Longitudinal profile of routine biomarkers for mortality prediction using unsupervised clustering algorithm in severely burned patients: a retrospective cohort study with prospectively collected data

Purpose@#Burn injury has high clinical heterogeneity and worse prognosis in severely burned patients. Clustering algorithms using unsupervised methods to identify groups with similar trajectories in heterogeneous disease patients can provide insight into mechanisms of disease pathogenesis. This study analyzed routinely collected biomarkers to evaluate mortality prediction, find clinical meanings for these or their subtypes, and evaluate patterns. @*Methods@#This retrospective cohort study included patients aged >18 years, between July 2012 and June 2021. All eligible patients received fluid resuscitation and survived for at least 7 days. Characteristics of clinical interest to the physician at 4 clinically important time points were evaluated. @*Results@#Eligible patients were divided into 4 subgroups according to these time points: from 1st week to 4th week. Total of 1,249 patients admitted within 2 days after burns and receiving fluid resuscitation were included. Mean Harrell’s C-index of pH was the highest (0.816), followed by platelets (0.807), creatinine (0.796), red cell distribution width (RDW, 0.778), and lactate (0.759). Longitudinal profiles among biomarkers were different. @*Conclusion@#The main predictors were pH, platelets, creatinine, RDW, and lactate. Creatinine and RDW showed consistent patterns. The other markers varied according to patient condition. Thus, these markers could provide clues into underlying mechanisms and predict mortality.

Multiple Organ Failure Resulted from Chromic Acid Burn

This case is about 68-years old male patients who was exposed to hexavalent chromic acid on whole body. After the accident, he was transferred to burn center and received massive fluid resuscitation. Despite of the resuscitation, renal failure had pro -gressed and pulmonary dysfunction happened subsequently. Pulmonary dysfunction had aggravated that ECMO was required on hospital day 3, the patient had been transferred to other hospital that could manage the condition of the patient. Soon after the transfer, the patient died. We report this case because the acute chromic acid poisoning lead to multiple organ failure including renal impairment.

Postoperative Clinical Outcomes of Colonic Stent Placement as Bridge-to-surgery vs. Emergency Surgery in Left-sided Malignant Colonic Obstruction / 대한소화기암학회지

Background/Aims@#Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction. However, since its benefits are uncertain, we aimed to establish whether it has better clinical outcomes. @*Methods@#The patients with acute malignant left-sided colon obstruction enrolled from January 2009 to December 2018 in National Health Insurance Service Ilsan Hospital. The patients were enrolled to undergo colonic stenting as a bridge to elective surgery or emergency surgery. The following oncological outcomes were assessed: incidence of complete remission, disease progression, local recurrence, and systemic recurrence. @*Results@#Out of 40 patients, 33 received self-expanding metallic stent (SEMS) as a bridge-tosurgery, and 7 underwent emergency surgery. More stoma was made in case of emergency surgery with statistical significance (p < 0.001). There were no significant differences in complete remission rate in curable left-sided malignant colonic obstruction between SEMS as a bridgeto-surgery and emergency surgery. Complete remission was achieved for 3 patients (42.9%) in the non-stent group and 27 patients (81.8%) in the stent group. There was no statistically significant difference in oncologic outcomes between the two groups (p = 0.069). According to multi-variate analysis, advanced TNM stage, Adjuvant chemotherapy, and SEMS bridge-tosurgery were significantly associated with disease-free survival. Disease-free survival rate differed significantly between the two groups (p = 0.024). @*Conclusions@#SEMS as a bridge-to-surgery might be an effective strategy and reduce stoma formation in acute malignant left-sided colon obstruction.

Nutrition Therapy in Major Burns

Major burns lead to a hypermetabolic response that is more dramatic than that identified in any other disease or injury. In addition, major burns increase the metabolic demands of the body, which can lead to severe weight body loss and an increased risk of mortality. The hyper-metabolic response is accompanied by severe catabolism and a loss of lean body mass as well as by a progressive decline of host defenses that impairs the immunological response. The protective functions of an intact skin are lost, leading to an increased risk of infection and protein loss. Therefore, adequate and timely provision of nutritional support is a vital component of the care of critically ill burn patients. In addition, nutrition therapy is important in burn care from the early resuscitation phase until the end of rehabilitation. A careful assessment of the nutritional state of burn patients is also important for reducing infection, recovery time, and long-term results. The nutritional therapy in severe burns has evidence-based specificities that help improve the clinical outcomes. The thumb 25 equation (25 kcal/kg of actual body weight) can be used as an alternative method to estimate the energy requirements of patients with major burns in cases where indirect calorimetry is unavailable or not applicable.

