Tivozanib-induced activation of the mitochondrial apoptotic pathway and suppression of epithelial-to-mesenchymal transition in oral squamous cell carcinoma.

The potential of tivozanib as a treatment for oral squamous cell carcinoma (OSCC) was explored in this study. We investigated the effects of tivozanib on OSCC using the Ca9-22 and CAL27 cell lines. OSCC is a highly prevalent cancer type with a significant risk of lymphatic metastasis and recurrence, which necessitates the development of innovative treatment approaches. Tivozanib, a vascular endothelial growth factor receptor inhibitor, has shown efficacy in inhibiting neovascularization in various cancer types but has not been thoroughly studied in OSCC. Our comprehensive assessment revealed that tivozanib effectively inhibited OSCC cells. This was accompanied by the suppression of Bcl-2, a reduction in matrix metalloproteinase levels, and the induction of intrinsic pathway-mediated apoptosis. Furthermore, tivozanib contributed to epithelial-to-mesenchymal transition (EMT) inhibition by increasing E-cadherin levels while decreasing N-cadherin levels. These findings highlight the substantial anticancer potential of tivozanib in OSCC and thus its promise as a therapeutic option. Beyond reducing cell viability and inducing apoptosis, the capacity of tivozanib to inhibit EMT and modulate key proteins presents the possibility of a paradigm shift in OSCC treatment.

How to handle a missed or delayed dose of lacosamide in pediatric patients with epilepsy? a mode-informed individual dosing.

This study aims to investigate the effects on the pharmacokinetic (PK) of lacosamide (LCM), and to guide the individual dosing regimens for children and ones with poor medication adherence. Population PK research was performed based on 164 plasma samples of 113 pediatric patients aged from 1.75 to 14.42 years old. The PK characteristic of LCM was developed by a one-compartment model with first-order elimination. The typical value of apparent clearance (CL) and apparent volume of distribution (Vd) was 1.91 L·h-1 and 56.53 L respectively. In the final model, the variability of CL was significantly associated with the body surface area (BSA) and elevated uric acid (UA) level. In contrast, the impact of some prevalent anti-seizure medicines, such as valproic acid, levetiracetam, oxcarbazepine, lamotrigine, and perampanel, and gene polymorphisms of Cytochrome P450 (CYP)2C19, ATP-binding cassette (ABC)B1, and ABCC2 had no clinical significance on the PK parameters of LCM. BSA-based dosing regimen of LCM was provided according to Monte Carlo simulation approach; while the dosage should reduce half in patients with an UA level of more than 400 µmol·L-1 comparing with an UA level of 100 µmol·L-1. Individualize remedial doses of about 0.5- to 1.5-fold of regular doses were recommended in six common scenarios of missed or delayed doses, that depended on the delayed time. In current study, the population PK model of LCM in children with epilepsy was developed successfully. The BSA-based dosing regimen and individualized remedial strategy were recommended to guarantee the precise administration of LCM.

Outcomes of surgery for coarctation of the aorta based on a new classification system.

OBJECTIVES: To evaluate early- and long-term outcomes of the surgical treatment for coarctation of the aorta based on a new classification system. METHODS: A retrospective clinical review of 111 patients with coarctation of the aorta who underwent surgery (March 2011 to August 2020) was performed. We categorised coarctation of the aorta into type I, with all three head vessels tightly packed; type II, with the left subclavian artery separated from the two other head vessels; and type III, with all three head vessels separated from one another. Each type included subtype a, with a short isthmic portion, and subtype b, with a long isthmic portion. RESULTS: The median patient age and weight at operation were 8 (range, 1-1490) days and 3.2 (range, 1.9-18.5) kg, respectively. Extended end-to-end anastomosis was performed via sternotomy in 54, via thoracotomy in 12, end-to-side anastomosis in 31, autologous main pulmonary artery patch augmentation in 12, and modified end-to-end anastomosis combined with subclavian artery flap aortoplasty in two patients. There was one (0.9%) case of early mortality and 12 (10.8%) cases of post-operative complications. Two (1.8%) late deaths occurred during follow-up. Five (4.5%) patients underwent balloon dilatation and three (2.7%) underwent reoperation for restenosis of coarctation of the aorta. All patients with type Ia (21 patients, 18.9%) underwent extended end-to-end anastomosis via sternotomy or thoracotomy. CONCLUSIONS: According to the early and late outcomes observed in this study, surgical treatment of coarctation of the aorta using the new classification system could be safe and low risk.

