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Background: Diabetes is a common disease marked by high blood sugars. An earlier clinical trial in type 1 diabetic subjects (T1Ds) found that repeat BCG vaccinations succeeded in lowering HbA1c values over a multi-year course. Here we seek to determine whether BCG therapy for bladder cancer may improve blood sugar levels in patients with comorbid T1D and type 2 diabetes (T2D). We also investigate whether BCG exposure may reduce onset of T1D and T2D by examining country-by-country impact of BCG childhood vaccination policies in relation to disease incidence. Methods and findings: We first analyzed three large US patient datasets (Optum Labs data [N = 45 million], Massachusetts General Brigham [N = 6.5 million], and Quest Diagnostics [N = 263 million adults]), by sorting out subjects with documented T1D (N = 19) or T2D (N = 106) undergoing BCG therapy for bladder cancer, and then by retrospectively assessing BCG's subsequent year-by-year impact on blood sugar trends. Additionally, we performed an ecological analysis of global data to assess the country-by-country associations between mandatory neonatal BCG vaccination programs and T1D and T2D incidence. Multi-dose BCG therapy in adults with comorbid diabetes and bladder cancer was associated with multi-year and stable lowering of HbA1c in T1Ds, but not in T2Ds. The lack of a similar benefit in T2D may be due to concurrent administration of the diabetes drug metformin, which inhibits BCG's beneficial effect on glycolysis pathways. Countries with mandatory neonatal BCG vaccination policies had a lower incidence of T1D in two international databases and a lower incidence of T2D in one of the databases. Conclusions: The epidemiological evidence analyzed here suggests that BCG may play a role in the prevention of T1D. It does not support prevention of T2D, most likely because of interference by metformin. Our ecological analysis of global data suggests a role for neonatal BCG in the prevention of T1D and, to a lesser extent, T2D. Randomized clinical trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Abstract: Background: Growing evidence suggests that the epicardial adipose tissue may have local interactions with coronary arteries. In addition, vasoactive peptides such as adrenomedullin and natriuretic peptide has an interaction with adipose tissue. In this study, we investigated the relationship between adipokines, adipocytokines, and vasoactive peptides expressed in epicardial adipose tissue and subcutaneous adipose tissue in patients with and without coronary artery disease (CAD). Methods: We studied 20 patients with CAD and 14 patients without CAD. We obtained blood samples and epicardial and subcutaneous adipose tissue at open-heart surgery. We measured serum cytokine levels and used real-time polymerase chain reaction (PCR) to measure mRNA levels of various molecules in epicardial and subcutaneous tissue and investigated the relation between mRNA levels and clinical parameters. Results: The mRNA levels of IL-6, IL-1beta, MCP-1, and TNF-alpha were significantly higher in epicardial adipose tissue than in subcutaneous adipose tissue. Interestingly, the mRNA levels of IL-6, IL-1beta, MCP-1, natriuretic peptide receptor-C (NPR-C), adrenomedullin, and leptin in epicardial adipose tissue were higher in patients with CAD than those without CAD. In contrast, mRNA levels of adiponectin, PPAR-gamma, and NPR-A were similar in the two groups. In subcutaneous tissue, mRNA expressions of IL-6, IL-1beta, MCP-1, NPR-C, adrenomedullin, and leptin were modestly higher in patients with CAD than in those without CAD. There were no differences in plasma cytokine levels between the two groups. Conclusion: The mRNA levels of inflammatory cytokines, adipokines, neurohumoral factors and their receptors appear to be increased in epicardial adipose tissue independent of plasma levels of these molecules. Further studies are necessary to elucidate the pathophysiological role of these molecules in CAD. [ABSTRACT FROM AUTHOR]

