[Residual Guidewire Removal in the Aorta Using Minimally Invasive Approach:Report of a Case].

An 80-year-old man had a guidewire in his aorta since catheter laboratory accident 4 years ago. He recently started to suffer mental distress and underwent coronary angiography that revealed an entrapped guidewire and significant stenoses in each of three major coronary arteries. The guidewire could not be removed using transcatheter technique. Thus, after careful consideration, we decided to perform entrapped guidewire removal through minimally invasive surgical approach instead of median sternotomy. Post-operative course was uneventful. Although surgical approach should be tailored in each case, minimally invasive approach can be a choice for entrapped guidewire removal.

Distribution and prognostic impact of EGFR and KRAS mutations according to histological subtype and tumor invasion status in pTis-3N0M0 lung adenocarcinoma.

BACKGROUND: The prognostic impact of EGFR mutation as major targetable somatic gene variant on lung adenocarcinoma is controversial. KRAS is another major somatic variant in lung adenocarcinoma, and a therapeutic agent for KRAS G12C became available in clinical settings. These mutations represent clinicopathological features of lung adenocarcinoma and can guide the treatment choice after recurrence. We evaluated the prognostic impact of EGFR and KRAS mutations by considering other clinicopathological recurrence risks in resected pTis-3N0M0 lung adenocarcinoma. METHODS: Clinicopathological features related to recurrence and genetic status were estimated in consecutive 877 resected cases. Recurrence-free survival (RFS), cumulative recurrence rate (CRR), and overall survival (OS) were compared. Uni- and multivariate analyses for RFS were performed after excluding cases with little or no recurrence risks. RESULTS: EGFR mutation was more likely to be harbored in female, never-smoker, or patients accompanied by > 5% lepidic component. KRAS mutation was more likely to be harbored in patients with current/ex-smoking history, International Association for the Study of Lung Cancer (IASLC) grade 3, or accompanied lymphatic or vascular invasion. In IASLC grade 2 and 3 patients, EGFR or KRAS mutation cases had significantly worse 5-year RFS than wild type patients (76.9% vs. 85.0%, hazard ratio [HR] = 1.55, 95% confidence interval [CI] = 1.62-6.41, P < 0.001). EGFR or KRAS mutation cases had significantly higher 5-year CRR than wild type patients (17.7% vs. 9.8%, HR = 1.69, 95% CI = 1.44-6.59, P = 0.0038). KRAS mutation cases had higher 5-year CRR than EGFR mutation cases (16.7% vs. 21.4%, HR = 1.62, 95% CI = 0.96-7.19, P = 0.061). There was no significant difference in OS between cohorts. Multivariate analysis revealed that a positive EGFR/KRAS mutation status was risk factor for worse RFS (HR = 2.007, 95% CI = 1.265-3.183, P = 0.003). CONCLUSION: Positive EGFR and KRAS mutation statuses were risk factors for recurrence in resected IASLC grade 2 and 3 patients. KRAS mutations were more likely to be confirmed in cases with an increased risk of recurrence. EGFR and KRAS mutation statuses should be evaluated simultaneously when assessing the risk of recurrence.

[Successful Treatment of Blow-out Type Left Ventricular Free Wall Rupture Using Sutureless Technique].

Blow-out type left ventricular free wall rupture is a serious complication of acute myocardial infarction, that carries high hospital mortality rates and poor surgical outcome. We report the case of an 88-year-old woman who developed cardiac tamponade following percutaneous coronary angioplasty for acute myocardial infarction. She was diagnosed with left ventricular free wall rupture, and rupture type was proved to be blow out after median sternotomy. To address this critical condition, we opted for the sutureless technique for its minimally invasive nature and ability to preserve left ventricular function. The patient was discharged from the hospital without any complications 22 days after surgery. Considering favorable, encouraging outcomes of this case, sutureless technique could be regarded as a viable option for blow-out type left ventricular free wall rupture.

Combinations of anti-GITR antibody and CD28 superagonist ameliorated dextran sodium sulfate-induced mouse colitis.

