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Filippo Mariano,1,2,&ast; Valeria Malvasio,3,4,&ast; Daniela Risso,3 Nadia Depetris,5 Anna Pensa,3,6 Giacomo Fucale,7 Fabrizio Gennari,4 Luigi Biancone,1,2 Maurizio Stella3 1Nephrology, Dialysis and Transplantation U, Department of General and Specialized Medicine, City of Science and Health, CTO Hospital, Torino, Italy; 2Department of Medical Sciences, University of Torino, Torino, Italy; 3Burn Center and Plastic Surgery, Department of General and Specialized Surgery, City of Science and Health, CTO Hospital, Torino, Italy; 4Department of Pediatric General Surgery, City of Science and Health, Regina Margherita Children’s Hospital, Torino, Italy; 5Anesthesia and Intensive Care 3, Department of Anesthesia and Intensive Care, City of Science and Health, CTO Hospital, Torino, Italy; 6Department of Surgical Sciences, University of Torino, Torino, Italy; 7Laboratory of Microbiology and Virology, City of Science and Health, Molinette Hospital, Torino, Italy&ast;These authors contributed equally to this workCorrespondence: Filippo Mariano, Nephrology, Dialysis and Transplantation U, AOU City of Science and Health, CTO Hospital, Via G. Zuretti 29, Torino, 10126, Italy, Tel +39-011-6933-674, Fax +39-011-6933-672, Email filippo.mariano@unito.itPurpose: Colistin is still a therapeutic cornerstone against multidrug-resistant gram-negative bacteria (MDRGN), mostly when other antibiotics do not gain adequate activity on these strains. In the present study, we evaluated in a cohort of burn patients the relationship between colistin therapy, survival and requirement of renal replacement therapy (CRRT).Patients and Methods: Retrospective study of 133 burn patients treated with iv colistimethate sodium (loading dose 9.0 × 106 IU, maintenance dose 4.5 × 106 IU BID) and 35 treated with other antibiotics for MDRGN infection including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae between January 2008 and December 2017. Multivariate analysis with logistic regression was used to determine the effect of the predictors such as age, total body surface area (TBSA), third-degree burn areas, Revised Baux score, Charlson comorbidity score, length of stay, colistin dose and duration of treatment, mechanical ventilation, and need of CRRT on in-hospital mortality. To investigate the relationship between colistin and renal function, we focused on survivor patients as the completion of the therapeutic course of colistin represented the basic requirement to analyze its impact on the kidney.Results: Out of 133 colistin- and 35 other antibiotics-treated patients, 83 (62.4%) and 31 (88.6%) survived, and 53 (39.8%) and 3 (9.7%) required CRRT, respectively. The severity of burns, as well as CRRT requirement and mortality, was significantly higher in colistin-treated patients than in other antibiotics-treated patients. Age and TBSA% were the significant predictors of mortality. Out of 83 colistin-treated survivors, 19 (22.9%) required CRRT (9 before and 10 after the start of colistin), and 64 (77.1%) had a normal renal function. No difference about the colistin dose and baseline characteristics, but the revised Baux score was found between the 9 patients requiring CRRT before the colistin course and the 10 patients after. Similarly, among the 64 patients not undergoing CRRT, no difference was found between the patients treated with the cumulative dose of colistin < 99.0 × 106 IU (n = 33, median daily dose of 4.0 × 106 IU) and > 99.0 × 106 IU (n = 31, median daily dose of 9.0 × 106 IU) about the baseline characteristics and the daily median plasma creatinine over 24 days of therapy.Conclusion: Colistin therapy was associated with more severe burns, mortality, and CRRT requirement. A short course therapy, at appropriate cumulative dosage, can lead to clinical success without a significant association with severe renal impairment.Keywords: colistin, burns, acute kidney injury, MDRGN infection, CRRT, clinical outcome

