Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans-Brief Report.

BACKGROUND: Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS. METHODS: We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis. RESULTS: CD4+ T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells. CONCLUSIONS: For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier: UMIN000040747.

Anterolateral thoracotomy with partial sternotomy: a feasible approach for treating the complex pathology of the aortic arch.

OBJECTIVES: Our goal was to review our surgical experiences in patients with complex pathologies of the aortic arch who have undergone anterolateral thoracotomy with a partial sternotomy (ALPS). METHODS: From October 2019 to November 2023, a total of 23 patients underwent one-stage repairs of complex pathologies of the aortic arch through the ALPS approach. The mean age was 61.9 ± 16.7 years old. The aortic pathologies were as follows: aorta-related infection in 11 (aorto-oesophageal fistula: 4, graft infection: 6, native aortic infection: 1); aortic dissection in 9 including shaggy aorta in 2, non-dissecting aneurysm in 1, and coarctation of the aorta (CoA) in 2. RESULTS: Eighteen patients underwent aortic replacement from either the sinotubular junction or the ascending aorta to the descending aorta; 1 patient underwent it from the aortic root to the descending aorta (redo Bentall procedure and extensive aortic arch replacement); 3 patients underwent it from the aortic arch between the left carotid artery and left subclavian artery to the descending aorta; and 1 patient underwent a descending aortic replacement. Ten patients underwent omentopexy, latissimus dorsi muscle flap installation or both procedures. The hospital mortality rate was 13.0% (3/23). The overall survival and freedom from aortic events were 73.3%±10.2% and 74.1%±10.2%, respectively, at the 3-year follow-up. There was an absence of aorta-related deaths, and no recurrent infections were identified. CONCLUSIONS: The short-term outcomes using the ALPS approach for the treatment of complex pathologies of the aortic arch were acceptable. Further studies will be required to determine the long-term results.

[Acute Aortic Dissection with Visceral Malperfusion Syndrome].

Malperfusion syndrome of the visceral branches associated with acute aortic dissection brings an extremely poor outcomes leading to perioperative and long-term mortality in both Stanford type A and type B acute aortic dissection. The conventional surgical strategy for these cases has been to prioritize aortic repair and to improve blood flow of true lumen in aorta and visceral branches. Today, various techniques for early reperfusion have been reported. For bowel ischemia, it is necessary to evaluate substantial ischemia of the intestinal tract and hypoperfusion of the superior mesenteric artery( SMA) using contrast-enhanced computed tomography( CT) and intraoperative transesophageal echocardiography in addition to clinical presentation. The most important factor of the surgical intervention is the improvement of true luminal blood flow by reconstruction of the central aorta. However, an intervention to SMA prior to central aortic repair might be an important process for patients with Stanford type A acute aortic dissection to avoid irreversible bowel necrosis. In type B aortic dissection, thoracic endovascular aortic repair (TEVAR) with or without provisional extension to induce complete attachment (PETTICOAT) technique and additional SMA intervention based on intraoperative contrast findings are necessary. Renal malperfusion is also a risk factor of postoperative accute kidney injury( AKI) and perioperative mortality. The revascularizations of renal arteries might improve outcomes when renal blood flow was not recovered with central aortic repair.

Open Conversion with Explantation of Stent Grafts After Endovascular Aneurysm Repair for Abdominal Aortic Aneurysm.

BACKGROUND: Although endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) is widely used worldwide, the fact that it is associated with increased rates of reintervention has been considered a problem. This study aimed to analyze the outcomes of primary open AAA repair and open conversion with explantation of stent grafts after EVAR. METHODS: In this retrospective study, we enrolled 1,120 patients (open repair, n = 664; EVAR, n = 456) who underwent AAA repair at Kobe University from 1999 to 2019. Of the 664 patients who underwent open repair, 121 (patients who underwent primary open repair (POR) as a concomitant procedure and patients with ruptured AAA) were excluded from the study. The outcomes of POR were compared with those of open conversion with explantation of stent grafts. RESULTS: Of the 543 patients who underwent open repair, 513 underwent POR and 30 underwent open conversion with explantation of stent grafts. The operation time for POR was significantly less than that for open conversion with explantation. During surgery, patients who underwent open conversion with explantation required significantly more transfusions of red cell concentrate, fresh frozen plasma, and platelet concentrate than those who underwent POR. Overall, 30 patients who underwent open conversion with explantation required a total of 48 reinterventions before surgery. Hospital mortality rates were 0.7% and 0% in the POR and open conversion with explantation groups, respectively (P = 0.62). Although overall survival at 5 years in the POR group was significantly better than that in the open conversion with explantation group (89.3 ± 1.7% vs. 79.5 ± 9.6%; P = 0.01), there were no significant differences between the 2 groups regarding the freedom from aortic event (hospital death, reintervention, and aortic death). According to the multivariate analysis, open conversion with explantation was not an independent risk factor for late death. There were 20 patients who were hesitant to undergo OCE, although we recommended OCE. In a subgroup analysis, the overall mean cost borne by patients who underwent EVAR was approximately 2.3 times higher compared with that borne by patients who underwent POR. CONCLUSIONS: Although demanding, both early and long-term outcomes of OCE have been favorable in our present study. OCE is highly recommended in patients with persistent sac enlargement after EVAR.

