[The Strategy for Aortic Root Pathology Due to Stanford Type A Acute Aortic Dissection].

The surgical outcomes of aortic root replacement for Stanford type A acute aortic dissection( AAAD) remain unacceptable with a 30-day mortality rate of 20%. Additionally, in young patients requiring aortic root replacement for AAAD, the preservation of native valve is desirable, yet challenging to achieve in emergent surgery with poor preoperative status. Ideally, we aim to avoid aortic root replacement whenever possible, opting instead for partial remodeling even in cases necessitating incision into the aortic root. We present our surgical outcomes in the strategy for aortic root pathology due to AAAD. We conducted an analysis of 517 cases of AAAD surgery from 2002 to 2023, wherein 499 cases( 96%) underwent aortic root preservation, 10 cases( 1.9%) underwent partial remodeling, and 8 cases( 1.5%)necessitated emergent aortic root replacement. Of these, 13 cases underwent aortic root replacement after AAAD repair( 8 David procedures and 5 Bentall procedures), all demonstrating favorable surgical outcomes, including long-term results. We believe that this strategy for aortic root pathology holds significant merit, particularly in AAAD in young patients with enlarged aortic root.

[The Long Outcome of the Left Atrial Appendage Preserving Maze Procedure].

We retrospectively study the outcome of left atrial appendage (LAA) preserving maze procedure, focus on thrombus formation in left atrium( LA), postoperative stroke, and LA function. PATIENTS AND METHODS: We studied 131 patients (mean age, 68.2y;77 men and 54 women) who underwent maze procedure for atrial fibrillation( Af) between 2008 and 2020. Full maze was performed for 116 patients with long-standing persistent Af or persistent Af. Pulmonary vein isolation alone was performed for 15 patients with paroxysmal Af. The mean follow-up period was 2.9( 10.1-0.4) years. RESULTS: In perioperative results, there were no death, cerebral infarction, and reoperation in this series. At discharge, 1 year, 3 years, 5 years, and 10 years after the surgery, sinus rhythm was maintained in 92%, 87%, 83%, 77%. Pacemaker was implanted in 8( early 3, late 5) patients. Despite adequate anticoagulant therapy, one patient developed cerebral infarction a month postoperatively. In other patients, there was no cerebral infarction in short-term nor long-term. CONCLUSIONS: The LAA preserving maze procedure was not a risk factor of cerebral infarction under appropriate medication. However, close follow-up is essential.

A case of primary cardiac angiosarcoma with surgical resection and reconstruction.

We report a 52-year-old man with primary cardiac angiosarcoma. He was referred to our hospital with a 3-month history of facial swelling and peripheral edema. Echocardiography and chest computed tomography revealed massive pericardial effusion and a right atrial tumor with a broad base at atrial septum which was extended into superior vena cava. We performed complete resection of the tumor and reconstruction of left atrium, atrial septum, right atrium, and superior vena cava with autologous pericardium and bovine pericardium. Histological examination exhibited angiosarcoma and a sign of radical excision. The patient, who made an uneventful recovery, was given postoperative radiotherapy and chemotherapy for liver metastasis 4 months postoperatively. The patient remains well without any signs of other metastasis for 2 years. We consider that an aggressive approach to resection with extensive reconstruction and multidisciplinary treatment can improve survival. Learning objective: Primary cardiac angiosarcoma is the most common primary malignant heart tumor with poor prognosis. We report a case of a 52-year-old man with primary cardiac angiosarcoma. We performed complete resection of the tumor and reconstruction of left atrium, atrial septum, right atrium, and superior vena cava with autologous pericardium and bovine pericardium. We think aggressive surgical resection with reconstruction is a feasible option.>.

HADHB, a fatty acid beta-oxidation enzyme, is a potential prognostic predictor in malignant lymphoma.