Correlation of extracellular enzymes activity of Candida glabrata clinical isolates with in vivo pathogenicity in Galleria mellonella larvae / 中华预防医学杂志

Objective: To explore the relationship between extracellular enzymes activity and virulence of Candida glabrata clinical isolates based on the infection model of Galleria mellonella larvae. Methods: Using experimental research methods, 71 strains of non-repetitive Candida glabrata were collected from Qinghai Provincial People's Hospital from June 2021 to January 2022. Bovine serum protein agar medium, egg yolk agar medium, sheep blood agar medium, Tween-80 agar medium and triglyceride agar medium were used to detect the aspartyl protease activity, phospholipase activity, hemolysis activity, esterase activity and lipase activity of Candida glabrata. Median lethal concentration (LC50) was calculated by using 1.25×108 CFU/ml,2.50×108 CFU/ml,3.75×108 CFU/ml,5.00×108 CFU/ml suspension of Candida glabrata ATCC2001 to infect Galleria mellonella larvae. Histopathological and etiological analysis was performed to determine whether the infection model was successfully established. The clinical isolates of Candida glabrata were configured to infect Galleria mellonella larvae with LC50 concentration to detect the pathogenicity of Galleria mellonella larvae.Spearman test or Pearson test were used to analyze the correlation between the extracellular enzyme activity of Candida glabrata clinical isolates and the pathogenicity of Galleria mellonella larvae. Results: 71 strains of Candida glabrata isolated clinically were detected to have low hemolytic activity after 2 days of culture. Aspartyl protease was detected after 4 days of culture, among which 7 strains (9.86%), 19 strains (26.76%) and 45 strains (63.38%) showed low, medium and high aspartyl protease activity. After 7 days of culture, 71 strains did not detect phospholipase, esterase and lipase activities. Candida glabrata on Galleria mellonella larvae of LC50=2.5×108 CFU/ml Fungal spore were found in the intestinal tissue pathological section of Galleria mellonella larvae in the experimental group, and Candida glabrata was identified by the microbial Mass Spectrometry after culture, while no fungi were found in the pathological section and culture of the control group. Spearman test shows that, there was a linear positive correlation between aspartyl protease activity and the survival rate of Galleria mellonella larvae (r = 0.73, P<0.01), the difference was statistically significant.Pearson test shows that, there was no significant linear relationship between hemolytic activity and survival rate of Galleria mellonella larvae (r = 0.16, P = 0.34), the difference was not statistically significant. Conclusion: The clinical isolates of Candida glabrata in this study had aspartyl protease activity and low hemolytic activity, but no phospholipase, esterase and lipase activity. The activity of aspartyl aspartyl protease of Candida glabrata was positively correlated with the pathogenicity of Galleria mellonella larvae.

Effect of ethanol washing on porcine pulmonary artery wall decellularization using sodium dodecyl sulfate.

BACKGROUND: To determine the effectiveness of ethanol (EtOH) washing on porcine pulmonary artery (PA) wall decellularization using sodium dodecyl sulfate (SDS), we compared three different washing methods (phosphate-buffered saline [PBS], pH 9 alkali, and EtOH washing). METHODS: Fresh porcine PA walls were decellularized using 0.5% SDS and 0.5% sodium deoxycholate (SDC). The decellularized tissues were rinsed using three different washing techniques. Histological, biochemical, and mechanical analyses were conducted. Implantation into the subcutaneous tissue of rats and patch implantation into the carotid artery of dogs were performed as preliminary in vivo studies. RESULTS: The decellularization protocol based on SDS and SDC effectively removed the cells. The major extracellular matrix (ECM) structures (collagen, elastic fiber, and glycosaminoglycan) were properly preserved with the 75% EtOH-washing method. Significantly reduced residual SDS content was identified in EtOH-washed tissues compared to that in the other methods. No significant difference in the mechanical strength test was observed between the washing methods, and the EtOH-washing method showed better results in the metabolic activity test compared to the PBS-washing method. In the rat study model, no acute rejection or massive calcification was observed. The in vivo preliminary canine study showed better cell repopulation in the EtOH-washed group. CONCLUSION: EtOH washing of SDS-based decellularized porcine PA wall can reduce the residual SDS content and preserve ECM structures, especially the elastin content, and could also enhance cell repopulation after re-implantation.