Detection of Tip Fold-Over of the Slim Modiolar Electrode Using Intraoperative Mobile Cone-Beam Computed Tomography.

OBJECTIVE: This study aimed to evaluate the importance of mobile cone-beam computed tomography in detecting tip fold-over of a slim modiolar electrode within the cochlea during surgery. STUDY DESIGN: Retrospective case review. SETTING: Tertiary medical center. METHODS: From January 2020 to June 2022, 33 ears of 30 patients with normal cochlear morphology underwent cochlear implantation with slim modiolar electrodes and intraoperative mobile cone-beam computed tomography imaging. Furthermore, we retrospectively reviewed the medical records and images. RESULTS: The tip fold-over of the electrodes was detected using mobile cone-beam computed tomography in 3 out of 33 ears (9.1%). We could not identify the tip fold-over by scouting plain X-ray images in 2 out of 3 cases before taking the cone-beam computed tomography images. Electrode removal and reinsertion were performed before wound closure and the successful reinsertion was confirmed by mobile cone-beam computed tomography. The folded electrode tips were located at 238.8°, 152°, and 185.8°. CONCLUSION: Intraoperative mobile cone-beam computed tomography is useful in detecting the tip fold-over of the slim modiolar electrodes during surgery. Therefore, it was possible to reinsert the electrodes in all cases before closing the wound, eliminating the need for revision surgeries. Moreover, the analysis of mobile cone-beam computed tomography images may help to elucidate the mechanisms of electrode tip fold-over.

Japanese single-center experience of abdominal aortic aneurysm repair over 20 years: should open or endovascular aneurysm repair be performed first?

PURPOSE: The present study analyzed the outcomes of our experience with abdominal aortic aneurysm (AAA) repair over 20 years using endovascular aortic repair (EVAR) with commercially available devices or open aortic repair (OAR) and reviewed our surgical strategy for AAA. METHODS: From 1999 to 2019, 1077 patients (659 OAR, 418 EVAR) underwent AAA repair. The OAR and EVAR groups were compared retrospectively, and a propensity matching analysis was performed. RESULTS: EVAR was first introduced in 2008. Our strategy was changed to an EVAR-first strategy in 2010. Beginning in 2018, this EVAR-first strategy was changed to an OAR-first strategy. After propensity matching, the overall survival in the OAR group was significantly better than that in the EVAR group at 10 years (p = 0.006). Two late deaths due to AAA rupture were identified in the EVAR group, although there were no significant differences between the OAR and EVAR groups with regard to the freedom from AAA-related death at 10 years. The rate of freedom from aortic events at 10 years was significantly higher in the OAR group than in the EVAR group (p < 0.0001). CONCLUSION: The rates of freedom from AAA-related death in both the OAR and EVAR groups were favorable, and the rate of freedom from aortic events was significantly lower in the EVAR group than in the OAR group. Close long-term follow-up after EVAR is mandatory.

Gut Microbiota Influence the Development of Abdominal Aortic Aneurysm by Suppressing Macrophage Accumulation in Mice.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease characterized by dilated abdominal aorta. Immune cells have been shown to contribute to the development of AAA, and that the gut microbiota is associated with numerous diseases, including cardiovascular diseases, by regulating immune systems or metabolic pathways of the host. However, the interaction between the gut microbiota and AAA remains unknown. METHODS: Apolipoprotein E-deficient male mice were fed a high-cholesterol diet and divided into three groups: the control group was maintained under normal water (control group), the oral AVNM group was maintained under drinking water supplemented with ampicillin, vancomycin, neomycin, and metronidazole, and the i.p. AVNM group was injected AVNM intraperitoneally. After 1 week of pretreatment with antibiotics, these mice were administrated Ang II via subcutaneous osmotic pumps for 4 weeks and euthanized to evaluate AAA formation. RESULTS: Depletion of gut microbiota by oral AVNM ameliorated the incidence of AAAs (control group: 58.9% versus oral AVNM group: 28.6% versus i.p. AVNM group: 75.0%, P = 0.0005) and prevented death due to ruptured aneurysms (control group: 11% versus oral AVNM group: 0% versus i.p. AVNM group: 15%). Oral AVNM suppressed monocyte storage in the spleen, but not in other organs. Despite possessing a higher level of cholesterol, recruitment of monocytes into the suprarenal aorta was suppressed in the oral AVNM group. In AVNM drinking mice, NOD1 ligand, a kind of PRR ligands, increased the development of AAAs and accumulation of macrophages in the aortae. CONCLUSIONS: The gut microbiota plays a critical role in AAA formation. Therefore, regulation of the microbiota or the immune system can be a therapeutic approach for AAA.

