Massive Burn Injuries: Characteristics and Outcomes From a Single Institution.

Massive burn injuries are a unique patient population with unique treatment paradigms. Data from 155 adult patients, admitted from 2009 to 2019, with >50% total body surface area burns (TBSA) were collected and analyzed. Average burn size was 70% TBSA and 63% had a concomitant inhalation injury. Approximately 30% of patients (46/155) transitioned to comfort care-only measures within 24 hours of admission. Standard treatment patients were younger (37 ± 13 vs 60 ± 19 years; p < .00001), male (94% vs 28%; p = .001) and had smaller TBSA (66 ± 13 vs 80 ± 16; p < .00001). Of the standard treatment group, 72 (66%) survived to discharge. Survivors had smaller TBSA (64 ± 13 vs 71 ± 13; p = .003), less third-degree TBSA (48 ± 25 vs 71 ± 13; p = .003) and lower incidence of renal failure requiring dialysis (22% vs 73%, p < .00001). Multivariate regression analysis showed that age (OR 1.05; p = .025), total TBSA (OR 1.07; p = .005), and renal failure (OR 10.2; p = .00005) were independently associated with mortality. Inhalation injury was not significantly associated with mortality. About 23% (35/155) of patients had a psychiatric condition on admission and 19% (30/155) of patients were burned attempting suicide. Patients with psychiatric conditions spent more time in the hospital (62 vs 30 days; p = .004), more time on ventilator (31 vs 12 days; p = .046), underwent more surgery (4 vs 2 operations, p = .03), and were less likely to die (34% vs 59%; p = .02). In summary, age, burn size, and renal failure were independently associated with mortality, with renal failure being the strongest factor. Psychiatric conditions are prevalent pre-injury and tend to require more inpatient care.

Perspectives on the fellowship training in cardiac, thoracic, and vascular anesthesia and critical care in Europe from program directors and educational leads around europe

ABSTRACT:This article reviews fellowship training in adult cardiac, thoracic, and vascular anesthesia and critical care from the perspective of European program initiators and educational leaders in these subspecialties together with current training fellows. Currently, the European Association of Cardiothoracic Anaesthesiology (EACTA) network has 20 certified fellowship positions each year in 10 hosting centers within 7 European countries, with 2 positions outside Europe (São Paulo, Brazil). Since 2009, 42 fellows have completed the fellowship training. The aim of this article is to provide an overview of the rationale, requirements, and contributions of the fellows, in the context of the developmental progression of the EACTA fellowship in adult cardiac, thoracic, and vascular anesthesia and critical care from inception to present. A summary of the program structure, accreditation of host centers, requirements to join the program, teaching and assessment tools, certification, and training requirements in transesophageal electrocardiography is outlined. In addition, a description of the current state of EACTA fellowships across Europe, and a perspective for future steps and challenges to the educational program, is provided. (AU)

Modelling the Effect of a Novel Autodissemination Trap on the Spread of Dengue in Shah Alam and Malaysia.

In this paper, we will start off by introducing the classical Ross-Macdonald model for vector-borne diseases which we use to describe the transmission of dengue between humans and Aedes mosquitoes in Shah Alam, which is a city and the state capital of Selangor, Malaysia. We will focus on analysing the effect of using the Mosquito Home System (MHS), which is an example of an autodissemination trap, in reducing the number of dengue cases by changing the Ross-Macdonald model. By using the national dengue data from Malaysia, we are able to estimate λ, which represents the initial growth rate of the dengue epidemic, and this allows us to estimate the number of mosquitoes in Malaysia. A mathematical expression is also constructed which allows us to estimate the potential number of breeding sites of Aedes mosquitoes. By using the data available from the MHS trial carried out in Section 15 of Shah Alam, we included the potential effect of the MHS into the dengue model and thus modelled the impact MHS has on the spread of dengue within the trial area. We then extended our results to analyse the effect of the MHSs on reducing the number of dengue cases in the whole of Malaysia. A new model was constructed with a basic reproduction number, R 0,Mala MHS, which allows us to identify the required MHSs coverage needed to achieve extinction in Malaysia. Numerical simulations and tables of results were also produced to illustrate our results.