In haematological malignancies, such as malignant lymphoma, reprogramming of fatty acid metabolism favours tumour cell survival and drug resistance. Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA), an enzyme involved in fatty acid beta-oxidation (FAO), is overexpressed in high-grade lymphoma and is a predictor of poor prognosis in diffuse large B-cell lymphoma (DLBCL). HADHB forms a heterodimer with HADHA and functions as an FAO enzyme together with HADHA; however, the relevance of its expression in malignant lymphoma is unknown. In this study, we investigated the roles and antitumour effects of HADHB expression in malignant lymphoma. Immunohistochemical analysis showed that HADHB was frequently overexpressed in the high-grade lymphoma subtype. HADHB overexpression was observed in 68% (87/128) of DLBCL cases and was an independent predictor of poor prognosis (p=0.001). In vitro analysis demonstrated that HADHB knockdown suppressed cell proliferation in LCL-K and MD901 cells (p<0.05). Additionally, treatment with the FAO inhibitor, ranolazine, increased cell death in control cells compared with that in HADHB knockdown LCL-K and MD901 cells (p<0.01). Cell death was also suppressed by the ferroptosis inhibitor, ferrosatin-1, in LCL-K and MD901 cells (p<0.05). Collectively, these findings provide basic evidence for the development of new cell death-based therapies for refractory malignant lymphoma. We plan to perform prospective studies and preclinical studies using animal models to confirm these results.

Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea: A Nationwide Study in Japan.

OBJECTIVE: To clarify clinical and genetic features of Japanese children with congenital chloride diarrhea (CCD). STUDY DESIGN: This was a multi-institutional, retrospective survey of 616 pediatric centers in Japan with identified patients with CCD between 2014 and 2018. Mutations involving SLC26A3 were detected by Sanger sequencing. RESULTS: Thirteen patients met all entry criteria including mutations in SLC26A3, and 14 patients satisfied clinical diagnostic criteria. Homozygous or compound heterozygous mutations in SLC26A3, including 6 novel mutations, were identified in 13 of these 14 patients (93%). The most common (detected in 7 of 13) was c.2063-1g>t. Median age at diagnosis was 1 day. Nine of the patients meeting all criteria were diagnosed as neonates (69%). Median follow-up duration was 10 years. When studied, 8 patients had <5 stools daily (62%), and all had fewer than in infancy. Only 1 patient had nephrocalcinosis, and 3 (23%) had mild chronic kidney disease. Neurodevelopment was generally good; only 1 patient required special education. Five patients (38%) received long-term sodium, potassium, and chloride supplementation. CONCLUSIONS: Early fetal ultrasound diagnosis and prompt long-term sodium, potassium, and chloride supplementation were common management features. Genetic analysis of SLC26A3 provided definitive diagnosis of CCD. In contrast with previously reported localities, c.2063-1g>t might be a founder mutation in East Asia.

Adventitial cystic disease of the popliteal artery with intimal tear.

We report the case of a 68-year-old man with right intermittent claudication by adventitial cystic disease. We performed resection of the cyst and affected popliteal artery with interposing an autologous vein graft. Intraoperative findings revealed an intimal tear between the cyst and the compressed artery. His symptoms resolved after surgery, and the postoperative course was uneventful. Although adventitial cystic disease with intimal tear is rare, we consider that conventional surgical intervention remains the favorable treatment option for adventitial cystic disease. .

Familial episodic limb pain in kindreds with novel Nav1.9 mutations.

