Search PubMed⌕ Search

Biomedical subjects

Richard L Gamelli

Publications and source records attributed to Richard L Gamelli.

64 records · Page 4Linked to original sources

Long-term follow-up of patients treated for toxic epidermal necrolysis.

Patient outcomes concerning toxic epidermal necrolysis (TEN) have improved over the years as a better understanding of the pathophysiology of the illness has been gained and enhancements have been made in the care of the acutely ill. With increase in survival, long-term complications these patients experience are beginning to be recognized. In this study, we analyzed the outcomes of a cohort of TEN survivors treated at our burn unit and sought to determine the impact of clinical variables from the initial hospitalization on mortality after discharge. We performed a retrospective review of data from patients with TEN treated at our burn unit from March 1993 to September 2002. Follow-up data on new health problems were collected on patients who were alive at discharge via questionnaire. Survival was estimated using the Kaplan-Meier method with Cox regression model. During the study period, of the 64 patients treated for TEN, 46 survived. After discharge, 15 patients died, whereas the remaining 31 patients continued to suffer from ocular (54%), skin (81%), and renal (23%) problems. Median survival for the whole cohort has not been reached, with an estimated 5-year survival of 65%. No patient in either group had a TEN recurrence. Seventy-nine percent of the patients with ocular involvement in the acute phase of TEN had long-term ocular complications, and 73% of patients with mucosal involvement had persistent mucosal lesions. Five individual factors were found to be predictors of postdischarge mortality on univariate analysis: age at diagnosis of TEN>or=60 years, SCORTEN 3 to 6, % maximal TBSA slough>or=50%, days from onset of symptoms to admission to a burn unit>or=5 days, and presence of multiple comorbidities at diagnosis of TEN. In multivariate analysis, only SCORTEN of 3 to 6 (P=.003) and days to admission>or=5 (P=.027) maintained significance as predictors of mortality and may be used to heighten surveillance during postdischarge care of patients with TEN.

Adult↗

Analysis of functional outcomes in patients discharged from an acute burn center.

Burn patients require careful consideration of their post-discharge needs to maximize their recovery. Patient-specific variables or a combination of variables that might allow clinicians to develop pathways and objective endpoints for appropriate discharge would assist in expediting the patient's post-discharge care. While there have been numerous studies examining a single variable and its ability to predict outcomes, these studies may not be directly applicable to burn patients. A burn clinician must incorporate a number of variables into their prediction of discharge disposition and outcomes. Our study included 202 burn patients aged 16 and older discharged from the acute burn unit from February 2004 to June 2005. Descriptive data collection included age, total body surface area, location of burn, presence/absence of inhalation injury, gender, length of stay, discharge disposition, insurance status, and presence/absence of social support. The analysis that also incorporated data containing functional status consisted of FIM scores for locomotion, transfers, dressing, and feeding. The classification tree analysis was utilized to demonstrate what variables could predict discharge disposition. The only variable that could strongly predict those patients that went home versus another setting was the FIM locomotion score. Of the patients who went home, 87.2% were at or above a supervision level for locomotion, whereas 85.2% of the patients not discharged to home were at or below a maximal assist level. The level of functional independence at the time of a patient's discharge as assessed by the patient's ability to walk was the most powerful identifier of their ongoing needs.

Activities of Daily Living↗

New perspectives for a new century: implications of pathogen responses for the future of antimicrobial therapy.

Although the discovery of new classes of antibiotics has lagged behind in the last three decades, the incidence of life-threatening nosocomial infections that are resistant to multiple antibacterial agents has increased steadily. Recent advances in bacterial pathogenicity through the identification of a number of virulence factors and the bacterial genetics behind it have opened the way to a clearer understanding of the pathogen-host relationship. Bacteria communicate with each other through specific signaling chemicals to act as a community rather than individual cells to achieve a critical density or a "quorum." Establishment of quorum is the initiating signal for turning on a variety of virulence factors essential for the pathogenicity and dissemination of pathogens through the host. Pathogenic bacteria use a variety of biochemical mediators, collectively called "virulence factors," to invade and attack host tissues and to avoid detection and elimination by the host immune system. Delineating the specific responses the host immune system elicits in response to specific virulence factors and quorum-sensing molecules is essential to the development of new diagnostic methods for early detection of an infection and the prognosis to a given antibacterial therapy. Identification of inhibitors of virulence factors will represent new antimicrobial therapeutic modalities, and this can be used synergistically with current antibiotic therapy because they act through independent prokaryotic pathways to inhibit bacterial growth and survival.

Anti-Bacterial Agents↗

Ventilator-associated pneumonia after combined burn and trauma is caused by associated injuries and not the burn wound.