ROCK2/rasHa co-operation induces malignant conversion via p53 loss, elevated NF-κB and tenascin C-associated rigidity, but p21 inhibits ROCK2/NF-κB-mediated progression.

To study ROCK2 activation in carcinogenesis, mice expressing 4-hydroxytamoxifen (4HT)-activated ROCK2 (K14.ROCKer) were crossed with mice expressing epidermal-activated rasHa (HK1.ras1205). At 8 weeks, 4HT-treated K14.ROCKer/HK1.ras1205 cohorts exhibited papillomas similar to HK1.ras1205 controls; however, K14.ROCKer/HK1.ras1205 histotypes comprised a mixed papilloma/well-differentiated squamous cell carcinoma (wdSCC), exhibiting p53 loss, increased proliferation and novel NF-κB expression. By 12 weeks, K14.ROCKer/HK1.ras1205 wdSCCs exhibited increased NF-κB and novel tenascin C, indicative of elevated rigidity; yet despite continued ROCK2 activities/p-Mypt1 inactivation, progression to SCC required loss of compensatory p21 expression. K14.ROCKer/HK1.ras1205 papillomatogenesis also required a wound promotion stimulus, confirmed by breeding K14.ROCKer into promotion-insensitive HK1.ras1276 mice, suggesting a permissive K14.ROCKer/HK1.ras1205 papilloma context (wound-promoted/NF-κB+/p53-/p21+) preceded K14.ROCKer-mediated (p-Mypt1/tenascin C/rigidity) malignant conversion. Malignancy depended on ROCKer/p-Mypt1 expression, as cessation of 4HT treatment induced disorganized tissue architecture and p21-associated differentiation in wdSCCs; yet tenascin C retention in connective tissue extracellular matrix suggests the rigidity laid down for conversion persists. Novel papilloma outgrowths appeared expressing intense, basal layer p21 that confined endogenous ROCK2/p-Mypt1/NF-κB to supra-basal layers, and was paralleled by restored basal layer p53. In later SCCs, 4HT cessation became irrelevant as endogenous ROCK2 expression increased, driving progression via p21 loss, elevated NF-κB expression and tenascin C-associated rigidity, with p-Mypt1 inactivation/actinomyosin-mediated contractility to facilitate invasion. However, p21-associated inhibition of early-stage malignant progression and the intense expression in papilloma outgrowths, identifies a novel, significant antagonism between p21 and rasHa/ROCK2/NF-κB signalling in skin carcinogenesis. Collectively, these data show that ROCK2 activation induces malignancy in rasHa-initiated/promoted papillomas in the context of p53 loss and novel NF-κB expression, whereas increased tissue rigidity and cell motility/contractility help mediate tumour progression.

Magnitude and frequency variations of vector-borne infection outbreaks using the Ross-Macdonald model: explaining and predicting outbreaks of dengue fever.

The classical Ross-Macdonald model is often utilized to model vector-borne infections; however, this model fails on several fronts. First, using measured (or estimated) parameters, which values are accepted from the literature, the model predicts a much greater number of cases than what is usually observed. Second, the model predicts a single large outbreak that is followed by decades of much smaller outbreaks, which is not consistent with what is observed. Usually towns or cities report a number of recurrences for many years, even when environmental changes cannot explain the disappearance of the infection between the peaks. In this paper, we continue to examine the pitfalls in modelling this class of infections, and explain that, if properly used, the Ross-Macdonald model works and can be used to understand the patterns of epidemics and even, to some extent, be used to make predictions. We model several outbreaks of dengue fever and show that the variable pattern of yearly recurrence (or its absence) can be understood and explained by a simple Ross-Macdonald model modified to take into account human movement across a range of neighbourhoods within a city. In addition, we analyse the effect of seasonal variations in the parameters that determine the number, longevity and biting behaviour of mosquitoes. Based on the size of the first outbreak, we show that it is possible to estimate the proportion of the remaining susceptible individuals and to predict the likelihood and magnitude of the eventual subsequent outbreaks. This approach is described based on actual dengue outbreaks with different recurrence patterns from some Brazilian regions.

Burn resuscitation on the African continent.