We previously performed genetic analysis in six unrelated families with infantile limb pain episodes, characterized by cold-induced deterioration and mitigation in adolescence, and reported two new mutations p.R222H/S in SCN11A responsible for these episodes. As no term described this syndrome (familial episodic pain: FEP) in Japanese, we named it as"". In the current study, we recruited an additional 42 new unrelated Japanese FEP families, between March 2016 and March 2018, and identified a total of 11 mutations in SCN11A: p.R222H in seven families, and p.R225C, p.F814C, p.F1146S, or p.V1184A, in independent families. A founder mutation, SCN11A p.R222H was confirmed to be frequently observed in patients with FEP in the Tohoku region of Japan. We also identified two novel missense variants of SCN11A, p.F814C and p.F1146S. To evaluate the effects of these latter two mutations, we generated knock-in mouse models harboring p.F802C (F802C) and p.F1125S (F1125S), orthologues of the human p.F814C and p.F1146S, respectively. We then performed electrophysiological investigations using dorsal root ganglion neurons dissected from the 6-8 week-old mice. Dissected neurons of F802C and F1125S mice showed increased resting membrane potentials and firing frequency of the action potentials (APs) by high input-current stimulus compared with WT mice. Furthermore, the firing probability of evoked APs increased in low stimulus input in F1125S mice, whereas several AP parameters and current threshold did not differ significantly between either of the mutations and WT mice. These results suggest a higher level of excitability in the F802C or F1125S mice than in WT, and indicate that these novel mutations are gain of function mutations. It can be expected that a considerable number of potential patients with FEP may be the result of gain of function SCN11A mutations.

A Novel Case of Somatic KCNJ5 Mutation in Pediatric-Onset Aldosterone-Producing Adenoma.

Aldosterone-producing adenoma (APA), a subtype of primary aldosteronism, is a common cause of secondary hypertension in adults. Somatic KCNJ5 mutations have been identified in about 12%-80% of adult-onset APA. In contrast, there has been no previous reported case of pediatric-onset APA in whom a somatic KCNJ5 mutation was confirmed. We report an 11-year-old Japanese girl who had experienced recurrent headaches and nausea for more than 2 years before hypertension was observed (blood pressure, 150/82 mm Hg). Plasma renin activity was <0.1 ng/mL per hour even after a captopril-challenge or upright furosemide-loading test. Plasma aldosterone concentrations (PACs) before and after saline-infusion test were 28.0 and 40.6 ng/dL, respectively. Plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels were 16.5 pg/mL and 16.7 µg/dL, respectively. The patient was diagnosed with APA in the left adrenal gland on the basis of selective adrenal venous sampling after ACTH stimulation (PAC in the left adrenal vein, 3630 ng/dL) and histopathologic findings of the tumor obtained by laparoscopic left adrenalectomy. Sanger sequencing of KCNJ5 using genomic DNA from peripheral lymphocytes and laser-captured microdissected APA tissues demonstrated the presence of a somatic KCNJ5 mutation p.L168R, previously reported only in adult-onset APA. Immunohistochemistry detected strong immunoreactivity for CYP11B2, but not for CYP11B1 in the APA, consistent with the endocrinologic findings in this patient. Somatic KCNJ5 mutations are also identified in pediatric-onset APA. Further cases are needed to elucidate functional characteristics of pediatric-onset APA with a somatic KCNJ5 mutation.

Heterozygous carriers of succinyl-CoA:3-oxoacid CoA transferase deficiency can develop severe ketoacidosis.

Succinyl-CoA:3-oxoacid CoA transferase (SCOT, gene symbol OXCT1) deficiency is an autosomal recessive disorder in ketone body utilization that results in severe recurrent ketoacidotic episodes in infancy, including neonatal periods. More than 30 patients with this disorder have been reported and to our knowledge, their heterozygous parents and siblings have had no apparent ketoacidotic episodes. Over 5 years (2008-2012), we investigated several patients that presented with severe ketoacidosis and identified a heterozygous OXCT1 mutation in four of these cases (Case1 p.R281C, Case2 p.T435N, Case3 p.W213*, Case4 c.493delG). To confirm their heterozygous state, we performed a multiplex ligation-dependent probe amplification analysis on the OXCT1 gene which excluded the presence of large deletions or insertions in another allele. A sequencing analysis of subcloned full-length SCOT cDNA showed that wild-type cDNA clones were present at reasonable rates to mutant cDNA clones. Over the following 2 years (2013-2014), we analyzed OXCT1 mutations in six more patients presenting with severe ketoacidosis (blood pH ≦7.25 and total ketone body ≧10 mmol/L) with non-specific urinary organic acid profiles. Of these, a heterozygous OXCT1 mutation was found in two cases (Case5 p.G391D, Case6 p.R281C). Moreover, transient expression analysis revealed R281C and T435N mutants to be temperature-sensitive. This characteristic may be important because most patients developed ketoacidosis during infections. Our data indicate that heterozygous carriers of OXCT1 mutations can develop severe ketoacidotic episodes in conjunction with ketogenic stresses.

