[Profuse Hemorage During Open Heart Surgery in a Patient Late After Liver Transplantation and Remission Stage Acquired Hemophilia].

A 72-year-old male presented with severe mitral regurgitation, moderate tricuspid regurgitation, and chronic atrial fibrillation. One month prior, he encountered difficulties with dialysis and was subsequently referred to our department for cardiac surgery. The patient's medical history includes living-donor liver transplantation for type C cirrhosis associated with acquired hemophilia A. The preoperative liver function was categorized as Child-Pugh grade B, with a model for end-stage liver disease( MELD) score of 23. His factor Ⅷ activity was close to the lower limit of the normal range. The patient underwent mitral valve replacement, tricuspid valve repair, and left atrial appendage closure. Initially, he experienced intractable bleeding, but hemostasis was easily achieved after administrating a factor Ⅷ preparation. Upon admission to the intensive care unit, his factor Ⅷ clotting activity was slightly below the normal range. Therefore, in cases where a patient with remission stage hemophilia A resulting in liver transplantation undergoes open heart surgery, it is crucial to have coagulation factor medication readily available, regardless of normal preoperative factor Ⅷ levels.

Rheocarna® therapy after distal bypass surgery.

Objectives: Rheocarna® therapy has recently been reported to improve peripherally measured blood flow as an adjuvant treatment after revascularization in patients with chronic limb-threatening ischemia. We investigated whether skin perfusion pressure and continuous walking distance were improved by performing Rheocarna® therapy after distal bypass surgery. Methods: This study included 10 patients who underwent Rheocarna® therapy after distal bypass surgery between June 2022 and March 2023. Rheocarna® therapy was performed five times after distal bypass surgery, and the skin perfusion pressure and continuous walking distance after distal bypass surgery were compared with those after Rheocarna® therapy. Results: The average age was 74.7 years, and nine patients (90%) were male. All patients were undergoing dialysis, with an average of 14.5 years of dialysis history. There were six patients (60%) with diabetes mellitus and five (50%) with hyperlipidemia. The ankle-brachial index was 0.62 ± 0.36 before distal bypass surgery and 0.936 ± 0.16 after Rheocarna® therapy, indicating a significant increase (p = 0.0117). Skin perfusion pressure dorsalis pedis was 71.5 ± 27.0 mmHg after Rheocarna® therapy, showing a marked increase from the preoperative value (p = 0.0020). Skin perfusion pressure planta pedis was 65.0 ± 26.3 mmHg after Rheocarna® therapy, which was a significant increase from the preoperative value (p = 0.0293). The continuous walking distance was 78.5 ± 102.7 m after the Rheocarna® therapy, which was a significant increase from the preoperative value (p = 0.0039). Conclusion: The skin perfusion pressure and continuous walking distance were significantly improved by Rheocarna® therapy after distal bypass surgery.

Extra-Anatomical Bypass for Chronic Mesenteric Ischemia with Saphenous Vein Grafts from a Previous Axillofemoral Artery Bypass Graft: A Case Report.

A 74-year-old woman who was diagnosed with chronic mesenteric ischemia was under hemodialysis maintenance and had previously undergone axillobifemoral bypass surgery because of abdominal aortoiliac occlusion. Endovascular and antegrade or retrograde surgical revascularizations from the aortoiliac artery were contraindicated because of a severely calcified arteriosclerotic lesion, which included aortoiliac occlusion. During median laparotomy, revascularization consisting of bypass grafting from a previous prosthetic graft to the mesenteric arteries was performed using saphenous vein grafts. Although extra-anatomical bypass for chronic mesenteric ischemia is challenging, it provides a feasible option in cases where conventional endovascular or surgical revascularization is contraindicated.

Combined Prognostic Value of Preprocedural Protein-Energy Wasting and Inflammation Status for Amputation and/or Mortality after Lower-Extremity Revascularization in Hemodialysis Patients with Peripheral Arterial Disease.

