• Journal of Genetic Medicine
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• 제20권1호
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• pp.6-14
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• 2023

Fabry disease (FD), a rare X-linked lysosomal storage disorder, is caused by mutations in the α-galactosidase A gene gene encoding α-galactosidase A (α-Gal A). The functional deficiency of α-Gal A results in progressive accumulation of neutral glycosphingolipids, causing multi-organ damages including cardiac, renal, cerebrovascular systems. The current treatment is comprised of enzyme replacement therapy (ERT), oral pharmacological chaperone therapy and adjunctive supportive therapy. ERT has been introduced 20 years ago, changing the outcome of FD patients with proven effectiveness. However, FD patients have many unmet needs. ERT needs a life-long intravenous therapy, inefficient bio-distribution, and generation of anti-drug antibodies. Migalastat, a pharmacological chaperone, augmenting α-Gal A enzyme activity only in patients with mutations amenable to the therapy, is now available for clinical practice. Furthermore, these therapies should be initiated before the organ damage becomes irreversible. Development of novel drugs aim at improving the clinical effectiveness and convenience of therapy. Clinical trial of next generation ERT is underway. Polyethylene glycolylated enzyme has a longer half-life and potentially reduced antigenicity, compared with standard preparations with longer dosing interval. Moss-derived enzyme has a higher affinity for mannose receptors, and seems to have more efficient access to podocytes of kidney which is relatively resistant to reach by conventional ERT. Substrate reduction therapy is currently under clinical trial. Gene therapy has now been started in several clinical trials using in vivo and ex vivo technologies. Early results are emerging. Other strategic approaches at preclinical research level are stem cell-based therapy with genome editing and systemic mRNA therapy.

• Journal of Chest Surgery
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• 제24권7호
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• pp.663-668
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• 1991

To evaluate risks, complications and mortality of reoperations on heart valve prosthesis, we reviewed clinical records of 53 patients who underwent reoperation because of prosthetic valve failure[PVF], from Jan 1959 through Jun. 1991. They had undergone 48 mitral, 10 aortic valve rereplacement Primary tissue failure was the main cause of reoperation : it occurred in 51 valves at a mean postoperative interval of 58 months. Calcification and collagen disruption of prosthesis were main causes of primary tissue failure in macro and micropathology, In 3 failing mechanical prostheses, paravalvular leak was in 2 cases, another one case had the thrombi at the hinge portion. If conditions such as emergency operation with or without endocarditis, thromboembolism and advanced NYHA functional class are prevented, we think that reoperative valve replacement has similar morbidity and mortality to initial valve replacement surgery. But our sturdy represents higher mortality [22.6%] because of late surgical intervention failing the prevention of conditions leading to myocardial damage. In conclusion if the tearing, calcification, and a new murmur were detected the early reoperation should be considered to increase late survival.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제27권1호
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• pp.53-61
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• 2024

Purpose: Although the 24-hours urinary copper excretion is useful for the diagnosis of Wilson disease (WD), there are practical difficulties in the accurate and timed collection of urine samples. The purpose of this study was to verify if the spot morning urinary Copper/Zinc (Cu/Zn) ratio could be used as a replacement parameter of 24-hours urinary copper excretion in the diagnosis of WD. Methods: A cross-sectional study was conducted at the Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from June 2019 to May 2021 on 67 children over three years of age who presented with liver disease. Twenty-seven children who fulfilled the inclusion criteria for WD were categorized into the test group, and the remaining forty children were considered to have non-Wilsonian liver disease and were categorized into the control group. Along with other laboratory investigations, spot morning urinary samples were estimated for the urinary Cu/Zn ratio in all patients and were compared to the 24-hour urinary copper excretion. The diagnostic value of the Cu/Zn ratio was then analyzed. Results: Correlation of spot morning urinary Cu/Zn ratio with 24-hours urinary copper excretion was found to be significant (r=0.60). The area under ROC curve with 95% confidence interval of morning urinary Cu/Zn ratio measured using 24-hours urine sample was 0.84 (standard error, 0.05; p<0.001). Conclusion: Spot morning urinary Cu/Zn ratio seems to be a promising parameter for the replacement of 24-hours urinary copper excretion in the diagnosis of WD.