Ulcerative colitis (UC) is one of the two main forms of inflammatory bowel disease (IBD) and is an idiopathic, chronic inflammatory disease of the colonic mucosa with an unclear etiology. Interleukin (IL)-10 has been reported to play a crucial role in the maintenance of immune homeostasis in the intestinal environment. Type 1 regulatory T (Tr1) cells are a subset of CD4+Foxp3- T cells able to secrete high amounts of IL-10 with potent immunosuppressive properties. In this study, we found that the combination of anti-GITR antibody (G3c) and CD28 superagonist (D665) treatment stimulated the generation of a large amount of Tr1 cells. Furthermore, G3c/D665 treatment not only significantly relieved severe mucosal damage but also reduced the incidence of colonic shortening, weight loss, and hematochezia. Dextran sodium sulfate (DSS) upregulated the mRNA levels of IL-6, IL-1ß, IL-17, IL-12, tumor necrosis factor-alpha, C-C chemokine receptor type 5, and Bax in splenic lymphocytes (SPLs) and colon tissues, while G3c/D665 treatment conversely inhibited the increase in mRNA levels of these genes. In addition, G3c/D665 treatment altered the proportion of CD4+ and CD8+ T cells and increased CD4+CD25+Foxp3+ regulatory T cells in SPLs, mesenteric lymph nodes (MLNs), and lamina propria lymphocytes (LPLs). Thus, the combination of G3c and D665 treatment showed efficacy against DSS-induced UC in mice by inducing a large amount of Tr1 cell generation via the musculoaponeurotic fibrosarcoma pathways in vivo and relieving inflammatory responses both systematically and locally.

[A Surgical Technique for Ascending Aorta-bifemoral Bypass and Coronary Artery Bypass Grafting without Aortic Cross-clamp].

A 69-year-old woman presented with symptoms of resting pain in the lower limb bilaterally. A computed tomography( CT) scan revealed occlusion of the infrarenal aorta and bilateral common iliac arteries, indicating Leriche syndrome. A coronary angiogram demonstrated in-stent restenosis in the left anterior descending coronary artery. Therefore, the patient underwent off-pump coronary artery bypass grafting (left mammary artery to left anterior descending coronary artery) and ascending aorta-bifemoral bypass using the HeartString device for the inflow anastomosis. The postoperative period was uneventful. Although an indication for this surgical technique should be tailored to the anatomy of the lesion, it is a reliable surgical option to achieve good outcomes.

[Right Anterior Minithoracotomy as an Effective Technique for Minimally Invasive Aortic Valve Replacement in Frail and Elderly Patient:Report of a Case].

Transcatheter aortic valve replacement has increasingly been used as a standard treatment option for patients with aortic valve stenosis, especially in the frail and the elderly. However, it is not recognized as a valid treatment for patients with aortic valve regurgitation. In this study, we report our experience in conducting a right anterior minithoracotomy for a minimally invasive aortic valve replacement in the elderly. An 87-year-old woman with severe aortic valve regurgitation was admitted to our department. Minimally invasive aortic valve replacement was performed, through a right anterior minithoracotomy in the second intercostal space. A localized transverse aortotomy was performed at a position higher than that in an ordinary aortotomy. Our procedure for aortic valve replacement was similar to the conventional method. The postoperative course was uneventful, and the patient was discharged after 10 days. Therefore, we conclude that right anterior minithoracotomy for a minimally invasive aortic valve replacement is a feasible, effective, and safe technique.

[Acute Aortic Dissection after Reoperative Aortic Valve Replacement with Early Diagnosis:Report of a Case].

Acute aortic dissection is a rare and potentially catastrophic perioperative complication of cardiac surgery. A 72-year-old woman underwent aortic valve replacement with a bioprosthetic valve for aortic regurgitation seven years earlier. She experienced respiratory distress on exertion and was diagnosed with prosthetic valve dysfunction. Reoperative aortic valve replacement with a bioprosthetic valve was performed. On postoperative day eight, contrast-enhanced computed tomography, which was performed to evaluate persistent high levels of inflammatory response, revealed acute DeBakey typeⅠaortic dissection. Emergency ascending aortic replacement was successfully performed. The patient was discharged on postoperative day 19 without any complications. Acute aortic dissection after cardiac surgery is rare;however, physicians should be aware of this possible complication.

Hypo-attenuated leaflet thickening and reduced leaflet motion after the implantation of the Perceval S sutureless bioprosthesis.

