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We herein report a 48-year-old man with a history of chronic atrial fibrillation (AF) and repeated hemoptysis after radiofrequency ablation. Contrast tomography showed soft tissue thickening of the left hilar region and left pulmonary vein stenosis. We performed bronchial artery embolization, but the hemoptysis did not disappear, and AF was not controlled. We performed left lung lobectomy and maze procedures since we considered surgical removal necessary as radical treatment. After the surgery, hemoptysis and atrial fibrillation did not recur. Refractory hemoptysis after catheter ablation is rare, but occasionally occurs in patients with severe pulmonary vein stenosis.

An 83-year-old man was hospitalized for coronavirus disease 2019 (COVID-19) after a 10-day history of a persistent fever. Chest computed tomography showed extensive non-segmental ground glass opacity. Despite the initiation of lopinavir and ritonavir, respiratory failure progressed. Two days of polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP) with adjunctive corticosteroid prevented his respiratory condition from worsening. For rapidly progressive COVID-19 cases, the early use of PMX-DHP may avoid the need for mechanical ventilation by suppressing local inflammation of the lung.

In vitro proliferation of functional islet mass/beta-cells by transduction of cell cycle regulatory genes has not been well documented due to the lack of either an effective method for gene transduction to islets or effective genes for beta-cell proliferation. Signal transducers and activators of transcription- 3 (Stat3) are among the most important molecules for cell proliferation and for cell antiapoptosis. In this study, adenovirus-mediated gene transduction was performed on dispersed islet cells, and reaggregated islet mass functions, such as capabilities for reaggregation, proliferation, and glucose- stimulated insulin secretion (GSIS), were evaluated. The constitutively activated form of Stat3 (Stat3-C) was effectively transduced to most of the islet cells, even at a low density of adenovirus vector. There was no difference in the spontaneous reaggregation capability between Stat3-C transduced and control islet cells. BrdU incorporation in Stat3-C-transduced islet cells was significantly higher (2.8-fold) than that in the control cells, and it was significantly elevated (4-fold) by the addition of HGF in culture media. GSIS in Stat3-C-transduced islet cells was preserved to the level in controls by 5 days in culture. The results indicated that gene transduction into islet cells could be enhanced by first dispersing the cells. Stat3-C induced cell proliferation of beta-cells without loss of insulin secretion activity at the glucose challenge, and HGF enhanced the beta-cell proliferative activity of Stat3-C.

Background Currently, pancreatic islet transplantation to achieve normoglycemia in insulin-dependent diabetes mellitus (IDDM) requires two or more donors. This may be due to the inability to transplant functionally preserved and viable islets after isolation. Islets have already been subjected to various harmful stresses during the isolation process leading to apoptosis. One of the intracellular signaling pathways, the transcription factor nuclear factor-κB (NF-κB)-related pathway, is relevant to the mechanism of β-cell apoptosis in isolated islets. We attempted to prevent islet apoptosis during isolation by a novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ). Materials and Methods DHMEQ was injected intraperitoneally into donor mice 2 h prior to isolation. NF-κB activation, the functioning of isolated islets, apoptosis after isolation, and cytokine- and apoptosis-related genes were analyzed. After 160 equivalents of islets were transplanted into diabetic mice, graft survival and function were evaluated. Results Intra-islet NF-κB was activated immediately after isolation, and DHMEQ inhibited NF-κB activation without deterioration of islet function. DHMEQ significantly prevented apoptosis by inhibiting caspase 3/7 activities and down-regulated Bax, a pro-apoptotic gene. Donor pretreatment with DHMEQ significantly improved engraftment in syngeneic islet transplantation in mice, thus preserving insulin contents in the graft liver, as assessed by functional and histologic analyses. Conclusions DHMEQ is a promising agent in islet transplantation because it protects islets from apoptosis during isolation stress. Donor pretreatment with DHMEQ can significantly affect the success of islet engraftment.

Adenovirus-mediated gene transduction into the intact islets has thus far been limited to the surface cells of islets. We evaluated the efficiency of gene delivery by singularization of islets, followed by self-reorganization into islet-like masses. Adenovirus-mediated gene transduction was performed on dispersed islet cells, obtained by two-step digestion of collagenase and ethylene glycol tetraacetic acid/dispase. Good self-reorganization of islet cells in culture was observed until 120 h in islet cells of a control group, a group with a multiplicity of infection (MOI) of 1, and a group with an MOI of 5, with their sizes of 66.7 +/-14.17, 64.0 +/- 15.14, and 60.8 +/- 23.71 microm, respectively. No significant difference in spontaneous reaggregation capability among the islet cell masses was noticed. However, fragmentation of the reaggregated islet mass was observed in the groups with an MOI of 10 and 50 at 72 and 48 h, respectively. The gene transduction rates at an MOI of 0.5, 1, and 5 into islet cells were 56.1 +/- 1.43, 97.6 +/- 0.92, and 100 +/- 0.00%, respectively. The insulin stimulation indices of the reaggregated islet mass at an MOI of 0.5 and 1 were preserved to the level of a nontransduced islet mass; those at an MOI greater than 5 were significantly low. Efficient adenovirus-mediated gene transduction into islet/beta-cells was achieved by adding a process of dispersion of islets into single cells prior to gene transduction without losing the characteristic ability of islet cells to form a functional islet mass in culture.