Clearance of NT-proBNP and Procalcitonin during Continuous Venovenous Hemodialysis with the Medium Cutoff Filter in Patients with Rhabdomyolysis-Associated Early Acute Kidney Injury.

INTRODUCTION: In polytrauma patients with AKI continuous venovenous hemodialysis (CVVHD) with medium cutoff membrane filters is commonly adopted to increase the removal of both myoglobin and inflammatory mediators, but its impact on increasing molecular weight markers of inflammation and cardiac damage is debated. METHODS: Twelve critically ill patients with rhabdomyolysis (4 burns and 8 polytrauma patients) and early AKI requiring CVVHD with EMIc2 filter were tested for 72 h on serum and effluent levels for NT-proBNP, procalcitonin (PCT), myoglobin, C-reactive protein (CRP), alpha1-glycoprotein, albumin, and total protein. RESULTS: The sieving coefficients (SCs) for proBNP and myoglobin were as higher as 0.5 at the start, decreased to 0.3 at the 2nd h, and then slowly declined to the final value of 0.25 and 0.20 at the 72nd h, respectively. PCT showed a negligible SC at the 1st h, a peak of 0.4 at the 12th h, and a final value of 0.3. SCs for albumin, alpha1-glycoprotein, and total protein were negligible. A similar trend was observed for the clearances (17-25 mL/min for proBNP and myoglobin; 12 mL/for PCT; <2 mL/min for albumin, alpha1-glycoprotein, and total protein). No correlation was found between systemic determinations and filter clearances of proBNP, PCT, and myoglobin. Net fluid loss/hour during CVVHD positively correlated with systemic myoglobin for all patients and NT-proBNP in the burn patients. CONCLUSION: CVVHD with EMiC2 filter showed low clearances for NT-proBNP and procalcitonin. CVVHD did not significantly affect the serum levels of these biomarkers, which could be adopted in the clinical management of early CVVHD patients.

The relationship between alexithymia, sensory phenotype and neurophysiological parameters in patients with chronic upper limb neuropathy.

In this study, we investigated the relationship between sensory abnormalities evaluated by quantitative sensory testing (QST) and alexithymia, depression and anxiety in patients with neuropathic pain involving the upper limbs. We enrolled 62 patients (34 with carpal tunnel syndrome, 7 with brachial plexopathy, 3 with cervical painful radiculopathy, 5 with ulnar entrapment neuropathy at elbow and 13 with post-burn hypertrophic scars) and 48 healthy controls. All underwent nerve conduction studies (NCS), evaluation of cold, heat pain and vibration detection threshold (VDT) by QST and evaluation of alexithymia by Toronto Alexithymia Scale (TAS-20), depression by Beck Depression Inventory II (BDI-II), anxiety by State-Trait Anxiety Inventory (STAI-Y), level of psychological distress by 12-item General Health Questionnaire (GHQ-12) and perceived social support by the Multidimensional Scale of Perceived Social Support (MSPSS). The general linear model analysis revealed a significant relationship between TAS-20 overall and TAS-20 sub-score for difficulty identifying feelings and VDT z-scores in the left index with no interaction by year of education and sensory NCS results. Our results demonstrated the association between impairment of vibratory sensation of the left hand, reflecting cutaneous mechanoceptor dysfunction, and alexithymia, particularly the difficulty to identify feelings. The importance of delivering to patients with neuropathic pain personalized care that takes into account not only the neurophysiological aspects but also the aspects of mental functioning is discussed.

Long-term follow-up of negative pressure wound therapy with instillation: a limb salvage procedure?

Negative pressure wound therapy (NPWT) is a treatment to reduce oedema, stimulate granulation tissue formation, remove wound exudate and diminish wound area, thus preparing it for secondary healing, skin grafting or coverage with flaps. The association of instillation to NPWT (NPWTi) is a new method for treating severe wounds, in particular, limb lesions at high risk for amputation. This therapy helps to deliver instillation fluid automatically into the contaminated wound, before application of negative pressure. These steps, repeated cyclically, help to remove infectious material, leading to a better moist environment, a necessary condition for wound healing. We report our experience of treating three patients with complex wounds and associated noble structure exposition conservatively with NPWTi and flap coverage. In a long-term follow-up (5 years), we were able to achieve a stable surgery reconstruction on preserved limbs, without evidence of chronic infection and other sequelae or complications. Despite the fact that our experience is limited , as it is based on only a few cases, it suggests how NPWTi could be considered useful in a conservative approach to the treatment of acute complex wounds of the lower extremities. In these patients with high risk of amputation, a long-term follow-up becomes fundamental in order to evaluate wound bed status after NPTWi.