[Up to Date for Treatment of Stanford Type A Acute Aortic Dissection].

Surgical outcomes for acute type A aortic dissection (ATAAD) have been improving, but mortality rate remains about 10% in the last decade. Based on the current literatures including American Association for Thoracic Surgery (AATS) expert consensus, we presented the latest treatments and our surgical strategies for ATAAD. This section states about cannulation strategies for cardio-pulmonary bypass, aortic root managements, aggressive arch strategies, distal anastomosis strategies and the managements of malperfusion syndrome. We recommended the ascending aorta using the Seldinger technique as the cannulation site. As the aortic root management, valve resuspension is effective, but valve-sparing aortic root repair may be an option for young patients with annulo-aortic ectasia, intimal tear located in Valsalva sinus or Valsalva sinus rupture. The tear-oriented surgery is the standard for the range of the graft replacement, however, aggressive arch repair is also good indication for young patients. Distal anastomoses are felt sandwich technique for hemi-arch replacement or partial arch replacement and frozen elephant trunk is useful to total arch replacement. Early reperfusion strategies were important to the malperfusion syndrome of coronary arteries, supra-aortic vessels and superior mesenteric artery. To the dissected common carotid arteries (CCAs), early reperfusion and direct reconstruction of CCAs were effective.

Early and late outcomes of type A acute aortic dissection with common carotid artery involvement.

Objective: The relationship between common carotid artery (CCA) involvement in acute type A aortic dissection (ATAAD) and postoperative outcomes remains unclear. We investigated outcomes and described our current advanced strategy. Methods: Of 492 patients who underwent surgical repair for ATAAD between September 1999 and February 2021, CCA involvement was identified in 114. Eighty of these 114 patients (70.2%) were classified as having a thrombosed CCA and 34 (29.8%) were classified as nonthrombosed. To prevent postoperative cerebral malperfusion, we initiated a strategy of early reperfusion and direct reconstruction of dissected and thrombosed CCAs regardless of neurologic symptoms. Results: Fifty-five patients (48.2%) showed preoperative neurologic symptoms. No significant differences between the thrombosed and nonthrombosed groups were seen in postoperative mortality (20.0% vs 11.8%; P = .421) or frequency of postoperative modified Rankin scale (mRS) score ≥5 (30.0% vs 17.6%; P = .245). The rate of postoperative neurologic deficit was significantly higher (48.8% vs 23.5%; P = .013) and long-term survival rate was significantly lower (5 years; 59.1 ± 6.3% vs 77.9 ± 7.4%; 10 years: 50.0 ± 7.9% vs 72.3 ± 8.7%; P = .041) in the thrombosed group. Risk factors for mRS ≥5 from multivariable analysis included occluded thrombosed CCA, preoperative coma, preoperative shock, and prolonged operation time. Fifteen patients were treated with the early reperfusion and direct reconstruction strategy; postoperative mortality 13.3% (2 patients). No patients showed cerebral reperfusion syndrome. Conclusions: In patients with CCA involvement, a thrombosed false lumen, especially an occluded CCA, resulted in worse outcomes regardless of preoperative neurologic symptoms. Further study is needed to evaluate the efficacy of the current strategy.

[Does Surgeons' Experience Affect the Surgical Outcomes of Total Arch Replacement?]

OBJECTIVES: Total arch replacement( TAR) is used to be a complicated and quite invasive aortic procedure. To perform TAR safely and effectively under all circumstances, we have constructed standardization of the procedures of TAR. The aim of this study is to analyze the impact of surgeons' experience on surgical outcome of TAR to evaluate our standardization. METHODS: From January 2008 to December 2020, 346 consecutive patients (mean age 73.6±10.2) underwent elective TAR through a median sternotomy at our institute. TAR was performed by three types of surgeon classified by their experience( A:over 20 years, B:15~20 years, C:under 15 years). The surgical outcomes were examined. Our standard approach include( 1) meticulous selection of arterial cannulation site and type of arterial cannula;(2) antegrade selective cerebral perfusion;(3) maintenance of minimal tympanic temperature between 20 ℃ and 23 ℃;(4) early rewarming just after distal anastomosis;(5) maintaining fluid balance below 1,000 ml during cardiopulmonary bypass. RESULTS: The operative cases were 227 in A, 86 in B and 33 in C. Surgeon A operated more complicated TAR with higher operative risk compared with B and C. The hospital mortality and major complication rate was not significant difference among surgeons( hospital mortality A:3.5%, B:2.3%, C:3.0%). Multivariate analysis showed the surgeons' experience was not associated with hospital mortality and major complications. Long-term outcomes were also compatible among three groups. CONCLUSIONS: Our standardization for TAR seemed to be an useful approach to eliminate the impact of surgeon experience on surgical outcomes if the type of surgeon was appropriately selected according to the level of operative difficulty.