The Clinical Investigation Study of Pancreatitis Developed in Burn Patients

PURPOSE: To find progression and prognosis of pancreatitis developed in massive burn patients through retrospective analysis. METHODS: A retrospective study was conducted on 32 patients with abnormal increase of serum lipase level among 2523 acute burn patients admitted to our burn center from January 1, 2017 to June 30, 2018. Pancreatitis in this study was defined as a serum lipase concentration level that is higher than 180 IU/L which is three times more than the normal level (less than 60 IU/L). In this study, a retrospective analysis was performed on patients with serum lipase level higher than 300 IU/L to better understand causality of burns and pancreatitis. RESULTS: 32 patients (1.27%) had serum lipase level higher than 180 IU/L among 2523 acute burn subjects. And 13 patients (0.52%) of these 32 patients had serum lipase level elevated more than 300 IU/L. The study indicated serum lipase level was increased around 7 days after the injury. It returned to normal level early as after 1 to 2 weeks and late as after 4 to 6 weeks of injury. The serum amylase level was increased as similar modality as to the serum lipase level increase. The serum bilirubin, AST, ALT, LD, and GGT were also observed to be elevated when serum lipase was more than 1000 IU/L. CONCLUSION: The pancreatitis developed in burn patients are mostly as mild symptom. It could due to the ischemic injury and can easily be treated by a temporary fasting, TPN, and Gabexate intravenous injection.

Intravenous Colistin Therapy for Multidrug-Resistant Gram-Negative Bacterial Infections in Major Burn Injuries

PURPOSE: The aim of this study was to investigate the characteristics of Acute Kidney Injury Network (AKIN)-defined nephrotoxicity in patients undergoing intravenous colistimethate sodium (CMS) therapy for major burns. METHODS: This retrospective study included burn patients who received more than 48 h of intravenous CMS between September 2009 and December 2015. Data collection was performed using the institution's electronic medical record system. Patients assigned to the developed nephrotoxic group experienced aggravation of current AKIN stage during CMS treatment; those assigned to the non-nephrotoxic group experienced no change in current or exhibited improved AKIN stage during CMS therapy. RESULTS: A total of 306 patients were included in this study. All patients were grouped according to AKIN stage: AKIN 0 (n=152); AKIN 1 (n=6); AKIN 2 (n=9); AKIN 3 (n=139). The baseline creatinine (Cr) level was 0.73 mg/dL. The incidence of nephrotoxicity was 50.3% according to AKIN stage; overall mortality was 45.8%. The non-nephrotoxic group consisted of 127 (74.7%) patients and 43 (25.3%) were in the developed nephrotoxic group. In patients requiring continuous renal replacement therapy (CRRT), baseline Cr level was 0.83 mg/dL, pre-CMS Cr level was 1.17 mg/dL, and post-CMS Cr level was 1.34 mg/dL. CONCLUSION: CMS can be administered without signs of nephrotoxicity for a certain period (approximately 1 week), it can be used relatively safely for 2 weeks. Application of CMS is a reasonable option for treating infections caused by multi-drug resistant gram-negative bacteria in patients with major burns. The caution should be exercised nevertheless.

The Clinical Investigation of Necrotizing Fasciitis in Burn Center

Pulmonary Extraintestinal Manifestation of Crohn's Disease Treated Successfully with Adalimumab / 대한소화기학회지

Pulmonary extraintestinal manifestation is rare in Crohn's disease and has been reported in only a few cases. Despite the presence of pulmonary abnormalities in a significant proportion of patients with inflammatory bowel disease, there are only few case reports, due to complicated diagnosis and low recognition by clinicians. Currently, treatment guidelines for pulmonary Crohn's disease have not been established. There are some case reports of pulmonary Crohn's disease that achieved remission after infliximab treatment. Clinical and radiological remission of pulmonary extraintestinal involvement in Crohn's disease after adalimumab therapy has not been reported yet. Here, we report one case of lung involvement of Crohn's disease, which shows radiological and clinical remission after adalimumab treatment.

