Predictive Factors for Limb Salvage and Foot Ulcer Recurrence in Patients with Chronic Limb-Threatening Ischemia After Multidisciplinary Team Treatment: A 6-Year Japanese Single-Center Study.

Chronic limb-threatening ischemia (CLTI) is associated with a short-term risk of limb loss. Multidisciplinary teams are often involved in CLTI treatment; however, in Asian countries, multidisciplinary teams that include podiatrists specializing in foot wounds and vascular surgeons who can perform distal bypass surgery are lacking. We investigated predictive factors for limb salvage and foot ulcer recurrence in patients with CLTI treated by a Japanese single-center intensive multidisciplinary team over 6 years. We retrospectively investigated 84 patients with CLTI and foot ulcers who had undergone revascularization and wound treatment between October 2013 and December 2019. Following postrevascularization treatment, including undertaking minor amputations, the healing rate was 77.8%, and the average wound healing time was 75 ± 68 days. To achieve adequate blood supply, 17.7% of patients were treated using a combination of endovascular revascularization and bypass surgeries. Thirty-three (44%) patients had wound recurrence and there was wound recurrence within 6 months in 58.9% of these patients. Multivariate logistic regression analysis showed that postrevascularization skin perfusion pressure was significantly associated with wound healing (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.033-1.243, P = .0078). Diabetes mellitus (OR 9.72, 95% CI 1.855-50.937, P = .0071), and heart disease (OR 3.51, 95% CI 1.052-11.693, P = .0411) were significantly associated with wound recurrence (P < .05). Treatment within a single-center intensive multidisciplinary team resulted in good patient outcomes. Our study indicates that the revascularization endpoint of CLTI treatment should be marked by attainment of adequate blood supply and wound healing. The timing of revascularization and debridement is of utmost importance for the successful treatment of CLTI wounds.

Treatment of sick sinus syndrome in a patient with cardiac lymphoma via chemotherapy without pacemaker implantation: A case report.

Successful treatment of the acute phase of bradycardia in patients with cardiac lymphoma via medical therapy alone has not been reported. This case report describes the successful treatment of sick sinus syndrome in an 84-year-old man with cardiac lymphoma via chemotherapy without pacemaker implantation.

Novel mechanism of regulation of the 5-lipoxygenase/leukotriene B4 pathway by high-density lipoprotein in macrophages.

High-density lipoprotein (HDL) interacts with various cells, particularly macrophages, in functional cell-HDL interactions. Here, we found that HDL protein quality and lipid quality play critical roles in HDL functions. HDL fractions from healthy volunteers (HDLHealthy) and patients with recurrent coronary atherosclerotic disease (HDLCAD) were prepared. To analyse functional HDL-macrophage interactions, macrophages were co-incubated with each HDL, and lipid mediator production was assessed by liquid chromatography/mass spectrometry-based metabololipidomics. HDLHealthy treatment attenuated the pro-inflammatory lipid mediator production, particularly that of leukotriene (LT) B4, and this treatment enhanced lipoxin (LX) B4 and resolvin (Rv) E2 production. HDLHealthy treatment enhanced the proteasome-mediated degradation of the LTB4-producing enzyme 5-lipoxygenase (LO) in activated macrophages; however, HDLCAD did not show these anti-inflammatory effects. HDLHealthy was engulfed by macrophages via clathrin-mediated endocytosis, which was a critical step in 5-LO/LTB4 regulation. We also found that HDLCAD showed higher levels of the LTB4-producing enzymes and thus promoted LTB4 production from HDLCAD. In addition, LTB4 attenuated HDL endocytosis, HDL-mediated 5-LO degradation in macrophages, and HDL-derived augmentation of macrophage phagocytosis. These results indicated that local LTB4 produced de novo from HDLCAD regulates HDL-macrophage functional interactions and plays critical roles in dysfunctional, inflammatory HDL characteristics.

2-Aminobutyric acid modulates glutathione homeostasis in the myocardium.

A previous report showed that the consumption of glutathione through oxidative stress activates the glutathione synthetic pathway, which is accompanied by production of ophthalmic acid from 2-aminobutyric acid (2-AB). We conducted a comprehensive quantification of serum metabolites using gas chromatography-mass spectrometry in patients with atrial septal defect to find clues for understanding myocardial metabolic regulation, and demonstrated that circulating 2-AB levels reflect hemodynamic changes. However, the metabolism and pathophysiological role of 2-AB remains unclear. We revealed that 2-AB is generated by an amino group transfer reaction to 2-oxobutyric acid, a byproduct of cysteine biosynthesis from cystathionine. Because cysteine is a rate-limiting substrate for glutathione synthesis, we hypothesized that 2-AB reflects glutathione compensation against oxidative stress. A murine cardiomyopathy model induced by doxorubicin supported our hypothesis, i.e., increased reactive oxygen species are accompanied by 2-AB accumulation and compensatory maintenance of myocardial glutathione levels. Intriguingly, we also found that 2-AB increases intracellular glutathione levels by activating AMPK and exerts protective effects against oxidative stress. Finally, we demonstrated that oral administration of 2-AB efficiently raises both circulating and myocardial glutathione levels and protects against doxorubicin-induced cardiomyopathy in mice. This is the first study to demonstrate that 2-AB modulates glutathione homeostasis in the myocardium.