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Due to its high polyunsaturated fatty acid content, acellular fish skin has emerged as a dermal substitute for the promotion of wound healing as it decreases scar formation while providing pain relief. However, various systematic studies on acellular fish skin, such as its biophysical analysis, in vitro activities, and clinical application, have not been sufficiently investigated. In this study, we conducted a comparative study to evaluate the wound-healing ability of acellular fish skin graft (Kerecis®) with that of the widely used bovine collagen skin graft (ProHeal®). The skin grafts were evaluated not only in terms of their biophysical properties, but also their in vitro cellular activities, using fibroblasts, keratinocytes, and human endothelial cells. The clinical study evaluated wound healing in 52 patients with acute burns who underwent skin grafting on donor sites from January 2019 to December 2020. The study was conducted with two groups; while only Kerecis® was tested in one group, Kerecis® and ProHeal® were compared in the other. In both groups, the application time of the dressing material was one to two days after split-thickness skin grafting to the donor sites. The Kerecis®-treatment group experienced faster healing than the other treatment group. In particular, the average wound healing time using the Kerecis® treatment and the ProHeal® treatment was 10.7 ± 1.5 days and 13.1 ± 1.4 days, respectively. We believe that the faster healing of the Kerecis® treatment, compared to that of the ProHeal® treatment, maybe due to the synergistic effect of the unique biophysical structure and the bioactive components of acellular fish skin.

Very few population-based studies have examined the epidemiology of Wilson’s disease (WD). We investigated the epidemiology of WD using the National Health Insurance Service (NHIS) database in South Korea. We analyzed not only the statistical variables of WD, but also those of WD-related diseases. WD patients were identified with the relevant International Classification of Diseases-10 code out of 50.5 million people. We used the NHIS database from 2009 to 2016 and analyzed the incidence rate, prevalence, and clinical symptoms of WD. A total of 1,333 patients were identified. The average annual incidence rate was 3.8 per million person-years. The prevalence was 38.7 per million people. The mean diagnostic age was 26.1 ± 17.2 with earlier diagnosis in men (P = 0.0003). Among the patients, 988 (74.1%) had hepatic symptoms, 510 (38.3%) had neurologic symptoms, and 601 (45.1%) had psychiatric symptoms. Before the diagnosis of WD, 350 (26.3%) had neurologic symptoms, and 427 (32%) had psychiatric symptoms. The annual mortality rate was 0.7%. Age, liver cirrhosis, and liver failure correlated with a fatal prognosis (P

Human skin incurs damage in various ways; a few of the recognizable factors are electric burns, chemical burns, scalding burns, surgery, and physical injuries, such as automobile accidents. If skin damage is extensive and severe enough [second degree and total body surface area (TBSA) involvement of >20%], the skin will lose the ability to regenerate itself. Burn wounds are treated in various ways. For full-thickness skin defects, the mainstay of treatment is an autologous split-thickness skin graft. However, there are some limitations due to scars, poor elasticity, and limitations in the joint movements due to contractures. Recently, artificial dermis has been widely used to minimize contractures. The use of dermal replacements for the treatment of burns brings new hope in maintaining the characteristics of the normal dermis. Herein, Insuregraf® was used for skin regeneration in patients who had burn injury from flames, electricity, heat, or steam. The mean take-rate values at 7 and 14 days after operation were 94.55 ± 3.02% and 97.40 ± 2.57%, respectively. Furthermore, areas covered by Insuregraf® showed higher mean values of trans-epidermal water loss (24.6 ± 3.9 g h-1 m-2), gross elasticity (Ua/Uf = 0.76 ± 0.24), and biological elasticity (Ur/Uf = 0.55 ± 0.1). These values were much better than those of the control where Insuregraf® was not used (p = 0.030, p = 0.040, and p = 0.013, respectively). Furthermore, the biomechanical scar properties of Insuregraf® and Matriderm were very similar. Hence, we suggest that Insuregraf® can be used in the medical field.

Hippo signaling restricts tissue growth by inhibiting the transcriptional effector YAP. Here we uncover a role of Hippo signaling and a tumor suppressor function of YAP in estrogen receptor positive (ER

OBJECTIVE: To evaluate the efficacy of fibrin sealant as a topical hemostatic agent and for graft fixation during skin grafting of hand burns. METHODS: This prospective cohort study enrolled 40 patients with hand burns from January 2013 to December 2016. They were all treated with excision and split-thickness skin graft and divided into the fibrin sealant with tourniquet group (20 patients) and epinephrine tumescence group (20 patients). MAIN OUTCOME MEASURES: Demographic and clinical data such as age, sex, burn characteristics, operation time, estimated blood loss, and take rate were collected from each patient. MAIN RESULTS: The demographic and burn characteristics were not statistically different between the two groups. Estimated blood loss per cm2 (0.30 vs 1.00; P < .001) was significantly lower and the graft take rate (99.2% vs 98.2%; P = .032) was significantly higher in the fibrin sealant with tourniquet group. CONCLUSIONS: The use of fibrin sealants accompanied by tourniquets for hand burns exhibited superior results in terms of decreasing blood loss and had a better graft take rate compared with treatment with epinephrine tumescence.

Background The progression of biomarkers over time is considered an indicator of disease progression and helps in the early detection of disease, thereby reducing disease-related mortality. Their ability to predict outcomes has been evaluated using conventional cross-sectional methods. This study investigated the prognostic performance of biomarkers over time. Methods Patients aged > 18 years admitted to the burn intensive care unit within 24 h of a burn incident were enrolled. Information regarding longitudinal biomarkers, including white blood cells; platelet count; lactate, creatinine, and total bilirubin levels; and prothrombin time (PT), were retrieved from a clinical database. Time-dependent receiver operating characteristic curves using cumulative/dynamic and incident/dynamic (ID) approaches were used to evaluate prognostic performance. Results Overall, 2259 patients were included and divided into survival and non-survival groups. By determining the area under the curve using the ID approach, platelets showed the highest c-index [0.930 (0.919–0.941)] across all time points. Conversely, the c-index of PT and creatinine levels were 0.862 (0.843–0.881) and 0.828 (0.809–0.848), respectively. Conclusions Platelet count was the best prognostic marker, followed by PT. Total bilirubin and creatinine levels also showed good prognostic ability. Although lactate was a strong predictor, it showed relatively poor prognostic performance in burns patients.

This study aimed to investigate the differences in the trajectory of blood biomarkers routinely assessed through forward- and backward-looking approaches among burn patients. This cohort study included patients above 18 years of age from February 2007 to December 2018. All the biomarkers were estimated from admission to discharge from the intensive care unit. Significant differences were observed in the platelet count at 40 days, prothrombin time (PT) at 32 days, white blood cell count at 26 days, creatinine levels at 22 days, and lactate and total bilirubin levels at 19 days before death. In reverse order, significant differences were observed in the fitted model in platelet count at 44 days and in the platelet count and PT at 33 days. We obtained more valuable information from the longitudinal biomarker trajectory using the backward-looking method than using the forward-looking method. The platelet count served as the earliest predictor of mortality among burn patients.