Hypo-attenuated leaflet thickening (HALT) is gaining attention as a relatively common issue after surgical or transcatheter aortic valve replacement (AVR). However, only a few reports have described HALT in sutureless bioprosthesis, which has emerged as a promising tool with excellent hemodynamics and enhanced implantability. We herein report a 75-year-old woman who underwent quintuple coronary artery bypass grafting and sutureless AVR with a Perceval S bioprosthesis (LivaNova PLC, London, UK). Despite an uneventful perioperative course, her recovery was slow with persistent pleural effusion. Echocardiography revealed an increased transvalvular pressure gradient, and HALT was confirmed by computed tomography. The patient received aggressive anticoagulation therapy with resolution of the HALT and made an uneventful recovery. Current guidelines provide no specific recommendations for peri-procedural antithrombotic therapy for sutureless AVR. However, HALT is not rare after sutureless AVR and can lead to significant clinical consequences. In this case, aggressive anticoagulation therapy with systemic heparinization was effective as HALT treatment following early post-sutureless AVR. Further investigation is required to determine the optimal antithrombotic strategy for sutureless AVR.

Extrusion of the medial meniscus is a potential predisposing factor for post-arthroscopy osteonecrosis of the knee.

BACKGROUND: Post-arthroscopic osteonecrosis of the knee (PAONK) is a rare condition. No studies have analyzed the relationship between the meniscus extrusion and PAONK. The purpose of this retrospective study is to test a hypothesis that the degree of the medial meniscus (MM) extrusion might be significantly greater in the knees with PAONK than in the matched control knees both before and after the meniscectomy. METHODS: Ten knees with PAONK were detected out of a total of 876 knees which had undergone arthroscopic partial meniscectomy of the MM. Ten matched control knees were randomly selected out of the remaining 866 knees without PAONK. The clinical data of these 20 patients were retrospectively collected from the medical records. To evaluate the location of the menisci on the joint line, Extrusion width and Inner width were defined on a coronal section of magnetic resonance imaging (MRI). The intra- and inter-rater reliability was evaluated by calculating the intra- and inter-class coefficients. Statistical comparisons between the 2 groups were made using the 3 non-parametric tests. RESULTS: Before the meniscectomy, the Extrusion width of the MM (mean 4.7 ± 1.4 mm) was significantly greater than that (3.0 ± 1.3 mm) in the Control group (P = 0.0195). In the MRI taken in a range from 3 to 50 weeks after the meniscectomy, the Extrusion width of the MM (5.9 ± 1.1 mm) in the PAONK group was significantly greater than that (3.4 ± 1.4 mm) in the Control group (P = 0.0009), and the Inner width of the MM (0.6 ± 1.7 mm) in the PAONK group was significantly less than that (3.9 ± 1.0 mm) in the Control group (P = 0.0001). CONCLUSION: A significant relationship was found between the degree of the MM extrusion and the onset of PAONK. This study suggested that the extrusion of the MM is a potential predisposing factor for PAONK.

Polyglycolic acid mesh for preventing post-thoracoscopic bullectomy recurrence.

PURPOSE: Thoracoscopic bullectomy is a common treatment modality for spontaneous pneumothorax but can result in a high frequency of postoperative recurrent pneumothorax in young patients. This retrospective study compared the recurrence rate of pneumothorax following conventional thoracoscopic bullectomy to that following bullectomy using a low-density polyglycolic acid mesh to cover the staple line. METHODS: Group A comprised 237 patients who experienced 294 episodes of pneumothorax and underwent thoracoscopic bullectomy alone, and Group B comprised 130 patients who experienced 155 episodes of pneumothorax and underwent bullectomy with polyglycolic acid mesh used to cover the visceral pleura. To compare the postoperative inflammatory response between the two groups, we measured three inflammatory parameters: highest body temperature after surgery, C-reactive protein level on postoperative day 3, and change in eosinophil count from the day before the surgery to postoperative day 3. RESULTS: The recurrence rate was significantly lower in Group B than in Group A (2.6% vs. 24.8%, P < 0.000001). All three inflammatory parameters were significantly higher in Group B than in Group A. CONCLUSIONS: Using a polyglycolic acid mesh covering after thoracoscopic bullectomy resulted in acceptable long-term results (recurrence rate: 2.6%). This method was associated with a slightly elevated inflammatory response.

A Case of Non-hereditary White Sponge Nevus in the Oral Cavity Successfully Treated with Tetracycline Ointment and Oral Multivitamins.