Protein-energy wasting is associated with inflammation and advanced atherosclerosis in hemodialysis patients. We enrolled 800 patients who had undergone successful lower-extremity revascularization, and we investigated the association among the Geriatric Nutritional Risk Index (GNRI) as a surrogate marker of protein-energy wasting, C-reactive protein (CRP), and their joint roles in predicting amputation and mortality. They were divided into lower, middle, and upper tertiles (T1, T2, and T3) according to GNRI and CRP levels, respectively. Regarding the results, the amputation-free survival rates over 8 years were 47.0%, 56.9%, and 69.5% in T1, T2, and T3 of the GNRI and 65.8%, 58.7%, and 33.2% for T1, T2, and T3 of CRP, respectively (p < 0.0001 for both). A reduced GNRI [adjusted hazard ratio (aHR) 1.78, 95% confidence interval (CI) 1.24-2.59, p = 0.0016 for T1 vs. T3] and elevated CRP (aHR 1.86, 95% CI 1.30-2.70, p = 0.0007 for T3 vs. T1) independently predicted amputation and/or mortality. When the two variables were combined, the risk was 3.77-fold higher (95% CI 1.97-7.69, p < 0.0001) in patients who occupied both T1 of the GNRI and T3 of CRP than in those who occupied both T3 of the GNRI and T1 of CRP. In conclusion, patients with preprocedurally decreased GNRI and elevated CRP levels frequently experienced amputation and mortality, and a combination of these two variables could more accurately stratify the risk.

Thoracic endovascular aortic repair for chronic aortic dissection after total arch replacement for aberrant right subclavian artery: A case report.

An aberrant right subclavian artery (ARSA) is an extremely rare congenital anomaly that forms during aortic arch development. Most reports of thoracic endovascular aortic repair (TEVAR) described an ARSA in the right aortic arch, but it is rare in the left aortic arch. We present the case of a 66-year-old man who underwent total arch replacement because of acute type A aortic dissection. An outpatient follow-up examination revealed that the aortic diameter enlargement exceeded 60 mm because of false lumen entry from the ARSA. Therefore, surgical intervention was planned. TEVAR, ARSA embolization, and bilateral axillary bypass surgery were successfully performed for a chronic dissecting aortic aneurysm for which the ARSA was the inflow route. He was discharged 12 days after surgery. Four years later, no enlargement of the aneurysm diameter was observed. TEVAR is a minimally invasive and useful treatment option for chronic type B dissections with an ARSA associated with the left aortic arch; however, patients with an ARSA have fragile blood vessels and require careful follow-up.

Rare epithelioid hemangioendothelioma in the brachiocephalic vein for long-term survival after surgery: A case report.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor. In this report, we describe the case of a 62-year-old man who presented with pain in the left clavicle and swelling of the left upper limb. Contrast-enhanced computed tomography revealed an intravascular tumor, which was completely resected surgically. Histopathological examination and immunohistochemical staining revealed that it was epithelioid hemangioendothelioma with occurrence in the left brachiocephalic vein. It has been 6 years since the surgery was performed, and no recurrence has been observed. Epithelioid hemangioendothelioma may recur or metastasize and therefore requires careful follow-up.

[Huge Tricuspid Pouch with Heart Failure:Report of a Case].

Tricuspid pouch forms during the spontaneous closure of a ventricular septal defect (VSD). Cases have been reported in which the tricuspid pouch was discovered for the first time during surgery and could not be distinguished from an aneurysm of the membranous septum( AMS). A 58-year-old woman had a heart murmur. Transthoracic echocardiography showed an aneurysm-like pouch protruding into the right ventricle. Magnetic resonance imaging could not distinguish between AMS and tricuspid pouch;however, contrast-enhanced computed tomography showed a VSD. The membranous structure comprised multiple lobules, and the tendon of the papillary muscles was continuous with the tricuspid valve. Intraoperatively, the tricuspid valve septal leaflet was adhered to the defect hole. It was incised along the annulus, the VSD was closed with a bovine pericardial patch, and the annulus of the tricuspid valve septal leaflet was suture closed. The patient was discharged after a good postoperative course.

Impact of Hemodialysis on Clinical Outcomes in Patients Undergoing Lower Extremity Bypass Surgery for Peripheral Artery Disease-10-year Follow-Up Study.