A survey of members of the International Society of Burn Injuries (ISBI) and the American Burn Association (ABA) indicated that although there was difference in burn resuscitation protocols, they all fulfilled their functions. This study presents the findings of the same survey replicated in Africa, the only continent not included in the original survey. One hundred and eight responses were received. The mean annual number of admissions per unit was ninety-eight. Fluid resuscitation was usually initiated with total body surface area burns of either more than ten or more than fifteen percent. Twenty-six respondents made use of enteral resuscitation. The preferred resuscitation formula was the Parkland formula, and Ringer's Lactate was the favoured intravenous fluid. Despite satisfaction with the formula, many respondents believed that patients received volumes that differed from that predicted. Urine output was the principle guide to adequate resuscitation, with only twenty-one using the evolving clinical picture and thirty using invasive monitoring methods. Only fifty-one respondents replied to the question relating to the method of adjusting resuscitation. While colloids are not available in many parts of the African continent on account of cost, one might infer than African burn surgeons make better use of enteral resuscitation.

PTEN ablation in Ras(Ha)/Fos skin carcinogenesis invokes p53-dependent p21 to delay conversion while p53-independent p21 limits progression via cyclin D1/E2 inhibition.

To investigate tumour progression mechanism in transgenic mouse skin carcinogenesis, inducible PTEN ablation (Δ5PTEN(flx)) was targeted to the epidermis of mice expressing activated ras(Ha)/fos oncogenes (HK1.ras and HK1.fos). RU486-treated HK1.ras/fos-Δ5PTEN(flx) epidermis exhibited significant keratinocyte proliferation resulting in hyperplasia and proliferating cysts. While HK1.ras/fos-Δ5PTEN(flx) papillomatogenesis was accelerated, malignant conversion was delayed and tumours exhibited well-differentiated squamous cell carcinoma (wdSCC) histotypes, suggesting inhibition of early-stage malignant progression. Immediate elevated p53/p21 expression was observed in HK1.ras/fos-Δ5PTEN(flx) hyperplasia, cysts and papillomas, and while malignant conversion required p53 loss, elevated p21 expression persisted in most wdSCCs to limit further progression, unless p21 was also lost and wdSCC progressed to more aggressive carcinomas. In contrast, TPA-promoted (that is, c-fos-activated) bi-genic HK1.ras-Δ5PTEN(flx) cohorts lost p53/p21 expression during early papillomatogenesis and rapidly produced poorly differentiated carcinomas (pdSCCs) with high BrdU-labelling and elevated cyclin D1/E2 expression levels, indicative of a progression mechanism driven by failures in cell-cycle control. Intriguingly, HK1.ras/fos-Δ5PTEN(flx) wdSCCs did not exhibit similar failures, as western and immunofluorescence analysis found downregulated cyclin E2 whenever p21 persisted; further, while westerns detected elevated cyclin D1, immunofluorescence identified reduced expression in proliferative basal layer nuclei and a redistributed expression profile throughout p21-positive wdSCC keratinocytes. These data demonstrate that rapid early epidermal responses to ras(Ha)/fos/ΔPTEN co-operation involve induction of p53/p21 to alter differentiation and divert excessive proliferation into cyst formation. Further, despite three potent oncogenic insults p53 loss was required for malignant conversion, and following p53 loss persistent, p53-independent p21 expression possessed the potency to limit early-stage malignant progression via cyclin D1/E2 inhibition.

A time since onset of injection model for hepatitis C spread amongst injecting drug users.

Studies of hepatitis C virus (HCV) infection amongst injecting drug users (IDUs) have suggested that this population can be separated into two risk groups (naive and experienced) with different injecting risk behaviours. Understanding the differences between these two groups and how they interact could lead to a better allocation of prevention measures designed to reduce the burden of HCV in this population. In this paper we develop a deterministic, compartmental mathematical model for the spread of HCV in an IDU population that has been separated into two groups (naive and experienced) by time since onset of injection. We will first describe the model. After deriving the system of governing equations, we will examine the basic reproductive number R0, the existence and uniqueness of equilibrium solutions and the global stability of the disease free equilibrium (DFE) solution. The model behaviour is determined by the basic reproductive number, with R0 = 1 a critical threshold for endemic HCV prevalence. We will show that when R0 ≤ 1, and HCV is initially present in the population, the system will tend towards the globally asymptotically stable DFE where HCV has been eliminated from the population. We also show that when R0 > 1 there exists a unique non-zero equilibrium solution. Then we estimate the value of R0 from epidemiological data for Glasgow and verify our theoretical results using simulations with realistic parameter values. The numerical results suggest that if R0 > 1 and the disease is initially present then the system will tend to the unique endemic equilibrium.