Rare spinal cord infarction in a patient with acute type B aortic dissection.

A 69-year-old man was admitted to our hospital with acute epigastric discomfort and subsequent paraplegia. Computed tomography revealed acute type B aortic dissection with a thrombosed false lumen. Magnetic resonance imaging did not reveal spinal cord infarction. Paraplegia resolved completely within 1 h. However, on the following day, the patient developed motor impairment in the left leg, sensory disorder of the bilateral legs and urinary retention. The symptoms gradually improved with conservative medical therapy. Magnetic resonance imaging on hospitalization Day 20 revealed spinal cord infarction limited to the right posterior area at level T7/T8 and the conus medullaris. The patient was discharged 44 days after admission. The presented case is notable for its atypical presentation of spinal cord infarction resulting from acute aortic dissection. The aetiology of neurological symptoms, especially that of lower extremity monoplegia, remained undiagnosed.

Immunoglobulin G4-related large thoraco-abdominal aortic aneurysm.

We report a case of immunoglobulin G4-related large thoraco-abdominal aortic aneurysm in a 38-year old man. Preoperative contrast-enhanced computed tomography revealed that the mid-descending thoracic aorta was extremely enlarged and the maximum diameter of the aneurysm was 92 mm. The patient underwent thoraco-abdominal aortic replacement through a thoraco-abdominal incision under left heart bypass. The postoperative pathological examination diagnosed immunoglobulin G4-related aortic aneurysm.

Beveled reversed elephant trunk procedure for complex aortic aneurysm.

The reversed elephant trunk procedure uses an inverted graft for distal aortic replacement before aortic arch replacement in patients with mega aorta, to reduce the risk in the second stage. However, the conventional technique restricts the maximum diameter of the inverted graft to the aortic graft diameter. We employed a beveled reversed elephant trunk procedure to overcome the discrepancy between graft diameters in a 54-year-old woman with a severely twisted ascending aortic graft and enlarging chronic dissection of the aortic arch and descending thoracic aorta. The patient was discharged with a satisfactory repair and no neurologic deficit.

Surgical strategy for Kommerell's diverticulum with aberrant subclavian artery.

BACKGROUND: Kommerell's diverticulum is an extremely rare congenital aortic anomaly. Because of its rarity, the optimal surgical strategy for Kommerell's diverticulum has not been established. In this study, we reviewed our experience of surgical correction of this anomaly. METHODS: Between 2007 and 2013, we managed 9 surgical cases of Kommerell's diverticulum; 7 had a right aortic arch with an aberrant left subclavian artery, and 2 had a left aortic arch with an aberrant right subclavian artery. None of these patients had any symptom resulting from structural compression between the aneurysm and the aberrant subclavian artery. All patients underwent surgical treatment to prevent aneurysmal rupture. Six patients had replacement of the thoracic descending aorta and in-situ reconstruction of the aberrant subclavian artery through a right thoracotomy, and 3 underwent the same procedures through a left thoracotomy. Three different methods of extracorporeal circulation were applied, according to the anatomical features of each case. RESULTS: There was one hospital death. This patient developed severe cerebral infarction and died of multiple organ failure on the 65th postoperative day. There were no other major complications nor any need for rehospitalization. CONCLUSION: Kommerell's diverticulum should be treated using an optimal strategy based on each patient's anatomical features and other characteristics.

Predictors of paraplegia with current thoracoabdominal aortic aneurysm repair.