• Journal of Cardiovascular Imaging
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• 제31권2호
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• pp.108-115
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• 2023

BACKGROUND: Minimizing contrast dose and radiation exposure while maintaining image quality during computed tomography angiography (CTA) for transcatheter aortic valve replacement (TAVR) is desirable, but not well established. This systematic review compares image quality for low contrast and low kV CTA versus conventional CTA in patients with aortic stenosis undergoing TAVR planning. METHODS: We performed a systematic literature review to identify clinical studies comparing imaging strategies for patients with aortic stenosis undergoing TAVR planning. The primary outcomes of image quality as assessed by the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were reported as random effects mean difference with 95% confidence interval (CI). RESULTS: We included 6 studies reporting on 353 patients. There was no difference in cardiac SNR (mean difference, -1.42; 95% CI, -5.71 to 2.88; p = 0.52), cardiac CNR (mean difference, -3.83; 95% CI, -9.98 to 2.32; p = 0.22), aortic SNR (mean difference, -0.23; 95% CI, -7.83 to 7.37; p = 0.95), aortic CNR (mean difference, -3.95; 95% CI, -12.03 to 4.13; p = 0.34), and ileofemoral SNR (mean difference, -6.09; 95% CI, -13.80 to 1.62; p = 0.12) between the low dose and conventional protocols. There was a difference in ileofemoral CNR between the low dose and conventional protocols with a mean difference of -9.26 (95% CI, -15.06 to -3.46; p = 0.002). Overall, subjective image quality was similar between the 2 protocols. CONCLUSIONS: This systematic review suggests that low contrast and low kV CTA for TAVR planning provides similar image quality to conventional CTA.

• Korean Circulation Journal
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• 제52권2호
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• pp.136-146
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• 2022

Background and Objectives: There still are controversies on which type between bovine pericardial and porcine valves is superior in the setting of aortic valve replacement (AVR). This study aims to compare clinical outcomes of AVR using between pericardial or porcine valves. Methods: The study involved consecutive 636 patients underwent isolated AVR using stented bioprosthetic valves between January 2000 and May 2016. Of these, pericardial and porcine valves were implanted in 410 (pericardial group) and 226 patients (porcine group), respectively. Clinical outcomes including survival, structural valve deterioration (SVD) and trans-valvular pressure gradient were compared between the groups. To adjust for potential selection bias, inverse probability treatment weighting (IPTW) was conducted. Results: The mean follow-up duration was 60.1±50.2 months. There were no significant differences in the rates of early mortality (3.1% vs. 3.1%; p=0.81) and SVD (0.3%/patient-year [PY] vs. 0.5%/PY; p=0.33) between groups. After adjustment using IPTW, however, landmark mortality analyses showed a significantly lower late (>8 years) mortality risk in pericardial group over porcine group (hazard ratio [HR], 0.61; 95% confidence interval, [CI] 0.41-0.90; p=0.01) while the risks of SVD were not significantly difference between groups (HR, 0.45; 95% CI, 0.12-1.70; p=0.24). Mean pressure gradient across prosthetic AV was lower in the Pericardial group than the Porcine group at both immediate postoperative point and latest follow-up (p values <0.001). Conclusions: In patients undergoing bioprosthetic surgical AVR, bovine pericardial valves showed superior results in terms of postoperative hemodynamic profiles and late survival rates over porcine valves.

• 대한두경부종양학회지
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• 제15권1호
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• pp.52-60
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• 1999

Objectives: For investigation of the differentiation between transient and permanent hypocalcemia, we focused on a postoperative calcium requirement and an interval of normalization in serum hypocalcemic level and studied for the causes of postoperative hypocalcemia. Material and Method: Postthyroidectomy hypocalcemia was studied in 193 patients who were admitted from January, 1991 to December, 1998 and underwent lobectomy, subtotal thyroidectomy or total thyroidectomy. We compared postoperative serum calcium, phosphate and ionized calcium levels among three groups which were lobectomy, subtotal thyroidectomy and total thyroidectomy, respectively. Result: All patients revealed postoperative decline in serum calcium and ionized calcium, especially, the lowest serum calcium level was seen in 48 hours after surgery. Serum calcium level was returned to normal in five to six postoperative days in most patients. But 24 patients required calcium supplementation due to symptomatic hypocalcemia. In this series, we discovered that the important period for monitoring of serum calcium level was 24 to 96 hours after surgery. If the calcium replacement therapy was not required in the first 72 hours after surgery, it would not be needed during the remainder of the patient's hospital course. Symptomatic transient hypocalcemia was 22 cases(11.4%) and permanent hypocalcemia was 2 cases(1%). Conclusion : We found that hypoalbuminemia, preoperative hyperthyroidism and impairment of blood supply to parathyroid were the main causes of postthyroidectomy hypocalcemia. We also thought that the interval from initial medication to normalization in serum calcium level, and the increase of requirement in calcium and vitamin D were the important factors for differentiation between transient and permanent hypocalcemia.