Renal Infarction in Vascular Ehlers-Danlos Syndrome / 대한내과학회지

Renal infarction is a condition caused by sudden disturbance of renal arterial blood flow, which occurs frequently in cardioembolic disease, renal artery injury (trauma, Marfan syndrome, rarely Ehlers-Danlos syndrome), and in association with a hypercoagulable state. Ehlers-Danlos syndrome is a rare hereditary connective tissue disease characterized by skin fragility, hyperelasticity, hypermobility of small joints, and easy bruising. Among the subtypes, vascular Ehlers-Danlos syndrome is a very rare genetic disease caused by a mutation in the COL3A1 gene. As blood vessels are fragile due dysfunctional collagen synthesis, complications of bleeding due to arterial dissection or rupture are common in patients with this disease. Here, we report a case of vascular Ehlers-Danlos syndrome diagnosed based on a renal infarction caused by thrombus and renal artery injury; we also present a review of the relevant literature.

Persistent fifth aortic arch associated with aortic coarctation: a case of surgical correction without artificial material.

BACKGROUND: Persistent fifth aortic arch (PFAA) is a rare anomaly often associated with aortic coarctation or interruption, and various surgical techniques for this anomaly have been reported. Herein, we show a case of an infant with PFAA and severe aortic coarctation. CASE PRESENTATION: A 41-day-old female infant was admitted for sustained fever. Initially, the patient was diagnosed with bacterial meningitis, and echocardiography showed PFAA with severe aortic coarctation. Because the patient presented progressive oliguria and metabolic acidosis, she was transferred for emergency cardiac surgical intervention. The aortic arch was reconstructed using end-to-side anastomosis between the fifth aortic arch and the descending aorta without any artificial conduit or patching material. CONCLUSIONS: PFAA with aortic coarctation can be repaired by various surgical methods. Among them, our surgical approach is easy and effective, has growth potential, and an additional surgery is not needed.

Effectiveness of posterior aortopexy for the left pulmonary vein obstruction between the left atrium and the descending aorta.

BACKGROUND: Left pulmonary vein (PV) obstruction can occur due to compression between the left atrium (LA) and the descending aorta (DA). One of the effective solutions for this problem is posterior aortopexy. In this study, we have reported five cases of posterior aortopexy to relieve left PV obstruction between the LA and the DA. METHODS: Since August 2012, five patients have undergone posterior aortopexy for compression of the left PV between the LA and the DA. The median age and weight of the patients at the time of operation were 5.5 months (range, 1-131 months) and 5.2 kg (range, 4.2-29.5 kg), respectively. The left PV obstruction was initially diagnosed on echocardiography in four patients and computed tomography angiography in one patient. The median peak pressure gradient across the obstructed left PV was 7.3 mmHg (range, 4-20 mmHg). Concomitant procedures were ventricular septal defect closure in one patient and patent ductus arteriosus ligation in one patient. RESULTS: There was no PV obstruction on echocardiography in any of the patients after the operation except in the case of one patient who had diffuse pulmonary vein stenosis. The median follow-up duration was 34 months (range, 14-89 months), and during follow-up no incidence of the left PV obstruction was observed in any of the surviving patients. CONCLUSIONS: The posterior aortopexy technique could be a good surgical option for the left PV obstruction caused by compression between the LA and the anteriorly positioned DA.

Is the pleating technique superior to the invaginating technique for plication of diaphragmatic eventration in infants?