BACKGROUND: Although the results of surgical repair of thoracoabdominal aortic aneurysm continue to improve, the incidence of paraplegia remains within a wide range depending on each institution. The purpose of this study was to find predictors of paraplegia following thoracoabdominal aortic aneurysm repair in our institute, using the current spinal cord protection strategies. METHODS: From January 2007 to December 2011, 200 consecutive patients underwent thoracoabdominal aortic aneurysm repair. Of these, 24 (12%) had Crawford extent I repair, 82 (41%) had extent II, 51 (25.5%) had extent III, 10 (5%) had extent IV, and 33 (16.5%) had extent V (modified by Safi). Aortic dissection was present in 101 (50.5%) patients. Adjuncts used during the procedures included left heart bypass in all patients, cerebrospinal fluid drainage in 164 (82%), and intercostal artery reimplantation in 76 (38%). RESULTS: There were 20 (10%) hospital deaths including 6 (3%) within 30 days; hospital mortality was 8.8% in elective operations. Postoperative complications included paraplegia in 17 (8.5%) patients, stroke in 5 (2.5%), and acute renal failure requiring dialysis in 5 (2.5%). Logistic regression analysis revealed that significant factors for the development of paraplegia were preoperative hypotension (p = 0.005, odds ratio 18.5), intraoperative hypotension (p = 0.001, odds ratio 77.6), and an open distal anastomosis technique (p = 0.012, odds ratio 4.6). CONCLUSIONS: The predictors of postoperative paraplegia in our institution were perioperative hypotension and an open distal anastomosis technique. Avoidance of these risk factors might diminish the incidence of postoperative paraplegia.

Surgical repair for giant ascending aortic aneurysm to superior vena cava fistula with positive syphilitic test.

Syphilitic aortitis is usually associated with thoracic aortic saccular aneurysm, aortic regurgitation and coronary ostial stenosis. However, syphilitic aneurysms have rarely been reported today. Here, we report a patient with ascending aortic aneurysm with aorta-superior vena cava (SVC) fistula with positive syphilitic test. A 52-year-old man was admitted to our institution with a giant ascending aortic aneurysm complicated with SVC syndrome. Computed tomography revealed a giant ascending aneurysm 79 mm in diameter. The result of serodiagnostic tests for syphilis had not been judged yet preoperatively. Total arch replacement concomitant with elephant trunk was performed. Intraoperatively, we detected the ascending aorta to SVC fistula. Postoperatively, we suspected the syphilitic aneurysm strongly, because preoperative serodiagnostic test was concluded to be positive. However, histological examination did not show typical syphilitic features. The patient remains asymptomatic 1 year later. Although extremely rarely today, syphilitic aneurysm should be still considered in the differential diagnosis of ascending aortic aneurysm.

Haemolytic anaemia resulting from the surgical repair of acute type A aortic dissection.

OBJECTIVES: Haemolytic anaemia after acute aortic dissection surgery is extremely rare. We report 4 cases of haemolytic anaemia with different aetiologies. METHODS: Four patients underwent emergency operation for acute type A aortic dissection and subsequently developed haemolytic anaemia. RESULTS: Case 1: a 41-year old man underwent hemiarch replacement. We performed total arch replacement 3 years postoperatively, which revealed that haemolytic anaemia was induced by proximal anastomotic stenosis caused by inverted internal felt strip. Case 2: a 28-year old man diagnosed with Marfan syndrome underwent total arch replacement. Five months postoperatively, we noted severe stenosis at the previous distal anastomotic site, which caused the haemolytic anaemia, and performed descending thoracic aortic replacement for a residual dissecting aneurysm. Case 3: a 49-year old man underwent hemiarch replacement. Three years postoperatively, we performed total arch replacement for a residual dissecting aortic arch aneurysm and repaired a kinked graft responsible for haemolytic anaemia. Case 4: a 42-year old man underwent total arch replacement. Eighteen months later, we performed descending thoracic aortic replacement. We repaired a portion of the ascending aorta as haemolityc anaemia was induced by kinking of a total arch replacement redundant graft. CONCLUSIONS: All the haemolityc anaemia patients were successfully released after surgical reintervention.

