[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.

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.

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.

Use of the Endurant stent graft system for ruptured infrarenal aortic aneurysms: short-term experience in nine patients.

PURPOSE: To report the early results of use of the Endurant stent graft in the treatment of ruptured abdominal aortic aneurysms (AAAs). MATERIALS AND METHODS: Nine consecutive patients (seven men and two women; mean age, 76 y; range, 65-87 y) underwent endovascular aneurysm repair (EVAR) for a ruptured AAA with the Endurant stent graft between April and December 2012. EVAR was emergent in all cases. Early technical success, clinical success, major complication, and mortality rates were analyzed. RESULTS: Intraoperative immediate technical success was achieved in all nine patients. The 30-day clinical success rate was 67% (six of nine patients). The 30-day mortality rate was 33% (three of nine patients). During a mean follow-up of 6 months (range, 3-10 mo), none of the cases required reintervention; there was one late death attributed to probable endograft infection. CONCLUSIONS: The short-term results of EVAR with the Endurant stent graft in patients with ruptured AAAs are encouraging.

Long-term clinical outcomes and predictors of survival after prosthetic valve endocarditis surgery.

BACKGROUND AND AIM OF THE STUDY: The study aim was to comprehend the outcomes of surgery for prosthetic valve endocarditis (PVE) over 25 years and to identify predictors for patient survival. METHODS: A total of 47 consecutive patients (19 males, 28 females; mean age 67.0 +/- 11.5 years) whounderwent surgery for PVE between 1986 and 2011 was analyzed. Typically, PVE appeared at 4.2 +/- 6.2 years after valve replacement. Preoperative and postoperative clinical variables were evaluated; the mean follow up was 6.4 +/- 5.3 years. RESULTS: The incidence of PVE was 3.9% for 1,185 cases of valve replacement through the study period. Operative mortality was 17.0%. NYHA functional class IV (p = 0.01), preoperative shock (p = 0.03) and renal failure (p = 0.02) were each independent predictors of operative mortality. Survival was 69.1 +/- 9.3% at 10 years and 59.2 +/- 12.1% at both 15 and 20 years. Preoperative impaired left ventricular function (p = 0.02) and preoperative renal failure (p = 0.04) were independent predictors of late mortality. Freedom from recurrent PVE remained at 82.5 +/- 6.0% from two years up to 20 years after surgery. Initial infective endocarditis (p = 0.03) and postoperative heart failure (p = 0.04) were predictors of recurrent PVE. Freedom from reoperation was 84.8 +/- 5.7% at 10 years, and 72.6 +/- 12.2% at both 15 and 20 years. CONCLUSION: This extensive examination revealed that critical preoperative conditions determine not only short-term but also long-term mortality after surgery to treat PVE. Hence, a timely surgical intervention and close follow up are crucial for patient survival.

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.

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.

[Aortic valve replacement for quadricuspid aortic valve complicated with idiopathic thrombocytopenic purpura; report of a case].

An 83-year-old woman, who had suffered from idiopathic thrombocytopenic purpura (ITP), was admitted to our hospital because of cardiac heart failure and chest pain. The platelet was 42 x 10(4) in microl. Echocardiography revealed moderate aortic stenosis and regurgitation and left ventricular dysfunction. Preoperatively, we tapered oral steroid and administered high-dose immunoglobulin intravenously. Intraoperatively, we found quadricuspid aortic valve and the rudimentary accessory cusp was located between the right coronary cusp and noncoronary cusp. Aortic valve replacement was performed with bioprosthetic valve. The postoperative course was uneventful. Postoperative echocardiography revealed no perivalvular leakage. Preoperative administration of high-dose immunoglobulin and intraoperative platelet transfusion is very effective to minimize hemorrhagic complication in patients with ITP. We herein report an extremely rare quadricuspid aortic valve complicated with ITP.

[Lethal cholesterol crystal embolization syndrome after operation for abdominal aortic aneurysm].