White spongiform nevus is an autosomal dominant inherited disorder first reported by Cannon in 1935. It is a rare disease in which the oral mucosa thickens into an edematous and spongy state and is often accompanied by difficult to recognize subjective symptoms. We report a case of multiple non-hereditary white cavernous nevi in the oral mucosa. The subject was a 22-year-old man with a chief complaint of white lesions in his oral cavity. Examination revealed thick edematous and sponge-like white lesions on the bilateral buccal mucosa, upper and lower lip mucosa, and bilateral lingual margins. There was no history of similar lesions in his family or among his relatives. We diagnosed the case as non-hereditary white sponge nevus, based on clinical and histopathological findings. Although difficult to treat, the lesions disappeared with tetracycline ointment application and oral intake of multiple vitamin supplements. No recurrence of the lesion was observed thereafter.

Predicting the presence of breast cancer using circulating small RNAs, including those in the extracellular vesicles.

Emerging evidence indicates that small RNAs, including microRNAs (miRNAs) and their isoforms (isomiRs), and transfer RNA fragments (tRFs), are differently expressed in breast cancer (BC) and can be detected in blood circulation. Circulating small RNAs and small RNAs in extracellular vesicles (EVs) have emerged as ideal markers in small RNA-based applications for cancer detection. In this study, we first undertook small RNA sequencing to assess the expression of circulating small RNAs in the serum of BC patients and cancer-free individuals (controls). Expression of 3 small RNAs, namely isomiR of miR-21-5p (3' addition C), miR-23a-3p and tRF-Lys (TTT), was significantly higher in BC samples and was validated by small RNA sequencing in an independent cohort. Our constructed model using 3 small RNAs showed high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.92 and discriminated early-stage BCs at stage 0 from control. To test the possibility that these small RNAs are released from cancer cells, we next examined EVs from the serum of BC patients and controls. Two of the 3 candidate small RNAs were identified, and shown to be abundant in EVs of BC patients. Interestingly, these 2 small RNAs are also more abundantly detected in culture media of breast cancer cell lines (MCF-7 and MDA-MB-231). The same tendency in selective elevation seen in total serum, serum EV, and EV derived from cell culture media could indicate the efficiency of this model using total serum of patients. These findings indicate that small RNAs serve as significant biomarkers for BC detection.

Familial cases of pseudohypoaldosteronism type II harboring a novel mutation in the Cullin 3 gene.

Pseudohypoaldosteronism type II (PHA II) is inherited in an autosomal dominant manner and is characterized by hypertension, hyperkalemia, and hyperchloremic metabolic acidosis. The enhancement of with-no-lysine kinase (WNK) functions is correlated to the pathogenesis of the condition. Cullin 3 (CUL3) forms an E3 ubiquitin ligase complex, and it can ubiquitinate WNK. Most CUL3 gene mutations are distributed in sites, such as intron 8 splice acceptor, intron 9 splice donor, and putative intron 8 splice branch sites, which are involved in the splicing of exon 9. These mutations result in the deletion of exon 9, which reduces the activity of ubiquitination against WNK and inhibits the degradation of WNK. In this report, we identified a novel CUL3 c.1312A>G mutation in familial cases. A mutation prediction software showed that the significance of these mutations was not clear. However, using the Human Splicing Finder 3.1 software, in silico analyses revealed that these mutations induced splicing alterations, which affected the sites of exon 9, altered the balance between predicted exonic splicing enhancers and silencers, and led to the deletions of exon 9. This study presented a novel pathogenic splicing variant to the CUL3 mutation and provided a reference for further research about the mechanisms of splicing. Moreover, it showed that not only amino acid substitution caused by nonsynonymous mutations but also splicing motif changes due to base substitutions have important roles in the pathogenesis of PHA II.

Sutureless aortic valve replacement with concomitant aortic arch reconstruction.

Sutureless aortic valve replacement (AVR) offers an alternative approach to the standard AVR in aortic valve disease. We herein report a case of an 82-year-old woman with severe aortic insufficiency and a persistent type 1 endoleak following a thoracic endovascular aortic repair, who underwent successful combined aortic arch reconstruction and sutureless AVR. The bioprosthesis, Perceval (LivaNova PLC, London, UK), a self-anchoring, self-expanding, sutureless valve, which can be implanted in selected patients with aortic insufficiency was used. Although the patient was frail and at a high risk of open-heart surgery, she had an uneventful postoperative course. Hence, Perceval may be a useful option for combined aortic arch reconstruction and aortic valve surgery in high-risk elderly patients.