Citrate pharmacokinetics at high levels of circuit citratemia during coupled plasma filtration adsorption.

BACKGROUND: The heparin requirement for coupled plasma filtration adsorption (CPFA) is usually high. Heparin administration often cannot be adherent to prescription, leading to a premature clotting of circuit and an insufficient volume of treated plasma. Regional citrate anticoagulation (RCA) could be an attractive alternative; however, no data are available on citrate pharmacokinetics at high levels of circuit citratemia. METHODS: Fifteen septic shock patients with acute kidney injury undergoing CPFA with RCA at target circuit citratemia of 6 mmol/L were treated with CPFA-haemofiltration in pure predilution (CPFA-HF predilution group, n = 5 patients), or predilution haemodiafiltration (CPFA-HDF predilution group, n = 5 patients) or pre- and postdilution haemofiltration (CPFA-HF pre/postdilution group, n = 5 patients). Citrate pharmacokinetics was carried out through its determination in systemic and circuit blood, and effluent at time 0, 0.2, 1, 3, 6 and 9 h. RESULTS: The systemic concentrations of citrate in the CPFA-HF predilution group significantly increased over the sessions (from basal level of 0.21 to 0.76 mmol/L at 3 h), whereas they did not change in CPFA-HDF predilution and CPFA-HF pre/postdilution groups. Circuit plasma citrate concentrations (from 3 to 8 mmol/L) correlated strongly with circuit iCa++ levels (Spearman R = -0.7022, P < 0.01). Sieving coefficients of citrate were near the unit in all three groups and unrelated to blood and infusion flow rates in predilution. However, the amount of citrate removed by effluent was ∼40% for the CPFA-HF predilution group and reached 60% for both the CPFA-HDF predilution and CPFA-HF pre/postdilution groups (P < 0.05). As for the efficiency of plasmafiltration, the plasmafiltrate volume (from 17 to 20 mL/kg/day) was not significantly different among the groups. CONCLUSIONS: These results demonstrated that in refractory septic shock patients on CPFA at circuit citratemia of 6 mmol/L both HDF predilution and HF pre/postdilution were the best dialysis modalities to maintain a normal systemic citratemia through a high rate of citrate loss in the effluent.

Negative pressure surgical management after pathological scar surgical excision: a first report.

Wound dehiscence is a surgical complication caused by the application of opposing and distracting forces tending to pull apart the suture line. In recent years, a novel negative pressure surgical management system has been developed to prevent surgical wound complications. This system creates a closed environment that removes exudates and other potentially infectious material, protects the surgical site from external contamination, provides support in holding the edges of the incision together and promotes wound healing. In this study, we describe our first experience with Prevena™, a closed incision negative pressure management system used on suture line following wide pathological scars excision for the prevention of postoperative wound dehiscence. Eight patients with wide and mature pathological skin scars were treated with Prevena™. The device was positioned directly after surgical correction for 8 days with a continuous application of -125 mmHg negative pressure. All treated patients had no postoperative surgical wound dehiscence. In one case, a limit of the device was represented by its poor adherence on hairy surface, hampering the maintenance of an appropriate local negative pressure. In another case, suture line was longer than Prevena™ foam and it was covered partially. Prevena™ system appears to be safe, easy to use and may represent a support technique to wide pathological skin scars surgical correction.

Determination by LC-MS/MS of colistins A and B in plasma and ultrafiltrate from critically ill patients undergoing continuous venovenous hemodiafiltration.