Anterolateral Partial Sternotomy for Treatment of Graft Infection with Fungal Vegetation on the Frozen Elephant Trunk: A Case Report.

A 49-year-old man, who had undergone total arch replacement (TAR) with frozen elephant trunk (FET) technique for type A acute aortic dissection, was subsequently transferred to our hospital for uncontrollable infection. Since multiple blood cultures were positive for Candida parapsilosis and transesophageal echocardiography revealed vegetation attached to the FET, he was diagnosed with a graft infection. In addition, on the 18-fluorodeoxyglucose positron emission tomography scans, high uptake lesions were found around the quadrifurcated graft as well as the FET. Therefore, an extensive TAR through anterolateral thoracotomy with partial sternotomy was performed to remove all infected prothesis. Consequently, the patient completely recovered.

Alternative transcription start sites of the enolase-encoding gene enoA are stringently used in glycolytic/gluconeogenic conditions in Aspergillus oryzae.

Gene expression using alternative transcription start sites (TSSs) is an important transcriptional regulatory mechanism for environmental responses in eukaryotes. Here, we identify two alternative TSSs in the enolase-encoding gene (enoA) in Aspergillus oryzae, an industrially important filamentous fungus. TSS use in enoA is strictly dependent on the difference in glycolytic and gluconeogenic carbon sources. Transcription from the upstream TSS (uTSS) or downstream TSS (dTSS) predominantly occurs under gluconeogenic or glycolytic conditions, respectively. In addition to enoA, most glycolytic genes involved in reversible reactions possess alternative TSSs. The fbaA gene, which encodes fructose-bisphosphate aldolase, also shows stringent alternative TSS selection, similar to enoA. Alignment of promoter sequences of enolase-encoding genes in Aspergillus predicted two conserved regions that contain a putative cis-element required for enoA transcription from each TSS. However, uTSS-mediated transcription of the acuN gene, an enoA ortholog in Aspergillus nidulans, is not strictly dependent on carbon source, unlike enoA. Furthermore, enoA transcript levels in glycolytic conditions are higher than in gluconeogenic conditions. Conversely, acuN is more highly transcribed in gluconeogenic conditions. This suggests that the stringent usage of alternative TSSs and higher transcription in glycolytic conditions in enoA may reflect that the A. oryzae evolutionary genetic background was domesticated by exclusive growth in starch-rich environments. These findings provide novel insights into the complexity and diversity of transcriptional regulation of glycolytic/gluconeogenic genes among Aspergilli.

Type IIIB endoleak from stent suture lines of a thoracic endograft.

We report a case of a patient with type IIIB endoleak after thoracic endovascular aortic repair that remained undetected by computed tomography and was first diagnosed during open conversion surgery. The aneurysm enlarged gradually from 60 to 78 mm without type I and type II endoleaks during 3 to 6 years after thoracic endovascular aortic repair. Type IIIB endoleaks from nitinol stent suture lines were detected, and the endograft was then explanted and replaced by a vascular graft.

Photoluminescence spectral change in layered titanate oxide intercalated with hydrated Eu3+.

A number of interesting photoluminescence properties of titanate layered oxide intercalated with hydrated Eu3+ have been demonstrated. Photoluminescence intensity of Eu3+ decreased rapidly with time during irradiation by UV light having energy higher than the band gap energy of the host TiO (Ti(1.81)O4) layer. This is presumably due to the decrease in energy transfer from the host TiO layer to Eu3+ as a result of the change in the hydration state of water molecules surrounding Eu3+, which is caused by the hole produced in the TiO valence band. When irradiation was discontinued, the emission intensity gradually recovered. The recovery time increased when the water in the interlayer is removed by heat treatment. This indicates that the state of interlayer water changes during irradiation and returns to its initial state after discontinuation of irradiation. The excitation spectra changed drastically at any given wavelength upon irradiation with UV light. A comparison of the excitation spectra before and after irradiation reveals that only the excitation peak at around the irradiation wavelength decreased upon irradiation, as in the case of spectral hole burning. The hydration state of water molecules surrounding Eu3+ presumably changes depending on the irradiation wavelength, leading to the above spectral change because the Eu/TiO film has a superlattice structure producing holes with different energies.