Primary lower limb joint replacement and tranexamic acid: an observational cohort study.

BACKGROUND: This work aimed to evaluate the efficacy and safety of routine tranexamic acid (TXA) use in elective orthopaedic lower limb joint replacement surgery. METHODS: This retrospective cohort study included all primary hip or knee replacement procedures by a single surgeon over a 6-year period. TXA was introduced during the study period as part of an enhanced recovery after surgery strategy. RESULTS: Of the 673 procedures, 446 cases (66.3%) received TXA. The median length of stay was 5 days (2-69) and 6 days (3-28) for the TXA and control groups, respectively (P < .001). Blood transfusion was required for 28 (6.3%) of the TXA cases versus 40 (17.6%) controls (P < .001). Complication rates were similar irrespective of TXA status. At multivariate analysis, TXA was significantly and independently associated with fewer blood transfusions (hazard ratio 0.309, 95% confidence interval: 0.168-0.568, P < .001), with a number needed to treat of 9 cases. TXA use was estimated to save between £67.89 and £155.90 per case. CONCLUSIONS: Routine prophylactic TXA administration for elective primary hip and knee replacement reduces the likelihood of postoperative transfusion with a number needed to treat of 9. Cost savings may be as high as £155.90 per case, and no safety concerns were noted.

The role of thermal physiology in recent declines of birds in a biodiversity hotspot.

We investigated whether observed avian range contractions and population declines in the Fynbos biome of South Africa were mechanistically linked to recent climate warming. We aimed to determine whether there were correlations between preferred temperature envelope, or changes in temperature within species' ranges, and recent changes in range and population size, for 12 Fynbos-resident bird species, including six that are endemic to the biome. We then measured the physiological responses of each species at air temperatures ranging from 24 to 42°C to determine whether physiological thermal thresholds could provide a mechanistic explanation for observed population trends. Our data show that Fynbos-endemic species occupying the coolest regions experienced the greatest recent reductions in range and population size (>30% range reduction between 1991 and the present). In addition, species experiencing the largest increases in air temperature within their ranges showed the greatest declines. However, evidence for a physiological mechanistic link between warming and population declines was equivocal, with only the larger species showing low thermal thresholds for their body mass, compared with other birds globally. In addition, some species appear more vulnerable than others to air temperatures in their ranges above physiological thermal thresholds. Of these, the high-altitude specialist Cape rockjumper (Chaetops frenatus) seems most at risk from climate warming. This species showed: (i) the lowest threshold for increasing evaporative water loss at high temperatures; and (ii) population declines specifically in those regions of its range recording significant warming trends. Our findings suggest that caution must be taken when attributing causality explicitly to thermal stress, even when population trends are clearly correlated with rates of warming. Studies explicitly investigating the mechanisms underlying such correlations will be key to appropriate conservation planning.

The detrimental effects of acute hyperglycemia on myocardial glucose uptake.

AIMS: Although acute hyperglycemic (AHG) episodes are linked to lower glucose uptake, underlying mechanisms remain unclear. We hypothesized that AHG triggers reactive oxygen species (ROS) production and increases non-oxidative glucose pathway (NOGP) activation, i.e. stimulation of advanced glycation end products (AGE), polyol pathway (PP), hexosamine biosynthetic pathway (HBP), PKC; thereby decreasing cardiac glucose uptake. MAIN METHODS: H9c2 cardiomyoblasts were exposed to 25 mM glucose for 24h vs. 5.5mM controls ± modulating agents during the last hour of glucose exposure: a) antioxidant #1 for mitochondrial ROS (250 µM 4-OHCA), b) antioxidant #2 for NADPH oxidase-generated ROS (100 µM DPI), c) NOGP inhibitors - 100 µM aminoguanidine (AGE), 5 µM chelerythrine (PKC); 40 µM DON (HBP); and 10 µM zopolrestat (PP). ROS levels (mitochondrial, intracellular) and glucose uptake were evaluated by flow cytometry. KEY FINDINGS: AHG elevated ROS, activated NOGPs and blunted glucose uptake. Transketolase activity (pentose phosphate pathway [PPP] marker) did not change. Respective 4-OHCA and DPI treatment blunted ROS production, diminished NOGP activation and normalized glucose uptake. NOGP inhibitory studies identified PKCßII as a key downstream player in lowering insulin-mediated glucose uptake. When we employed an agent (benfotiamine) known to shunt flux away from NOGPs (into PPP), it decreased ROS generation and NOGP activation, and restored glucose uptake under AHG conditions. SIGNIFICANCE: This study demonstrates that AHG elicits maladaptive events that function in tandem to reduce glucose uptake, and that antioxidant treatment and/or attenuation of NOGP activation (PKC, polyol pathway) may limit the onset of insulin resistance.