Long-term follow-up of inpatients with traumatic fractures who received integrative Korean Medicine treatment: A retrospective analysis and questionnaire survey study.

Previous studies have reported pain reduction after Korean medicine (KM) treatment in patients with fractures. However, these studies were limited by small sample sizes and short observation periods. To address these limitations, we aimed to analyze the outcomes of patients with traumatic fractures who received integrative KM treatment and investigate their long-term progress through follow-up observations. This study was a retrospective analysis and questionnaire survey conducted at a multi-center inpatient care setting in Korea. A total of 1150 patients who had traumatic fractures and received at least 5-day inpatient care at one of 5 KM hospitals. Finally, 339 patients completed the follow-up survey. The questionnaire survey was administered 3 months post discharge. The primary outcome was the difference in numeric rating scale (NRS) scores at admission and discharge for fracture-related pain. The secondary outcomes were EuroQol 5-Dimension 5-Level (EQ-5D-5L) score, Oswestry Disability Index, Neck Disability Index, Western Ontario and McMaster Universities Arthritis Index, Shoulder Pain and Disability Index, and Patient Global Impression of Change (PGIC) score. The follow-up questionnaire survey included questions on surgery and imaging before admission and after discharge and treatment within the past 3 months. The mean NRS score at follow-up showed a significant decrease of 4.41 points compared with that at admission (P < .001). The mean EQ-5D-5L score at follow-up showed a significant increase of 0.18 points compared with that at admission (P < .05). In the follow-up survey on PGIC, 307 participants (90.56%) were "minimally improved" or better. Integrative KM treatment can help improve pain, functional impairment, and long-term quality of life in patients with traumatic fractures.

Phonozen-mediated photodynamic therapy comparing two wavelengths in a mouse model of peritoneal carcinomatosis.

BACKGROUND: This study assessed the therapeutic efficacy of intraperitoneal photodynamic therapy (PDT) using photosensitizer activation at two different wavelengths, 405 and 664 nm, in a mouse model of peritoneal carcinomatosis. METHODS: The dark and light cytotoxicity of chlorin e6-polyvinylpyrrolidone (Phonozen) were measured in vitro under 402 ± 14 and 670 ± 18 nm LED activation in bioluminescent human gastric cancer cells, MKN45-luc. Cell viability was measured at 6 h after irradiation using the PrestoBlue assay. Corresponding in vivo studies were performed in athymic nude mice by intraperitoneal injection of 1 × 106 MKN45-luc cells. PDT was performed 10 d after tumor induction and comprised intraperitoneal injection of Phonozen followed by light irradiation at 3 h, delivered by a diffusing-tip optical fiber placed in the peritoneal cavity and coupled to a 405 or 664 nm diode laser to deliver a total energy of 50 J (20 mice per cohort). Whole-body bioluminescence imaging was used to track the tumor burden after PDT out to 130 days, and 5 mice in each cohort were sacrificed at 4 h post treatment to measure the acute tumor necrosis. RESULTS: Photosensitizer dose-dependent photocytotoxicity was higher in vitro at 405 than 664 nm. In vivo, PDT reduced the tumor growth rate at both wavelengths, with no statistically significant difference. There was substantial necrosis, and median survival was significantly prolonged at both wavelengths compared with controls (46 and 46 vs. 34 days). CONCLUSIONS: Phonozen-mediated PDT results in significant cytotoxicity in vitro as well as tumor necrosis and prolonged survival in vivo following intraperitoneal light irradiation. Blue light was more photocytotoxic than red in vitro and had marginally higher efficacy in vivo.

Contrasting Prognostic Effects of Tumor-Infiltrating Lymphocyte Density in Cardia and Non-cardia Gastric Adenocarcinomas.