An increased risk of ventilator-associated pneumonia (VAP) has previously been demonstrated in trauma patients urgently intubated in the prehospital (ie, field) and emergency department (ED) settings. This study investigated the impact of urgent intubation on subsequent VAP in patients who sustained both a burn injury and a traumatic injury. We undertook a retrospective review of both trauma registry data and medical records for all patients with combined thermal and traumatic injuries admitted to a single verified burn center and level I trauma center. Patients undergoing field or ED intubation during the 5-year period ending December 2002 were identified and studied. Data abstracted included admission demographics and vital signs, presence of inhalation injury, location at the time of intubation, presence of associated injury, percentage TBSA burn, hospital and intensive care unit length of stay, and hospital day of VAP diagnosis. Seventy-eight of the 3388 patients (2.3%) admitted during the study period sustained a combination of burn wounds and trauma and underwent urgent field or ED intubation. The majority of patients were men (71%), with a mean age of 46 +/- 24 years. There was one failed oral intubation, which required cricothyroidotomy. The location of the patient at the time of intubation was ED, 66%; burn center ED, 17%; and field, 17%. Eighty percent of all patients were diagnosed with an inhalation injury. VAP was diagnosed in 39 patients (50%), with a mean time to diagnosis of 10 +/- 9 days. TBSA burn, smoke inhalation, and time (in days) to diagnosis of VAP were not independent risk factors for the occurrence of pneumonia in any of the 3 groups. However, those intubated at the initial ED were more likely to develop VAP (P = .028) compared to those intubated in the field or in the burn center. The incidence of associated injuries was significantly greater (P < .0001) in the initial ED group. Only a small percentage of burn patients also sustain blunt trauma. VAP occurs in 50% of the patients requiring urgent intubation. Independent risk factors appear to be intubation at an initial ED before transfer and associated injuries.

Adult↗

Inflammation and the host response to injury: an overview of the multicenter study of the genomic and proteomic response to burn injury.

Inflammation and the Host Response to Injury is a prospective, multicenter, federally funded collaborative study of the genomic and proteomic basis for injury response. This study has brought together clinical specialists in burn injury with experts in genomics, proteomics, and bioinformatics to answer questions related to immunoinflammatory responses to injury. The purpose of this report is to describe the structure, organization, goals, and current progress of this Glue Grant project.

Burns↗

Gastric rupture after cardiopulmonary resuscitation in a burn patient.

Burn injury, especially severe facial burn injury, poses a unique challenge for emergency health care personnel in administering cardiopulmonary resuscitation. Because of the perioral and oral edema with severe facial burns, intubation may be difficult, and bag-valve mask or mouth-to-mouth resuscitation may be prolonged. As a result of the difficulty in establishing a patent airway, various complications can arise. One of these includes gastric perforation which, although rare in the setting of difficult intubation or prolonged oral ventilation, may be possible. To our knowledge, acute gastric perforation after prolonged cardiopulmonary resuscitation in burn injured patients has not previously been reported thus the incidence is unknown. We report here a case of gastric perforation after a difficult tracheal intubation in a patient with extensive burns of the head and neck and 63% TBSA burn.

Aged↗

A novel antibacterial gene transfer treatment for multidrug-resistant Acinetobacter baumannii-induced burn sepsis.

Sepsis caused by multidrug-resistant bacterial infections in critically injured patients has become a major clinical problem. Recently, Acinetobacter baumannii (AB) wound infections, especially in our critically injured soldiers fighting in Iraq and Afghanistan, is posing a major clinical problem and an economic burden. ConjuGon, Inc., has developed a novel antibacterial therapeutic technology using bacterial conjugation. The donor cells are attenuated Escherichia coli carrying a conjugative plasmid. The expression of bactericidal genes cloned on the plasmid is tightly repressed in the donor cells but becomes de-repressed once mobilized into a pathogen and disrupts protein synthesis. Here, we tested the efficacy of this novel conjugation technology to control and eradicate a drug-resistant clinical isolate of AB wound infection both in vitro and in a murine burn sepsis model. C57Blk/6J mice were divided into burn (B) and burn sepsis (BS) groups. All animals received a 12% TBSA dorsal scald full-thickness burn. The BS group was inoculated with multidrug-resistant AB (1 x 10(5) colony-forming units [CFU]) at the burn wound site. BS animals were either untreated or treated with increasing concentrations (10(3) - 19(10) CFU) of attenuated donor E. coli encoding bactericidal proteins. The survival rate was monitored for 10 days. The ability of donor cells to significantly diminish AB levels in the burn wound 24 hours after injury was determined by quantitative cultures. Donor cells were highly effective in killing AB in vitro. In the burn sepsis model, 90% B group animals survived, and 40% to 50% BS animals survived with no treatment in 5 to 6 days. Treatment with donor cells at 10(10) to 10(6) provided significant survival advantage (P < .05). Quantitative cultures of burn wounds revealed that AB numbers increased from 3 x 10(4) CFU to 7.8 +/- 4.4 x 10(9) CFU in 24 hours in the untreated group. Single treatment with donor cells (10(10) CFU) significantly reduced AB in the burn wound to less than the levels seeded into the wound (1.23 +/- 0.5 x 10(4) CFU; P < .05). Taken together, these results indicate that this novel technology is an efficient method to control drug-resistant AB burn wound infections and prevent their systemic spread.