Heart-lung transplantation (HLT), followed by single lung transplantation (SLT) and subsequently bilateral lung transplantation (BLT) have been developed as treatments for patients with end-stage pulmonary diseases. Initially, SLT was limited to idiopathic pulmonary fibrosis (IPF) cases and thought to be contraindicated not only for infectious diseases, but also for non-infectious diseases, including pulmonary emphysema (PE) and primary pulmonary hypertension (PPH), based on physiologic points of view. However, SLT is now widely performed for those non-infectious diseases and most of the recipients return to a normal active life. It is quite possible that BLT is superior to SLT in terms of pulmonary function, and it has been reported that BLT is better for PE and PPH patients in regards to perioperative course, postoperative exercise capacity, and long-term survival. For those situations and because of the present scarcity of donor organs, SLT must be utilized for selected non-infectious diseases for which it is safe and effective. When a single lung is replaced for IPF, PE, and PPH recipients, different physiologic situations are produced postoperatively, the understanding of which is extremely important to achieve good results, not only in the perioperative but also in the long term.

Brachiocephalic artery aneurysm with concomitant coronary artery aneurysm is rare. We describe a case of a patient with a history of prosthetic graft placement following resection of an abdominal aortic aneurysm and was subsequently found to have a brachiocephalic artery aneurysm. After surgical correction of the brachiocephalic aneurysm, postoperative coronary arteriography demonstrated coronary artery aneurysms, and the patient subsequently underwent coronary artery bypass grafting (CABG).

Severe mitral annular calcification is frequently encountered in patients with chronic renal failure requiring dialysis. The procedures are described for the implantation of mitral prostheses in two dialysis patients with mitral stenosis who exhibited heavily calcified mitral annuli. In both cases the calcifications extended around the entire mitral annulus as well as the valve leaflets, papillary muscle, atrial wall and ventricular myocardium, making it impossible to secure prosthetic valves to the mitral annuli. Before implantation, the calcification was partially debrided ultrasonically, and an 'atrioventricular channel' created. A mechanical valve with a polyester fabric collar was fixed on the atrial side of the calcified annulus using double sutures and gelatin-resorcin-formol glue. Perivalvular leakage, obstruction of valve opening or tortuous movements of prosthetic valve ring were not observed, and neither patient developed heart failure after surgery. This technique represents a potentially useful approach in the surgical treatment of patients with severely calcified mitral annuli.

Experimental studies have demonstrated that adrenomedullin (AM) has a positive inotropic action and exerts inhibitory effects against ventricular remodelling as an autocrine and paracrine factor. However, there is no clinical evidence for AM acting as a local regulator in the human heart. We measured the levels of various molecular forms of AM, i.e. an active form of mature AM (AM-m), an intermediate inactive form of glycine-extended AM (AM-Gly) and total AM (AM-T=AM-m+AM-Gly), in plasma and pericardial fluid using our newly developed immunoradiometric assay in consecutive 67 patients undergoing coronary artery bypass graft surgery. Pericardial fluid and plasma cAMP, atrial natriuretic peptide and brain natriuretic peptide levels were also measured. The relationships between pericardial fluid AM levels and ventricular functions and other hormone levels were analysed. The level of each molecular form of AM in pericardial fluid was closely correlated with that of the other molecular forms of AM in the fluid. However, levels were not correlated with those in plasma. AM-T levels were slightly higher in pericardial fluid than in plasma (+72%; P<0.05), whereas AM-m levels and AM-m/AM-T ratios were markedly higher in pericardial fluid than in plasma (AM-m, +994%; AM-m/AM-T ratio, +443%; both P<0.01). AM-m, AM-Gly and AM-T levels in pericardial fluid were correlated with indices of left ventricular function, and with atrial natriuretic peptide and brain natriuretic peptide levels. Interestingly, AM and cAMP levels were positively correlated in plasma, but negatively correlated in pericardial fluid. In addition, AM-m, AM-Gly and AM-T levels in pericardial fluid were higher in patients with acute coronary syndrome than in those with stable ischaemic heart disease (AM-m, +80%; AM-Gly, +96%; AM-T, +83%; all P<0.01). These results suggest that AM in pericardial fluid reflects cardiac synthesis, and that enhanced cardiac secretion of AM is associated with left ventricular dysfunction, ventricular overload and myocardial ischaemia. Considering that AM has positive inotropic, coronary vasodilatory and anti-remodelling actions, increased cardiac AM may play a compensatory role in the ischaemic and failing myocardium.