Hippo (Hpo) signaling pathway controls tissue growth by regulating the subcellular localization of Yorkie (Yki)/Yap via a cytoplasmic kinase cassette containing an upstream kinase Hpo/MST1/2 and a downstream kinase Warts (Wts)/Lats1/2. Here we show that PRP4K, a kinase involved in mRNA splicing, phosphorylates Yki/Yap in the nucleus to prevent its nuclear accumulation and restrict Hpo pathway target gene expression. PRP4K inactivation accelerates whereas excessive PRP4K inhibits Yki-driven tissue overgrowth. PRP4K phosphorylates a subset of Wts/Lats1/2 sites on Yki/Yap to inhibit the binding of Yki/Yap to the Scalloped (Sd)/TEAD transcription factor and exclude Yki/Yap nuclear localization depending on nuclear export. Furthermore, PRP4K inhibits proliferation and invasiveness of cultured breast cancer cells and its high expression correlates with good prognosis in breast cancer patients. Our study unravels an unanticipated layer of Hpo pathway regulation and suggests that PRP4K-mediated Yki/Yap phosphorylation in the nucleus provides a fail-safe mechanism to restrict aberrant pathway activation., The Hippo signaling pathway controls tissue growth by regulating the subcellular localization of Yorkie /Yap. Here the authors show that PRP4K, a kinase involved in mRNA splicing, phosphorylates Yki/Yap in the nucleus, which prevents its nuclear accumulation and inhibits Hippo signaling.

OBJECTIVE To retest the safety and effectiveness of a thermosensitive hydrogel-type cultured epithelial allograft (KeraHeal-Allo; MCTT, Seoul, South Korea) and identify the subjective experience of patients and doctors with this product. DESIGN AND SETTING Prospective interventional phase 3 study in 3 burn centers near Seoul, South Korea. PATIENTS Thirty-three patients with deep second-degree burns larger than 200 cm (for intervention and control sites of 100 cm each) were enrolled. INTERVENTION A cultured epithelial allograft containing 2 × 10/1.5 mL keratinocytes was applied to each patient's intervention site. Three principal investigators (1 in each institution) evaluated the effectiveness of the allograft at their institution and the others'. Researchers administered a subjective satisfaction survey during each patient's last visit. MAIN OUTCOME MEASURE The primary end point of the study was the re-epithelialization period. MAIN RESULTS The re-epithelialization period for the intervention was 2.8 ± 2.2 days faster than that of control sites at other institutions (P < .001) and 2.5 ± 3.4 days faster than that of control sites in the same institution (P < .001). There were no reported adverse events. Satisfaction scores provided by patients and doctors showed significantly high scores on all items. CONCLUSUIONS This type of cultured epithelial allograft is safe and well received by patients and providers and promotes re-epithelialization.

s Background Acute kidney injury (AKI) is a critical complications in severely burned patients associated with high morbidity and mortality. The purpose of this study was to investigate the impact of severity of AKI at the time of continuous renal replacement therapy (CRRT) start on patient outcome and to identify the prognostic factors in severely burned patients with CRRT application. Methods From January 2007 to June 2010, 84 burn patients with more than 40% of total body surface area (TBSA) burned who treated with continuous renal replacement therapy for acute kidney injury were analyzed retrospectively. Results There was no significant difference of mortality by the severity of AKI at the time of CRRT start. However, the mean TBSA burned, abbreviated burn severity index, arterial pH, partial pressure of carbon dioxide (PaCO 2 ) and blood urea nitrogen (BUN)/creatinine (Cr) ratio had a statistical significance to predict mortality in receiver operation characteristic curve. In a multivariate logistic regression analysis, only sepsis had an independent association with mortality. Conclusions The severity of the AKI at the time of CRRT start did not have significant relationship with patient outcome. CRRT can be applied to minimize the complication of AKI including electrolyte imbalance and volume overload. Because only the presence of sepsis was independently associated with mortality, treatment for sepsis should be focused to improve the survival of the severely burned patients with CRRT.

Hippo signaling controls organ size and tumor progression through a conserved pathway leading to nuclear translocation of the transcriptional effector Yki/Yap/Taz. Most of our understanding of Hippo signaling pertains to its cytoplasmic regulation, but how the pathway is controlled in the nucleus remains poorly understood. Here we uncover an evolutionarily conserved mechanism by which CDK7 promotes Yki/Yap/Taz stabilization in the nucleus to sustain Hippo pathway outputs. We found that a modular E3 ubiquitin ligase complex CRL4DCAF12 binds and targets Yki/Yap/Taz for ubiquitination and degradation, whereas CDK7 phosphorylates Yki/Yap/Taz at S169/S128/S90 to inhibit CRL4DCAF12 recruitment, leading to Yki/Yap/Taz stabilization. As a consequence, inactivation of CDK7 reduced organ size and inhibited tumor growth, which could be reversed by restoring Yki/Yap activity. Our study identifies an unanticipated layer of Hippo pathway regulation, defines a novel mechanism by which CDK7 regulates tissue growth, and implies CDK7 as a drug target for Yap/Taz-driven cancer.

The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C) Cdh1 E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities. CDH1 recognizes LATS kinases to promote their degradation and, hence, YAP/TAZ regulation by LATS phosphorylation is under cell cycle control. As a result, YAP/TAZ activities peak in G1 phase. Furthermore, we show in Drosophila eye and wing development that Cdh1 is required in vivo to regulate the LATS homolog Warts with a conserved mechanism. Cdh1 reduction increased Warts levels, which resulted in reduction of the eye and wing sizes in a Yorkie dependent manner. Therefore, LATS degradation by APC/C Cdh1 represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.

Hedgehog (Hh) signaling culminates in the conversion of the latent transcription factor Cubitus interruptus (Ci)/Gli into its activator form (Ci(A)/Gli(A)), but the underlying mechanism remains poorly understood. Here we demonstrate that Hh stimulates the phosphorylation of Ci by the Ser/Thr kinase Fused (Fu) and that Fu-mediated phosphorylation of Ci promotes its activation. We find that Fu directly phosphorylates Ci on Ser218 and Ser1230, which primes its further phosphorylation by CK1 on adjacent sties. These phosphorylation events alter Ci binding to the pathway inhibitor Suppressor of fused (Sufu) and facilitate the recruitment of Transportin and the transcriptional coactivator CBP. Furthermore, we provide evidence that Sonic hedgehog (Shh) activates Gli2 by stimulating its phosphorylation on conserved sites through the Fu family kinases ULK3 and mFu/STK36 in a manner depending on Gli2 ciliary localization. Hence, Fu family kinase-mediated phosphorylation of Ci/Gli serves as a conserved mechanism that activates the Hh pathway transcription factor.

Tissue engineering aims to repair or replace damaged tissues or organs using biomedical scaffolds cultured with cells. The scaffolds composed of biomaterials should guide the cells to mature into functional tissues or organs. An ideal scaffold to regenerate hard tissues should have mechanical stability as well as biocompatibilities. It has been well known that gelatin can provide outstanding biological activities, but its low mechanical stability can be one of obstacles to be used in hard tissue regeneration. To overcome the issue, we used PVA, which can reinforce the low mechanical stability of the gelatin. The gelatin/PVA scaffolds have been fabricated using a low temperature 3D-printing process. By manipulating various weight fractions of PVA/gelatin, we can obtain the optimal mixture ratio in aspect of the physical and biological properties of the scaffolds. As a result, a weight fraction of 5:5 showed appropriate mechanical strength and enhanced cell activities, such as cell proliferation and differentiation. The gelatin/PVA scaffold showed potential for future application as biomedical scaffold in soft and hard tissue regeneration.