PURPOSE: This study sought to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in relation to tumor location within the stomach. MATERIALS AND METHODS: The densities and prognostic significance of TIL subsets were evaluated in 542 gastric cancer patients who underwent gastrectomy. Immunohistochemical staining for CD3, CD4, CD8, forkhead/winged helix transcription factor (Foxp3), and granzyme B was performed. RESULTS: Cardia cancer was associated with significantly lower densities of CD8 T-cells and higher densities of Foxp3 and granzyme B T-cells than non-cardia tumors. Multivariate analysis showed that advanced age (hazard ratio [HR], 1.023; 95% confidence interval [CI], 1.006-1.040), advanced T classification (HR, 2.029; 95% CI, 1.106-3.721), lymph node metastasis (HR, 3.319; 95% CI, 1.947-5.658), low CD3 expression (HR, 0.997; 95% CI, 0.994-0.999), and a high Foxp3/CD4 ratio (HR, 1.007; 95% CI, 1.001-1.012) were independent predictors of poor overall survival in cardia cancer patients. In non-cardia cancer patients, total gastrectomy (HR, 2.147; 95% CI, 1.507-3.059), advanced T classification (HR, 2.158; 95% CI, 1.425-3.266), lymph node metastasis (HR, 1.854; 95% CI, 1.250-2.750), and a low Foxp3/CD4 ratio (HR, 0.978; 95% CI, 0.959-0.997) were poor prognostic factors for survival. CONCLUSIONS: The densities and prognostic effects of TILs differed in relation to the location of tumors within the stomach. The contrasting prognostic effects of Foxp3/CD4 ratio in cardia and non-cardia gastric cancer patients suggests that clinicians ought to consider tumor location when determining treatment strategies.

Parameters for Predicting Surgical Outcomes for Gastric Cancer Patients: Simple Is Better Than Complex.

BACKGROUND: Various parameters are used to predict perioperative surgical outcomes. However, no comprehensive studies in gastrectomy have been conducted. This study aimed to compare the performance of each parameter in patients with gastric cancer. METHODS: The medical records of 1032 gastric cancer patients who underwent curative gastrectomy between 2009 and 2015 were reviewed. Laboratory values and associated parameters (neutrophil count, lymphocyte count, platelet count, albumin level, Prognostic Nutritional Index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and Systemic Immune-Inflammation Index) as well as body weight-related data and associated parameters [body mass index (BMI), percentage of weight loss, Nutritional Risk Screening 2002 assessment, the Malnutrition Universal Screening Tool, and the Nutritional Risk Index] were measured and calculated. The study end points were major complications, operative mortality, prolonged hospital stay, overall survival (OS), and recurrence-free survival (RFS). RESULTS: Multivariable logistic regression analysis showed that male gender, total gastrectomy, advanced-stage gastric cancer, and low albumin level were risk factors for major complications. Old age, total gastrectomy, advanced-stage cancer, and high BMI were risk factors for operative mortality. Old age, open approach, and total gastrectomy were risk factors for prolonged hospital stay. Multivariable Cox proportional hazards models showed that old age, total gastrectomy, advanced-stage cancer, and high neutrophil count were unfavorable risk factors for OS. Old age, advanced-stage cancer, high neutrophil count, and high BMI were unfavorable risk factors for RFS. CONCLUSIONS: Albumin level, BMI, and neutrophil count are the most useful parameters for predicting short- and long-term surgical outcomes. Compared with complex parameters, simple-to-measure parameters are better for predicting surgical outcomes for gastric cancer patients.

A Korean family with the Muenke syndrome.

The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. The birth prevalence is approximately one in 10,000 live births, accounting for 8-10% of patients with coronal synostosis. Although MS is a relatively common diagnosis in patients with craniosynostosis syndromes, with autosomal dominant inheritance, there has been no report of MS, in an affected Korean family with typical cephalo-facial morphology that has been confirmed by molecular studies. Here, we report a familial case of MS in a female patient with a Pro250Arg mutation in exon 7 (IgII-IGIII linker domain) of the FGFR3 gene. This patient had mild midfacial hypoplasia, hypertelorism, downslanting palpebral fissures, a beak shaped nose, plagio-brachycephaly, and mild neurodevelopmental delay. The same mutation was confirmed in the patient's mother, two of the mother's sisters and the maternal grandfather. The severity of the cephalo-facial anomalies was variable among these family members.

De novo pericentric inversion of chromosome 9 in congenital anomaly.