BACKGROUNDS: The pleating technique is widely used in plication but is difficult to perform with thoracoscopy because of its complex procedure and the limited surgical space. Thus, the invaginating technique was introduced to facilitate thoracoscopic surgery and is now widely used in video-assisted thoracoscopic surgery (VATS) plication. However, the usefulness of the invaginating technique in children has not been established because of the lack of data on long-term outcomes after surgery using the technique. METHODS: From March 2007 to December 2017, 21 patients who were surgically treated for congenital diaphragmatic eventration and phrenic nerve palsy after congenital cardiac surgery were divided into 2 groups according to the surgical method used (pleating technique: 10 patients, invaginating technique: 11 patients). We evaluated the patients for postoperative outcomes and recurrence of diaphragmatic eventration over 5 years. Postoperative recurrence of diaphragmatic eventration was confirmed by calculating the ratio of the eventration level between the eventrated and normal diaphragms. RESULTS: In the 21 patients who underwent diaphragmatic plication, the pleating and invaginating techniques were used in 10 and 11 patients, respectively. The mean follow-up duration was 63.4 ±â€¯48.4 months (pleating group [P] vs invaginating group [I]: 89.1 ±â€¯52.4 vs 40.1 ±â€¯30.8 months, p = 0.022). The mean eventration rates in the 21 patients was 26.7% ±â€¯9.1% (P vs I: 26.6% ±â€¯6.1% vs 26.9% ±â€¯11.3%, p = 0.945) before operation and -2.1% ±â€¯7.3% (-2.8% ±â€¯7.5% vs -1.5% ±â€¯7.4%, p = 0.695) in the immediate postoperative period. From the first to the fifth postoperative year, no recurrence of diaphragmatic eventration was found in any of the groups during the follow-up. CONCLUSIONS: The invaginating technique was easier to perform but showed a similar long-term result as compared with the pleating technique in terms of the growth and development of the chest cavity in the pediatric patients in this study. Thus, we recommend that the invaginating technique be applied in VATS plication for children as an alternative to the pleating technique. LEVEL OF EVIDENCE: Level III.

Population Pharmacokinetics and Pharmacodynamics of Norvancomycin in Children With Malignant Hematological Disease.

Knowledge of pharmacokinetic (PK) behavior of norvancomycin (NVCM) in pediatric patients is lacking, which leads to empirical therapy in clinical practice. This study developed a population PK model of children aged 0-15 years; 112 opportunistic samples in total from 90 children were analyzed. The stability and prediction of the final model were evaluated by goodness-of-fit plots, nonparametric bootstrap, visual predictive check, and normalized prediction distribution errors. The PKs of NVCM in children was described by a 2-compartment model with first-order elimination along with body weight and estimated glomerular filtration rate as significant covariates on clearance. The population typical values of the PK parameters were as follows: clearance 0.12 L/kg/h, central compartment distribution volume 0.17 L/kg, peripheral compartment distribution volume 0.38 L/kg, and intercompartmental clearance 0.35 L/kg/h. Logistic analysis showed that the ratio of area under the concentration-time curve over 24 hours (AUC0-24 ) to minimum inhibitory concentration (MIC) had the strongest correlation with clinical efficacy, and at least 80% clinical efficiency could be achieved when AUC0-24 /MIC ≥ 221.06 was defined as the target. Monte Carlo simulation results suggested that a higher dose was required for this pediatric population in order to reach the target. The dosing regimen was optimized based on the final model. A population PK model of NVCM was first characterized in children with hematologic malignancy, and an evidence-based approach for NVCM dosage individualization was provided.

Modification of the Senning procedure in the double-switch operation: The triangular double-door technique.

We developed a modified Senning procedure in the double-switch operation for the patients with congenitally corrected transposition of the great arteries (ccTGA). In our technique, the right atrial (RA) free wall is not used as a baffle for draining systemic venous blood to the left atrium. Instead, a patch material is used for the baffling. A wide communication between the pulmonary venous chamber and RA is created by making the triangular double door with the RA-free wall, and the window is closed with in situ pericardial flap. We have successfully adopted this technique in our recent two consecutive ccTGA patients.

Photo-Functionalized Magnetic Nanoparticles as a Nanocarrier of Photodynamic Anticancer Agent for Biomedical Theragnostics.