Mathematically modelling the spread of hepatitis C in injecting drug users.

Mathematical modelling can provide valuable insights into the biological and epidemiological properties of infectious diseases as well as the potential impact of intervention strategies employed by health organizations worldwide. In this paper, we develop a deterministic, compartmental mathematical model to approximate the spread of the hepatitis C virus (HCV) in an injecting drug user (IDU) population. Using analytical techniques, we find that the model behaviour is determined by the basic reproductive number R(0), where R(0) = 1 is a critical threshold separating two different outcomes. If R(0) ≤ 1 and HCV is initially present in the population, we find that the system will reach a disease-free equilibrium where HCV has been eliminated in all IDUs and needles. If R(0) > 1, then there is a unique positive endemic equilibrium which we show is locally stable. We then use simulations to verify our analytical results and examine the effect of different parameter values and intervention measures on HCV prevalence estimates.

Sedation during ophthalmic surgery.

Sedation is frequently used during ophthalmic regional anaesthesia. There is no 'ideal' drug for sedation or analgesia. Various drugs either alone or in combination have been used with different methods of administration. This review includes the roles of sedation, the pharmacology of drugs and the safety of sedation in patients undergoing ophthalmic surgery.

CD14-mediated alterations in transcription and splicing of endogenous retroviruses after injury.

Increase in systemic levels of lipopolysaccharide (LPS) contributes to the pathogenesis of distant organ injury after burn. Stress signals elicited from burn influence transcriptional activities of mouse endogenous retroviruses (MuERVs) in various distant organs. The involvement of LPS pathways in the burn-mediated regulation of MuERVs in the spleen was investigated in this study. Spleen harbors substantial numbers of tissue macrophages, a key responder to LPS stimulation. Spleen tissues collected from CD14 (LPS receptor) knockout (KO) and wild type (WT) mice after burn were subjected to RT-PCR analysis of MuERV expression. There was a substantial induction of 2 bands and a marked downregulation of a band in CD14 KO mice compared to WT mice after burn. Sequence analysis of these CD14- and burn-dependent bands identified 3 new alternatively spliced and 2 defective env transcripts of MuERVs as well as novel splicing signals. Chromosomal loci of putative MuERVs sharing the unique U3 sequences of these transcripts were mapped by surveying the entire genome of C57BL/6J mice. In addition, coding potentials, transcriptional regulatory elements, and adjacent cellular genes of these putative MuERVs were analyzed. The results from these studies suggest that injury-triggered LPS/CD14 signaling events play roles in the transcriptional regulation of certain MuERVs carrying unique U3 promoter sequences.

A method for the morphological analysis of the regurgitant mitral valve using three dimensional echocardiography.

BACKGROUND: Atrial en-face reconstructions are commonly used to assess mitral valve morphology in three dimensional (3D) echocardiography but may miss important abnormalities. OBJECTIVE: To present a systematic method for the analysis of the regurgitant mitral valve using a combination of en-face and longitudinal views for better anatomical evaluation. METHODS: Detailed 3D assessment was done on 58 patients undergoing mitral valve repair. En-face and longitudinal views were compared for detection and location of primary pathology. The quality of acquisitions under general anaesthesia and sedation was also compared. RESULTS: Recognition of valve structure was significantly better with longitudinal reconstruction for both mitral leaflets but not for the commissures. Accurate identification of pathology was possible in 95% cases, compared with 50% for en-face reconstruction (p < 0.001). There was no significant difference between imaging under sedation and anaesthesia. CONCLUSION: En-face reconstructions alone are inadequate. Additional longitudinal reconstructions are necessary to ensure full inspection of valve morphology.

Current management of purpura fulminans: a multicenter study.