Survival Time Analysis of Severly Burned Patients

PURPOSE: The authors analyzed the survival time of severely burned patients who died and reviewed the time of the death after the burn injury. We aimed to determine any relation to the survival time with most important prognostic factors of the surface area burned and the age. METHODS: Statistical analysis was performed on 275 severely burned victims who died at our burn center of Hangang Sacred Heart Hospital from January 1, 2010 to December 31, 2015 for 6 years. RESULTS: 1. The mean age was 50.12±18.2 years and the average burn size was 61.0±27.1% of total body surface area. 2. Most of the patients (90%) died within 45 days, and 80% died within 30 days. 40% of the patients died within 10 days after burn injury, 20% of the patients died between 10 to 20 days after burn injury, 20% of the patients died between 20 to 30 days after burn injury and the rapid decrease in the number of death was observed after 30 days of burn injury time. 3. The shorter survival time (x-axis) time was observed in the patients with larger area of the burned size (y-axis) and the longer survival time was observed with smaller area of the burned size. The negative correlation was shown as figure 1. 4. There was no correlation shown between the age and the survival time of burn victims after burn injury. CONCLUSION: The mortality rate was significantly decreased at 30 to 40 days after burn injury. Therefore, the burn surgeons need more carefully and diversely plan and perform for the initial treatments since the initial surgical procedures determine the survival of severely burned patients.

Real World Experience of Telbivudine Versus Entecavir in Patients with Chronic Hepatitis B, Including Long-Term Outcomes after Treatment Modification

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)-naïve 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.

Clinical Effectiveness of a Newly Developed Collagen Substitute (InsureGraf®)

PURPOSE: Aim of this study was to assess effects of InsureGraf® (SK-Bioland Co., Korea), an artificial dermis developed by using tissue engineering technology in severe burn patients. METHODS: To examine the clinical effectiveness of InsureGraf®, we transplanted them in patients with severe burns. A total of 14 joint regions in 8 patients received InsureGraf® graft selectively from July to December, 2014. The graft results were determined after confirming the take rate of the transplanted skin graft on top of the InsureGraf®. Take rates were examined twice, at 7 and 14 days after grafting. Photographs of the skin grafts were evaluated individually by two burn surgeon specialists, and the mean values were recorded. RESULTS: The take rate was 99% after day 7 and 100% after day 14 respectively. CONCLUSION: InsureGraf® can be used successfully as an artificial dermis that allows one-stage operation in severe burn patients, exhibiting a successful early-stage graft take rate that is close to 100%.

Entecavir to Telbivudine Switch Therapy in Entecavir-Treated Patients with Undetectable Hepatitis B Viral DNA

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.

Usefulness of Negative Pressure Wound Therapy (NPWT) in Burn Center

PURPOSE: Negative pressure wound therapy (NPWT) is an adjunct therapy using negative pressure to remove fluid from open wounds through a sealed dressing and a specialized tubing that is connected to a collection container. NPWT is suitable for acute and chronic wound condition because it was designed to accelerate granulation formation on deep wound. Therefore, we performed this study to assess the effectiveness of NPWT for various wound condition in burn center. METHODS: We enrolled 17 patients who were treated with NPWT from January 2014 to April 2016. We analyzed the characteristics and outcomes of the patients through retrospectively. RESULTS: Among 17 patients, there were 13 patients for contact burn, 2 patients for electrical injury, 1 patient for diabetic foot ulcer and 1 patient for Flame burn. Most of the contact burn victims were injured by the exposure of relatively low temperature for a long time and some of them were injured under the condition of sensory deterioration including spinal cord injury, diabetes or sedatives. Wound coverage was accomplished by split thickness skin graft (STSG) in 12 patients. Local flap was done in 1 patient. STSG with local flap was done in 3 patients. And there were 1 patient who got a conservative management. The duration of NPWT application was from 8 days to 101 days (average 36.2 days). CONCLUSION: NPWT showed good clinical outcomes under various wound condition. Therefore, we think that it can be a new treatment paradigm for difficult wound management in burn center.