• Advances in pediatric surgery
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• 제13권2호
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• pp.105-111
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• 2007

We reviewed the records of 25 patients who were re-operated upon after primary repair of esophageal atresia with or without fistula at the Department of Pediatric Surgery, Seoul National University Children's Hospital, from January 1997 to March 2007. Types of the esophageal atresia anomalies were Gross type A in 5 patients, C in 18, and E in 2. The indications for re-operation were anastomosis stricture (n = 14), tracheo-bronchial remnant (n = 4), persistent anastomosis leakage (n = 3), recurrent tracheo-esophageal fistula (n = 2) and esophageal web (n = 2). The interval between primary and secondary surgery was from 48 days to 26 years 5 months (mean: 2 years and 4 months). Four patients required a third operation. The interval between the second and third operation was between 1 year 1 month and 3 year 10 month (mean: 2 years 5 months). Mean follow up period after last operation was 35 months (1 years-8 years 6 months). The secondary surgery was end-to-end esophageal anastomosis in 15, esophagoplasty in 5, gastric tube replacement in 5. After secondary operation, 6 patients had anastomosis stricture (4 patients were relieved of the symptoms by balloon dilatation, 2 patients underwent tertiary operation). Five patients had leakage (sealed on conservative management in all). Two patients had recurrent tracheo-esophagel fistula (1 patient received chemical cauterization and 1 patient underwent tertiary operation). Currently, only one patient has feeding problems. There were no mortalities. Secondary esophageal surgery after primary surgery for esophageal atresia was effective and safe, should be positively considered when complications do not respond to nonoperative therapy.

• Journal of Chest Surgery
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• 제35권4호
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• pp.274-282
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• 2002

배경: Behcet씨 병과 동반된 대동맥판막 폐쇄부전에서 인공 대동맥판막 치환술 후 발생하는 인공판륜 주위 누출이나 가성동맥류는 가장 심각한 합병증의 하나로써, 재수술을 필요로 한다. 저자들은 Behcet씨 병과 동반된 대동맥판막 폐쇄부전 환자에서 동종이식편을 이용한 대동맥근부 치환술 결과를 알아보고자 하였다. 방법 및 대상: 1992년 1월부터 2001년 12월까지 저자들은 6명의 Behcet씨 병 환자에서 동종이식편을 이용한 근부치환술 7례와 1례의 Ross 술식을 시행하였다. 남자 5명, 여자가 1명이었으며 수술 당시 평균 연령은 37$\pm$9세(27~51세)였다. 2명은 1차 수술에서 동종이식편을 이용한 근부치환술을 시행하였고 다른 4명은 대동맥판막 치환술 후 발생한 인공판륜 주위 누출로 동종이식편을 이용하여 근부치환술을 시행하였다. 인공판막치환술 후 재수술까지 평균 기간은 21 $\pm$29개월(5 ~73.3개월, 중앙값, 7.6 개월)이였다. 결과: 동종이식편을 이용한 근부치환술 후 조기 사망은 없었다. 6명에서 평균 18.9$\pm$24.0개월(1.9~68.9개월, 중앙값, 8.4개월)을 추적 관찰하였다. 판막치 환술 후 동종이식편을 이용한 근부치환술 환자 4명중 2명에서 상행대동맥에 발생한 가성동맥류와 폐동맥 동종이식편의 기능 부전으로 재수술이 필요하였다. 1명은 대동맥 동종이식편을 이용하여 대동맥근부, 상행대동맥 및 부분 대동맥궁을 재치환하였으며 다른 1명은 Ross수술을 시행하였다. 결론: 본 연구 결과 Behcet씨 병과 동반된 대동맥판막 폐쇄부전에서 동종이식편이나 폐동맥 자가이식편을 이용한 대동맥근부.치환술은 양호한 조기 수술 결과를 보이며, 인공판막 치환술 후 발생할 수 있는 인공판륜 주위 누출이나 가성동맥류의 발생을 줄일 수 있다. 그렇지만 Behcet씨 병의 정확한 진단과 수술 전후 적절한 내과적인 치료 및 수술시 염증 조직의 완전한 제거가 장기 결과의 향상을 위해 매우 중요할 것으로 사료된다.