We investigated the clinical impact of hemodialysis on long-term outcomes of bypass surgery in patients with peripheral artery disease. We evaluated 660 consecutive patients who underwent successful bypass surgery (392 hemodialysis and 268 non-hemodialysis). The endpoint was amputation-free survival (AFS). To minimize differences in clinical characteristics between the 2 groups, propensity score matching was performed. The AFS rates for 10-year follow-up were 39.3% and 67.7% in hemodialysis and non-hemodialysis patients [hazard ratio (HR) 2.21, 95% confidence interval (CI) 1.65-3.01, P < .0001]. Cumulative incidence of amputation was higher in the hemodialysis group than in the non-hemodialysis group [(19.4 vs 8.4%, HR 2.15, 95% CI 1.29-3.74, P = .0027). In a matched cohort (n = 210 each), AFS was still lower in the hemodialysis patients (53.1 vs 66.3%, HR 1.94, 95% CI 1.36-2.82, P = .0003). However, there was no significant difference in amputation rate between the groups (10.5 vs 10.6%, HR .97, 95% CI 0.49-1.87, P = .93). In a sub-analysis of patients with critical limb ischemia, similar results were obtained. The 10-year AFS was consistently lower in the hemodialysis group than in the non-hemodialysis group. However, the amputation rate was comparable between the groups when matched for the differences in clinical characteristics.

Case of persistent sciatic artery in a dialysis patient with critical limb ischemia.

Persistent sciatic artery is a rare congenital malformation (incidence rate, 0.03%-0.06%). We report the case of a 72-year-old male patient with persistent sciatic artery suffering from pain at rest and an ulcer on the left first toe. Angiography findings showed 90% stenosis in the distal persistent sciatic artery. Endovascular therapy was considered difficult because of a long stenotic lesion from the persistent sciatic artery to the popliteal artery and extremely high calcification of the whole body. Because of poor blood flow to the lower leg, vascular prosthesis would have increased the risk of thrombotic occlusion. Therefore, below-knee femoropopliteal bypass using the great saphenous vein graft was performed, which led to the healing of the ulcer on the left first toe. Contrast-enhanced computed tomography of the lower limbs was performed to confirm that the bypass blood flow was good. The patient was discharged on postoperative day 5.

Surgical treatment for secondary spontaneous pneumothorax: a risk factor analysis.

PURPOSE: While surgery is an effective treatment for secondary spontaneous pneumothorax (SSP), it can be difficult, because affected patients are usually in a poor general condition. The present study investigated the risk factors of postoperative complications after surgery for SSP. METHODS: Eighty-eight patients with SSP who underwent surgery from January 2006 to March 2018 were investigated. Clinical data were reviewed, and a multivariate analysis was performed. RESULTS: Eighty-four patients (95%) were males, and the median patient age was 72 years. Underlying lung diseases were chronic obstructive pulmonary disease in 58 patients (65.9%), interstitial pneumonia in 26 (29.5%), and others in 4 (4.5%). Postoperative complications developed in 21 patients (24%). Hospital mortality/prolonged length of stay occurred in 6 patients (7%). A multivariate analysis showed that the preoperative performance status (performance status 0-2 vs. 3, hazard ratio: 6.570, 95% confidence interval: 1.980-21.800) was an independent predictor of postoperative complications. CONCLUSION: Surgery for SSP contributed to early chest tube removal and favorable outcomes. However, rare fatal events occurred, and the patient performance status was a risk factor for postoperative complications. A careful evaluation of each patient's performance status is needed to determine the need for surgical intervention for SSP.

Status of pleural lavage cytology in cases of pulmonary metastasis: a single-institution retrospective study.

OBJECTIVE: In primary lung cancer surgery, intraoperative pleural lavage cytology (PLC) has been identified as a prognostic marker. However, there have been no reports on PLC for pulmonary metastasectomies. Therefore, the impact of PLC status for patients undergoing pulmonary metastasectomy remains unknown. We aimed to know the incidence and prognostic impact of positive PLC findings in pulmonary metastasectomies. METHODS: We retrospectively reviewed patients undergoing pulmonary metastasectomies between January 2013 and December 2018. One hundred and eighty-nine PLC procedures in 159 patients undergoing pulmonary metastasectomy were analyzed. Follow-up information was available in 107 patients who underwent 132 procedure, and they were investigated for pleural recurrence-free probability (PRFP) and overall survival (OS) after pulmonary metastasectomy. RESULTS: The type of primary lesion was colorectal cancer (101/189, 53%), urothelial/kidney cancer (17/189, 9%), skeletal/soft tissue tumor (18/189, 10%), hepatobiliary/pancreatic cancer (19/189, 10%), uterine/ovarian cancer (14/189, 7%), otorhinolaryngological cancer (11/189, 6%), and other minor lesions (9/189, 5%). Nine PLC-positive metastasectomies were revealed (9/189, 4.8%). They consisted of six metastasectomies from pancreatic cancer, two from osteosarcoma, and one from tongue cancer. Significant predictors for PLC status was type of primary tumor (P < 0.001). PRFP and OS rate of PLC-positive group were significantly lower than PLC-negative (P < 0.001, respectively). CONCLUSION: PLC-positive results were rarely seen in pulmonary metastasectomies. PLC status was associated with the incidence of ipsilateral pleural recurrence and survival after metastasectomy. Cytologic examination of PLC should be considered in patients undergoing pulmonary metastasectomy.