Evaluation of diagnostic biomarkers for acute kidney injury in major burn patients

PURPOSE: Acute kidney injury (AKI) in major burn patients is a common complication with high morbidity and mortality. The mainstream treatment is early diagnosis and rapid termination and prevention of the underlying insult. Therefore, it's essential to identify early biomarkers predicting AKI. METHODS: A total of 85 patients who were admitted to the burn intensive care unit from June 2012 to July 2013 were included in this prospective cohort study. Ten biomarkers (blood urea nitrogen, serum creatinine, urine creatinine, cystatin C, cystatin C glomerular filtration rate, AST, lacate dehydrogenase [LD], creatine kinase, lactic acid, and myoglobin) were obtained at time of admission and evaluated as diagnostic biomarkers to predicting AKI and early AKI. RESULTS: Out of 85 patients, 35 patients were dead and overall mortality was 41.2%. The mean age was 49.4 years and mean percentage of total body surface area was 53.2%. Area under the curve (AUC) of receiver operating characteristic curve of biomarkers on predicting AKI were 0.746, 0.718, and 0.717 in LD, lactic acid, and serum creatinine, respectively. AUC of cystatin C predicting AKI was much lower at 0.555. AUC of biomarkers on predicting early AKI were 0.833, 0.816, 0.790, and 0.759 in LD, serum creatinine, AST, and serum myoglobin. CONCLUSION: LD, lactic acid and serum creatinine were acceptable as diagnostic biomarkers of AKI and LD, serum creatinine, AST, and serum myoglobin were reasonable as diagnostic biomarkers of early AKI. However, cystatin C was an unfavorable biomarker in major burn patients.

Nutrition Therapy in Major Burns

Major burns lead to a hypermetabolic response that is more dramatic than that observed in any other disease or injury. In addition, major burns increase the metabolic demands of the body and can lead to severe loss of body weight and increased risk of mortality. The hyper-metabolic response is accompanied by severe catabolism and a loss of lean body mass and by a progressive decline of host defenses, which results in impairment of the immunological response. The protective functions of intact skin are lost, leading to increased risk of infection and protein loss. Therefore, adequate and timely provision of nutritional support is an essential component of care of the critically ill burn patient. Nutrition therapy is also important in burn care from the early resuscitation phase until the end of rehabilitation. Careful assessment of the nutritional state of the burn patient is also important to reducing infection, recovery time, and long-term results. Nutritional therapy in severe burns has evidence-based specificities that contribute to improve clinical outcomes.

Nutrition therapy for burn patients

Severe burns evoke a substantial metabolic response causing physiological derangement leading to a hyper-metabolic state. The hyper-metabolic response is accompanied by severe catabolism and a loss of lean body mass and also by a progressive decline of host defenses that impairs the immunological response. The protective functions of an intact skin are lost, leading to increased risk of infection and protein loss. Therefore, nutritional therapy is a cornerstone of burn care from the early resuscitation phase to the end of rehabilitation. Careful assessment of the nutritional state of the burn patient is also important to reduce infection and recovery time, and improve long-term outcomes. Evidence-based research has shown that nutritional therapy contributes to improved clinical outcomes.

Effect of Plant Extracts Contained Dressing Material Which Is Rich in Procyanidins for Treatment of Deep Second Degree Burn

PURPOSE: This study was planned to evaluate the effect of plant extracts contained dressing material which is rich in procyanidins for treatment of deep second degree burn. METHODS: This study conducted from September 1, 2013 to February 28, 2014. Patients with the deep dermal burn wound which is larger than 200 cm2 were enrolled in this study. The test material was applied total 3 times every 2 days when the wounds were relatively clean, with thin eschar and scab removed and the dermal layer exposed. The test and control sites were treated with hydro-foam equally. The effectiveness was evaluated by comparing the re-epithelialization rates between the test and control sites. Two burn surgeons blindly evaluated for re-epithelialization. Evaluation of adverse reaction was also performed during study period. RESULTS: Total of 40 patients were enrolled. Mean total body surface area burned% was 12.3+/-5.5% and the test material was first applied at mean post burn day # 7.2+/-2.0.The re-epithelialization period was 9.0+/-1.7 days in the test site and 11.1+/-2.0 days in the control site. In the test site, re-epithelialization was 2.1+/-1.0 days faster than in the control site (P<0.0001). There was no significant adverse reaction during study period. CONCLUSION: The plant extracts contained dressing material which is rich in procyanidins accelerates wound healing time and shows the safety.