• Journal of Chest Surgery
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• 제51권2호
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• pp.100-108
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• 2018

Background: The question of which type of prosthetic aortic valve leads to the best outcomes in patients in their 60s remains controversial. We examined the hemodynamic and clinical outcomes of aortic valve replacement in sexagenarians according to the type of prosthesis. Methods: We retrospectively reviewed 270 patients in their 60s who underwent first-time aortic valve replacement from 1995 to 2011. Early and late mortality, major adverse valve-related events, anticoagulation-related events, and hemodynamic outcomes were assessed. The mean follow-up duration was $58.7{\pm}44.0$ months. Results: Of the 270 patients, 93 had a mechanical prosthesis (mechanical group), and 177 had a bioprosthesis (tissue group). The tissue group had a higher mean age and prevalence of preoperative stroke than the mechanical group. The groups had no differences in the aortic valve mean pressure gradient (AVMPG) or the left ventricular mass index (LVMI) at 5 years after surgery. In a sub-analysis limited to prostheses in the supra-annular position, the AVMPG was higher in the tissue group, but the LVMI was still not significantly different. There was no early mortality. The 10-year survival rate was 83% in the mechanical group and 90% in the tissue group. The type of aortic prosthesis did not influence overall mortality, cardiac mortality, or major adverse valve-related events. Anticoagulation-related events were more common in the mechanical group than in the tissue group (p=0.034; hazard ratio, 4.100; 95% confidence interval, 1.111-15.132). Conclusion: The type of aortic prosthesis was not associated with hemodynamic or clinical outcomes, except for anticoagulation-related events.

• Journal of Chest Surgery
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• 제34권8호
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• pp.604-610
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• 2001

배경: Stanford 제A형(type A) 대동맥 박리증은 상행대동맥이나 대동맥궁의 인조혈관 치환 수술 후에도 남은 대동맥의 가강이 확장되거나 파열의 가능성이 있기 때문에 철저한 추적관리가 필요하다. 연세대학교 세브란스병원에서는 1984년 6월부터 2000년 3월까지 Stanford 제A형의 대동맥박리 수술이 124예 있었다. 수술 후 가강의 확장이나 파열로 재수술한 6예에서 Marfan 증후군과의 관련성 등 원인을 조사하고 재수술의 방법과 결과, 재수술의 위험을 줄일 수 있는 방법 등을 알아보고자 한다. 대상 및 방법: 처음 대동맥 박리로 수술시급성인 경우가 4예 만성이 2예였으며 이중 3예가 Marfan 증후군이였다. 1예를 제외한 모든 환자에서 상행대동맥내에 내막파열이 있어 대동맥판막의 폐쇄부전의 정도에 따라 상행대동맥 인조혈관 치한수술(2례) 또는 Bentall 수술을 시행하였으며(3례) 1예는 여러 개의 가강과의 연결부위가 있는 만성 박리 환자로 Bentall 수술과 더불어 대동맥궁까지 인조혈관으로 치환을 하였다. 재수술은 평균 67.6개월(4개월-14년4개월) 후에 시행하였는데 1예는 만성 하행대동맥 박리 및 동맥류로 1예는 염증성 가성동맥류로 나머지 4예는 급성대동맥 박리로 재수술을 시행하였다. 수술은 하행흉부대동맥만을 치환한 경우가 1예, Hemiarch로 시행한 경우가 1예 그리고 나머지 4예는 원위부 상행대동맥에서 대동맥궁을 포함하여 근위부 또는 중간부위의 하행 흉부대동맥까지 인조혈관으로 치환하였다. 결과: 전체 124예 중 Marfan 증후군이 동반된 경우는 18예였다.