PURPOSE: The pericentric inversion of chromosome 9 is one of the most common structural balanced chromosomal variations and has been found in both normal populations and patients with various abnormal phenotypes and diseases. The aim of this study was to re-evaluate the clinical impact of inv(9)(p11q13). MATERIALS AND METHODS: We studied the karyotypes of 431 neonates with congenital anomalies at the Pediatric Clinic in Ajou University Hospital between 2004 and 2008 and retrospectively reviewed their clinical data. RESULTS: Chromosomal aberrations were detected in 60 patients (13.9%). The most common type of structural abnormality was inv(9)(p11q13), found in eight patients. Clinical investigation revealed that all eight cases with inv(9)(p11q13) had various congenital anomalies including: polydactyly, club foot, microtia, deafness, asymmetric face, giant Meckel's diverticulum, duodenal diaphragm, small bowel malrotation, pulmonary stenosis, cardiomyopathy, arrhythmia, and intrauterine growth restriction. The cytogenetic analysis of parents showed that all of the cases were de novo heterozygous inv(9)(p11q13). CONCLUSION: Since our results indicate that the incidence of inv(9)(p11q13) in patients with congenital anomalies was not significantly different from the normal population, inv(9)(p11q13) does not appear to be pathogenic with regard to the congenital anomalies. Some other, to date unknown, causes of the anomalies remain to be identified.

Full-thickness contact burn from a warming bottle in a newborn.

Major full-thickness burn injuries in newborns are rare but have been reported following the use of medical and warming devices during the early neonatal period. In this report, we present a newborn infant with major full-thickness contact burn injuries of 15% of the total body surface area (TBSA) caused by a water-filled warming bottle applied to the naked skin, and describe the sequential progress of epidermal necrosis and wound healing with autografting.

Comparison of four pancreatic islet implantation sites.

Although the liver is the most common site for pancreatic islet transplantation, it is not optimal. We compared kidney, liver, muscle, and omentum as transplantation sites with regard to operative feasibility, and the efficiency of implantation and glycemic control. Islets from C57BL/6 mice were transplanted into diabetic syngeneic recipients. The mean operative time and mortality were measured to assess feasibility. To assess implantation efficiency, the marginal mass required to cure diabetes and the mean time taken to achieve normoglycemia were measured. A glucose tolerance test was performed to assess glycemic control efficiency. The data are listed in the order of the kidney, liver, muscle, and omentum, respectively. The mean mortality rate was 6.7, 20.0, 7.1, and 12.5%; the mean operative time was 10.2, 27.4, 11.2, and 19.8 min; the marginal islet mass was 100, 600, 600, and 200 islet equivalence units and the mean time to reach euglycemia was 3.0, 15.1, 26.6, and 13.9 days. The glucose kinetics of omental pouch islets was the most similar to controls. Thus, a strategic approach is required for deciding on the best transplantation recipient sites after considering donor sources and islet volume. Alternatives can be chosen based on safety or efficacy.

Outcomes of palivizumab prophylaxis for respiratory syncytial virus infection in preterm children with bronchopulmonary dysplasia at a single hospital in Korea from 2005 to 2009.

This study was performed to evaluate the utilization and outcomes of palivizumab in high risk children born prematurely with chronic lung disease (CLD). A retrospective review of 128 patients was conducted from September 2004 to March 2009 at the Ajou University Hospital. All patients were diagnosed with CLD, were born at

Acute peritoneal dialysis in very low birth weight neonates using a vascular catheter.

We report on our experience with acute peritoneal dialysis (APD) in 16 very low birth weight neonates ranging from 24.6 to 30.2 weeks' gestation with a birth weight ranging from 630 g to 1,430 g using a 14-gauge Arrow vascular catheter for APD access. The underlying causes of acute renal failure were: sepsis (7), necrotizing enterocolitis (4), patent ductus arteriosus (3), hydrops fetalis (1), intracranial hemorrhage (3), pulmonary hemorrhage (2), pneumonia (1), and perinatal asphyxia (1). Among 12 patients, the APD was successful for the control of hyperkalemia, fluid overload, and metabolic acidosis. The peritoneal permeability and transport were at their maximum at a short dwell time with rapid exchanges. Complications associated with the APD were: peritonitis (2), leakage (2), hemoperitoneum (1), and hernia (1). During the dialysis, four patients died; there were three episodes of catheter-related complications in these patients. At 60 days after the withdrawal of the APD, 10 patients were alive, and had full recovery of their renal function. Therefore, APD in premature neonates with a 14-gauge Arrow vascular catheter was safe and effective. This procedure helped manage the hemodynamic and metabolic imbalance of acute renal failure and was associated with few complications.