A 70-year-old man underwent graft replacement for infrarenal abdominal aortic aneurysm, 50 mm in diameter. Postoperatively, he suffered from bilateral lower extremital ischemia. Although he underwent emergency embolectomy of both legs under general anesthesia, severe purplish discoloration of the distal lower extremities developed, and acute renal dysfunction occurred. He was diagnosed with cholesterol crystal embolization syndrome (CCE). We initiated intravenous steroid therapy and infused prostagrandin intraarterially and conducted low density lipoprotein (LDL) apheresis. However, his renal function did not improve and his bilateral toes became necrotic completely. Multiple organ failure rapidly worsened and he died at 38 days after surgery. CCE complicated with severe renal dysfunction is a lethal iatrogenic complication after surgery for abdominal aortic aneurysm. Because the number of CCE is likely to increase in the near future, we should study about CCE more seriously.

Amino acid transporter LAT3 is required for podocyte development and function.

LAT3 is a Na+-independent neutral l-amino acid transporter recently isolated from a human hepatocellular carcinoma cell line. Although liver, skeletal muscle, and pancreas are known to express LAT3, the tissue distribution and physiologic function of this transporter are not completely understood. Here, we observed that glomeruli express LAT3. Immunofluorescence, confocal microscopy, and immunoelectron microscopy revealed that LAT3 localizes to the apical plasma membrane of podocyte foot processes. In mice, starvation upregulated glomerular LAT3, phosphorylated AKT1, reconstituted the actin network, and elongated foot processes. In the fetal kidney, we observed intense LAT3 expression at the capillary loops stage of renal development. Finally, zebrafish morphants lacking lat3 function showed collapsed glomeruli with thickened glomerular basement membranes. Permeability studies of the glomerular filtration barrier in these zebrafish morphants demonstrated a disruption of selective glomerular permeability. Our data suggest that LAT3 may play a crucial role in the development and maintenance of podocyte structure and function by regulating protein synthesis and the actin cytoskeleton.

Expression of galectin-1, a new component of slit diaphragm, is altered in minimal change nephrotic syndrome.

Nephrin is an essential structural component of the glomerular slit diaphragm (SD), a highly organized intercellular junction that constitutes the ultrafiltration barrier of the kidney. Recent studies have identified two additional nephrin-interacting SD proteins (NEPH1 and NEPH2), suggesting that the zipper-like pattern of the SD is formed through complex intra- and intermolecular interactions of these proteins. However, the complexity of the SD structure suggests that additional SD components remain to be discovered. In this study, we identified galectin-1 (Gal-1) as a new component of the SD, binding to the ectodomain of nephrin. Using dual-immunofluorescence and confocal microscopy and dual-immunoelectron microscopy, we found Gal-1 co-localizing with the ectodomain of nephrin at the SD in normal human kidney. By immunoprecipitation and surface plasmon resonance, we confirmed a direct molecular interaction between Gal-1 and nephrin. Moreover, recombinant Gal-1 induced tyrosine phosphorylation of the cytoplasmic domain of nephrin and activation of the extracellular signal-regulated kinase 1/2 in podocytes. We also showed that podocytes are a major site of biosynthesis of Gal-1 in the glomerulus and that the normal expression patterns and levels of Gal-1 are altered in patients with minimal change nephrotic syndrome. Finally, in puromycin aminonucleoside-induced rat nephrosis, an apparent reduction in the levels of Gal-1 and nephrin around the onset of heavy proteinuria was also revealed. Our data present Gal-1 as a new extracellular ligand of nephrin localized at the glomerular SD, and provide further insight into the complex molecular organization, interaction, and structure of the SD, which is an active site of intracellular signaling necessary for podocyte function.

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.

[Isolated intracavitary metastatic hepatocellular carcinoma of the right atrium without inferior vena cava involvement; report of a case].

A 63-year-old female had been treated for liver cirrhosis and hepatocellular carcinoma (HCC) since 3 years before. She developed symptoms of dyspnea and echocardiography revealed a large tumor in the right atrium. The stalk of tumor was attached to the intraatrial septum just above the tricuspid valve and the tumor was floating between the right atrium and the right ventricle according to cardiac rhythm. The size of tumor was 30 x 15 mm in diameter. She was admitted to our hospital for emergency operation. She was operated for cardiac tumor under cardiopulmonary bypass successfully and the postoperative course was uneventful. But the pathology reported direct intracavitary metastasis of HCC without intravascular involvement. She was discharged on the 7th postoperative day for the treatment of HCC.

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.

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.

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.