Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden

Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r²=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 μM [54.8–133.0 μM] for dialysis-dependent patients versus 3.3 μM [3.1–6.0 μM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min–max] 71.2 μM [29.2–189.7 μM] pretransplant versus 11.4 μM [8.9–20.2 μM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 μM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography.     

Low vs Standard Pressures in Gynecologic Laparoscopy: a Systematic Review

Background:

The optimal intraperitoneal pressure during laparoscopy is not known. Recent literature found benefits of using lower pressures, but the safety of doing abdominal surgery with low peritoneal pressures needs to be assessed. This systematic review compares low with standard pneumoperitoneum during gynecologic laparoscopy.

Database:

We searched Medline, Embase, and the Cochrane Library for randomized controlled trials comparing intraperitoneal pressures during gynecologic laparoscopy. Two authors reviewed references and extracted data from included trials. Risk ratios, mean differences, and standard mean differences were calculated and pooled using RevMan5. Of 2251 studies identified, three were included in the systematic review, for a total of 238 patients. We found a statistically significant but modest diminution in postoperative pain of 0.38 standardized unit based on an original 10-point scale (95% confidence interval [CI], –0.67 to –0.08) during the immediate postoperative period when using low intraperitoneal pressure of 8 mm Hg compared with ≥12 mm Hg and of 0.50 (95% CI, –0.80 to –0.21) 24 hours after the surgery. Lower pressures were associated with worse visualization of the surgical field (risk ratio, 10.31; 95% CI, 1.29–82.38). We found no difference between groups over blood loss, duration of surgery, hospital length of stay, or the need for increased pressure.

Conclusion:

Low intraperitoneal pressures during gynecologic laparoscopy cannot be recommended on the behalf of this review because improvement in pain scores is minimal and visualization of the surgical field is affected. The safety of this intervention as well as cost-effectiveness considerations need to be further studied.     

Neurokinin receptors modulate the impact of uncontrollable stimulation on adaptive spinal plasticity

Previous research has demonstrated that spinally transected rats can acquire a prolonged flexion response to prevent the delivery of shock. However, rats that receive shock irrespective of leg position cannot learn to maintain the same response. The present experiments examined the role of neurokinin receptors in this learning deficit. Results demonstrated that neurokinin (NK1 and NK2) antagonists blocked the induction of the learning deficit, whereas NK agonists induced a learning deficit. The study found that NK agonist administration did not substitute for uncontrollable shock exposure. Finally, administration of an NK1 agonist prior to uncontrollable shock prevented the induction of the deficit. These results provide additional evidence that engaging nociceptive plasticity undermines the capability of spinal neurons to support adaptive changes.     

Neonatal hind-paw injury disrupts acquisition of an instrumental response in adult spinal rats

The present study was designed to evaluate the impact of neonatal injury on adult spinal plasticity in rats. Subjects were randomly assigned to 1 of 4 experimental conditions: (a) hind-paw injury at Postnatal Day (PD) 2, (b) hind-paw injury at PD 5, (c) anesthesia exposure only on PD 2, or (d) anesthesia exposure only on PD 5. Subjects receiving a unilateral neonatal hind-paw injury showed decreased mechanical threshold (hyperalgesia) on the previously injured hind paw throughout development. This decrease in threshold survived spinal transection (at T2) at 12 weeks of age. Injured subjects also showed significant impairment in a spinal instrumental learning task performed by the previously injured hind paw. This disruption of learning indicates a disruption of spinal plasticity that may be due to induction of long-term changes in nociceptive processing within the spinal cord.