Abstract: Background and study aims: Among benign oesophageal lesions, caustic strictures are the most difficult to dilate. In low-income countries, children suffering caustic oesophageal injury are frequently referred to the hospitals late, sometimes weeks after ingestion. Therefore, dilatation may be performed late and in highly fibrotic strictures. Reports about endoscopic and clinical outcome of such delayed dilatations are scanty. The aim of this study was to evaluate the safety and efficacy of late caustic stricture dilatations in children, comparing it with the results of timely dilatations, both performed at the Hospital of the Italian Non-Governmental Organization “Emergency” at Goderich, Sierra Leone. Patients and methods: From December 2005 to May 2007, 78 children (<15 years) complaining alkaline caustic ingestion were submitted to oesophageal dilatation, mainly (97%) using Savary dilators. Two groups were identified: children (group 1) with a late treatment (>6 weeks, 37±12 weeks), having arrived to the hospital late after ingestion, and children (group 2) dilated timely, i.e. at <6 weeks (4±1.4 weeks) after injury. Results: Strictures were severe in all patients. Twenty-five children were dilated late after injury (6.4 dilatations/patient) with a follow-up of 11±2.5 months. A successful clinical outcome was observed in 91.6%. Four perforations (2.6% procedure-related) and one death (4.0%) were observed. Strictures recurred once in 72% of patients, twice in 31.8%. Thirty-one children were dilated timely (4.5 dilatations/patient) with a follow-up of 10±2.1 months and a clinical success rate of 96.7%. Procedure-related perforation rate was 0.7% with one death (3.2%). Stricture recurred once in 30% and twice in 3.3%. Conclusions: Delayed dilatation of caustic oesophageal strictures in children carries a higher risk of perforation and a higher recurrence rate. [Copyright &y& Elsevier]

Background: In burn patients, septic shock and acute kidney injury (AKI) with use of continuous renal replacement therapy (CRRT) severely increase morbidity and mortality. Sorbent therapies could be an adjunctive therapy to address the underlying metabolic changes in inflammatory and anti-inflammatory cytokines dysregulated production., Methods: A retrospectively observational study of 35 severe burn patients admitted to the Burn Center (Turin, Italy, from January 2017 to December 2022), who underwent CRRT for AKI-associated septic shock. Out of 35 patients, 11 were treated with CytoSorb® as adjunctive therapy to CRRT (Sorbent group) and 24 patients only with CRRT (Control group)., Results: The application of CytoSorb® took place in a very dispersed way. Out of 11 patients, 7 started the CRRT together with the sorbent application. The patients of the sorbent group exhibited a significant reduction in norepinephrine use compared to that of the control group. A clinical improvement over the first 4 days of Cytosorb® was observed in both survivors and no survivors of the sorbent group, with significant norepinephrine decreased use on day 4 compared to day 1. In-hospital mortality was 45.4% and 70.8% in the sorbent and control group, respectively, and significantly better at Kaplan-Meier survival analysis at 270 days (p = 0.0445). In both groups, all survivor patients recovered renal function at discharge, whereas no survivors did not., Conclusions: Adjunctive treatment with CytoSorb® for burn patients with AKI-CRRT and septic shock poorly responsive to standard therapy led to a significant clinical improvement, and was associated with a lower mortality rate compared to CRRT alone., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Quality indicators (QIs) are tools for improving and maintaining the standard of care. Although burn injuries are a major global health threat, requiring standardized management, there is a lack of worldwide accepted quality indicators for burn care. This study aims to identify the best burn care-specific QIs as perceived by worldwide burn practitioners., Methods: The ISBI Burn Care Committee developed a survey to analyze which burn care- specific QIs were relevant to international burn care professionals. The questionnaire was based on the three dimensions of the Donabedian model (i.e., Structure, Process, and Outcome) to evaluate the quality of care. The study was conducted from April to September 2021 and analyzed and reported following the Checklist for Reporting Results of Internet E-Surveys (CHERRIES)., Results: According to the 124 worldwide respondents, the most relevant QIs were: access to intensive care, burn surgeons, and dedicated burn care nurses (Structure category), 24-hours access to burn services, local protocols based on documented guidelines (Process category), and in-hospital mortality and incidence of severe infections (Outcome category)., Conclusions: Specific QIs related to structures, clinical processes, and outcomes are needed to monitor the treatment of burn patients globally, assess the efficiency of the provided treatment, and harmonize the worldwide standard of burn care., Competing Interests: Conflict of interests The authors confirm that they do not have conflicts of interest to disclose. Nadia Depetris, Suvashish Dash, Laura Pompermeir, Athina Lavrentieva, Alan Rogers, (Copyright © 2023 International Society of Burns Injuries. All rights reserved.)

Background: Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation., Methods: In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk., Results: A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed., Conclusions: In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.)., (Copyright © 2022 Massachusetts Medical Society.)