Risk factors in the treatment of abdominal aortic aneurysms in the endovascular ERA.

PURPOSE: Endovascular aneurysm repair (EVAR) is a minimally invasive treatment that is becoming standard in abdominal aortic aneurysm treatment. We examine the risk factors of death by comparing the short-term results of abdominal aortic aneurysm by open surgical repair with EVAR. METHODS: We performed elective abdominal aortic aneurysm treatment on 122 cases during the period from January 2008 to December 2009. Seventy one cases were treated with open surgical repair while 51 cases were treated with EVAR. RESULTS: Compared to the open surgical repair group, the EVAR group was significantly older and had a higher complication rate and past laparotomy rates. No significant difference in hospital deaths was observed between the two groups. Two deaths with thromboembolism due to shaggy aorta were observed in the EVAR group. Two cases in the open surgical repair group developed postoperative myocardial infarction and one death was observed. Both patients underwent coronary artery treatment using drug eluting stents (DES) prior to surgery. CONCLUSION: Shaggy aorta has a high possibility of causing thromboembolism and EVAR should not be performed unless there is a considerable reason. In cases in which coronary artery treatment is performed with DES in recent days, EVAR is more preferable.

Hybrid procedure for a Kommerell's diverticulum in a right-sided aortic arch.

A rare case of an aneurysmal Kommerell's diverticulum in a right-sided aortic arch was successfully treated using a hybrid procedure comprising total arch replacement and percutaneous stent grafting. A 65-year-old man with dysphagia was diagnosed with an ectatic right-sided aortic arch and a saccular aneurysm of the Kommerell's diverticulum. Since its radical resection during a single surgery was unfeasible because of its complex configuration, a 2-stage procedure was adopted.

Comparison between early and late prosthetic valve endocarditis: clinical characteristics and outcomes.

BACKGROUND AND AIM OF THE STUDY: Prosthetic valve endocarditis (PVE) is considered a time-related event. The study aim was to compare the clinical characteristics and outcomes of early- and late-onset PVE, and to investigate potential preventive measures for each condition. METHODS: A total of 47 consecutive patients undergoing surgery for PVE between January 1986 and December 2011 were analyzed retrospectively, and classified as an early-onset group (n = 26; PVE occurring within 12 months after previous surgery) and late-onset group (n = 21; PVE occurring after 12 months). RESULTS: The prosthetic valve position significantly affected the incidence of endocarditis: 21 cases (80.7%) in the early-onset group had infected aortic prostheses, while 18 (85.7%) in the late-onset group had infected mitral prostheses (p = 0.028). PVE significantly affected bioprosthetic valves in the early-onset group (18 cases, 69.2%) and mechanical valves in the late-onset group (17 cases, 80.9%) (p < 0.01). Staphylococcus spp. infections were predominant in the early-onset group (21 cases, 80.7%), and Streptococcus spp. in the late-onset group (five cases, 23.8%) (p = 0.03). Operative deaths occurred in both the early-onset (n = 6; 23.0%) and late-onset (n = 2; 9.5%) groups (p = 0.11). The long-term mortality in the early-onset and late-onset groups, respectively, was 40.3 +/- 17.7% and 85.1 +/- 7.9% at 10 years, and 40.3 +/- 17.7% and 72.9 +/- 13.1% at 15 years (p 0.047). Freedom from recurrent endocarditis after two years in the early- and late-onset groups, respectively, was 67.8 +/- 10.1% and 88.8 +/- 7.4% (p = 0.048). CONCLUSION: Clinical characteristics and outcomes differed significantly between early- and late-onset PVE. The clinical outcomes of patients with early PVE tend to be serious, and therefore stringent care should be taken to avoid contamination during the initial surgery and hence to reduce the incidence of the condition.