Non-suppressive regulatory T cell subset expansion in pulmonary arterial hypertension.

Regulatory T cells (Tregs) have been reported to play a pivotal role in the vascular remodeling of pulmonary arterial hypertension (PAH). Recent studies have revealed that Tregs are heterogeneous and can be characterized by three phenotypically and functionally different subsets. In this study, we investigated the roles of Treg subsets in the pathogenesis of PAH in eight patients with PAH and 14 healthy controls. Tregs and their subsets in peripheral blood samples were analyzed by flow cytometry. Treg subsets were defined as CD4(+)CD45RA(+)FoxP3(low) resting Tregs (rTregs), CD4(+)CD45RA(-)FoxP3(high) activated Tregs (aTregs), and CD4(+)CD45RA(-)FoxP3(low) non-suppressive Tregs (non-Tregs). The proportion of Tregs among CD4(+) T cells was significantly higher in PAH patients than in controls (6.54 ± 1.10 vs. 3.81 ± 0.28 %, p < 0.05). Of the three subsets, the proportion of non-Tregs was significantly elevated in PAH patients compared with controls (4.06 ± 0.40 vs. 2.79 ± 0.14 %, p < 0.01), whereas those of rTregs and aTregs were not different between the two groups. Moreover, the expression levels of cytotoxic T lymphocyte antigen 4, a functional cell surface molecule, in aTregs (p < 0.05) and non-Tregs (p < 0.05) were significantly higher in PAH patients compared with controls. These results suggested the non-Treg subset was expanded and functionally activated in peripheral lymphocytes obtained from IPAH patients. We hypothesize that immunoreactions involving the specific activation of the non-Treg subset might play a role in the vascular remodeling of PAH.

The Potential Role of Inflammation Associated with Interaction between Osteopontin and CD44 in a Case of Pulmonary Tumor Thrombotic Microangiopathy Caused by Breast Cancer.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and fatal cancer-related complication. We herein present a case of PTTM that diagnosed antemortem by lung scintigraphy and pulmonary microvascular cytology. The patient was treated with steroid pulse therapy. Although her symptoms temporarily improved, she died of respiratory failure. An autopsy showed PTTM, and an immunohistochemical analysis revealed the expression of osteopontin and CD44 in macrophages that had migrated into the PTTM lesions. These findings suggest that inflammation associated with the interaction between osteopontin and CD44 may play an important role in PTTM.

A case of residual inferior sinus venosus defect after ineffective surgical closure.

A 38-year-old woman presented with cyanosis and heart failure 34 years after patch closure of an atrial septal defect and partial anomalous pulmonary venous connection. CT and cardiac catheterisation showed a residual defect that caused right-to-left shunting. The patch almost blocked the inferior vena cava from the right atrium, resulting in uncommon drainage of the inferior vena cava into the left atrium. Other anomalies included the coronary-to-pulmonary artery fistula and duplicate inferior vena cava with dilated azygos venous system. A second surgery was performed, and we confirmed an inferior sinus venosus defect, which is rare and can be misdiagnosed. The ineffective patch closure had caused a haemodynamic status that rarely occurs. We describe the diagnostic process and emphasise the importance of correctly understanding the entity.

Spontaneous disappearance of coronary pseudoaneurysm due to coronary artery perforation following percutaneous coronary intervention.

In recent years, while therapeutic outcome after percutaneous coronary intervention is improving due to the introduction of drug-eluting stent and device development, procedure-related complications including coronary perforation may ineluctably occur though at low-frequency, even if careful manipulations are performed under IVUS guidance. Meanwhile, coronary pseudoaneurysm subsequent to coronary perforation is one of the complications at chronic phase infrequently experienced following percutaneous coronary intervention. To date, the incidence and natural history of pseudoaneurysm following coronary artery perforation remain unclear. We experienced a case with coronary pseudoaneurysm developed 2 weeks after Ellis II-type coronary artery perforation which spontaneously disappeared 4 months later. As the mechanism of disappearance, thrombotic occlusion was confirmed upon intravascular ultrasound.

An autopsy case of acute cor pulmonale and paradoxical systemic embolism due to tumour cell microemboli in a patient with breast cancer.

A 62-year-old woman was admitted to our hospital because of severe respiratory distress. Diagnostic imaging studies suggested the existence of inexplicable cor pulmonale. Although we immediately sought the aetiology of her severe condition, she died suddenly on the fourth day after admission. Postmortem autopsy revealed tumour cell microemboli in the small pulmonary arteries. In addition, tumour cell embolisation identical to that in primary breast cancer cells was also observed in microvessels in systemic multiple organs, such as the liver, brain, kidneys, spleen, uterus, bone marrow and adrenal glands-with simultaneous findings of peripheral infarction. Systemic tumour cell embolism mediated through the patent foramen ovale superimposed on pulmonary tumour cell emboli (PTCE) is considered to be the mechanism underlying inexplicable cor pulmonale. The rapid aggravation of her condition terminated in death.

A case of idiopathic ventricular fibrillation in which implanted loop recorder was useful in application decision for implantation of implantable cardioverter-defibrillator.

Establishing a symptom-rhythm correlation in patients with unexplained syncope is complicated because of its sporadic, infrequent, and unpredictable nature. Recently, an implantable loop recorder (ILR) has become available to evaluate undiagnosed recurrent arrhythmic episodes particularly in unexplained syncopes, and its usefulness has been reported in patients with recurrent syncopes that remain unexplained after conventional work-up. A 65-year-old man was referred to our hospital for loss of consciousness with nocturnal paroxysmal seizures. He had experienced several similar episodes. No family history of sudden death was evident, and apparent structural heart disease was absent. Coronary angiography with intracoronary ergonovine provocation showed vasospasm in left coronary artery without organic stenosis. Ventricular tachyarrhythmias were not induced by programmed electrical stimuli. According to the guideline, he was at once categorized as having class IIb indication for implantable cardioverter defibrillator implantation. However, his symptoms were not relieved despite administration of anti-anginal medications including nitrates and calcium antagonist. Implantation of an ILR was performed and revealed an episode of ventricular fibrillation during generalized-convulsion attack during sleep. ILR is useful in determining the presence of fatal arrhythmias during syncope, although conventional diagnostic testing, such as electrocardiogram, Holter monitoring, and external loop recording, is inconclusive.