Enhanced prediction of porcine islet yield and posttransplant outcome using a combination of quantitative histomorphometric parameters and flow cytometry.

Prediction of islet yield and posttransplant outcome is essential for clinical porcine islet xenotransplantation. Although several histomorphometric parameters of biopsied porcine pancreases are predictive of islet yield, their role in the prediction of in vivo islet potency is unknown. We investigated which histomorphometrical parameter best predicts islet yield and function, and determined whether it enhanced the predictive value of in vitro islet function tests for the prediction of posttransplant outcome. We analyzed the histomorphometry of pancreases from which 60 adult pig islet isolations were obtained. Islet function was assessed using the beta-cell viability index based on flow cytometry analysis, oxygen consumption rate, ADP/ATP ratio, and/or concurrent transplantation into NOD/SCID mice. Receiver operating characteristic (ROC) analysis revealed that only islet equivalent (IEQ)/cm(2) and the number of islets >200 microm in diameter significantly predicted an islet yield of >2000 IEQ/g (p < 0.001 for both) and in vivo islet potency (p = 0.024 and p = 0.019, respectively). Although not predictive of islet yield, a high proportion of large islets (>100 microm in diameter) best predicted diabetes reversal (p = 0.001). Multiple regression analysis revealed that the beta-cell viability index (p = 0.003) and the proportion of islets >100 microm in diameter (p = 0.048) independently predicted mean posttransplant blood glucose level (BGL). When BGL was estimated using both these parameters [area under the ROC curve (AUC), 0.868; 95% confidence interval (CI), 0.730-1.006], it predicted posttransplant outcome more accurately than the beta-cell viability index alone (AUC, 0.742; 95% CI, 0.544-0.939). In conclusion, we identified the best histomorphometric predictors of islet yield and posttransplant outcome. This further enhanced the predictive value of the flow cytometry analysis. These parameters should be useful for predicting islet yield and in vivo potency before clinical adult porcine islet xenotransplantation.

The effect of composite pig islet-human endothelial cell grafts on the instant blood-mediated inflammatory reaction.

Instant blood-mediated inflammatory reaction (IBMIR) causes rapid islet loss in portal vein islet transplantation. Endothelial cells are known to protect against complement-mediated lysis and activation of coagulation. We tested composite pig islet-human endothelial cell grafts as a strategy to overcome IBMIR. Porcine islets were cocultured with human endothelial cells in specially modified culture medium composed of M199 and M200 for 1-9 days. A positive control group, negative control group, and the endothelial cell-coated group were examined with an in vitro tubing loop assay using human blood. The endothelial cell-coated group was subdivided and analyzed by degree of surface coverage by endothelial cells (< or = 50% vs. > 50%) or coculture time (< 5 days vs. > or = 5 days). Platelet consumption and complement and coagulation activation were assessed by platelet count, C3a, and thrombin-antithrombin complex (TAT), respectively. After 60-min incubation in human blood, the endothelial cell-coated group showed platelet consumption inhibition and low C3a and TAT assay results compared to uncoated controls. When the endothelial cell-coated group was subdivided by degree of surface coverage, the < or = 50% coated group showed less platelet consumption and less activation of complement and coagulation compared with the positive control (uncoated) group. On analysis by coculture time, only the subgroup cocultured for < 5 days showed the same protective effect. Human endothelial cell-coated pig islets, especially the partially coated and short-term cocultured pig islet-human endothelial cell composites, reduced all components of IBMIR. If the optimal endothelial cell-islet coculture method could be identified, human endothelial cell coating of pig islets would offer new strategies to improve xenogenic islet transplantation outcomes.

Parameters for successful pig islet isolation as determined using 68 specific-pathogen-free miniature pigs.