Objectives We evaluated the ability of new sepsis (S3) criteria (compared with previous definitions of sepsis [S1] and burn sepsis criteria) to accurately determine the mortality in severe burns patients with sepsis. Design This was retrospective cohort study. Setting The Burn ICU of Burn Center, Hangang Sacred Heart Hospital, Hallym University, Seoul, Korea. Patients A total of 1,185 adult patients (mean age, 49.1 yr) were admitted between January 2009 and December 2015. Interventions The 1,185 patients enrolled in the present study and were then re-evaluated based on S1, burn sepsis, and S3 criteria, following which 565 patients, 812 patients, and 809 patients were diagnosed with sepsis based on S1, burn sepsis, S3 criteria, respectively. Measurements and main results For diagnostic performance, sensitivity, specificity, predictive value, and likelihood ratio were calculated. The area under the curve of the receiver operating characteristic curve was calculated to determine the accuracy of mortality prediction. The optimal cutoff value of Sequential Organ Failure Assessment score was calculated by the decision tree method. Total body surface area burned was 33.4%. Patients were identified with sepsis using S1 (812), S3 (809), and burn sepsis (565) criteria. Overall mortality was 20.3%, highest (82.2%) and lowest (26.5%) occurred with new septic shock (SH3) and S3, respectively. The sensitivity and specificity for burn sepsis (84.6% and 61.8%) and SH3 (63.1% and 96.5%) were reported. Area under the curve values for Sequential Organ Failure Assessment scores were the highest in all sepsis categories. With Sequential Organ Failure Assessment score greater than or equal to 6 (with infection), the accuracy was 0.86 (95% CI, 0.82-0.89). Conclusions The S3 criteria failed to show superior prognostic accuracy for mortality in severely burned patients. Sequential Organ Failure Assessment score greater than or equal to 6 may be a better criterion for the diagnosis of sepsis in burns patients.

Background Diagnosing acute kidney injury quickly is imperative since it is known as an independent risk factor for mortality in burn patients. We evaluated the diagnostic power of creatinine, cystatin, serum and urine neutrophil gelatinase-associated lipocalin at different time periods and observed the changes from baseline for each biomarker. Methods This was a prospective observation study from January 2015 to February 2016. A total of 84 patients were enrolled consecutively. Serum creatinine, serum cystatin C, and serum and urine neutrophil gelatinase-associated lipocalin were measured at admission, 7th, 14th, 21st, and 28th days after admission. All samples were collected until acute kidney injury developed. Results Acute kidney injury developed in 35 patients. The mean age was 49.6 years with a male predominance. The median urine neutrophil gelatinase-associated lipocalin was the lowest (11.6 ng/dL) at admission, and the highest at 85.5 ng/dL on day 7. Mean creatinine level was the highest (0.88 mg/dL) at admission and the median creatinine level was the lowest (0.56 mg/dL) on the 14th day. The area under the curve of creatinine levels was the highest with 0.857 during the 1st week. The area under the curve of urine neutrophil gelatinase-associated lipocalin was the highest with 0.803 during the 5th week. Conclusions Within 1 week of acute kidney injury, creatinine level was the optimal biomarker for diagnosis while urine neutrophil gelatinase-associated lipocalin showed better diagnostic performance following the 4- week period.

Purpose To estimate long-term outcomes after treatment modification in patients with chronic hepatitis B (CHB) treated with entecavir (ETV) and telbivudine (LdT). Materials and methods The study enrolled 131 nucleos(t)ide analogue (NA)-naive CHB patients treated with ETV or LdT. During the 3-year study, NA treatment history including the incidence, the type of treatment modification, reasons for the modification, and overall complete virologic response (CVR) rate were retrospectively evaluated using the patients' medical records. Results Among the 131 patients, 84 and 47 were initially treated with ETV and LdT, respectively. During the course of 3-year study, 82 patients in the ETV group (97.6%) maintained initial treatment whereas only 19 in the LdT group (40.4%). In the LdT group, 26 patients (92.9%) switched to another NA and another NA was added in 2 (7.1%) patients. An assessment of the CVR rate at 3 years, including treatment modification, showed that 89.3% and 95.7% of patients in the ETV and LdT groups, respectively, had undetectable serum hepatitis B virus DNA levels (p=0.329). Among LdT patients with treatment modification, the cumulative incidence rate of a CVR for rescue therapy was significantly higher in the tenofovir than in the ETV group (p=0.009). Conclusion During the 3-year study, there were no significant differences in the CVR between the ETV and LdT groups if appropriate rescue therapy was considered.

PURPOSE: To determine epidemiological trends among burns patients admitted to our burns center during 2003-2012, and the usefulness of the Abbreviated Burns Severity Index (ABSI) for predicting burns-related mortality. METHODS: We retrospectively reviewed the data of 4481 burns patients. We analyzed the epidemiological trends and ABSI scores using Student t-test and one-way analysis of variance (continuous variables), chi-square test (categorical variables) and stepwise logistic-regression analysis (predictors of mortality). RESULTS: The mean age and male-to-female ratio were 39.9±19.7 years and 2.88, respectively. ABSI scores decreased from 7.7±3.0 in 2003 to 6.9±3.0 in 2012. Mortality rate improved from 24.5% in 2003 to 15.8% in 2012. Burns were caused by flames (67.3%), scalding (22.0%) and electrical (7.5%), chemical (1.6%) and contact (1.5%) injuries. Scalding and flames were the most common causes in patients aged ≤20 years and ≥21 years, respectively. Female sex, inhalation injury, full-thickness burns, large total body surface area (TBSA) burned and old age predicted mortality. ABSI scores 14 were associated with 0.7% and >90% mortality, respectively. CONCLUSIONS: The mortality of major burns has decreased but remains high. ABSI scores predict burns-related mortality. Language: en

This study was to re-evaluate inhalation injury as a prognostic factor in burn patients and to determine the factors that should be considered when refining the definition of inhalation injury. A total of 192 burn patients (152 men, 40 women; mean age, 46.1±13.8 years) who were suspected to have an inhalation injury and underwent bronchoscopy between January 2010 and June 2012 were included in this prospective observational study. All patients underwent bronchoscopy within 24h of sustaining the burn. The bronchoscopic findings were classified as normal, mild, moderate, and severe. Mechanical ventilation was administered, when required. Age, percentage of TBSA burned, ABSI score, requirement of mechanical ventilation and PF ratio, but not inhalation injury, COHb level, and bronchoscopic grades, significantly differed between the survivors and non-survivors (p

Pruritus, a common, chronically disabling condition is often refractory to treatment. The pruritus sensation is mediated in the spinal cord and post-burn pruritus is considered a form of neuropathic pain. We investigated cold pack therapy as a treatment modality for post-burn pruritus.We studied 23 patients with severe pruritus scoring at least 5 on the visual analogue scale (VAS) and refractory to antihistamine and gabapentin administration. Each cold pack therapy lasted more than 20min. Patients participated in more than three sessions daily for 4 consecutive weeks. The numerical rating scale (NRS), 5-D Itch Scale, Leuven Itch Scale, and perfusion units were evaluated before, within 30min after, 2, and 4 weeks cold pack therapy.In all patients, the NRS was 9.37±1.47 pre-therapy, 3.48±2.19 at 2 weeks, and 2.78±2.13 at 4 weeks following therapy, the pre-scores being significantly different (p0.001). Pruritus severity and consequences scores (Leuven Itch Scale) were improved after therapy compared to pre-therapy. Perfusion unit (PU) scores were statistically insignificant compared to PU scores measured before the application of cold pack therapy. Degree, direction, and disability scores (5-D Itch scale) significantly differed (p.05).Cold pack therapy, a non-invasive, non-pharmacological treatment modality significantly reduces post-burn pruritus and could be useful in burn patients.

