT exposure may have important effects on the epigenome.     

Risk factors for nosocomial transmission of multidrug-resistant tuberculosis due to Mycobacterium bovis among HIV-infected patients.

OBJECTIVE: To identify risk factors for transmission of multidrug-resistant tuberculosis (MDR-TB) among hospitalized human immunodeficiency virus (HIV) infected patients exposed during a nosocomial outbreak. DESIGN: Case control study. Cases were HIV-infected patients with MDR-TB due to Mycobacterium bovis (MDR-TBMb) who acquired the disease after exposure to an MDR-TBMb patient in an hospital ward. Controls were HIV-infected patients exposed to a case of MDR-TBMb in an hospital ward but who did not develop MDR-TBMb during the follow-up. RESULTS: Nineteen cases and 31 controls were included. CD4 cell counts were significantly lower among cases. Exposure in the infectious diseases ward or exposure to the index patient were associated with development of MDR-TBMb, while exposure during a single-room hospital stay and exposure in the respiratory isolation ward were associated with non-development of MDR-TBMb. A multiple regression logistic model showed that only a CD4 cell count below 50/microL and exposure to the index patient increased the risk of developing MDR-TBMb (P < 0.05). Hospitalization in a single room seemed to protect HIV-infected patients from developing nosocomial MDR-TBMb (P = 0.052). CONCLUSIONS: Over classic risk factors, such as length of exposure or sharing a room with a case, severe immunosuppression independently increases the risk of MDR-TB transmission in the context of a nosocomial MDR-TB outbreak among HIV-infected patients. This information must be considered in the management of tuberculosis outbreaks. Patients with CD4 cell counts below 50/microL should be the principal group targeted for prevention strategies in nosocomial outbreaks.