BACKGROUND: Islet cell transplantation is a novel therapeutic modality for the cure of diabetes. Pig islet cells are an attractive substitute for human islet cells; however, they are known to be particularly difficult to isolate because of a weak islet capsule and a tendency to be fragmented during enzymatic digestion. Therefore, parameters favoring successful pig islet isolation were investigated using specific-pathogen-free (SPF) miniature pigs. METHODS: Sixty-eight SPF miniature pigs were used for islet isolation. Birth weight, body weight, age, sex, pregnancy history, and the fasting blood glucose levels of each pig were determined. Each pig's general condition was assessed with regard to feeding status and physical activity. Pancreas procurement was performed by one surgical team. Anesthesia duration, operation duration, procedure quality, and perfusate type were recorded. After pancreatectomy, a biopsy was performed for islet density analysis. Decapsulation, cannulation duration, degree of distension, and cold ischemic time were assessed. During islet isolation, pancreas weight, digestion time, and digested tissue proportion were recorded. Isolation results were evaluated by total islet equivalents (IEQ), islet equivalents per gram of pancreas (IEQ/g), isolation index, islet recovery rate, purity, and visual grade. To identify the predictors of higher islet isolation yield, we performed binary logistic regression analysis with significant (P < 0.05) variables from the univariate analysis. RESULTS: The pigs were categorized into high (n = 34) and low yield (n = 34) groups according to the median IEQ/g or total IEQ values. Body weight and age were significantly different between the two groups. Being male or a positive history of pregnancy in females was factors favoring successful islet isolation. General condition assessments failed to estimate islet isolation results. Long anesthesia duration, which might have caused ischemic injury to the pancreas, negatively affected islet isolation results. Decapsulation, cannulation duration, and subsequent pancreas distension were significantly important in successful islet isolation. Inter-lot variability of Liberase was not observed because of screening processes performed before purchase. Isolation index and islet recovery rate correlated well with islet yields. CONCLUSIONS: Multivariate analysis using total IEQ and IEQ/g as outcome variables indicated that age older than 2, being male and moderate distension by Liberase injection are major determinants influencing successful islet isolation.

ATP measurement predicts porcine islet transplantation outcome in nude mice.

Current nude mice islet transplantation studies cannot be used prospectively. Therefore, to predict transplantation outcomes, reliable and rapid assays for islet quality assessment are warranted. This study evaluated the predictive power of the porcine islet ATP content on the outcomes of islet transplantation in nude mice. Here, we report that the ATP measurement using a small number of handpicked islets with a diameter of 100 to 150 mum is a good predictor of islet graft efficacy in nude mice. Using receiver-operator characteristic analysis, the area under the curve of the ATP content using a small number of handpicked islets was 0.867 (95% confidence interval 0.744-0.989, P<0.001). The sensitivity and the specificity measured were 83.3% and 73.3%, respectively. In conclusion, a simple and a rapid measurement of intraislet ATP content could be a promising substitute for current nude mice islet transplantation studies.

Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs.

BACKGROUND: Porcine pancreas is a potential source of material for islet xenotransplantation. However, the difficulty in isolating islets, because of their fragility and the variability of isolation outcome in donor age and breed, represents a major obstacle to porcine islet xenotransplantation. In this study, we compared the islet isolation yield of specific pathogen-free (SPF) Chicago Medical School (CMS) miniature pigs with that of another miniature pig breed and market pigs from a local slaughterhouse. METHODS: Nine adult CMS miniature (ACM) pigs (>12 months), six young CMS miniature (YCM) pigs (6-7 months), four adult Prestige World Genetics (PWG) miniature (APM) pigs (>12 months), and 13 adult market (AM) pigs from a local slaughterhouse were used for islet isolation. RESULTS: The islet yield per gram of pancreas from ACM pigs (9589 +/- 2823 IEQ/g) was significantly higher than that from APM pigs (1752 +/- 874 IEQ/g, P < 0.05), AM pigs (1931 +/- 947 IEQ/g, P < 0.05), or YCM pigs (3460 +/- 1985 IEQ/g, P < 0.05). Isolated islets from ACM pigs were significantly larger than those from AM pigs or YCM pigs. The in vitro and in vivo function of isolated islets showed no difference among experimental groups. The pancreases of ACM pigs contained higher mean islet volume density percentages and larger size of islets than those of AM or APM pigs. CONCLUSIONS: We isolated extremely high yields of well-functioning islets from ACM pigs bred under SPF conditions. SPF CMS miniature pigs should be one of the best porcine islet donors for clinical porcine islet xenotransplantation.