Background of the Study: Acute kidney injury (AKI) is a common complication in critically ill burn patients and is associated with a number of serious adverse outcomes. The clinical decision-making process related to the management of AKI in burn patients is complex and has not been sufficiently standardized. The main aim of this study was to explore the diagnostic approach and clinician's attitudes toward the management of AKI and RRT in burn patients around the world., Methods: The questionnaire was widely distributed among the members of International Society for Burn Injury (ISBI), who were invited to complete the survey. Data collection and report was compliant with the the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) Web-survey guidelines. The survey form with multiple-choice questions was divided into 3 parts: a. physician and institutional demographics, b. AKI diagnostic information, c. technical aspects of RRT., Results: A total of 44 respondents worldwide submitted valuable data in the 2-month period. Of all respondents, 43.2% were from Europe, 30% from North America, 7% from South-East Asia 2.3% from Africa and 18.2% from other regions. 93.1% of participants declare that they use specific definitions to detect AKI, while 11.4% declare the use of renal ultrasonography for AKI diagnosis. CRRT appeared to be the most preferred option by 43.2% of participants, followed by intermittent hemodialysis (25%), and prolonged intermittent RRT (6.8%). The expertise to deliver a modality and the availability of resources were considered important factors when selecting the optimal RRT modality by 20.5% and 29.6% of respondents. The use of specific serum biomarkers for AKI diagnosis are stated by 16% of respondents; 25% of specialists refer to the use of biomarkers of AKI as a criterium for discontinuing the RRT. Femoral vena and right jugular vena were the most frequently used location for RRT temporary catheter placement, 54.6% of respondents declared using ultrasound guidance for catheter placement., Conclusions: The majority of burn specialists use specific consensus classifications to detect acute kidney injury. Continuous renal replacement therapy appeared to be the most preferred option, while the expertise to deliver a particular modality and resources availability play a significant role in modality selection. The use of ultrasound and specific biomarkers for AKI evaluation is infrequent in routine clinical practice., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

Background: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28)., Methods: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume ( V T ) was defined as V T  ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma., Results: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma ( p  = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T ( p  = 0.98). All patients were ventilated with PEEP levels ≥5 cmH 2 O; 80% of patients had maximum airway pressures <30 cmH 2 O., Conclusion: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28., Trial Registration: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014., (© The Author(s) 2021. Published by Oxford University Press.)

The novel coronavirus, SARS-CO V2 responsible for COVID-19 pandemic is rapidly escalating across the globe. Burn centers gearing for the pandemic must strike a balance between contributing to the pandemic response and preserving ongoing burn care in a safe and ethical fashion. The authors of the present communication represent seven burn centers from China, Singapore, Japan, Italy, Spain, the United Kingdom (UK), and the United States (US). Each center is located at a different point along the pandemic curve and serves different patient populations within their healthcare systems. We review our experience with the virus to date, our strategic approach to burn center function under these circumstances, and lessons learned. The purpose of this communication is to share experiences that will assist with continued preparations to help burn centers advocate for optimum burn care and overcome challenges as this pandemic continues., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Background: Coupled-plasma filtration adsorption (CPFA) is a sorbent-based technology aimed at removing soluble mediators of septic shock. We present our experience on the use of CPFA in septic shock severe burn patients with acute kidney injury (AKI) needing renal replacement therapy (RRT) with the main goal to evaluate efficacy and safety of CPFA in this specific subset of septic shock patients., Methods: In this observational study, we retrospectively reviewed the medical notes of all burn patients admitted to our adult Burn Center who received CPFA, as part of the septic shock treatment requiring RRT, between January 2001 and December 2017 (CPFA group). We compared CPFA group with all the burn patients admitted to our Center in the same period of time, with the same range of relevant clinical characteristics, who developed AKI and were treated with RRT, but not CPFA (control group). We collected demographic characteristics, burn size, Sequential Organ Assessment Failure (SOFA) score, microbiological data, and patient outcome, in terms of in-hospital mortality rate and the probability of survival calculated using the revised Baux score. We also collected data regarding CPFA safety (hemorrhagic episodes, catheter associated-complications, hypersensitivity reactions) and efficiency (number and duration of CPFA sessions, plasma treated amount, plasma processed dose)., Results: 39 severe burn patients were treated with CPFA (CPFA group) (mean age 46.0 years, range 40.0-56.0 years; mean burn size 48.0% TBSA, range 35.0-60.0% TBSA), and 87 patients treated with RRT, but not CPFA, who had similar clinical characteristics (control group). Observed mortality rate was 51.3% in the CPFA group and 77.1% in the control group (p 0.004). Regarding factors affecting survival in the CPFA group, SOFA score on the 1st day of CPFA resulted significant (OR 2.016, 95% CI, 1.221-3.326; p < 0.004) in the multivariate analysis logistic model., Conclusions: CPFA treatment for burn patients with AKI-RRT and septic shock, sustained by bacterial strains non or poorly responsive to therapy, was associated with a lower mortality rate, compared to RRT alone. However, further research, such as large prospective studies, is required to clarify the role of CPFA in the treatment of burns with septic shock and AKI-RRT., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Management of pain, agitation and anxiety is crucial in critically ill patients, and has a significant impact on clinical and functional outcome. This study aims to assess current management of analgesia, sedation and delirium in adult burn ICUs, and determine if discrepancies exist between current guidelines and actual practices.An online survey was created and sent to burn specialists worldwide.A total of 40 respondents submitted valuable data. Of all respondents, 20 (50%) were from Europe, 7 (17.5%) from North America, 6 (15%) from Africa and 12 (30%) from other regions. The majority of respondents were from burn centres with more than 60 admissions per year (32 centres, 80%); 36 respondents (90%) were affiliated with a University Hospital. 92.5% reported that they routinely screen severe burn patients for pain, while 27.5% declared that no particular pain assessment tool is used. The most common analgesics were opioids, mainly administered intravenously (90%). 70% affirmed they routinely screen burn ICU patients for sedation, but 30% declared that they do not use a specific sedation scoring scale. The most commonly used sedatives were midazolam (72.5%) and propofol (55%). 70% claimed to assess burn ICU patients routinely for delirium, but 57.5% reported they did not use a specific scoring system. 62.5% stated that they prevent delirium by combining pharmacological and non-pharmacological approaches. Our results indicate that awareness regarding the systematic and correct management of pain, sedation and delirium is increasing among burn specialists. However, a substantial gap between guidelines and clinical practices exist. Efforts should be directed at creating specific burn care guidelines and enhancing the implementation of existing recommendations.