Meta-Analysis and Meta-Regression of Transcatheter Aortic Valve Implantation for Pure Native Aortic Regurgitation.

AIM: To assess outcomes of transcatheter aortic valve implantation (TAVI) for pure native aortic regurgitation (AR) and to evaluate whether 30-day all-cause mortality is modulated by patient characteristics, we performed a meta-analysis and meta-regression of currently available studies. METHOD: Studies enrolling ≥20 patients undergoing TAVI for AR were considered for inclusion. Study-specific estimates (incidence rates of outcomes) were combined using one-group meta-analysis in a random-effects model. Subgroup meta-analysis of studies exclusively using early-generation devices (EGD) and new-generation devices (NGD) and stepwise random-effects multivariate meta-regression were also performed. RESULTS: The search identified 11 eligible studies including a total of 911 patients undergoing TAVI for AR. Pooled analysis demonstrated an incidence of device success of 80.4% (NGD 90.2%, EGD 67.2%; p < 0.001), moderate or higher paravalvular aortic regurgitation (PAR) of 7.4% (NGD 3.4%, EGD 17.3%; p < 0.001), 30-day all-cause mortality of 9.5% (NGD 6.1%, EGD 14.7%; p < 0.001), mid-term (4 mo - 1 yr) all-cause mortality of 18.8% (NGD 11.8%, EGD 32.2%; p < 0.001), life-threatening/major bleeding complications (BC) 5.7% (NGD 3.5%, EGD 12.4%; p = 0.015), and major vascular complications (MVC) of 3.9% (NGD 3.0%, EGD 6.2%; p = 0.041). All coefficients in the multivariate meta-regression adjusting simultaneously for the proportion of diabetes mellitus, chronic obstructive pulmonary disease, peripheral arterial disease, concomitant moderate or higher mitral regurgitation, and mean left ventricular ejection fraction (with significant coefficients in the univariate meta-regression) were not statistically significant. CONCLUSIONS: Thirty (30)-day all-cause mortality after TAVI for AR was high (9.5%) with a high incidence of moderate or higher PAR (7.4%). Compared with EGD, NGD was associated with significantly higher device success rates and significantly lower rates of second-valve deployment, moderate or higher PAR, 30-day/mid-term all-cause mortality, serious BC, and MVC.

A meta-analysis of impact of low-flow/low-gradient aortic stenosis on survival after transcatheter aortic valve implantation.

AIMS: To determine whether low-flow/low-gradient (LF/LG) aortic stenosis affects survival after transcatheter aortic valve implantation (TAVI), we performed a meta-analysis of currently available studies. METHODS: MEDLINE and EMBASE were searched through January 2019 using PubMed and OVID. Observational studies comparing all-cause mortality after TAVI for patients with classical LF/LG (C/LF/LG) aortic stenosis versus normal-flow/high-gradient (NF/HG) aortic stenosis, paradoxical LF/LG (P/LF/LG) aortic stenosis versus NF/HG aortic stenosis, and (3) C/LF/LG aortic stenosis versus P/LF/LG aortic stenosis were included. Study-specific estimates, risk and hazard ratios of mortality, were combined in the random-effects model. RESULTS: Our search identified nine eligible studies including a total of 5512 TAVI patients. Pooled analysis demonstrated significantly higher early mortality in C/LF/LG aortic stenosis than NF/HG aortic stenosis (risk ratio, 1.72; P = 0.02) and no statistically significant difference in early mortality between P/LF/LG aortic stenosis and NF/HG aortic stenosis (P = 0.67) and between C/LF/LG aortic stenosis and P/LF/LG aortic stenosis (P = 0.51). Midterm mortality in C/LF/LG (risk ratio/hazard ratio, 1.73; P = 0.0003) and P/LF/LG aortic stenosis (risk ratio/hazard ratio, 1.48; P < 0.0001) was significantly higher than that in NF/HG aortic stenosis. There was no statistically significant difference in midterm mortality between C/LF/LG aortic stenosis and P/LF/LG aortic stenosis (P = 0.63). CONCLUSION: After TAVI, C/LF/LG aortic stenosis is associated with increased early mortality compared with NF/HG, and C/LF/LG and P/LF/LG aortic stenosis is associated with increased midterm mortality compared with NF/HG aortic stenosis despite no difference in early mortality between P/LF/LG aortic stenosis and NF/HG aortic stenosis. There is no difference in early and midterm mortality between C/LF/LG aortic stenosis and P/LF/LG aortic stenosis.