BACKGROUND: Colistin is a 50-year-old antibiotic, the use of which was ceased in the 70s and recently resumed as a "salvage therapy" against multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii. The narrow therapeutic range of colistin makes the choice of its correct dosage crucial, and monitoring of blood concentration is occasionally necessary for critically ill patients, including intensive care patients subjected to continuous renal replacement therapy. METHODS: Two LC-MS/MS methods were developed and fully validated for the quantitative determination of colistins A and B in plasma and dialysis ultrafiltrate (UF) samples, ultimately arising from 4 patients undergoing continuous venovenous hemodiafiltration (CVVHDF). RESULTS: The developed methods proved to be both specific and selective. They showed good fit and linearity over the entire range of interest. Trueness and accuracy proved satisfactory. Both methods have excellent intraassay precision (percent coefficient of variations were lower than 10%) and limit of detection values in the range 20-100 ng/mL, about 1-2 orders of magnitude below the concentrations commonly detected in real samples. The mean sieving coefficient (SC) values, measured after 10 minutes of CVVHDF, were 0.42 for colistin A and 0.48 for colistin B. SC values proved to be quite stable for 24 hours, but then declined to 0.24 for colistin A and 0.32 for colistin B, respectively, after 48 hours. At the median blood flow and effluent flow rate of 120 and 28 mL/min, clearance values for colistin B were higher than 15 mL/min. During the entire duration of CVVHDF sessions, the SC and clearance values for colistin A were significantly lower than colistin B. CONCLUSIONS: Two simple methods for the simultaneous determination of colistins A and B have been developed and validated. Their application in the clinical setting demonstrates that CVVHDF treatment lasting 48 hours produces a relatively constant and efficient removal of the drug.

SJS/TEN overlap associated with lomefloxacin: case report and molecular typing studies.

BACKGROUND: Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) may develop in susceptible patients after administration of different drugs. Only mild cutaneous reactions have been related to lomefloxacin. A correlation between human leucocyte antigen (HLA) and cutaneous adverse reaction has been identified. CASE REPORT: Twenty-four hours after intake of lomefloxacin, a 30-year-old Caucasian woman developed a severe skin reaction with symptoms suggesting SJS/TEN. The fast onset reaction worsened with skin blisters and 20% body surface area skin detachment within 48 h. Burn unit admittance was required; corticosteroids and human immunoglobulins were administered. Complete recovery occurred within 3 months, except for epidermal discoloration. Molecular studies showed a peculiar profile characterized by HLA class I genotype rich of ligands for natural killer cell immunoglobulin-like receptors (KIR) and HLA class II haplotype, HLA-DRB1*03:01,DQB1*02:01, prone to autoimmunity. CONCLUSION: While the HLA profile approaches our case to other well-documented drug-induced SJS/TEN, KIR involvement still remains puzzling.

Predicting severity of pathological scarring due to burn injuries: a clinical decision making tool using Bayesian networks.

It is important for clinicians to understand which are the clinical signs, the patient characteristics and the procedures that are related with the occurrence of hypertrophic burn scars in order to carry out a possible prognostic assessment. Providing clinicians with an easy-to- use tool for predicting the risk of pathological scars. A total of 703 patients with 2440 anatomical burn sites who were admitted to the Department of Plastic and Reconstructive Surgery, Burn Center of the Traumatological Hospital in Torino between January 1994 and May 2006 were included in the analysis. A Bayesian network (BN) model was implemented. The probability of developing a hypertrophic scar was evaluated on a number of scenarios. The error rate of the BN model was assessed internally and it was equal to 24·83%. While classical statistical method as logistic models can infer only which variables are related to the final outcome, the BN approach displays a set of relationships between the final outcome (scar type) and the explanatory covariates (patient's age and gender, burn surface area, full-thickness burn surface area, burn anatomical area and wound-healing time; burn treatment options such as advanced dressings, type of surgical approach, number of surgical procedures, type of skin graft, excision and coverage timing). A web-based interface to handle the BN model was developed on the website www.pubchild.org (burns header). Clinicians who registered at the website could submit their data in order to get from the BN model the predicted probability of observing a pathological scar type.

CytoSorb® in burn patients with septic shock and Acute Kidney Injury on Continuous Kidney Replacement Therapy is associated with improved clinical outcome and survival.

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.

Neuropathic pain in post-burn hypertrophic scars: a psychophysical and neurophysiological study.