Various theragnostic agents have been devised and developed as cancer treatments; however, existing agents are often limited by their specific functions and complexities. Here, we report multifunctional magnetite (Fe3O4) nanoparticles functionalized with chlorin e6 (Ce6) and folic acid (FA) using a simple fabrication process to be used as theragnostic agents in photodynamic therapy (PDT). The effectiveness of cellular uptake of Fe3O4-Ce6-FA nanoparticles (FCF NPs) and its visualization as well as the photodynamic anticancer activities were evaluated. The mechanism of cancer cell death by the FCF NPs was also verified with qualitative and quantitative methods. Results indicate that FCF NPs have good penetration efficacy, resulting in excellent in vitro fluorescence and magnetic resonance imaging in cancer cells. FCF NPs exhibited promising anticancer activity in an irradiation time- and FCF NPs-dose-dependent manner in various cancer cell lines, leading to apoptotic cell death via morphological changes in cell membrane, nuclear, and DNA damage, and via overexpression of apoptosis-related genes, such as ZFP36L1, CYR61, GADD45G, caspases-2, -3, -9, 10, and -14. This study suggests that FCF NPs may be safely used in cancer therapy via PDT and could be a versatile therapeutic tool and biocompatible theragnostic agent, which may be used in diagnostic imaging.

[Application of Three-Dimensional Printed Models in Congenital Heart Surgery: Surgeon's Perspective]. / ì„ ì²œì„± 심기형의 ìˆ˜ìˆ ì— 있어서 삼차원 í”„ë¦°íŒ ëª¨ë¸ì˜ ì ìš©: 심장외과의사의 ê´€ì .

To treat congenital heart disease, it is important to understand the anatomical structure correctly. Three-dimensional (3D) printed models of the heart effectively demonstrate the structural features of congenital heart disease. Occasionally, the exact characteristics of complex cardiac malformations are difficult to identify on conventional computed tomography, magnetic resonance imaging, and echocardiography, and the use of 3D printed models can help overcome their limitations. Recently, 3D printed models have been used for congenital heart disease education, preoperative simulation, and decision-making processes. In addition, we will pave the way for the development of this technology in the future and discuss various aspects of its use, such as the development of surgical techniques and training of cardiac surgeons.

Erratum: Application of Three Dimensional Printed Models in Congenital Heart Surgery: Surgeon's Perspective.

[This corrects the article on p. 310 in vol. 81.].

Application of Three-Dimensional Printed Models in Congenital Heart Surgery: Surgeon's Perspective

To treat congenital heart disease, it is important to understand the anatomical structure correctly. Three-dimensional (3D) printed models of the heart effectively demonstrate the structural features of congenital heart disease. Occasionally, the exact characteristics of complex cardiac malformations are difficult to identify on conventional computed tomography, magnetic resonance imaging, and echocardiography, and the use of 3D printed models can help overcome their limitations. Recently, 3D printed models have been used for congenital heart disease education, preoperative simulation, and decision-making processes. In addition, we will pave the way for the development of this technology in the future and discuss various aspects of its use, such as the development of surgical techniques and training of cardiac surgeons.

Application of Three-Dimensional Printed Models in Congenital Heart Surgery: Surgeon's Perspective

To treat congenital heart disease, it is important to understand the anatomical structure correctly. Three-dimensional (3D) printed models of the heart effectively demonstrate the structural features of congenital heart disease. Occasionally, the exact characteristics of complex cardiac malformations are difficult to identify on conventional computed tomography, magnetic resonance imaging, and echocardiography, and the use of 3D printed models can help overcome their limitations. Recently, 3D printed models have been used for congenital heart disease education, preoperative simulation, and decision-making processes. In addition, we will pave the way for the development of this technology in the future and discuss various aspects of its use, such as the development of surgical techniques and training of cardiac surgeons.

The coronary reimplantation after neoaortic reconstruction technique can make a difference in arterial switch operation.

