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.

First case of Chryseobacterium gallinarum bloodstream infection: a diagnostic and therapeutic challenge for an emerging pathogen.

Chryseobacterium spp. belongs to the Flavobacteriaceae family and is a rod-shaped gram-negative, glucose non-fermenting, non-motile bacterium ubiquitous in the environment. In humans, Chryseobacterium may be responsible for infections such as urinary tract infections (UTI) and ventriculitis with a pathogenic burden increasing in recent years. Chryseobacterium gallinarum was isolated for the first time in 2014 in a pharyngeal scrape sample of chicken and, until now, only one case of human UTI has been described in a pregnant 20-year-old Indian patient. Herein, we report the first case of bloodstream infection caused by C. gallinarum in a 67-year-old female burn patient, correctly identified by 16S-rRNA sequencing and successfully treated with cefepime and fosfomycin.

Cholesterol redistribution triggered by CYP46A1 gene therapy improves major hallmarks of Niemann-Pick type C disease but is not sufficient to halt neurodegeneration.

Cholesterol 24-hydroxylase (CYP46A1) is an exclusively neuronal cytochrome P450 enzyme responsible for converting cholesterol into 24S-hydroxycholesterol, which serves as the primary pathway for eliminating cholesterol in the brain. We and others have shown that increased activity of CYP46A1 leads to reduced levels of cholesterol and has a positive effect on cognition. Therefore, we hypothesized that CYP46A1 could be a potential therapeutic target in Niemann-Pick type C (NPC) disease, a rare and fatal neurodegenerative disorder, characterized by cholesterol accumulation in endolysosomal compartments. Herein, we show that CYP46A1 ectopic expression, in cellular models of NPC and in Npc1tm(I1061T) mice by adeno-associated virus-mediated gene therapy improved NPC disease phenotype. Amelioration in functional, biochemical, molecular and neuropathological hallmarks of NPC disease were characterized. In vivo, CYP46A1 expression partially prevented weight loss and hepatomegaly, corrected the expression levels of genes involved in cholesterol homeostasis, and promoted a redistribution of brain cholesterol accumulated in late endosomes/lysosomes. Moreover, concomitant with the amelioration of cholesterol metabolism dysregulation, CYP46A1 attenuated microgliosis and lysosomal dysfunction in mouse cerebellum, favoring a pro-resolving phenotype. In vivo CYP46A1 ectopic expression improves important features of NPC disease and may represent a valid therapeutic approach to be used concomitantly with other drugs. However, promoting cholesterol redistribution does not appear to be enough to prevent Purkinje neuronal death in the cerebellum. This indicates that cholesterol buildup in neurons might not be the main cause of neurodegeneration in this human lipidosis.

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.

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.

Epidemiology and risk factors for pathologic scarring after burn wounds.

OBJECTIVE: To describe the clinical characteristics of postburn scars and determine the independent risk factors specific to these patients. While burns may generate widespread and disfiguring scars and have a dramatic influence on patient quality of life, the prevalence of postburn pathologic scarring is not well documented, and the impact of certain risk factors is poorly understood. METHODS: A retrospective analysis was conducted of the clinical records of 703 patients (2440 anatomic burn sites) treated at the Turin Burn Outpatient Clinic between January 1994 and May 15, 2006. Prevalence and evolution time of postburn pathologic scarring were analyzed with univariate and multivariate risk factor analysis by sex, age, burn surface and full-thickness area, cause of the burn, wound healing time, type of burn treatment, number of surgical procedures, type of surgery, type of skin graft, and excision and graft timing. RESULTS: Pathologic scarring was diagnosed in 540 patients (77%): 310 had hypertrophic scars (44%); 34, contractures (5%); and 196, hypertrophic-contracted scars (28%). The hypertrophic induction was assessed at a median of 23 days after reepithelialization and lasted 15 months (median). A nomogram, based on the multivariate regression model, showed that female sex, young age, burn sites on the neck and/or upper limbs, multiple surgical procedures, and meshed skin grafts were independent risk factors for postburn pathologic scarring (Dxy 0.30). CONCLUSION: The identification of the principal risk factors for postburn pathologic scarring not only would be a valuable aid in early risk stratification but also might help in assessing outcomes adjusted for patient risk.

Acute complex traumas of the lower limbs: a modern reconstructive approach with negative pressure therapy.

Acute traumas of the lower limbs cause complex functional damage for the association of skin loss with exposed tendons, bones, and/or vessels, requiring a multidisciplinary approach. Once bone fixation and vascular repair have been carried out, the surgical treatment for skin damage is usually based on early coverage with conventional or microsurgical flaps. Negative pressure therapy can play a primary role in the management of the elderly or intensive care patients, where wounds are secondary to life-threatening problems. A total of 35 patients with 37 acute traumatic wounds of the lower limbs were treated with vacuum-assisted closure (VAC) therapy for an average of 22 days (range 3-46 days). The sponge was applied the day after bone fixation, vascular repair, and surgical debridement of nonviable tissues, so as to obtain a better control of bleeding. After VAC treatment, all patients quickly developed healthy granulation tissue and a significant reduction in both extent and depth of wounds. Split-thickness skin grafts were used to cover granulation tissue in most of the cases (66% -- 24 cases), and then local flaps (13% -- five cases) or direct sutures (8% -- three cases). The wounds healed spontaneously without surgical management in four patients. One patient died during the treatment period for concomitant diseases. No relevant complications directly related to VAC therapy were observed other than one case of severe pain in an amputated stump. The average follow-up duration was 265 days (range 33-874 days). No further tegumentary reconstruction was required. VAC therapy may represent a valid alternative to immediate reconstruction in selected cases of acute complex traumas of the lower limb and allows for a stable functional result, using a minimally invasive approach.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS): experience with high-dose intravenous immunoglobulins and topical conservative approach. A retrospective analysis.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare, drug-induced, severe acute exfoliative skin and mucosal disorders. Several treatments previously proposed have produced contradictory results in small series; in 1998 the use of intravenous immunoglobulins (IVIG) was introduced with excellent clinical findings. Our experience (1999-2005) using IVIG in the therapy of TEN/SJS, together with a local conservative approach, is reported and related to our previous treatments (1993-1998). The SCORTEN and the standardized mortality ratio (SMR) was used to evaluate the efficacy of our therapeutic modalities. Eight patients were treated before IVIG era and 23 patients have been treated with IVIG. There was no significant difference in SCORTEN between the two groups. Concerning the local approach, a conservative wound management in IVIG series replaced an extensive epidermal debridment and coverage with artificial skin substitutes of the pre-IVIG series. Overall mortality in patients treated before IVIG was 75% (6/8), in the IVIG group it decreased to 26% (6/23) with a cessation of further epidermal detachment after an average of 5 days (3-10 days) from the onset of the therapy. The SMR showed a trend to lower actual mortality (not significative) with IVIG treatment than the predicted mortality (SMR=0.728; 95% CI: 0.327-1.620).