There is no consensus whether patients who underwent endoscopic common bile duct (CBD) stone removal should be followed up periodically and whether patients with gallbladder (GB) stones should undergo cholecystectomy. Thus, this study aimed to investigate the recurrence rate of CBD stones and the difference in recurrence rate according to cholecystectomy. We conducted a population-based study using the National Health Insurance database. Patients diagnosed with CBD stones and with procedure registry of endoscopic stone removal were included. The primary outcome was the recurrence rate of CBD stones. The secondary outcome was the difference in recurrence rate of CBD stones according to cholecystectomy. A total of 46,181 patients were identified. The mean follow-up was 4.2 years. The first CBD stone recurrence occurred in 5228 (11.3%) patients. The cumulative first recurrence rate was low. However, the second and third recurrence rates were 23.4 and 33.4%, respectively. The cumulative second and third recurrence rates were high and gradually increased with time. The recurrence rate in the non-cholecystectomy group was higher than that in the cholecystectomy group (p

Inhalation injury is known to be an important factor in predicting mortality in burns patients. However, the diagnosis is complicated by the heterogeneous presentation and inability to determine the severity of inhalation injury. The purpose of this study was to identify clinical features of inhalation injury that affect mortality and the values that could predict the outcome more precisely in burns patients with inhalation injury. This retrospective observational study included 676 burns patients who were over 18 years of age and hospitalized in the Burns Intensive Care Unit between January 2012 and December 2015. We analyzed variables that are already known to be prognostic factors (age, percentage of total body surface area (%TBSA) burned, and inhalation injury) and factors associated with inhalation injury (carboxyhemoglobin and PaO2/FiO2 [PF] ratio) by univariate and multivariate logistic regression. Age group (odds ratio [OR] 1.069, p

PURPOSE This study examined 2-year outcome of consecutive therapy using entecavir (ETV) followed by telbivudine (LdT) in subjects with undetectable hepatitis B virus (HBV) DNA level and normal alanine aminotransferase level after the initial 6 months of ETV treatment. MATERIALS AND METHODS Sixty subjects were randomized to continue with ETV or switch to LdT. Significant difference in baseline characteristics was not found between the two groups. Persistent HBV DNA level of 20-60 IU/mL in three consecutive samples collected three months apart or singly measured HBV DNA level of >60 IU/mL was defined as virological rebound. RESULTS During 96 weeks of follow-up, all subjects of the ETV-only group (n=30) resulted in undetectable HBV DNA level. On the other hand, 83.3% (n=25) of the LdT-switched group showed treatment success. Virological rebound time varied from week 24 to 84 after switching to LdT. HBV DNA level was 180 to 2940 IU/mL at rebound time. All subjects with virological rebound (n=5) showed drug-resistant mutation: three had mutation rtM204I, and two had mutation rtM204V. Consecutive treatment using ETV followed by LdT showed virological rebound in 16.7% of subjects during 96 weeks of follow-up. HBV DNA negativity during initial ETV therapy could not be achieved in patients who switched to LdT. CONCLUSION Consecutive treatment using ETV followed by lamivudine was ineffective for treating chronic hepatitis B. LdT was found as a more potent antiviral agent than lamivudine. However, this conclusion requires larger-scale, long-term prospective reviews of the treatment effects of ETV-LdT switch therapy.

Purpose The purpose of this study was to develop a new prediction model to reflect the risk of mortality and severity of disease and to evaluate the ability of the developed model to predict mortality among adult burn patients. Methods This study included 2009 patients aged more than 18 years who were admitted to the intensive care unit (ICU) within 24 hours after a burn. We divided the patients into two groups; those admitted from January 2007 to December 2013 were included in the derivation group and those admitted from January 2014 to September 2017 were included in the validation group. Shrinkage methods with 10-folds cross-validation were performed to identify variables and limit overfitting of the model. The discrimination was analyzed using the area under the curve (AUC) of the receiver operating characteristic curve. The Brier score, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were also calculated. The calibration was analyzed using the Hosmer-Lemeshow goodness-of-fit test (HL test). The clinical usefulness was evaluated using a decision-curve analysis. Results The Hangang model showed good calibration with the HL test (χ2 = 8.785, p = 0.361); the highest AUC and the lowest Brier score were 0.943 and 0.068, respectively. The NRI and IDI were 0.124 (p-value = 0.003) and 0.079 (p-value

The purpose of this study is to clarify the clinical significance of serum transthyretin (TTR) in massively burned patients in nutrition support and clinical severity.A retrospective study was performed with 204 patients admitted to Hangang Sacred Heart Hospital's Burn Center September 2010-September 2012 with burn wounds20% of total body surface area (TBSA) burned. Serum TTR, C-reactive protein (CRP), lactic acid, and an NST index (calculated by dividing real caloric intake by estimated caloric need for 7 days) were analyzed on a weekly basis for 5 weeks after admission.When we classified patients with severity according to mortality, percentage of TBSA burned, serum lactic acid, and CRP, mean serum TTR level was significantly higher in the less severe patient group than in the severe patient group in each week for every severity index. And the serum TTR level did not show significant differences by NST index in both the severe patient group and the less severe patient group. In a multivariate logistic regression, percentage TBSA burned, TTR, and lactic acid had an independent association with mortality.Serum TTR did not show a significant difference by nutrition support in massively burned patients with20% of TBSA burned. But serum TTR was significantly different by the severity of the patient and independently associated with mortality. Hence, serum TTR level can be 1 of the useful biomarkers for comprehending the severity of the illness in massively burned patients.

We address the clinical application of the suspension type cultured epithelial autografts (CEAs), Keraheal™ (MCTT, Seoul, Korea), along with the effects, application method, merits and demerits thereof. From February 2007 to June 2010, 29 burn patients with extensive burns, participated in the suspension type of CEA clinical test. A widely meshed autograft (1:4-6 ratio) was applied to the wound bed and the suspension type CEA was sprayed with a Tissomat cell sprayer, followed by a Tissucol spray, a fibrin sealant. The patients' (men/women=26/3) median (interquartile ranges) age was 42 (30-49) years old, the burned TBSA was 55 (44-60) %, and the full thickness burn area was 40 (30-46.5) %. The area of Keraheal™ applied was 800 (400-1200) cm(2). The take rate was 96 (90.5-99) % and 100 (98.5-100) % at 2 and 4 weeks after treatment with Keraheal™, respectively. The Vancouver burn scar scale was 5 (4-6.5), 4 (3-6), and 3 (2-4) at 8, 12 and 24 weeks after the Keraheal™ application. Widely meshed autograft must be applied in massive burns but it's take rate is greatly reduced. The CEAs enhance the take rate of a wide meshed autograft in massive burns and allow for grafting wide meshed autograft together with acellular dermal matrix in some cases.

