Cell-sheet Therapy With Omentopexy Promotes Arteriogenesis and Improves Coronary Circulation Physiology in Failing Heart

Cell-sheet transplantation induces angiogenesis for chronic myocardial infarction (MI), though insufficient capillary maturation and paucity of arteriogenesis may limit its therapeutic effects. Omentum has been used clinically to promote revascularization and healing of ischemic tissues. We hypothesized that cell-sheet transplantation covered with an omentum-flap would effectively establish mature blood vessels and improve coronary microcirculation physiology, enhancing the therapeutic effects of cell-sheet therapy. Rats were divided into four groups after coronary ligation; skeletal myoblast cell-sheet plus omentum-flap (combined), cell-sheet only, omentum-flap only, and sham operation. At 4 weeks after the treatment, the combined group showed attenuated cardiac hypertrophy and fibrosis, and a greater amount of functionally (CD31⁺/lectin⁺) and structurally (CD31⁺/α-SMA⁺) mature blood vessels, along with myocardial upregulation of relevant genes. Synchrotron-based microangiography revealed that the combined procedure increased vascularization in resistance arterial vessels with better dilatory responses to endothelium-dependent agents. Serial ¹³N-ammonia PET showed better global coronary flow reserve in the combined group, mainly attributed to improvement in the basal left ventricle. Consequently, the combined group had sustained improvements in cardiac function parameters and better functional capacity. Cell-sheet transplantation with an omentum-flap better promoted arteriogenesis and improved coronary microcirculation physiology in ischemic myocardium, leading to potent functional recovery in the failing heart.     

Salvage esophagectomy combined with partial aortic wall resection following thoracic endovascular aortic repair

Objective

Definitive chemoradiotherapy is useful for locally advanced esophageal cancer. However, salvage esophagectomy is required when residual or recurrent tumor is evident after chemoradiotherapy. We performed salvage esophagectomy combined with partial aortic wall resection after thoracic endovascular aortic repair for aortic invasion, and we evaluated the results.

Methods

Four patients underwent esophagectomy combined with aortic wall resection after thoracic endovascular aortic repair because the lesion was diagnosed as stage T4b. We evaluated short-term outcomes, including duration of thoracic surgery, blood loss, duration of intubation, intensive care unit stay, and postoperative morbidity, as well as survival after salvage surgery.

Results

Lesions were resected with no intraoperative procedural adverse events. Mean thoracic operation time was 444 min, and mean thoracic blood loss was 506 g. In all patients, complete resection of the lesion was possible with no intraoperative adverse events. All patients were extubated on postoperative day 0, and all were discharged from the intensive care unit on postoperative day 1. One patient experienced grade II wound pain (bilateral chest pain), and another patient experienced difficult sputum expectoration (grade IIIA). The mean follow-up time was 19.8 months, and two patients were alive with no disease recurrence at the time of this report. However, the remaining two patients had died secondary to lymph node metastasis.

Conclusions

Salvage esophagectomy combined with partial aortic wall resection after thoracic endovascular aortic repair provides acceptable short-term outcomes. Future studies are needed to evaluate long-term survival and patient selection criteria.

     

Identification of Human Neutrophil-derived Cathepsin G and Azurocidin/CAP37 as Chemoattractants for Mononuclear Cells and Neutrophils

Macrophage infiltration into inflammatory sites is generally preceded by neutrophils. This suggests neutrophils may be the source of chemotactic factors for monocytes. To identify these putative monocyte attractants, we have systematically prepared neutrophil granules, lysed them, and sequentially purified the released proteins by several reverse phase chromatography procedures. Assays for monocyte chemotactic activity of the chromatography fractions yielded a major peak of activity associated with a protein of 30 kD, according to SDS-PAGE analysis. NH₂-terminal sequence of the protein revealed this to be identical to cathepsin G. The monocyte chemotactic activity of human cathepsin G was dose dependent with optimal concentration at 0.5–1 μg/ml. Cathepsin G is chemotactic rather than chemokinetic for monocytes, as demonstrated by checkerboard analysis. Cathepsin G–induced monocyte chemotaxis is partially pertussis toxin sensitive implying the involvement of a G protein–coupled receptor. Enzymatic activity of cathepsin G is associated with its monocyte chemotactic activity, since DFP- or PMSF-inactivated cathepsin G no longer induced monocyte migration. The chemotactic activity of cathepsin G can also be completely blocked by α₁ antichymotrypsin, a specific inhibitor of chymotrypsin-like proteinases present in human plasma. In addition, cathepsin G is also a potent chemoattractant for neutrophils and a chemokinetic stimulant for T cells. In the course of pursuing these in vitro studies, we established that the T cell chemoattractant, azurocidin/CAP37 from human neutrophil granules, at doses of 0.05 to 5 μg/ml, was chemotactic for monocytes and neutrophils. As predicted from the in vitro chemotactic activity, subcutaneous injection of cathepsin G into BALB/c mice led to infiltration of both mononuclear cells and neutrophils. Thus, the transition of inflammatory exudate from neutrophil to mononuclear cells can be mediated, at least in part, by extracellular release of neutrophil granule proteins such as cathepsin G and azurocidin/CAP37.     

Influence of intra-operative parameters on postoperative early recovery of active knee flexion in posterior-stabilized total knee arthroplasty

Purpose

Active knee flexion is more important for daily activities than passive knee flexion. The hypothesis is that the intra-operative parameters such as osteotomized bone thickness and soft tissue balance affect the postoperative active flexion angle in total knee arthroplasty (TKA). Therefore, we evaluate the influence of intra-operative parameters on postoperative early recovery of active flexion after posterior-stabilized (PS) TKA.

Methods

The subjects were 45 osteoarthritic knees undergoing primary PS TKA with anterior-reference technique. Intra-operative soft tissue balance was measured using an offset type tensor, and each osteotomized bone thickness was also measured. Pre- and postoperative active knee flexion angles were measured using lateral radiographs. Liner regression analysis was used to determine the influence of these intra-operative parameters on postoperative active flexion angles or recovery of active flexion angles.

Results

Pre-operative flexion angle was positively correlated with postoperative flexion angle (R?=?0.52, P?=?0.0002). Postoperative flexion angle was negatively correlated with the osteotomized bone thickness of femoral medial posterior condyle (R?=??0.37, P?=?0.012), and femoral lateral posterior condyle (R?=??0.36, P?=?0.015). Recovery of flexion angle was slightly negatively correlated with gap difference calculated by subtracting joint gap at extension from that at flexion between osteotomized surfaces (R?=??0.30, P?=?0.046).

Conclusions

The osteotomized bone thickness of the femoral posterior condyle is a significant independent factor of postoperative flexion angles. This indicates that the restoration of the posterior condyle offset may lead to larger postoperative active flexion angles in PS TKA.     

Development of a new immunoassay for the accurate determination of anti-infliximab antibodies in inflammatory bowel disease

Background  

The formation of antibodies to infliximab (ATIs) is closely associated with the loss of response to infliximab in patients with inflammatory bowel disease (IBD). We evaluated the clinical utility of a novel method to measure serum ATI levels in the presence of infliximab.