A Novel Approach to Prevent Perioperative Stroke in Patients Undergoing Debranching Thoracic Endovascular Aortic Repair with a Mini-Cardiopulmonary Bypass Support.

BACKGROUND: Perioperative stroke is a major complication after debranching thoracic endovascular aortic repair (TEVAR), with a reported incidence of 7.0-26.9%. Subsequent functional recovery is difficult in most cases. This study was performed to evaluate the efficacy of mini-cardiopulmonary bypass (mini-CPB) support in debranching TEVAR to prevent perioperative stroke. METHODS: From December 2010 to July 2017, 32 patients with a shaggy aorta or intimal irregularity in the aortic arch identified on preoperative computed tomography underwent debranching TEVAR. Nineteen patients underwent debranching TEVAR without mini-CPB, and 13 patients underwent debranching TEVAR with a mini-CPB support. Mini-CPB support had been used in November 2014 to treat perioperative stroke, which had occurred in 8 (42%) patients at that time. The form of the debranching arch vessels was not changed; bypass from the right axillary artery to the left axillary artery was performed for one debranching, and bypass from the right axillary artery to the left common carotid artery and left axillary artery was performed for two debranchings. After establishment of mini-CPB support through this debranching graft and right femoral vein cannulation, all endovascular manipulations were initiated. The left subclavian artery was occluded with a plug at the end of the procedure. RESULTS: The proximal landing zones of the endoprosthesis were as follows: zone 0 in 9 patients, zone 1 in 5 patients, and zone 2 in 5 patients in the no-CPB era and zone 1 in 3 patients and zone 2 in 10 patients in the CPB era. The mean mini-CPB support period was 51 minutes. Postoperative respiratory support and hospitalization were not prolonged with mini-CPB support. The incidence of perioperative stroke was 42% in the no-CPB era and 8% in the CPB era. No operative mortality was observed in the CPB era, although 5 (26%) patients died in the no-CPB era. The cause of operative mortality in the no-CPB era was perioperative stroke in 4 patients and acute myocardial infarction in 1 patient. No significant difference in the cumulative survival rate was found between patients with and without mini-CPB support. CONCLUSIONS: Our mini-CPB system may have the potential to prevent perioperative stroke during debranching TEVAR for treatment of aortic arch pathologies.

Beta-tricalcium phosphate shows superior absorption rate and osteoconductivity compared to hydroxyapatite in open-wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to clinically and radiologically compare the utility, osteoconductivity, and absorbability of hydroxyapatite (HAp) and beta-tricalcium phosphate (TCP) spacers in medial open-wedge high tibial osteotomy (HTO). METHODS: Thirty-eight patients underwent medial open-wedge HTO with a locking plate. In the first 19 knees, a HAp spacer was implanted in the opening space (HAp group). In the remaining 19 knees, a TCP spacer was implanted in the same manner (TCP group). All patients underwent clinical and radiological examinations before surgery and at 18 months after surgery. RESULTS: Concerning the background factors, there were no statistical differences between the two groups. Post-operatively, the knee score significantly improved in each group. Concerning the post-operative knee alignment and clinical outcome, there was no statistical difference in each parameter between the two groups. Regarding the osteoconductivity, the modified van Hemert's score of the TCP group was significantly higher (p = 0.0009) than that of the HAp group in the most medial osteotomy zone. The absorption rate was significantly greater in the TCP group than in the HAp group (p = 0.00039). CONCLUSIONS: The present study demonstrated that a TCP spacer was significantly superior to a HAp spacer concerning osteoconductivity and absorbability at 18 months after medial open-wedge HTO. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Surgical treatment for coarctation of the aorta.

Key Clinical Message: Surgical treatment is a better option for coarctation of the aorta. Abstract: A 56-year-old man was admitted to the hospital due to chest pain. Computed tomography showed severe coarctation of the aorta distal to the left subclavian artery, with poststenotic dilatation of the descending aorta. A descending aortic replacement was performed in an uneventful manner. The postoperative course was good without symptoms.

Coral calcium carried hydrogen ameliorates the severity of non-alcoholic steatohepatitis induced by a choline deficient high carbohydrate fat-free diet in elderly rats.