In efforts to prevent and reduce joint contracture and scar formation after burn, we used the acellular human dermis (AlloDerm) as a dermal replacement in the acute stage. A total of 64 patients received AlloDerm graft selectively on joint areas during the study period from March, 2005 to July, 2007. From January to March, 2008, a total of 31 patients returned to our burn center to examine the functional results by measuring range of motion of joints. Additionally, the quality of grafted skin condition criteria of skin elasticity, scar thickness, trans-epidermal water loss, melanin and erythema level was measured in a total of 11 patients among them. By analyzing the limitation level of 55 joints excluding hand areas, we found that 24 joints (43.6%) showed no limitations, 12 joints (21.8%) showed limitations below 10%, 16 joints (29.1%) showed limitations between 10 and 19% and 3 joints (5.5%) showed limitations over 20%. The scar thickness of non-AlloDerm applied areas was 2.5+/-0.9 mm and AlloDerm applied areas was 1.8+/-0.7 mm (p = 0.396). Trans-epidermal water loss for non-AlloDerm applied areas was 20.9+/-7.7 g/h/m(2) and AlloDerm applied areas was 10.8+/-3.4 g/h/m(2) (p

Continuous renal replacement therapy (CRRT) is administered to critically ill patients with renal injuries as renal replacement or renal support. We aimed to identify predictors of mortality among burn patients receiving CRRT, and to investigate clinical differences according to acute kidney injury (AKI) status. This retrospective observational study evaluated 216 Korean burn patients who received CRRT at a burn intensive care unit. Patients were categorized by AKI status. Data were collected regarding arterial pH, laboratory results, ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio), and urine production. Among surviving patients, CRRT duration and the sequential organ failure assessment score were 6.5 days and 4.7 in the non-AKI group and 23.4 days and 7.4 in the AKI group, respectively (p = 0.003 and p = 0.008). On logistic regression analyses, mortality was significantly associated with a pH of 5.0 mEg/L (p = 0.045), creatinine levels of >2.0 mg/dL (p = 0.011), lactate levels of >2 mmol/L (p2 mmol/L, and a platelet count of 2 mg/dL. In the non-AKI group, poor outcomes were associated with lactate levels of >1.5 mmol/L, a PF ratio of 1.2 mg/dL. Duration of the CRRT application and the requirement for either renal replacement or renal support at the initiation of CRRT application are important considerations depending on its application.

Constitutive activation of the telomerase is a key step in the development of human cancers. Interferon-gamma (IFN-gamma) signaling induces growth arrest in many tumors through multiple regulatory mechanisms. In this study, we show that IFN-gamma signaling represses telomerase activity and human telomerase reverse transcriptase (hTERT) transcription, and suggest that this signaling is mediated by IRF-1. Ectopic expression of IRF-1 attenuated hTERT promoter activity. Murine embryonic fibroblasts (MEFs) genetically deficient in IRF-1 (IRF-1(-/-)) showed an elevated level (15 times) of hTERT promoter activity as compared to the hTERT promoter activity of wild-type MEFs. The telomerase activity and hTERT expression in IRF-1(-/-) MEFs were downregulated by IRF-1 transfection. Interestingly, less extent of telomerase repression was observed in HPV E6 and E7 negative, p53 mutant HT-3 cells than in HPV 18 E6 and E7 positive HeLa cells (intact p53). These findings provide evidence that IRF-1 is a potential mediator of IFN-gamma-induced attenuation of telomerase activity and hTERT expression.

Objective. The coxsackievirus and adenovirus receptor (CAR) is known to be a primary receptor for attachment during adenovirus infection of target cells and thus is closely related to adenoviral infection efficiency. To extend this notion to human ovarian cancer, we investigated the difference in expression levels of CAR in human ovarian cancer cell lines and whether their adenoviral sensitivities are enhanced by transient transfection of the CAR gene. Methods. Adenoviral infection efficiency was examined by flow cytometry analysis, β-galactosidase staining, and β-galactosidase activity assay. Expression of the CAR-specific mRNA and protein was analyzed by reverse transcription polymerase chain reaction and flow cytometry, respectively. Results. Expression of CAR in human ovarian cancer cell lines (SKOV3, 2774, PA-1, and OVCAR3) appeared to be correlated with their susceptibilities to adenovirus-mediated gene delivery. The 2774 and PA-1 cells expressing an easily detectable level of CAR on the cell surface showed a higher susceptibility to infection with both AdCMVGFP and AdRSVβgal than SKOV3 and OVCAR3 cells, both of which had hardly detectable levels of CAR. Ectopic expression of the CAR gene by transient transfection of these ovarian cancer cells resulted in a dramatic increase in their adenoviral sensitivities. Conclusion. These data show that the expression of CAR is closely related to susceptibility to adenovirus infection in human ovarian cancer cells. These results indicate that the CAR gene can be a useful tool in boosting the efficiency of adenoviral vector-mediated gene therapy against human ovarian cancer.

This prospective observational study was performed to analyze the clinical outcomes of patients with massive burns treated using cultured epithelial autografts (CEAs) and to determine the association of this treatment with survival outcomes. During 2006-2013, total 177 massive-burns subjects treated with (96 subjects) or without (81 subjects) CEAs. Data were analyzed using the independent t test or chi-square test. Multivariate logistic regression, Kaplan-Meier survival, and Cox regression analyses were performed to evaluate the factors that influenced mortality. Age, percentage of total body surface area burned, incidence of inhalation injury, allograft-application rate, Abbreviated Burn Severity Index score, length of hospital stay, and mortality significantly differed between the CEA and noncultured epithelial autograft groups. Mortality and other clinical parameters did not differ between the sheet-type and spray-type CEA groups. Allograft application (odds ratio, 4.44; p 0.01) significantly influenced CEA application. The CEA group showed significantly higher survival rates (p = 0.05). Cultured epithelial autografting had a hazard ratio of 0.55 (p = 0.02) and 0.59 (p = 0.05) according to the uni- and multivariate Cox regression analysis, respectively. In conclusion, early and aggressive allograft application is required to facilitate CEA application. Furthermore, the use of CEAs was associated with a lower mortality, but this result should be interpreted with caution as the groups were not randomized.