[Preoperative Detection of Pleural Adhesions Using Transthoracic Ultrasonography].

Recently, there has been an increase in the experience of lung surgery in cases with a history of thoracotomy or pneumonia. In these cases, pleural adhesion is often seen and makes the surgery to be difficult. Especially in thoracoscopic surgery, lung damage must be care at the 1st port insertion. In this report, the usefulness of the extent of pleural adhesion to the chest wall before surgery by using a transthoracic ultrasonography was assessed. Between April 2017 and September 2018, 32 patients underwent preoperative ultrasound examination, and 128 ports were evaluated whether had adhesions or not using lung sliding sign. All patients of 128, 24 adhesions were found at surgery, resulting in 14 true positive, 10 false negative, 0 false positive, and 104 true negative findings [sensitivity:58.3% (14/24), specificity: 100.0% (104/104), accuracy:92.2% (118/128)]. Especially, about the 1st port, accuracy was 93.8 % (30/32). In Conclusion, preoperative transthoracic ultrasonography could provide useful information on the pleural adhesion leading safe initial thoracoscopic access without lung injury.

Differentiation of embryonic stem cells into inner ear vestibular hair cells using vestibular cell derived-conditioned medium.

Vestibular hair cells (V-HCs) in the inner ear have important roles and various functions. When V-HCs are damaged, crippling symptoms, such as vertigo, visual field oscillation, and imbalance, are often seen. Recently, several studies have reported differentiation of embryonic stem (ES) cells, as pluripotent stem cells, to HCs, though a method for producing V-HCs has yet to be established. In the present study, we used vestibular cell conditioned medium (V-CM) and effectively induced ES cells to differentiate into V-HCs. Expressions of V-HC-related markers (Math1, Myosin6, Brn3c, Dnah5) were significantly increased in ES cells cultured in V-CM for 2 weeks, while those were not observed in ES cells cultured without V-CM. On the other hand, the cochlear HC-related marker Lmod3 was either not detected or detected only faintly in those cells when cultured in V-CM. Our results demonstrate that V-CM has an ability to specifically induce differentiation of ES cells into V-HCs.

Isolation and culture of pleural mesothelial cells.

Purpose: Although the isolation of rat and mouse mesothelial cells has previously been reported, most mesothelial cells used for experimental studies are obtained from peritoneal cells. Here, we describe an optimized method for the isolation and in vitro propagation of rodent pleural mesothelial cells without the requirement for specialized surgical techniques. Materials and Methods: To harvest pleural mesothelial cells, the pleural space of 8-9-week-old rats or older mice was filled with 0.25% trypsin in ethylenediaminetetraacetic acid (EDTA) buffer for 20 min at 37 °C. Cells were then harvested, and incubated at 37 °C in a humidified atmosphere with 5% CO2. Immunofluorescence analysis of plated pleural mesothelial cells was performed using Alexa 546 (calretinin). To investigate optimal proliferation conditions, medium enriched with various concentrations of fetal calf serum (FCS) was used for pleural mesothelial cell proliferation. Results: By day 10, confluent cell cultures were established, and the cells displayed an obvious cobblestone morphology. Immunofluorescence analysis of the cells demonstrated that all stained positive for Alexa 546 (calretinin) expression. Mesothelial cells grew better in medium containing 20% FCS than with 10% FCS. Conclusions: This is a simple procedure for the efficient collection of primary pleural mesothelial cells, which were obtained in defined culture conditions from the euthanized rodent thoracic cavity using trypsin-EDTA treatment. The ability to easily culture and maintain identifiable pleural mesothelial cells from rodents will be helpful for future experiments using these cells.