INTRODUCTION: Pain complicates hypertrophic post-burn pathologic scars (PPS) METHODS: To investigate the possible neuropathic origin of pain, 13 patients with painful PPS involving at least 1 hand underwent clinical examination, including the Douleur Neuropathique en 4 questions (DN4) questionnaire; median, ulnar, and radial nerve conduction studies (NCS); cold- (CDT) and heat-induced pain threshold evaluation by quantitative sensory testing; and cutaneous silent period (CSP) testing of the abductor pollicis brevis. Controls included 9 patients with non-painful PPS, 52 healthy subjects, and 28 patients with carpal tunnel syndrome (CTS). RESULTS: All patients with painful PPS had possible neuropathic pain (DN4 score ≥4). NCS signs of CTS were similarly present in PPS subjects with or without pain. Hands with painful PPS had lower CDT and CSP duration, more frequent cold- and heat-pain hypesthesia, and more thermal allodynia than controls. CONCLUSIONS: In PPS, possible neuropathic pain is associated with psychophysical and neurophysiological abnormalities suggestive of small-fiber damage.

In vitro CMV-infection model in fresh and glycerolized skin graft.

Viral infections, especially cytomegalovirus (CMV), are a cause of death in burned patients. Aim of this study was to perform an in vitro CMV-infection model comparing fresh and glycerol-treated fibroblasts and keratinocytes. Cells were plated in plates for the two conditions. Each plate was set up with CMV dilutions. Immunofluorescence and real time PCR assays were performed. The assays were negative in both fresh and glycerolized keratinocytes. For fibroblasts, CMV-DNA was positive in both conditions and immunofluorescence test only in fresh cells. Glycerol at 85% confirms its strong virucidal effect as reported also for other viruses.

Colistin Therapy, Survival and Renal Replacement Therapy in Burn Patients: A 10-Year Single-Center Cohort Study.

Purpose: 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.

Blood and ultrafiltrate dosage of citrate as a useful and routine tool during continuous venovenous haemodiafiltration in septic shock patients.

BACKGROUND: Citrate anticoagulation is gaining popularity in renal replacement therapies (RRT) for critically ill patients. In order to study whether citrate accumulates in septic shock patients, we determined citrate in plasma and dialysate during continuous venovenous haemodiafiltration (CVVHDF). METHODS: An automated routine determination of citrate was set up using a commercial kit (citrate lyase method). Twelve patients with septic shock on CVVHDF and citrate anticoagulation were studied ex vivo for citrate levels in systemic and circuit blood and in the ultrafiltrate (at 0, 0.5, 1, 3, 6, 9, 12, 24, 48 and 72 h). RESULTS: In vitro blood studies showed a near unit correlation between the plasma measured and predicted citrate concentrations for an exclusive extracellular distribution of citrate. Median systemic arterial citratemias were 0.09 (0.06-0.12) mmol/L (Time 0) and 0.23 (0.18-0.31) mmol/L during treatment; median sieving coefficient for citrate was 0.95 (0.88-1.02) and did not change with different volumes of CVVHDF effluent (from 1350 to 5100 mL/h). Net citrate and calcium removal by filter significantly correlated with effluent volume (r = 0.85 and 0.78, respectively). Median citrate load entering in the patients' bloodstream was 13.60 (9.1-19.6, n = 68) mmol/h. Although cost analysis of the citrate test demonstrated a minimally increased daily cost (from 2.96 to 3.51€), saving costs could be potentially relevant with more extended use of citrate anticoagulation. CONCLUSIONS: In septic shock patients with liver dysfunction citratemia is useful in guiding clinical application of RRT, where the citrate losses in the ultrafiltrate can be efficiently modulated by increasing the effluent volume.

Enhanced Antimicrobial and Antibiofilm Effect of New Colistin-Loaded Human Albumin Nanoparticles.