Hydrogen has been reported to act as an antioxidant, anti-apoptosis and anti-inflammatory agent. Coral calcium carried hydrogen (G2-SUISO) is a safer and more convenient form of hydrogen agent than others. The mechanism underlying the hepatoprotective effects of G2-SUISO using an elderly non-alcoholic steatohepatitis (NASH) rat model was investigated. Two days after fasting, six-month-old elderly male F344/NSlc rats were given a choline deficient high carbohydrate fat-free (CDHCFF) diet from day 0 to day 3 as CDHCFF control group, and then switched to a normal diet from days 4 to 7 with or without 300 mg/kg G2-SUISO. Rats in each group were finally being sacrificed on day 3 or day 7. In the CDHCFF diet group, G2-SUISO decreased the liver weight-to-body weight ratio, the serum AST, ALT, total cholesterol levels, inflammatory infiltration, pro-inflammatory cytokine expression and lipid droplets with inhibiting lipogenic pathways by reducing sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase and fatty acid synthase gene expression compared with the CDHCFF diet alone. G2-SUISO had beneficial effects of anti-apoptosis as well the down-regulation of pro-apoptotic molecules including NF-κB, caspase-3, caspase-9 and Bax. These findings suggest that G2-SUISO treatment exerts a significant hepatoprotective effect against steatosis, inflammation and apoptosis in elderly NASH rats.

Serum steroid metabolite profiling by LC-MS/MS in two phenotypic male patients with HSD17B3 deficiency: Implications for hormonal diagnosis.

Although 17ß-hydroxysteroid dehydrogenase type 3 (HSD17B3) deficiency is diagnosed when a testosterone/androstenedione (T/A-dione) ratio after human chorionic gonadotropin (hCG) stimulation is below 0.8, this cut-off value is primarily based on hormonal data measured by conventional immunoassay (IA) in patients with feminized or ambiguous genitalia. We examined two 46,XY Japanese patients with undermasculinized genitalia including hypospadias (patient 1 and patient 2). Endocrine studies by IA showed well increased serum T value after hCG stimulation (2.91 ng/mL) and a high T/A-dione ratio (4.04) in patient 1 at 2 weeks of age and sufficiently elevated basal serum T value (2.60 ng/mL) in patient 2 at 1.5 months of age. Despite such partial androgen insensitivity syndrome-like findings, whole exome sequencing identified biallelic ″pathogenic″ or ″likely pathogenic″ variants in HSD17B3 (c .188 C>T:p.(Ala63Val) and c .194 C>T:p.(Ser65Leu) in patient 1, and c.139 A>G:p.(Met47Val) and c.672 + 1 G>A in patient 2) (NM_000197.2), and functional analysis revealed reduced HSD17B3 activities of the missense variants (∼ 43% for p.Met47Val, ∼ 14% for p.Ala63Val, and ∼ 0% for p.Ser65Leu). Thus, we investigated hCG-stimulated serum steroid metabolite profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patient 1 at 7 months of age and in patient 2 at 11 months of age as well as in five control males with idiopathic micropenis aged 1 - 8 years, and found markedly high T/A-dione ratios (12.3 in patient 1 and 5.4 in patient 2) which were, however, obviously lower than those in the control boys (25.3 - 56.1) and sufficiently increased T values comparable to those of control males. The elevated T/A-dione ratios are considered be due to the residual HSD17B3 function and the measurement by LC-MS/MS. Thus, it is recommended to establish the cut-off value for the T/A-dione ratio according to the phenotypic sex reflecting the residual function and the measurement method.

Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance.

The liver has long been deemed a tolerogenic organ. We employed high-dimensional mass cytometry and immunohistochemistry to depict the temporal and spatial dynamics of immune cells in the spleen and liver in a murine model of spontaneous liver allograft acceptance. We depicted the immune landscape of spontaneous liver tolerance throughout the rejection and acceptance stages after liver transplantation and highlighted several points of importance. Of note, the CD4+/CD8+ T cell ratio remained low, even in the tolerance phase. Furthermore, a PhenoGraph clustering analysis revealed that exhausted CD8+ T cells were the most dominant metacluster in graft-infiltrating lymphocytes (GILs), which highly expressed the costimulatory molecule CD86. The temporal and spatial dynamics of immune cells revealed by high-dimensional analyses enable a fine-grained analysis of GIL subsets, contribute to new insights for the discovery of immunological mechanisms of liver tolerance, and provide potential ways to achieve clinical operational tolerance after liver transplantation.