Ultrasonography for Detecting Adhesions: Aspirin Continuation for Lung Resection Patients.

BACKGROUND/AIM: Aspirin reduces cardiovascular disease and/or stroke risks. However, perioperative aspirin use remains controversial. We assessed the efficacy of ultrasonography to facilitate video-assisted thoracic surgery (VATS). We analyzed the perioperative management of patients using aspirin and its association with bleeding events during lung cancer surgery. PATIENTS AND METHODS: A total of 38 patients who underwent VATS after continuing or discontinuing aspirin were examined. Ultrasound was performed preoperatively to evaluate the pleural adhesions. Fisher's exact test was used to analyze correlations between the two groups. RESULTS: Dense adhesions were found at VATS ports using ultrasonography (accuracy: 100%). No differences were detected in bleeding, thrombotic events, or operative times between the aspirin and non-aspirin groups. There were differences in bleeding (p=0.009) and operative times (p=0.021) between the dense adhesion and non-dense adhesion groups. CONCLUSION: Preoperative detection of pleural adhesions using ultrasonography was useful in selecting pulmonary resection patients who continued aspirin perioperatively.

Meta-analysis of transcatheter aortic valve implantation for bicuspid versus tricuspid aortic valves.

BACKGROUND: We performed meta-analysis and meta-regression of transcatheter aortic valve implantation (TAVI) for the bicuspid aortic valve (B-AV) versus the tricuspid aortic valve (T-AV). METHODS: MEDLINE and EMBASE were searched through June 2018 using PubMed and OVID. We included comparative studies of TAVI patients with B-AV versus T-AV reporting at least one of postprocedural transcatheter valve regurgitation (TVR)/pacemaker implantation (PMI) incidence and early (30-day or in-hospital)/late (including early) mortality. For each study, crude (unadjusted) data regarding TVR/PMI incidence and early/late mortality in both the B-AV and T-AV groups were used to generate risk ratios (RRs). Study-specific estimates were combined in the random-effects model. Using meta-regression, we assessed potential confounders identified in preliminary meta-analysis. RESULTS: We identified 12 eligible studies including a total of 1045 B-AV and 4069 T-AV patients. Pooled analysis demonstrated an association of B-AV with a statistically significant increase in TVR incidence (RR, 1.42; p=0.006) but no statistically significant difference in PMI incidence (p=0.54) and 30-day (p=0.11)/midterm (1-year to 2-year) mortality (p=0.99) between patients with B-AV and those with T-AV. All meta-regression coefficients of 6 identified potential confounders (age, mean aortic valve gradient, aortic valve area, left ventricular ejection fraction, aortic calcification, and B-AV types) for the outcomes (TVR/PMI incidence and early/late mortality) were statistically non-significant. CONCLUSIONS: Postprocedural PMI incidence and 30-day/midterm (1-year to 2-year) mortality after TAVI may be similar between patients with B-AV and those with T-AV despite the significant association of B-AV with increased postprocedural TVR incidence.

Analysis of Histological Grade in Resected Lung-invasive Adenocarcinoma.

BACKGROUND/AIM: Although the histological grading systems (Grading) with respect to lung adenocarcinoma are defined using architectural approaches in the eighth cancer Tumor, Node, and Metastasis (TNM) Classification, the prognostic value of the architectural subtypes in advanced stages of the disease remains unclear. We aimed to assess which Grading was more suitable as a prognostic factor: i) (conventional) Grading based on differentiation or ii) (new) Grading based on architectural subtypes. PATIENTS AND METHODS: We analyzed the outcomes and Gradings of resected 449 patients with adenocarcinoma using receiver operating characteristic (ROC) curves. RESULTS: The tumor histological grade of 147 out of 449 patients changed using the results from the revised Grading. In these 147 patients, ROC curves showed that the area under the curve was 0.710 using the conventional Grading and 0.567 using the new Grading. CONCLUSION: The conventional Grading might be more suitable for lung adenocarcinoma recurrence compared to the new Grading.