97 research outputs found
Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension
Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (Ppa) is achieved during the early symptomatic stage, indicating that the elevation of the mean Ppa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease. However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease
Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia
Objectives: To evaluate the efficacy and safety of nafamostat combined with favipiravir for the treatment of COVID-19.
Methods: We conducted a multicenter, randomized, single-blind, placebo-controlled, parallel assignment study in hospitalized patients with mild-to-moderate COVID-19 pneumonia. Patients were randomly assigned to receive favipiravir alone (n = 24) or nafamostat with favipiravir (n = 21). The outcomes included changes in the World Health Organization clinical progression scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpO2).
Results: There was no significant difference in the changes in the clinical progression scale between nafamostat with favipiravir and favipiravir alone groups (median, -0.444 vs -0.150, respectively; least-squares mean difference, -0.294; P = 0.364). The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% confidence interval, 4.0-7.0) than in the favipiravir group (9.0 days; 95% confidence interval, 7.0-18.0; P =0.009). The changes in SpO2 were greater in the combination group than in the favipiravir group (0.526% vs -1.304%, respectively; least-squares mean difference, 1.831; P = 0.022). No serious adverse events or deaths were reported, but phlebitis occurred in 57.1% of the patients in the combination group.
Conclusion: Although our study showed no differences in clinical progression, earlier defervescence, and recovery of SpO2 were observed in the combination group
Crosstalk between endothelial cell and thrombus in chronic thromboembolic pulmonary hypertension: perspective
It is generally accepted that chronic
thromboembolic pulmonary hypertension (CTEPH)
results from pulmonary emboli originating from deep
vein thrombosis. However, this consensus opinion has
been challenged, and the concept that some aspects of
CTEPH exacerbation might result from a small-vessel
disease leading to secondary thrombosis has been
suggested.
In addition to the effect of recurrent thromboembolism,
a number of lines of clinical evidence
indicate that progressive worsening is contributed to by
remodeling in the small pulmonary arteries.
Histopathological studies of the microvascular changes
in CTEPH have identified vascular lesions similar to
those seen in idiopathic pulmonary arterial hypertension
(IPAH). Especially in in vitro and ex vivo experiments,
pulmonary artery endothelial cells (ECs) in pulmonary
hypertensive diseases are suggested to exhibit an
unusual hyperproliferative potential with decreased
susceptibility to apoptosis, indicating that dysfunctional
ECs may contribute to the progression of the diseases.
Although the degree and mechanisms of EC dysfunction
as a contributor to CTEPH are unclear, EC dysfunction
may occur in small arteries. Indeed, the cells stimulated
by the microenvironment created by the unresolved clot
may release substances that induce EC dysfunction. The
EC dysfunctions in CTEPH may lead to disorders of the
anti-coagulation properties in ECs and may result in
additional clots in situ. Moreover, these may lead to the
progression, not only of distal thrombus, but also of
proximal clotting.
This article reviews the pathobiological concepts of
CTEPH and explains a crosstalk between EC
dysfunction and in situ thrombi which may contribute to
the vascular lesions of CTEPH
The vascular bed in COPD: pulmonary hypertension and pulmonary vascular alterations
The loss of pulmonary vessels has been shown to be related to the severity of pulmonary hypertension in patients with chronic obstructive pulmonary disease (COPD). The severity of hypoxaemia is also related to pulmonary hypertension and pulmonary vascular resistance in these patients, suggesting that the hypoxic condition probably plays an important role in this form of pulmonary hypertension.
However, pulmonary hypertension also develops in patients with mild COPD without hypoxaemia. Oxygen supplementation therapy often fails to reverse the pulmonary hypertension in these COPD patients, thus suggesting that the pulmonary vascular alterations in those patients may involve different sites of the pulmonary vasculature or a different form of vascular remodelling. It has recently been demonstrated that pulmonary vascular remodelling, resulting in pulmonary hypertension in COPD patients, can develop independently from parenchymal destruction and loss of lung vessels.
We wonder whether the changes in the lung microenvironment due to hypoxia and vessel loss have a causative role in the development of pulmonary hypertension in patients with COPD. Herein we review the pathobiological features of the pulmonary vasculature in COPD patients and suggest that pulmonary hypertension can occur with and without emphysematous lung tissue destruction and with and without loss of lung vessels
Reversible or Irreversible Remodeling in Pulmonary Arterial Hypertension
Vascular remodeling is an important pathological feature of pulmonary arterial hypertension (PAH), which leads to increased pulmonary vascular resistance, with marked proliferation of pulmonary artery smooth muscle cells (SMC) and/or endothelial cells (EC). Successful treatment of experimental PAH with a platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitor offers the perspective of “reverse remodeling” (i.e., the regression of established pulmonary vascular lesions). Here we ask the question: which forms of pulmonary vascular remodeling are reversible and can such remodeling caused by angiogenic proliferation of EC be reversed? It is important to emphasize that the report showing reduction of vascular remodeling by PDGF receptor tyrosine kinase inhibitor showed only a reduction of the pulmonary artery muscularization in chronic hypoxia and monocrotaline models, which lack the feature of clustered proliferated EC in the lumen of pulmonary arteries. The regression of vascular muscularization is an important manifestation, whereby proliferative adult SMC convert back to a nonproliferative state. In contrast, in vitro experiments assessing the contribution of EC to the development of PAH demonstrated that phenotypically altered EC generated as a consequence of a vascular endothelial growth factor receptor blockade did not reverse to normal EC. Whereas it is suggested that the proliferative state of SMC may be reversible, it remains unknown whether phenotypically altered EC can switch back to a normal monolayer-forming EC. This article reviews the pathogenetic concepts of severe PAH and explains the many forms in PAH with reversible or irreversible remodeling
Yellow nail syndrome with massive chylothorax after esophagectomy: A case report
Yellow nail syndrome (YNS) is a rare condition characterized by the triad of yellow nails, lymphedema, and respiratory manifestations. Diuretics and thoracic drainage are often not effective in YNS, and the most effective treatments are pleurodesis and decortication/pleurectomy. A 66-year-old man was admitted to our hospital for YNS after esophagectomy with gastric tube reconstruction for esophageal cancer. The patient presented with yellow nails and lymphedema. Chest X-rays and computed tomography showed massive pleural effusions and ascites that were both chylous. The patient was considered to have YNS that became apparent after surgery. He recovered with diuretics and a low-fat diet without pleurodesis and decortication/pleurectomy. Thoracic surgery can exacerbate the functional impairment of lymphatic drainage in patients with asymptomatic and undiagnosed YNS, and can lead to further development of YNS-related clinical symptoms. Despite relatively massive chylothorax following thoracic surgery, chylothorax related to YNS could be successfully controlled with conservative treatment without pleurodesis and decortication/pleurectomy
Apoptosis of pulmonary microvascular endothelial cells stimulates vascular smooth muscle cell growth
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