Seven burn centers performed a 10-yr retrospective chart review of patients diagnosed with purpura fulminans. Patient demographics, etiology, presentation, medical and surgical treatment, and outcome were reviewed. A total of 70 patients were identified. Mean patient age was 13 yr. Neisseria meningitidis was the most common etiologic agent in infants and adolescents whereas Streptococcus commonly afflicted the adult population. Acute management consisted of antibiotic administration, volume resuscitation, ventilatory and inotropic support, with occasional use of corticosteroids (38%) and protein C replacement (9%). Full-thickness skin and soft-tissue necrosis was extensive, requiring skin grafting and amputations in 90% of the patients. One fourth of the patients required amputations of all extremities. Fasciotomies when performed early appeared to limit the level of amputation in 6 of 14 patients. Therefore, fasciotomies during the initial management of these patients may reduce the depth of soft-tissue involvement and the extent of amputations.

Influence of refractive index matching on the photon diffuse reflectance.

Photon migration in a randomly inhomogeneous, highly scattering and absorbing semi-infinite medium with a plane boundary is considered by a Monte Carlo (MC) technique. The employed MC technique combines the statistical weight scheme and real photon paths simulation, allowing the exclusion of the energy conservation problem. The internal reflection of the scattered radiation on the medium interface is taken into account by allowing the trajectories of photon packets to be split into reflected and transmitted parts. The spatial photon sensitivity profile (SPSP), spatially resolved diffuse reflectance and angular and spatial photon detector weight distributions are considered in terms of Fresnel's reflection/refraction on the boundary of the medium. The effect of the refractive index match is predicted correctly by the MC method and by the diffusion approximation. The results demonstrate that matching of the refractive index of the medium significantly improves the contrast and spatial resolution of the spatial photon sensitivity profile (SPSP). The results of simulation of the spatially resolved diffuse reflectance agree well with the results predicted by the diffusion approximation and the experimental results reported earlier.

Use of an improved Watusi collar to manage pediatric neck burn contractures.

Burns to the neck present a serious challenge to the pediatric burn team. Even when full neck range of motion is maintained, scarring may lead to banding and a loss of the neck's natural contour. Conventional thermoplastic neck conformers have been used to maintain neck position and provide pressure to maturing scars, but they are rigid and limit functional mobility. This is of particular concern in the pediatric population where limiting neck mobility can disrupt the development of sensory and motor patterns that are essential to normal developmental progression. The Multi-Ring Watusi collar is a flexible neck orthosis that allows mobility and provides circumferential pressure to the neck. We modified this collar to improve its comfort, cosmetic appearance and ease in donning/doffing. The improved Watusi collar is a flexible splint that supports neck position, provides circumferential pressure, and allows for functional neck mobility.

A multicenter review of toxic epidermal necrolysis treated in U.S. burn centers at the end of the twentieth century.

Toxic epidermal necrolysis (TEN) is a potentially fatal disorder that involves large areas of skin desquamation. Patients with TEN are often referred to burn centers for expert wound management and comprehensive care. The purpose of this study was to define the presenting characteristics and treatment of TEN before and after admission to regional burn centers and to evaluate the efficacy of burn center treatment for this disorder. A retrospective multicenter chart review was completed for patients admitted with TEN to 15 burn centers from 1995 to 2000. Charts were reviewed for patient characteristics, non-burn hospital and burn center treatment, and outcome. A total of 199 patients were admitted. Patients had a mean age of 47 years, mean 67.7% total body surface area skin slough, and mean Acute Physiology and Chronic Health Evaluation (APACHE II) score of 10. Sixty-four patients died, for a mortality rate of 32%. Mortality increased to 51% for patients transferred to a burn center more than one week after onset of disease. Burn centers and non-burn hospitals differed in their use of enteral nutrition (70 vs 12%, respectively, P < 0.05), prophylactic antibiotics (22 vs 37.9%, P < 0.05), corticosteroid use (22 vs 51%, P < 0.05), and wound management. Age, body surface area involvement, APACHE II score, complications, and parenteral nutrition before transfer correlated with increased mortality. The treatment of TEN differs markedly between burn centers and non-burn centers. Early transport to a burn unit is warranted to improve patient outcome.