Assessment and treatment of pain, agitation and delirium are integral parts of the management of critically ill patients. The purpose of this review is to describe how pain, delirium and agitation are managed in general intensive care units and in burn units, and to address whether management of these issues is compatible with internationally accepted recommendations. A substantial gap exists between the conception of the guidelines, clinical practice and physicians' statements regarding pain, sedation and delirium management. Specific training programs might be required to increase the implementation rate of guidelines and best practices on sedation, pain and delirium assessment and management in burn units.

The magnitude of coagulation abnormalities, and the definition and treatment of coagulopathy in burn patients are inadequately understood and continue to be discussed in the literature. We aimed to analyse physicians' views on monitoring and treating coagulation abnormalities in burn patients. A total of 350 questionnaires were distributed electronically to burn ICU physicians. Participation was voluntary and anonymous. Responses were analysed electronically and comparisons were made according to the region of the ICU or the specialty of the physician. Of the 350 questionnaires distributed, 55 (15.7%) were returned. The majority of burn specialists consider sepsis-induced coagulopathy to be the most frequent coagulopathy in burn patients, and 74.5% declare that they do not use any specific definition/scoring system in their department to detect coagulopathy. The majority of specialists (70.8%) use standard coagulation tests. The most frequent indications for plasma transfusion are massive bleeding (32.8%) and Disseminated Intravascular Coagulation syndrome treatment (20%). The main specific factors reported in our study are cryoprecipitate (23.2%) and fibrinogen concentrate (18.9%). 21.1% of respondents state that they do not use any specific coagulation factor substitution in burn patients. Specific coagulation factor substitution is not a routine practice. The low response rate precludes the generalization of our results.

This study aims to determine the presence of the components of the metabolic syndrome in primary nonalcoholic steatohepatitis (NASH) and to assess the role of liver disease in the genesis of peripheral hyperinsulinemia. Nineteen patients (18 men and 1 woman; mean age, +/- SD, 38 +/- 10 years; body mass index [BMI], 26 +/- 2 kg/m(2)) with histologic evidence of NASH were enrolled; 19 age- and sex-matched normal subjects were investigated as controls. Plasma glucose, insulin, and C-peptide levels were measured during an oral glucose tolerance test, and a frequently sampled intravenous glucose tolerance test (FSIGT), analyzed by minimal modeling technique, was performed. Compared with controls, the NASH group had lower insulin sensitivity (3.84 +/- 2.44 vs. 7.48 +/- 3.01 10(-4) x min(-1)/microU/mL; P =.0003) and higher total insulin secretion (21 +/- 13 vs. 10 +/- 3 nmol/L in 240 minutes; P =.001). Hepatic insulin extraction was similar in both groups (69.8% +/- 16.1% vs. 70.2% +/- 18.3%; P =.854). According to the results of the oral glucose tolerance test, no patient was classified as diabetic, 5 were classified as glucose intolerant, and 1 was classified as having impaired fasting glycemia. Nine patients (47%) had at least the 2 minimum criteria required to define the metabolic syndrome according to the European Group for the Study of Insulin Resistance (EGIR). In conclusion, hyperinsulinemia and insulin resistance occur frequently in patients with NASH; these conditions do not stem from a reduced hepatic insulin extraction but from an enhanced pancreatic insulin secretion compensatory to reduced insulin sensitivity. The derangement of insulin regulation, often associated with the metabolic syndrome, may play a causal role in the pathogenesis of NASH.

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.