Acinetobacter baumannii↗

Inhalation injury, pulmonary perturbations, and fluid resuscitation.

Inhalation injury (INHI) associated with thermal injury has been shown to increase the rate of mortality. Several investigators have shown that patients with inhalation and burn injuries will require increased fluid volumes during acute resuscitation when compared with patients with burn injury alone. Other groups have examined the use of lung compliance and airway resistance as predictors of outcome in patients with INHI. We hypothesized that increased fluid requirements would more closely correlate with perturbations in pulmonary performance than with mere presence or absence of INHI or the degree of injury by bronchoscopic criteria. We performed a retrospective chart review during a period of 3 years. We identified 80 patients with suspected INHI that required intubation, mechanical ventilation, and fiber optic bronchoscopy in the first 24 hours of their admission. Variables collected included age, sex, weight and %TBSA burned, as well as blood alcohol level, the presence of head and neck burns and escharotomies, and admission carbon monoxide levels. Patients were classified into five groups according to a grading system of INHI (0, 1, 2, 3, and 4), derived from findings at initial bronchoscopy and based on AIS criteria. The following pulmonary parameters were noted at regular intervals: mode of ventilation, tidal volume, peak inspiratory pressures, mean airway pressures, and compliance. The P:F ratio also was recorded at regular intervals. Total fluid volume infused was noted at 0-, 24-, and 48-hour intervals, and was calculated as ml/kg/%TBSA. Outcomes were measured by in-hospital survival, ventilator days, intensive care unit days, and total length of stay. Patients were well matched for %TBSA among the different bronchoscopic grades of INHI, and those with grades 2, 3, and 4 injuries had a significantly worse survival than those with grades 0 or 1 (P = .03). However, grades 2, 3, and 4 did not have increased acute fluid requirements when compared with grades 1 and 2 injuries. Initial pulmonary compliance likewise did not correlate with acute fluid requirements. However, those patients with a P:F ratio less than 350 at presentation had a statistically significant increase in ml/kg/%TBSA compared with those with P:F >350 (P = .03). They did not have more ventilator days or a statistically worse survival. Fiber optic bronchoscopy is useful in the diagnosis of INHI, and overall survival is worse in those patients with worse grades of injury by bronchoscopic criteria. However, the P:F ratio may be a more accurate predictor of increased fluid requirements during the acute resuscitation.

Adult↗

The early acute phase response after burn injury in mice.

In the hours immediately after burn injury, the body enters into an acute phase reaction characterized, in part, by the augmentation of cytokine and acute phase protein production. This reaction has been poorly characterized in the 24 hours immediately after injury. To better understand the early acute phase response, 8- to 10-week-old BALB/C female mice were subjected to a 15% total body surface area (TBSA). Hepatic levels of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were monitored. In addition, the circulating level of serum amyloid A, an acute phase protein, also was measured at the same time points. Tumor necrosis factor-alpha levels peaked 2 hours after burn injury, whereas interleukin-1beta had a biphasic response, increasing 2 hours after injury and again at 12 hours. Interleukin-6 and serum amyloid A were not increased until 12 hours after injury and began to decline at 24 hours. These results demonstrate that within the liver, the acute phase response after burn injury initially involves tumor necrosis factor-alpha and interleukin-1beta, whereas interleukin-6 is not involved until later and that systemic serum amyloid A levels are not increased until interleukin-6 is also increased.

Acute-Phase Reaction↗

Immunologic responses to critical injury and sepsis.

Almost 2 million patients are admitted to hospitals in the United States each year for treatment of traumatic injuries, and these patients are at increased risk of late infections and complications of systemic inflammation as a result of injury. Host response to injury involves a general activation of multiple systems in defending the organism from hemorrhagic or infectious death. Clinicians have the capability to support the critically injured through their traumatic insult with surgery and improved critical care, but the inflammatory response generated by such injuries creates new challenges in the management of these patients. It has long been known that local tissue injury induces systemic changes in the traumatized patient that are often maladaptive. This article reviews the effects of injury on the function of immune system cells and highlights some of the clinical sequelae of this deranged inflammatory-immune interaction.

Antibody Formation↗