Background This study was aimed at evaluating the effectiveness of serum cystatin C and microalbuminuria as diagnostic markers for acute kidney injury (AKI) in major burn patients. Materials and methods Major burn adult patients admitted to the burn intensive care unit within 24 h from the onset of injury were enrolled. Serum cystatin C and microalbuminuria (albumin–creatinine ratio, ACR) were obtained at postburn days 1, 3, 7, 14, 21 and 28. The patients were divided into two groups of the AKI group and the nonacute kidney injury group. Results A total of 97 patients were enrolled in this study. Acute kidney injury was diagnosed in 40 patients (41·2%) at postburn day 17·3 ± 7·9. The area under the curve of the receiver operating characteristic curve for serum cystatin C was 0·808 (95% CI, 0·711–0·905, P

Smad proteins activated by TGF-beta form complexes with Smad4. Upon activation, these complexes translocate to the nucleus of the cell, where they induce transcription of genes related to inhibition of cell growth, cell differentiation and apoptosis. We investigated the role of Smads in the TGF-beta-mediated signal-transduction cascade in 4 human cervical cancer cell lines: HeLa, Caski, HT-3 and SiHa. Based on our results, SiHa cells show low mRNA expression of mutated Smad4 (Gly(230)Ala, Ala(488)Val) and of Smads 2, 3, 5 and 6. SiHa cells were likewise defective in TGF-beta signaling, as evidenced by a lack of significant growth inhibition following TGF-beta treatment. In addition, TGF-beta did not induce transcription of the PAI-1 gene or change Smad protein levels. Introduction of Smad3 and/or Smad4 into SiHa cells restored TGF-beta signaling, as determined by activation of the 3TP-lux reporter gene and by prominent apoptotic cell death with PAI-1 induction. Analysis of the downstream targets activated by TGF-beta yielded rapid activation of p38 with subsequent phosphorylation of the transcription factor ATF-2 but unchanged SAPK/JNK activation in the 4 cervical cancer cell lines. Our findings demonstrate that (i) decrease of Smad4 mRNA expression is closely associated with defective TGF-beta response and lack of growth inhibition, (ii) activation of PAI-1 by TGF-beta may be Smad4-dependent and (iii) the Smad and the p38 cascades are triggered by TGF-beta independently of each other in human cervical cancer.

A human embryonic kidney cell line 293 is widely used for adenovirus production and propagation. With this cell line, however, replication-competent virus (RCV) is frequently generated, especially during large-scale production and successive propagation because 293 cells contain not only E1 gene but also non-E1 adenovirus gene. Homologous recombination between non-E1 region of 293 genomic DNA and its homologous region in the recombinant adenoviral vector generate RCV. To overcome this problem, we developed a new packaging cell line, Hela-E1, which contains minimum E1 region and from which non-E1 adenoviral region that is homologous with recombinant adenovirus vector was excluded. No RCV was detected during adenovirus propagation in Hela-E1 compared to in 293. In addition, adenovirus-p53 produced in HeLa-E1 was able to overexpress p53 protein when introduced into an ovarian cancer cell line, SKOV3. These results may have a significant impact on the development of packaging cell lines for replication-deficient adenovirus production.

This study is a phase 1 and 2 clinical trial for investigating the safety profile, effective treatment dose and effectiveness of the newly developed thermosensitive hydrogel-type cultured epidermal allograft. For phase 1, the keratinocytes were divided into 3 groups as follows, with 5 patients in each group: (1) low-dose group (6.7×10(6)/1.5mL), (2) medium-dose group (2×10(7)/1.5mL), and (3) high-dose group (6.0×10(7)/1.5mL). The second phase of the trial proceeded with 10 cases after choosing the most effective dose based on the analysis of the first phase. When comparing re-epithelialization time, medium- and high-dose group showed significantly shorter re-epithelialization time than low-dose group (p=0.003 and p=0.002). A total of 15 cases, 5 cases selected from phase 1 and 10 cases test in phase 2 with the medium dose, were compared with the re-epithelialization period. The re-epithelialization period was 9.6±4.0 days in the test site and 12.4±4.8 days in the control site. In the test site, re-epithelialization was 2.8±1.8 days faster than in the control site (p

a b s t r a c t Objective: To evaluate the effect of burn rehabilitation massage therapy on hypertrophic scar after burn. Method: One hundred and forty-six burn patients with hypertrophic scar(s) were randomly divided into an experimental group and a control group. All patients received standard rehabilitation therapy for hypertrophic scars and 76 patients (massage group) additionally received burn scar rehabilitation massage therapy. Both before and after the treatment, we determined the scores of visual analog scale (VAS) and itching scale and assessed the scar characteristics of thickness, melanin, erythema, transepidermal water loss (TEWL), sebum, and elasticity by using ultrasonography, Mexameter 1 , Tewameter 1 , Sebumeter 1 , and Cutometer 1 , respectively. Results: The scores of both VAS and itching scale decreased significantly in both groups, indicating a significant intragroup difference. With regard to the scar characteristics, the massage group showed a significant decrease after treatment in scar thickness, melanin, erythema, TEWL and a significant intergroup difference. In terms of scar elasticity, a significant intergroup difference was noted in immediate distension and gross skin elasticity, while the massage group significant improvement in skin distensibility, immediate distension, immediate retraction, and delayed distension. Conclusion: Our results suggest that burn rehabilitation massage therapy is effective in improving pain, pruritus, and scar characteristics in hypertrophic scars after burn.

A liposome-based fluorescence sensing system for apoptotic cells has been developed from stimuli-responsive poly(diacetylene)-liposomes for the first time. The combination of the liposome components, a phosphatidylserine-binding Zn(II)-dipicolylamine component and an alcohol-terminated component in the ratio of 2:1, has led to an efficient detection system for apoptotic cells, as demonstrated by confocal fluorescence microscopy and FACS analysis. The liposome shows a color change from blue to reddish purple and emits fluorescence in the turn-on mode upon interaction with phosphatidylserine. The present system thus avoids the washing steps required for "always-on"-type sensing systems.

BACKGROUND Hypophosphatemia is relatively common phenomenon in patients with massive burn injury. Therefore, we check serum phosphate level routinely and try to supply phosphate in a timely manner. The purpose of this study was to investigate the change of the serum phosphate level of early postburn period and the impact of hypophosphatemia on the prognosis of patients. METHODS A total of 227 patients with burn injury were reviewed retrospectively. We performed analysis of serum phosphate level within 20 days from burn injury. RESULTS Patients' mean (SD) age was 47.0 (14.1) years, and mean (SD) percentage of total body surface area burned were 47.7 (21.9). Severe hypophosphatemia (phosphate < 1.0 mg/dL) was observed in 35 patients (15.8%), and moderate hypophosphatemia (1.0 ≤ phosphate < 2.0 mg/dL) was found in 115 patients (50.6%). Therefore, overall incidence of hypophosphatemia was 66.4%. There was no significant difference in serum phosphate level with survival, total body surface area burned, and mechanical ventilation. Age (odds ratio [OR], 3.180; 95% confidence interval [CI], 1.025-9.871; p = 0.045), total body surface area burned (OR, 20.934; 95% CI, 6.845-64.024; p = 0.000), and mechanical ventilation (OR, 5.581; 95% CI, 2.380-13.085; p = 0.002) were independently associated with mortality. However, serum phosphate level (OR, 0.828; 95% CI, 0.275-2.495; p = 0.737) does not have a statistical significance. CONCLUSION Although multiple studies have evaluated the efficacy and safety of phosphate repletion regimens, the effect on mortality and morbidity is not well reported. However, our results show that patients with massive burn injury have high incidence of hypophosphatemia, and hypophosphatemia can result in many complications. Therefore, routine check and supply of phosphate can be suggested in patients with massive burn injury. LEVEL OF EVIDENCE Prognostic study, level II.

