‘All in a box’ a concept for optimizing microbiological diagnostic sampling in prosthetic joint infections

BACKGROUND: Accurate microbial diagnosis is crucial for effective management of prosthetic joint infections. Culturing of multiple intraoperative tissue samples has increased diagnostic accuracy, but new preparatory techniques and molecular methods hold promise of further improvement. The increased complexity of sampling is, however, a tough challenge for surgeons and assistants in the operation theatre, and therefore we devised and tested a new concept of pre-packed boxes with a complete assortment of swabs, vials and additional tools needed in the operating theatre for non-standard samples during a clinical study of prosthetic joint infections. FINDINGS: The protocol for the clinical study required triplicate samples of joint fluid, periprosthetic tissue, bone tissue, and swabs from the surface of the prosthesis. Separate boxes were prepared for percutaneous joint puncture and surgical revision; the latter included containers for prosthetic components or the entire prosthesis. During a 2-year project period 164 boxes were used by the surgeons, 98 of which contained a complete set of samples. In all, 1508 (89%) of 1685 scheduled samples were received. CONCLUSION: With this concept a high level of completeness of sample sets was achieved and thus secured a valid basis for evaluation of new diagnostics. Although enthusiasm for the project may have been a contributing factor, the extended project period suggests that the ‘All in a box’ concept is equally applicable in routine clinical settings with standardized but complex diagnostic sampling

Heart failure in patients with sick sinus syndrome treated with single lead atrial or dual-chamber pacing:no association with pacing mode or right ventricular pacing site

AIMS: Previous studies indicate that ventricular pacing may precipitate heart failure (HF). We investigated occurrence of HF during long-term follow-up among patients with sick sinus syndrome (SSS) randomized to AAIR or DDDR pacing. Furthermore, we investigated effects of percentage of ventricular pacing (%VP) and pacing site in the ventricle.METHODS AND RESULTS: We analysed data from 1415 patients randomized to AAIR (n = 707) or DDDR pacing (n = 708). Ventricular pacing leads were recorded as located in either an apical or a non-apical position. The %VP and HF hospitalizations were recorded during follow-up. Patients were classified with new HF, if in New York Heart Association (NYHA) functional class IV or if presence of ≥2 of: oedema; dyspnoea; NYHA functional class III. Mean follow-up was 5.4 ± 2.4 years. Heart failure hospitalizations did not differ between groups. In the AAIR group, 170 of the 707 (26%) patients developed HF vs. 169 of the 708 (26%) patients in the DDDR group, hazard rate ratio (HR) 1.00, 95% confidence interval (CI) 0.79-1.22, P = 0.87. In DDDR patients, 146 of the 512 patients (29%) with ventricular leads in an apical position developed HF vs. 28 of the 161 patients (17%) with the leads in a non-apical position, HR 0.67, CI 0.45-1.00, P = 0.05. After adjustments this difference was non-significant. The incidence of HF was not associated with %VP (P = 0.57).CONCLUSION: In patients with SSS, HF was not associated with pacing mode, %VP, or ventricular lead localization. This suggests that DDDR pacing is safe in patients with SSS without precipitating HF

Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery

Since their initial discovery around two decades ago, the yeast autophagy-related (Atg)8 protein and its mammalian homologues of the light chain 3 (LC3) and γ-aminobutyric acid receptor associated proteins (GABARAP) families have been key for the tremendous expansion of our knowledge about autophagy, a process in which cytoplasmic material become targeted for lysosomal degradation. These proteins are ubiquitin-like proteins that become directly conjugated to a lipid in the autophagy membrane upon induction of autophagy, thus providing a marker of the pathway, allowing studies of autophagosome biogenesis and maturation. Moreover, the ATG8 proteins function to recruit components of the core autophagy machinery as well as cargo for selective degradation. Importantly, comprehensive structural and biochemical in vitro studies of the machinery required for ATG8 protein lipidation, as well as their genetic manipulation in various model organisms, have provided novel insight into the molecular mechanisms and pathophysiological roles of the mATG8 proteins. Recently, it has become evident that the ATG8 proteins and their conjugation machinery are also involved in intracellular pathways and processes not related to autophagy. This review focuses on the molecular functions of ATG8 proteins and their conjugation machinery in autophagy and other pathways, as well as their links to disease.</jats:p