Different drugs, different sides: injection use of opioids alone, and not stimulants alone, predisposes to right-sided endocarditis.

OBJECTIVES: Many studies suggest that infective endocarditis (IE) in people who inject drugs is predominantly right sided, while other studies suggest left sided disease; few have differentiated by class of drug used. We hypothesised that based on differing physiological mechanisms, opioids but not stimulants would be associated with right sided IE. METHODS: A retrospective case series of 290 adult (age ≥18) patients with self-reported recent injection drug use, admitted for a first episode of IE to one of three hospitals in London Ontario between April 2007 and March 2018, stratified patients by drug class used (opioid, stimulant or both), and by site of endocarditis. Other outcomes captured included demographics, causative organisms, cardiac and non-cardiac complications, referral to addiction services, medical versus surgical management, and survival. RESULTS: Of those who injected only opioids, 47/71 (69%) developed right-sided IE, 17/71 (25%) developed left-sided IE and 4/71 (6%) had bilateral IE. Of those who injected only stimulants, 11/24 (46%) developed right-sided IE, 11/24 (46%) developed left-sided IE and 2/24 (8%) had bilateral IE. Relative to opioid-only users, stimulant-only users were 1.75 (95% CI 1.05 to 2.93; p=0.031) times more likely to have a left or bilateral IE versus right IE. CONCLUSIONS: While injection use of opioids is associated with a strong predisposition to right-sided IE, stimulants differ in producing a balanced ratio of right and left-sided disease. As the epidemic of crystal methamphetamine injection continues unabated, the rate of left-sided disease, with its attendant higher morbidity and mortality, may also grow.

The Relationship Between Arterial Stiffness and Resistance Training.

Exercise is a critical factor that impacts arterial stiffness. In this narrative review, we noted multiple findings that could not be reconciled with one another. Some studies indicated that arterial stiffness increases after a regimen of resistance training. However, such studies were limited by a lack of specification of the resistance training protocols, as well as varying results reported from different areas of the body, undermining the internal validity of the studies. Another factor explored in this review was how the order of performing exercises can affect arterial stiffness. Low-intensity resistance training before high-intensity resistance training resulted in increased arterial stiffness, whereas vice versa showed no change in arterial stiffness. Other studies indicated that resistance exercise results in reduced arterial stiffness. Intensity is a variable in studies that produces inconsistent results of arterial stiffness, with some studies suggesting high-intensity resistance training increases arterial stiffness and low-intensity resistance training decreases arterial stiffness, while other studies pointing to a significant decrease in arterial stiffness, regardless of the intensity of resistance training. Demographic factors such as gender, age, and diet play an important role in explaining these differences. In terms of future implications, there is potential clinical significance as increased arterial stiffness serves as a prognostic marker in diagnosing coronary heart disease.

A randomized double-blind controlled trial comparing three sedation regimens during flexible bronchoscopy: Dexmedetomidine, alfentanil and lidocaine.

INTRODUCTION: No standardized sedation protocol is available for flexible bronchoscopy (FB). OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of three regimens used for sedation during FB. METHODS: This randomized double-blind controlled trial assessed patients undergoing bronchoscopy and receiving lidocaine alone (C) or combined with dexmedetomidine (D) or alfentanil (A). Tolerance was assessed using the bronchoscopy score, and level of sedation was assessed using the Nursing Instrument for the Communication of Sedation. Safety was evaluated in terms of pulmonary function and vital signs. RESULTS: A total of 162 patients were enrolled. The bronchoscopy score was identical in all groups. Group D subjects were the most sedated (P = .013), whereas group A subjects were the least agitated. Linear regression showed a negative association between bronchoscopy score and age in A (ß = -0.06; P = .001). Positive predictors of bronchoscopy score were female gender (ß = 1.96; P = .003) in D and obesity (ß = 2.41; P = .012), longer procedures (ß = 0.08; P = .009) and female gender (ß = 1.15; P = .038) in C. Longer procedures (ß = -0.12; P = .010) was a negative predictor of bronchoscopy score in D. Desaturation, hypoxia and heart rate changes were most prevalent in group A. Hypotension was mostly observed in D. CONCLUSIONS: No consistent differences were present between the three regimens; however, each was more appropriate in certain patient profiles. We consequently proposed a protocol as a first step towards standardizing sedation practice in FB in a patient-tailored manner. A more comprehensive and detailed protocol including other sedative agents with their corresponding doses should be developed.

Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu.

The synthesis of a series of novel 3,4-cis- and 3,4-trans-substituted carbocyclic nucleoside analogs from protected uracil and thymine is described. The key reaction in the followed synthetic protocols utilized the Mitsunobu reaction to couple 3,4-substituted cyclopentanols to (3)N-benzoyl uracil or (3)N-benzoyl thymine. These molecules were evaluated with regard to their ability to treat diabetic nephropathy. Our results show that two analogs significantly reduced high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro and, more interestingly, exhibited an anti-oxidative effect suggesting that the activity may be mediated through ROS-dependent mechanism.