We observed that serum transthyretin (TTR) levels consistently remain low when patients' general conditions are poor, despite adequate nutritional support. We conducted this study to analyze the changes of serum TTR over time from injury in massively-burned patients and verify the validity of prediction by clinical outcomes, which are assessed via serum TTR in the early postburn period.From January 2005 to December 2010, the samples of serum TTR from 471 burn patients (mean % total body surface area [TBSA] burned, 51% ± 20%) were analyzed with time frames from injury retrospectively.Serum TTR significantly decreased during the period from day 5 to day 10 postinjury in both the survival group (n = 290, mean %TBSA burned, 42.9% ± 14.2%) and nonsurvival group (n = 181, mean %TBSA burned, 64.6% ± 20.8%). However, after this period, the serum TTR constantly increased in the survival group but remained low in nonsurvivors. At all time, the levels of serum TTR obtained from survivors were significantly higher than those of nonsurvivors. The serum TTR had weak correlation with the extent of the burn injury (r = -0.234). Survival rates of the patients increased significantly by the increase of the serum TTR of early postburn period. In multivariable model, age (odds ratio [OR], 1.054; 95% confidence interval [CI], 1.043-1.066; p = 0.000), TBSA burned (OR, 1.058; 95% CI, 1.051-1.066; p = 0.000), sex (OR, 0.720; 95% CI, 0.547-0.947; p = 0.019), and serum TTR during early postburn period (OR, 1.05; 95% CI, 0.873-0.972; p = 0.003) were independently associated with mortality.The serum TTR of early postburn period can be used as a prognostic markers, and low serum TTR can be used as a signal for screening out the patients at risk who need careful assessment and monitoring at an early stage.

Background: High retear rates of arthroscopic massive rotator cuff repair have been reported with relatively satisfactory functional outcomes.Purpose: To assess the clinical and radiological outcomes of an arthroscopic repair of massive rotator cuff tears using a suture bridge technique. We also aimed to explore the various factors that may affect retears.Study Design: Case-control study; Level of evidence, 3.Methods: Sixty-six patients included in the study were divided into 2 groups according to the presence of retears on magnetic resonance imaging (MRI) evaluation at a minimum of 1 year after surgery. We evaluated the visual analog scale (VAS) for pain during motions, the University of California, Los Angeles (UCLA) score, and the absolute and relative Constant scores (mean follow-up, 25.4 months).Results: Twenty-eight of the 66 patients (42.4%) in this study had a retear. At the final follow-up visit, pain VAS, UCLA score, and absolute and relative Constant scores in the completely healed group were significantly superior to those in the retear group, with 2, 29.5, 76.0, and 95.2 points and 4, 26.0, 70.6, and 87.3 points, respectively ( P < .05). From univariate analysis, the preoperative mean acromiohumeral distance, extent of retraction, and degree of fatty infiltration of the supraspinatus and infraspinatus were significantly different between the completely healed (7.83 mm, 2.97 cm, 1.74, and 0.71, respectively) and the retear group (6.36 mm, 3.97 cm, 2.54, and 2.07, respectively; P < .05). From multivariate logistic regression analysis, the preoperative degree of fatty infiltration of the infraspinatus and extent of retraction were the 2 most important factors associated with retears.Conclusion: Arthroscopic repair of massive rotator cuff tears using a suture bridge technique has a relatively high retear rate, and these structural failures appear to have a significant difference in clinical outcomes compared with the healed group. Degree of fatty infiltration of the infraspinatus and extent of retraction are the 2 most important factors associated with a retear. Orthopaedic surgeons should predict the possibility of retear before surgery and counsel patients about their expected functional results.

Background and Aims: Adefovir dipivoxil (ADV) is a nucleotide analogue that is known to be effective for lamivudine-resistant hepatitis B virus (HBV) mutants as well as wild-type HBV. The aim of this study is to assess the efficacy of ADV against lamivudine-resistant genotype C HBV mutants. Methods: Thirty-five patients with breakthrough hepatitis due to lamivudine-resistant HBV received ADV 10 mg daily with discontinuation of lamivudine. Quantitative HBV DNA, HBeAg, liver function test including alanine aminotransferase (ALT) was checked every 4–12 weeks to evaluate the efficacy of ADV. Results: ADV was administered for a median of 48 weeks (range: 24–120 weeks). The rate of serum HBV DNA loss was 68.6%, 80.0%, 84.0%, and 88.2% at weeks 12, 24, 36, and 48, respectively. The rate of serum HBeAg seroconversion was 8.3% and 14.3% at weeks 24 and 48, respectively. The rate of serum ALT normalization at week 48 was 70.6%. Within 32 weeks after stopping ADV therapy, serum HBV DNA levels increased to a median of 378.9 pg/ml in 88.9% of patients, who were treated for a median of 40 weeks. Moreover, in some patients, the ALT level increased to more than five times the upper limit of normal. Conclusions: Administration of ADV is an effective option for the treatment of patients with lamivudine-resistant genotype C HBV infection.

It has been unclear whether immediate antiviral therapy or observation under the expectation of spontaneous inactivation of hepatitis B virus (HBV), is more appropriate for the treatment of chronic hepatitis B (CHB) with acute exacerbation. We intended to analyze the short-term natural course of CHB with acute exacerbation and evaluate the efficacy of lamivudine.We analyzed 35 CHB patients with acute exacerbation (positive HBV DNA or HBeAg and ALT400 IU/L) between March 2000 and May 2003. We regularly checked serum HBV DNA, HBeAg and liver function tests including ALT every 1 to 3 months. If ALT was above 100 IU/L during the follow-up period, patients were treated with 100 mg lamivudine orally once a day. We compared the efficacy of lamivudine use between this group and the group provided with immediate lamivudine trial at their first visit.27 CHB patients with acute exacerbation were observed without immediate lamivudine trial. In 5 of these patients normal ALT, negative HBeAg and HBV DNA were maintained during 19 months (group 1a). Slightly elevated or normal ALT was maintained without HBeAg seroconversion in 3 patients (group 1b). However, serum ALT flared up above 100 IU/L in 19 patients within 5 months. So, lamivudine was tried on these patients (group 2). The serum HBV DNA was extremely low, being 6.5 pg/mL in group 1a compared to 518.1 pg/mL in group 2. Spontaneous inactivation of HBV was observed in 71.4% (5/7) of patients with HBV DNA less than 20 pg/ mL at the first visit. ALT was lower and HBV DNA was higher in group 2 than the 8 patients who received immediate lamivudine trial at the first visit (group 3). The response rate of lamivudine was similar between group 2, 56.3% (9/16) and group 3, 62.5% (5/8).Spontaneous inactivation of HBV was expected in CHB with acute exacerbation and extremely low level of HBV DNA (less than 20 pg/mL) in a short term follow-up period. Immediate lamivudine therapy might be more appropriate in most CHB patients with acute exacerbation.

