Early and late outcomes of coronary artery bypass surgery versus percutaneous coronary intervention with drug-eluting stents for dialysis patients

Abstract Background: Advances in percutaneous coronary intervention (PCI) using drug‐eluting stents (DES) have impacted clinical practice. However, the efficacy of DES for dialysis patients still remains controversial. This study compares the early and long‐term clinical outcomes of coronary artery bypass grafting (CABG) and PCI with DES in dialysis patients. Methods: A retrospective review was performed in 125 dialysis patients treated between 2004 and 2007. Fifty‐eight patients underwent CABG and 67 underwent PCI with DES. The overall death, cardiac death, and cardiac‐related event rates were analyzed using the Kaplan‐Meier method. For the risk‐adjusted comparisons, multivariable logistic and Cox regression analyses were used. Results: The preoperative characteristics of the patients were similar except for the ejection fraction (p = 0.002) and the number of diseased vessels (p < 0.001). The 30‐day mortality was 0 in both groups. The overall survival rates at one, three, and five years were 84.2%, 64.7%, and 56.2% in CABG group and 88.2%, 75.5%, and 61.7% in DES group, respectively (p = 0.202). The rates of freedom from cardiac‐related events at one, three, and five years were 76.6%, 68.1%, and 48.6%, and 63.0%, 31.4%, and 0% in CABG and DES groups (p < 0.001), respectively, including seven (10%) late thromboses in the DES group. Although the risk‐adjusted analysis showed no significant difference for overall and cardiac death rates, the rates of cardiac‐related events and graft/stent failure were significantly higher in the DES group. Conclusions: CABG is superior for revascularization in dialysis patients compared with PCI using DES in terms of freedom from cardiac‐related events. (J Card Surg 2012;27:281‐287)     

Rapid growth hormone measurement during transsphenoidal surgery: analysis of 252 acromegalic patients

The usefulness of rapid growth hormone (GH) measurement was retrospectively evaluated as an indicator of total tumor removal during surgery and compared with several reported criteria in 252 acromegalic patients who underwent transsphenoidal surgery at Toranomon Hospital between 2006 and 2008. GH levels were measured in blood samples obtained before surgery, at the start of tumor removal, and every 20 minutes thereafter until 20 minutes after total tumor removal as judged by the operator. Intraoperative GH dynamics were compared between 201 patients fulfilling the Cortina consensus criteria (successful group) and 37 patients who did not (unsuccessful group). Among several criteria indicating total tumor removal, only the ratio of serum GH level 20 minutes after the end of tumor removal to GH level at the end of tumor excision was significantly different between the groups; a reduction ratio of 65% was the most appropriate cut-off value based on sensitivity (59.2%) and specificity (59.5%). The ratio of GH level 20 minutes after the end of tumor removal/GH level at the end of tumor excision was the most reliable index to judge tumor removal during surgery, but this index is neither necessary nor sufficient and should be used as one of the indicators to judge complete tumor removal during surgery.     

3β-Hydroxysterol-Delta24 reductase plays an important role in long bone growth by protecting chondrocytes from reactive oxygen species

Desmosterolosis is an autosomal recessive disease caused by mutations in the 3β-hydroxysterol-Delta24 reductase (DHCR24) gene, with severe developmental anomalies including short limbs. We utilized DHCR24 knockout (KO) mice to study the underlying bone pathology. Because the KO mice died within a few hours after birth, we cultured metatarsal bones from newborn mice. The growth of bones from KO mice was significantly retarded after 1 week of culture. Absence of proliferating chondrocytes in the growth plate and abnormal hypertrophy of prehypertrophic chondrocytes were observed in the bones from KO mice. Hypertrophic differentiation was evidenced by higher expression of Indian hedgehog, alkaline phosphatase, and matrix metalloproteinase 13. Since elevated levels of reactive oxygen species (ROS) during chondrogenesis are known to inhibit proliferation and to initiate chondrocyte hypertrophy in the growth plate, and since DHCR24 acts as a potent ROS scavenger, we hypothesized that the abnormal chondrocyte proliferation and differentiation in KO mice were due to decreased ROS scavenging activity. Treatment with an antioxidant, N-acetyl cysteine, could correct the abnormalities observed in the bones from KO mice. Treatment of bones from wild-type mice with U18666A, a chemical inhibitor of DHCR24, resulted in short broad bones with a disrupted proliferating zone. Treatment of ATDC cells with hydrogen peroxide (H₂O₂) induced hypertrophic changes as evidenced by the expression of the marker genes specific for hypertrophic chondrocyte differentiation. H₂O₂-induced hypertrophic change was prevented by adenoviral delivery of DHCR24. Induction of chondrocyte differentiation in ATDC cells by insulin was associated with increased ROS production that was markedly enhanced by treatment of ATDC5 cells with DHCR24 siRNA. This is the first demonstration that DHCR24 plays an important role in long bone growth by protecting chondrocytes from ROS     

l-Leucine influx through Slc7a5 regulates inflammatory responses of human B cells via mammalian target of rapamycin complex 1 signaling

Abstract

Objectives: Increasing evidence has revealed the close correlation between immune cell functions and their intracellular metabolism. Mammalian target of rapamycin complex 1 (mTORC1) is the important metabolism-modulating signal that regulates cellular activities. In certain types of cell, it is known that mTORC1 activation depends on influx of l-leucine through an amino acid transporter, Slc7a5. In B cells, however, the expression and the role of Slc7a5 have never been investigated.

Methods: CD19⁺ B cells were obtained from peripheral blood of healthy adults and stimulated by a toll-like receptor 9 ligand, CpG oligodeoxynucleotides. The expression of Slc7a5 and l-leucine uptake were evaluated by RT-PCR, flow cytometry and radioisotope assay. Then the effect of Slc7a5 inhibition on mTORC1 activity, plasmablast differentiation and production of IgG and inflammatory cytokines were analyzed.

Results: CpG stimulation significantly induced the expression of Slc7a5 in B cells, resulting in l-leucine influx. Furthermore, inhibition of Slc7a5 abrogated mTORC1 activation, plasmablast differentiation, and production of IgG and inflammatory cytokines in CpG-stimulated B cells.

Conclusion: l-leucine influx through Slc7a5 critically regulates mTORC1 activity and the immunological responses of human B cells. Slc7a5-mTORC1 pathway may provide a novel therapeutic strategy for autoimmune diseases.