BACKGROUND: The aim of this study was to determine if there was a difference between coronary reimplantation after neoaortic reconstruction and open coronary reimplantation technique in arterial switch operation (ASO). METHODS: A total of 236 patients who underwent ASO from March 1994 to August 2018 were enrolled in this study. Multivariate analysis was performed for postoperative early mortality. Patients were divided into the open coronary reimplantation and coronary reimplantation after neoaortic reconstruction groups. The 30-day mortality, intraoperative and postoperative coronary artery (CA) revisions, CA-related late morbidity and mortality, and early and late neoaortic valve regurgitations after ASO were compared between the two groups. RESULTS: Overall postoperative early mortality was 7.2% (17/236). Patients who underwent open coronary reimplantation had higher early mortality as compared with those who underwent coronary reimplantation after neoaortic reconstruction. Risk factors for postoperative early mortality from multivariate analysis were cardiopulmonary bypass time and open coronary reimplantation. There was a higher incidence of CA-related late mortality or morbidity in the open coronary reimplantation group. The open coronary reimplantation group had a higher incidence of intraoperative or postoperative CA revision. There were no differences in the incidence of mild or more neoaortic valve regurgitation at discharge or in the 5-year freedom from mild or more neoaortic valve regurgitation. CONCLUSIONS: CA reimplantation after neoaortic reconstruction yields better results in mortality and intraoperative or postoperative CA-related problems in ASO without increasing postoperative neoaortic valve regurgitation.

Risk Factors for Prolonged Pleural Effusion After Extracardiac Fontan Operation.

Prolonged pleural effusion after Fontan operation is a significant morbidity that leads to long hospital stays. We investigated the association of multiple risk factors, including clinical characteristics, hemodynamic parameters, and preoperative, operative, and postoperative factors, with prolonged pleural effusion after Fontan operation. Eighty-five patients who underwent a Fontan operation between January 2005 and June 2018 in our center were included in this retrospective study. Patients were divided into two groups: group 1 (n = 36, 42.4%) included those with prolonged pleural effusion, defined as lasting > 14 days after the Fontan operation, and group 2 included patients without prolonged pleural effusion. Patients with hypoplastic left heart syndrome (HLHS) were more prevalent in group 1 (n = 15, P = 0.006). No differences in age at Fontan operation, central venous pressure at Fontan operation, or hemodynamic parameters during the pre-Fontan evaluation were found between the two groups. In multivariable analysis, HLHS (P = 0.002), non-fenestration (P = 0.018), and high central venous pressure at bidirectional cavopulmonary shunt (BCPS) operation (P = 0.043) were independent risk factors for prolonged pleural effusion after Fontan operation. Adverse outcomes such as death, need for heart transplantation, and Fontan failure were not associated with prolonged pleural effusion. In conclusion, patients with HLHS and higher central venous pressure at BCPS were more likely to have a prolonged pleural effusion after Fontan operation, but fenestration was more likely to decrease prolonged effusion. We should consider closer management of fluid status before, during, and after surgery in patients with these risk factors after Fontan operation.

Simplified Tricuspid Polytetrafluoroethylene Valved Conduit: Midterm Results of Multicenter Study.

BACKGROUND: Conduit survival without significant dysfunction is important when selecting the right ventricular outflow tract conduit. We made an expanded polytetrafluoroethylene tricuspid valved conduit using a simplified technique. We aimed to investigate the midterm functional results and longevity of this conduit. METHODS: Between November 2008 and December 2016, four hospitals in Korea implanted 145 valved conduits. We retrospectively analyzed their functional results and longevity. RESULTS: The patients' median age at operation was 36.6 months; the median body weight was 11.3 kg. The mean follow-up duration was 32.3 ± 24.5 months. There were four inhospital deaths and three late deaths, but there were no conduit-related deaths. The mean peak systolic pressure gradient across the conduit was 14.7 ± 8.3 mm Hg and 31.6 ± 17.7 mm Hg at discharge and last follow-up, respectively. Six patients (4.4%) had moderate or more conduit valve regurgitation at last follow-up. Conduit dysfunction was observed in 30 patients (21.9%), mainly caused by increased pressure gradient (24 of 30, 80%). Freedom from conduit dysfunction was 88.1% and 58.5% at 3 and 5 years, respectively. Lower freedom from conduit dysfunction was observed in small conduits. Eleven patients (7.8%) underwent conduit explantation, and freedom from explantation was 94.8% and 81.7% at 3 and 5 years, respectively. The main cause of explantation was conduit stenosis. Small conduits tended to have lower freedom from explantation. CONCLUSIONS: Functional results and longevity of our expanded polytetrafluoroethylene tricuspid valved conduit are acceptable. Although our conduits tend to have increasing pressure gradient over time, especially in small conduits, they have low incidence of moderate or more regurgitation.