Introduction The reported mortality rates range from 28% to 100% in burn patients who develop acute kidney injury (AKI) and from 50% to 100% among such patients treated with renal replacement therapy. Recently, the serum cystatin C and plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) levels have been introduced as early biomarkers for AKI; the levels of these biomarkers are known to increase 24 to 48 hours before the serum creatinine levels increase. In this study, we aimed to estimate the diagnostic utility of the cystatin C and plasma and urine NGAL levels in the early post-burn period as biomarkers for predicting AKI and mortality in patients with major burn injuries. Methods From May 2011 to July 2012, 90 consecutive patients with a burn wound area comprising ≥ 20% of the total body surface area (TBSA) were enrolled in this study. Whole blood and urine samples were obtained for measuring the serum creatinine, serum cystatin C, and urine and plasma NGAL levels at 0, 3, 6, 12, 24, and 48 hours after admission. Receiver operating characteristic curve, area under the curve, and multivariate logistic regression analyses were performed to assess the predictive values of these biomarkers for AKI and mortality. Results In the multivariate logistic regression analysis, all variables, including age, percentage TBSA burned, sex, inhalation injury, and serum creatinine levels, serum cystatin C levels, and plasma and urine NGAL levels were independently associated with AKI development. Moreover, age, sex, percentage TBSA burned, and plasma and urine NGAL levels were independently associated with mortality. However, inhalation injury and the serum creatinine and cystatin C levels were not independently associated with mortality. Conclusions Massively burned patients who maintained high plasma and urine NGAL levels until 12 hours after admission were at the risk of developing early AKI and early mortality with burn shock. However, the plasma and urine NGAL levels in the early post-burn period failed to predict late AKI and non-burn shock mortality in this study. Nevertheless, the plasma and urine NGAL levels were independently associated with AKI development and mortality within 48 hours after admission.

The expression level of the coxsackievirus and adenovirus receptor (CAR) gene in human cervical cancer cell lines (Hela, Caski, HT-3, and SiHa) appears to be correlated with their susceptibility to adenoviral vector-based gene transfer. Hela, Caski, and HT-3 cells, which express the CAR molecule on the cell surface, showed a higher susceptibility to infection of AdCMVGFP than SiHa cells with no detectable level of CAR expression. Transient expression of the CAR gene in SiHa cells dramatically enhanced the susceptibility to adenoviral infection. Furthermore, SiHa-CAR, a stable transfectant which expresses the CAR gene showed a highly increased susceptibility to adenoviral infection in contrast to SiHa. These results demonstrate that the low susceptibility of SiHa to adenoviral infection is closely related to its loss of the CAR gene expression. In addition, the low infection efficacy can be overcome by the ectopic expression of the CAR gene. These results also give insight into a possible application of the CAR gene to adenovirus-mediated gene delivery.

The aims of this study were to investigate the clinical and colonoscopic characteristics of patients with intestinal Behcet's disease and to compare the findings of typical and atypical intestinal Behcet's disease. Ninety-four patients diagnosed as having intestinal Behcet's disease were included. Of these, we considered 42 patients as having complete or incomplete type; these fulfilled the international criteria as "typical," and the other 52 patients were classified as having "atypical" intestinal Behcet's disease. Abdominal pain was the most common symptom (92%), followed by diarrhea and gastrointestinal bleeding. All of the 22 patients with a history of surgery had ulcers at the anastomotic site. Most of the patients, who had never been operated on, had lesions in the ileocecal area (96%). Sixty-three patients (67%) had a single ulcer. Many (76%) of the ulcers were larger than 1 cm, and the mean size of the ulcers was 2.9 cm. Most (99%) of the ulcers were round/oval or geographic in shape. Usually ulcers were deep (62%), and their margins discrete (80%). There was no difference in the endoscopic findings of typical and atypical intestinal Behcet's disease. Typical colonoscopic findings in intestinal Behcet's disease were single or a few deep ulcers with discrete margins in the ileocecal area or anastomotic site. Endoscopic characteristics of patients with intestinal involvement in the case of "suspect" or "possible" type of Behcet's disease that lack the systemic manifestations of Behcet's disease were in accord with those in "complete" or "incomplete" types of Behcet's disease, who fulfill the International Study Group for Behcet's Disease criteria.

The association between rectosigmoid polyps and polyps in the more proximal colon is still a matter of debate, and the need for colonoscopy in patients with rectosigmoid polyps that are detected by flexible sigmoidoscopy is controversial. The aim of this study was to determine whether or not certain characteristics of rectosigmoid polyps are associated with the presence and characteristics of proximal colonic polyps. Seven hundred and twenty-eight patients who underwent total colonoscopy between October 1995 and June 1998 and who had colorectal polyps were retrospectively analyzed. Patients with inflammatory bowel diseases, familial adenomatous polyposis, or any advanced cancer were excluded. The odds ratio (OR) and 95% confidence interval (CI) of prevalence of proximal colonic polyps according to the patients age and sex, as well as the characteristics of rectosigmoid polyps, were calculated. Advanced adenoma was defined as an adenoma larger than 10 mm or an adenoma of any size with villous component, high-grade dysplasia or invasive carcinoma. Among 728 patients with colorectal polyps, 356 patients (48.9%) had polyps only in the rectosigmoid region, 193 patients (26.5%) had polyps only in the proximal colon, and 179 patients (24.6%) had polyps in both the rectosigmoid and proximal colon. In 535 patients with rectosigmoid polyps, the prevalence of proximal colonic polyps, neoplastic polyps and advanced adenomas were 33.4%, 27.3% and 2.9%, respectively. The prevalence of proximal colonic polyps in patients with rectosigmoid polyps was found to be significantly related to the male gender and elderly patients, in addition to the neoplastic histology of the rectosigmoid polyps. However, the prevalence of the proximal colonic polyps was not related to the size, number and shape of rectosigmoid polyps. In 179 patients with both rectosigmoid and proximal colonic polyps, the characteristics of proximal colonic polyps such as size, number and shape were similar to those of rectosigmoid polyps. We recommend total colonoscopic examination in all patients with rectosigmoid adenomas, regardless of the size, number, and shape, especially in elderly males.

To compare, in terms of compliance, toxicity, quality of life (QOL) and efficacy, intravenous 5-fluorouracil plus folinic acid with oral tegafur-uracil plus folinic acid as postoperative adjuvant chemotherapy after curative resection in patients with Dukes' stage B2 and C2 colon cancer. Among all patients with adenocarcinoma of the colon operated on between July 1997 and June 1999, 122 with Dukes' stage B2 or C2 colon cancer were enrolled in this study. Fifty-three patients were treated with intravenous 5-fluorouracil plus folinic acid (5-FU group) and 69 with oral tegafur-uracil plus folinic acid (UFT group). Compliance, toxicity, QOL and efficacy were evaluated. Compared with the 5-FU group, patients in the UFT group experienced a lower incidence of grade 1 toxicity. The incidences of grade 2-4 toxicity were similar in the two treatment groups. However, severe toxicity (grade 3 or 4) was rare in both groups. A steady and significant increase of the QOL score, both during and after therapy, was evident in both groups suggesting that chemotherapy is quite tolerable and does not deteriorate the patients' QOL. At the median follow-up duration of 28 months, the survival rate and disease free survival rate for the UFT and 5-FU groups were 94.9% vs. 92.5% and 87.5% vs. 84.1%, respectively (p > 0.05). These data suggest that oral tegafur-uracil modulated with oral folinic acid as an adjuvant chemotherapy in patients with Dukes' stage B2 and C2 colon cancer may be a good alternative to infusional 5- fluorouracil.