Effectiveness of Early Enteral Feeding in Major Burn Patient

PURPOSE: Early enteral feeding is recommended in cases of critical illness. However, it is unclear whether this recommendation is of most benefit to extremely ill patients. From our experiences, our authors believed that early enteral nutrition can lead to better prognosis of ICU patients. We aim to clarify the efficacy of early enteral feeding. METHODS: Eighty six critically ill patients were enrolled and grouped as "Early enteral feeding (EF)" and "Delayed enteral feeding (DF)" for this cross-sectional, prospective randomized observational study. To reduce the selection bias, we compare our groups to 20~39% (group A) TBSA (total body surface area, and 40~59% (group B) TBSA burned. BMI (body mass index), length of ICU stay, length of hospital stay, hospital mortality, serum prealbumin, serum transfferin and lymphocyte count data were collected over 28 days. RESULTS: There were no statistical differences in measured outcomes between early and late feeding groups. In serologic test; prealbumin, transferrin and lymphocyte, there is also no statistical difference except 2nd, 4th week of lymphocyte. EF group has higher lymphocyte than DF group. In the group A, however, prealbumin and transferrin was high in EF group during the whole 4 weeks of study. Comparing the ICU stay and hospital mortality, there was also no statistical significance. CONCLUSION: In this study, there is no significant association between hospital outcomes and timing of enteral feeding initiation. More active trials and many-sided studies will be needed to maximize the effect of early enteral nutritional support as a method to improve treatment for major burned patients.

The Effects of Early Tracheostomy in Flame Burned Patients with Inhalation Injury

PURPOSE: We designed our study to find optimal timing for tracheostomy, and to determine the effects of early tracheostomy on clinical courses in flame burned patients with inhalation injury. METHODS: A retrospective chart review was completed for adult patients admitted to Hangang Sacred Heart Hospital Burn Center, Hallym University Medical Center, Seoul, Korea, between March 1, 2004 and February 28, 2009, who were diagnosed with flame burn with inhalation injury and who underwent tracheostomy during their hospitalization. One hundred eighteen patients were enrolled in this study. Patients were assigned to one of three groups based on the timing of tracheostomy: postburn days (PBD) 0 to 7 [Early tracheostomy (ET) group], 8 to 12 [Intermediate tracheostomy (IT) group], and greater than 13 [Late tracheostomy (LT) group]. We compared incidence of pneumonia, duration on mechanical ventilation, length of stay in intensive care unit (ICU LOS), and survival between groups. To assess the effect of tracheostomy on pulmonary function, we analyzed changes of PaO2/Fio2 (P/F) ratio. RESULTS: There were 46 patients in the ET group, 47 in the IT group and 25 in the LT group. Tracheostomy day (PBD) was 5.2+/-1.7 in ET group, 10.0+/-1.5 in IT group, and 14.8+/-1.9 in LT group (P<0.01). Statistics did not show the correlation between the timing of the tracheostomy and the incidence of pneumonia. Also mortality rate in each group showed no significant differences. There were significant differences between groups for duration on mechanical ventilation and ICU LOS (P<0.01). P/F ratio correlated with time flow showed no significant differences (P=0.10). Also there were no differences between groups in changes of P/F ratio (P=0.08). CONCLUSION: In flame burned patients with inhalation injury who require prolonged mechanical ventilation, performing tracheostomy within PBD 7 may shorten the duration on mechanical ventilation and length of stay in intensive care unit.

Clinical Benefit of Cryoderm in Full Thickness Burns

PURPOSE: CryoDerm (CGbio) is derived donated human skin. After removing epidermis and fibroblast of dermal layer, it preserved with cryo-preservation technique using control rate freezer system. To prevent post burn joint contracture in massive burns, we have used CryoDerm in acute stage. METHODS: From January of 2010 to July of 2012, 50 patients who undergone CryoDerm graft with split thickness skin graft were reviewed. The operative method was as follows: 1) Early wound excision and or cadaveric allograft skin coverage was performed within 5 days after burn injury 2) 2~3 weeks after wound excision, split thickness skin graft was performed with CryoDerm graft. Then graft take rate was investigated by inspection. Follow up duration was 3~32 months. RESULTS: Mean age of patients was 42.2 (2~70) years. Mean percentage of total body surface area burned was 27.22% (1~61%). Among 50 patients, 98 joints was operated including 14 hands, 4 wrists, 10 shoulders, 23 elbows, 4 necks, 3 hip joints, 31 knee joints and 9 ankles and feet. Total used graft size of Cryoderm was 10,945 cm2. Average take rate was near 100%. CONCLUSION: Cryoderm graft with split thickness skin graft can be used as a safe and effective operative method for one stage operation in acutely burned patients.