Multidrug-resistant (MDR) Gram-negative bacteria (GNB), such as Acinetobacter and Klebsiella, are responsible for severe hospital-acquired infections. Colistin, despite its toxicity and low tissue penetration, is considered the last resort antibiotic against these microorganisms. Of concern, the use of Colistin has recently been compromised by the emergence of Colistin resistance. Herein, we developed a new formulation consisting of multifunctional chitosan-coated human albumin nanoparticles for the delivery of Colistin (Col/haNPs). Col/haNPs were in vitro characterized for encapsulation efficiency, drug release, stability and cytotoxicity and were evaluated for antibacterial activity against MDR GNB (Acinetobacter baumannii and Klebsiella pneumoniae). Col/haNPs showed sizes lower than 200 nm, high encapsulation efficiency (98.65%) and prolonged in vitro release of Colistin. The safety of the nanoformulation was demonstrated by a negligible cytotoxicity on human fibroblasts and hemolytic activity. Col/haNPs evidenced a high antibacterial effect with a significant decrease in MIC values compared to free Colistin, in particular against Col-resistant strains with a pronounced decline of bacterial growth over time. Moreover, Col/haNPs exhibited an inhibitory effect on biofilm formation that was 4 and 60 fold higher compared to free Colistin, respectively for Colistin susceptible and resistant A. baumannii. Our findings suggest that Col/haNPs could represent a promising Colistin nanocarrier with high antimicrobial activity on MDR GNB.

Epidemiology, prevalence and risk factors for infections in burn patients: results from a regional burn centre's analysis.

Burn patients are at high risk of infections due to severe impairment of immunity and loss of skin barrier function. We aimed to describe the epidemiology, incidence and risk factors for infection in a cohort of burns patients. Two hundred patients were retrospectively enrolled and subdivided into infected (N = 81) and uninfected groups (N = 119). The cumulative prevalence of infections was 27% on day 7 and 43.8% on day 28. Skin and soft tissue infections (32%) were the most frequent. Carbapenem-resistant Acinetobacter baumannii (28%), Pseudomonas aeruginosa (26%) and methicillin-resistant Staphylococcus aureus (25%) infections were most prevalent. An indwelling central venous catheter (CVC; sub-hazard ratio [SHR] 7.41, 95% confidence interval [CI] 3.78-14.62) and revised Baux score (RBS; SHR 2.08, 95% CI 0.98-4.42) were associated with higher incremental infection rate while surgical treatment resulted in a protective factor (SHR 0.45, 95% CI 0.29-0.75). RBS may be useful to stratify the infection risk: a strict collaboration between surgeons and infectious disease specialists is needed to implement source control and antimicrobial surveillance.

Observed concentrations of amikacin and gentamycin in the setting of burn patients with gram-negative bacterial infections: Preliminary data from a prospective study.

AIM OF THE STUDY: Critically ill populations often have shown subtherapeutic aminoglycosides' concentrations mostly because of unavoidable changes in drug volume distribution and clearance. We present a real life prospective study evaluating plasma concentrations for once-daily dosing for amikacin and gentamycin among a population of severe burn adults. METHODS: We conducted a real life prospective study on the plasma observed concentrations of amikacin and gentamycin among severe burn patients, using aminoglycoside as combination therapy. Antibiotics were prescribed at the standard doses of 15-20mg/kg/day for amikacin and 3-5mg/kg/day for gentamycin. RESULTS: Eight patients (4 in amikacin and 4 in gentamycin groups, respectively) were enrolled in the study. All subjects were admitted for severe burns. The most common site of infection was bloodstream (5; 62.5%) and pneumonia (4; 50%). Pseudomonas aeruginosa, followed by Klebsiella pneumoniae and multi-drug resistant Acinetobacter baumannii were the most prevalent agents isolated. Amikacin and gentamycin never achieved the target peak concentration of 60mg/L and 30mg/L: in our study Cmax, for amikacin, was 33.1±15.6mg/L (SD), while for gentamycin was 14.3mg/L±9. Cmax and total body surface area have shown a strong negative correlation with borderline statistical significance (amikacin: ρ=0.922, P=0.078; gentamycin: ρ=0.937, P=0.063). At the standard dosage, the pharmacokinetic/pharmacodynamic (PK/PD) target of Cmax>8×highest MIC was reached for 8 (53.3%) out of 15 isolated pathogens. CONCLUSIONS: The present study found that, in a population of septic burn patients, standard doses of gentamycin and amikacin most often lead to plasma concentrations under the PK/PD target.

