Diagnosis and management for urosepsis

Urosepsis is defined as sepsis caused by a urogenital tract infection. Urosepsis in adults comprises approximately 25% of all sepsis cases, and is in most cases due to complicated urinary tract infections. The urinary tract is the infection site of severe sepsis or septic shock in approximately 10–30% of cases. Severe sepsis and septic shock is a critical situation, with a reported mortality rate nowadays still ranging from 30% to 40%. Urosepsis is mainly a result of obstructed uropathy of the upper urinary tract, with ureterolithiasis being the most common cause. The complex pathogenesis of sepsis is initiated when pathogen or damage‐associated molecular patterns recognized by pattern recognition receptors of the host innate immune system generate pro‐inflammatory cytokines. A transition from the innate to the adaptive immune system follows until a T_H2 anti‐inflammatory response takes over, leading to immunosuppression. Treatment of urosepsis comprises four major aspects: (i) early diagnosis; (ii) early goal‐directed therapy including optimal pharmacodynamic exposure to antimicrobials both in the plasma and in the urinary tract; (iii) identification and control of the complicating factor in the urinary tract; and (iv) specific sepsis therapy. Early adequate tissue oxygenation, adequate initial antibiotic therapy, and rapid identification and control of the septic focus in the urinary tract are critical steps in the successful management of a patient with urosepsis, which includes early imaging, and an optimal interdisciplinary approach encompassing emergency unit, urological and intensive‐care medicine specialists.     

Assessment of myocardial triglyceride oxidation with PET and 11C-palmitate

Background  The goal of this study was to test whether myocardial triglyceride (TG) turnover including oxidation of TG-derived fatty acids (FA) could be assessed with PET and ¹¹C-palmitate. Methods and Results  A total of 26 dogs were studied fasted (FAST), during Intralipid infusion (IL), during a hyperinsulinemic-euglycemic clamp without (HIEG), or with Intralipid infusion (HIEG + IL). ¹¹C-palmitate was injected, and 45 minutes were allowed for labeling of myocardial TG pool. 3D PET data were then acquired for 60 minutes, with first 15 minutes at baseline followed by 45 minutes during cardiac work stimulated with constant infusion of either phenylephrine (FAST, n = 6; IL, n = 6; HIEG + IL, n = 6) or dobutamine (FAST, n = 4; HIEG, n = 4). Myocardial ¹¹C washout during adrenergic stimulation (AS) was fitted to a mono-exponential function (Km(PET)). To determine the source of this ¹¹C clearance, Km(PET) was compared to direct coronary sinus-arterial measurements of total ¹¹C activity, ¹¹C-palmitate, and ¹¹CO₂. Before AS, PET curves in all groups were flat indicating absence of net clearance of ¹¹C activity from heart. In both FAST groups, AS resulted in negligible net ¹¹C activity and ¹¹CO₂ production higher than net ¹¹C-palmitate uptake. AS with phenylephrine resulted in net myocardial uptake of total ¹¹C activity and ¹¹C-palmitate in IL and HIEG + IL, and ¹¹CO₂ production lower than ¹¹C-palmitate uptake. In contrast, AS with dobutamine in HIEG resulted in net clearance of all ¹¹C metabolites (total ¹¹C activity, ¹¹C-palmitate and ¹¹CO₂) with ¹¹CO₂ contributing 66% to endogenous FA oxidation. The AS resulted in significant Km(PET) in all the groups, except HIEG + IL. However, positive correlation between Km(PET) and ¹¹CO₂ was observed only in HIEG (R ² = 0.83, P = .09). Conclusions  This is the first study to demonstrate that using PET and pre-labeling of intracardiac TG pool with ¹¹C-palmitate, noninvasive assessment of myocardial TG use is feasible under metabolic conditions that favor endogenous TG use such as increased metabolic demand (β-adrenergic stimulation of cardiac work) with limited availability of exogenous substrate (HIEG).