Long-Term Preservation of Renal Function in Septic Shock Burn Patients Requiring Renal Replacement Therapy for Acute Kidney Injury.

BACKGROUND: The real impact of septic shock-associated acute kidney injury (AKI) on the long-term renal outcome is still debated, and little is known about AKI-burn patients. In a cohort of burn survivors treated by continuous renal replacement therapy (CRRT) and sorbent technology (CPFA-CRRT), we investigated the long-term outcome of glomerular and tubular function. METHODS: Out of 211 burn patients undergoing CRRT from 2001 to 2017, 45 survived, 40 completed the clinical follow-up (cumulative observation period 4067 months, median 84 months, IR 44-173), and 30 were alive on 31 December 2020. Besides creatinine and urine albumin, in the 19 patients treated with CPFA-CRRT, we determined the normalized GFR by 99mTc-DTPA (NRI-GFR) and studied glomerular and tubular urine protein markers. RESULTS: At the follow-up endpoint, the median plasma creatinine and urine albumin were 0.99 (0.72-1.19) and 0.0 mg/dL (0.0-0.0), respectively. NRI-GFR was 103.0 mL/min (93.4-115). Four patients were diabetic, and 22/30 presented at least one risk factor for chronic disease (hypertension, dyslipidemia, and overweight). Proteinuria decreased over time, from 0.47 g/day (0.42-0.52) at 6 months to 0.134 g/day (0.09-0.17) at follow-up endpoint. Proteinuria positively correlated with the peak of plasma creatinine (r 0.6953, p 0.006) and the number of CRRT days (r 0.5650, p 0.035) during AKI course, and negatively with NRI-GFR (r -0.5545, p 0.049). In seven patients, urine protein profile showed a significant increase of glomerular marker albumin and glomerular/tubular index. CONCLUSIONS: Burn patients who experienced septic shock and AKI treated with CRRT had a long-term expectation of preserved renal function. However, these patients were more predisposed to microalbuminuria, diabetes, and the presence of risk factors for intercurrent comorbidities and chronic renal disease.

Italian recommendations on enzymatic debridement in burn surgery.

INTRODUCTION: Nexobrid®, a bromelain-based type of enzymatic debridement, has become more prevalent in recent years. We present the recommendations on enzymatic debridement (Nexobrid®)'s role based on the practice knowledge of expert Italian users. METHODS: The Italian recommendations, endorsed by SIUST (Italian Society of Burn Surgery), on using enzymatic debridement to remove eschars for burn treatment were defined. The definition followed a process to evaluate the level of agreement (a measure of consensus) among selected experts, representing Italian burn centers, concerning defined clinical aspects of enzymatic debridement. The consensus involved a multi-phase process based on the Delphi method. RESULTS: The consensus panel included experts from Italy with a combined experience of 1068 burn patients treated with enzymatic debridement. At the end of round 3 of the Delphi method, the panel reached 100% consensus on 26 out of 27 statements. The panel achieved full, strong consensus (all respondents strongly agreed on the statement) on 24 out of 27 statements. DISCUSSION: The statements provided by the Italian consensus panel represent a "ready to use" set of recommendations for enzymatic debridement in burn surgery that both draw from and complete the existing scientific literature on the topic. These recommendations are specific to the Italian experience and are neither static nor definitive. As such, they will be updated periodically as further quality evidence becomes available.

Preparation and characterization of a novel skin substitute.

Autologous epidermal cell cultures (CEA) represent a possibility to treat extensive burn lesions, since they allow a significative surface expansion which cannot be achieved with other surgical techniques based on autologous grafting. Moreover currently available CEA preparations are difficult to handle and their take rate is unpredictable. This study aimed at producing and evaluating a new cutaneous biosubstitute made up of alloplastic acellular glycerolized dermis (AAGD) and CEA to overcome these difficulties. A procedure that maintained an intact basement membrane was developed, so as to promote adhesion and growth of CEA on AAGD. Keratinocytes were seeded onto AAGD and cultured up to 21 days. Viability tests and immunohistochemical analysis with specific markers were carried out at 7, 14, and 21 days, to evaluate keratinocyte adhesion, growth, and maturation. Our results support the hypothesis that this newly formed skin substitute could allow its permanent engraftment in clinical application.