A Prospective Comparison of Frailty Scores and Fall Prediction in Acutely Injured Older Adults.

BACKGROUND: Elderly (65 and older) fall-related injuries are a significant cause of morbidity and mortality. Although frailty predicts poor outcomes in geriatric trauma, literature comparing frailty scoring systems remains limited. Herein, we evaluated which frailty scoring system best predicts falls over time in the elderly. MATERIALS AND METHODS: Acute surgical patients 65 y and older were enrolled and prospectively observed. Demographics and frailty, assessed using the FRAIL Scale, Trauma Specific Frailty Index (TSFI), and Canadian Frailty Scale (CSHA-CFS), were collected at enrollment and 3 mo intervals following discharge for 1 y. Surveys queried the total number and timing of falls. Changes in frailty over time were assessed by logistic regression and area under the curve (AUC). RESULTS: Fifty-eight patients were enrolled. FRAIL Scale and CSHA-CFS scores did not change over time, but TSFI scores did (P ≤ 0.01). Worsening frailty was observed using TSFI at 6 (P ≤ 0.01) and 12 mo (P ≤ 0.01) relative to baseline. Mortality did not differ based on frailty using any frailty score. Increasing frailty scores and time postdischarge was associated with increased odds of a fall. AUC estimates with 95% CI were 0.72 [0.64, 0.80], 0.81 [0.74, 0.88], and 0.76 [0.68, 0.84] for the FRAIL Scale, TSFI, and CSHA-CFS, respectively. CONCLUSIONS: The risk of falls postdischarge were associated with increased age, time postdischarge, and frailty in our population. No scale appeared to significantly outperform the other by AUC estimation. Further study on the longitudinal effects of frailty is warranted.

Initial management of severe burn injury.

PURPOSE OF REVIEW: Patients with severe burn injuries pose significant challenges for the intensivist. Though average burn sizes have decreased over time, severe burn injuries involving greater than 20% of the total body surface area still occur. Verified burn centers are limited, making the management of severely burn injured patients at nonspecialized ICUs likely. Current practices in burn care have increased survivability even from massive burns. It is important for intensivists to be aware of the unique complications and therapeutic options in burn critical care management. This review critically discusses current practices and recently published data regarding the evaluation and management of severe burn injury. RECENT FINDINGS: Burn patients have long, complex ICU stays with accompanying multiorgan dysfunction. Recent advances in burn intensive care have focused on acute respiratory distress syndrome from inhalation injury, acute kidney injury (AKI), and transfusion, resulting in new strategies for organ failure, including renal replacement therapy and extracorporeal life support. SUMMARY: Initial evaluation and treatment of acute severe burn injury remains an ongoing area of study. This manuscript reviews current practices and considerations in the acute management of the severely burn injured patient.

Neuropathy May Be an Independent Risk Factor for Amputation After Lower-Extremity Burn in Adults With Diabetes.

IN BRIEF Treatment of lower-extremity burn injuries in adults with diabetes can be complex, and some diabetes-related factors can lead to impaired healing of such wounds, putting patients at risk of amputation. In this retrospective review of adult patients with lower-extremity burns, patients with pre-injury neuropathy and higher A1C levels were more likely to require amputations after their burn injury. The authors conclude that lower-extremity burn injuries in patients with diabetes require close follow-up and possibly referral to a burn specialist for interventions and treatment strategies to offset more serious complications.

Frailty score on admission predicts mortality and discharge disposition in elderly trauma patients over the age of 65 y.

BACKGROUND: Although many frailty scales exist, a single scale has not been agreed upon to define frailty. Herein, we determined whether the Canadian Study on Health and Aging Clinical Frailty Scale (CSHA CFS) can predict the risk of elderly patients for hospital mortality and discharge to skilled nursing facilities (SNFs) following traumatic injury. METHODS: Charts from trauma patients aged ≥65 y admitted from December 1, 2011 to December 31, 2013 were retrospectively examined. Age, mechanism of injury, Glasgow coma score, systolic blood pressure and heart rate on arrival, injury severity score, hospital mortality, length of stay, and discharge disposition were recorded. Frailty scores were determined from admission data using the CSHA CFS. Univariate and multivariate analyses were performed. RESULTS: A total of 1403 patients were included. The mean age was 77.6 ± 8.6 y. Patients with falls presented higher frailty scores than patients who sustained injuries through other mechanisms (4.58 ± 1.2 versus 3.52 ± 1.15; P < 0.00001) and were significantly older (79.5 ± 8.6 versus 73.4 ± 7.4; P <0.00001). Frailty scores of nonsurvivors were significantly higher than those of survivors (4.6 ± 1.3 versus 4.2 ± 1.2; P <0.01). Age, Glasgow coma score, and CSHA CFS combined were associated with mortality (odds ratio: 1.52; confidence interval: 1.37-1.69). A higher frailty score was associated with earlier death and increased mortality. CONCLUSIONS: CSHA CFS is simple and provides frailty scores that can help identifying elderly patients at high risk for in-hospital mortality and discharge to SNF following traumatic injury.

Pediatric Burn Teams: Moving from Multidisciplinary to Transdisciplinary.

Pediatric burn care has improved to the point where even patients with massive burns have a reasonable chance of survival. An important component of this success is the pediatric multidisciplinary burn team. The pediatric burn team is made up of all the disciplines that are required to provide optimal care of the patient as well as their family. The pediatric burn team in its initial iteration was multidisciplinary, with each discipline focusing on their own area without much overlap. However, over time the burn team has become more cooperative and interdisciplinary leading to improved outcomes for children with burn injuries. Ultimately, pediatric burn teams may be able to function in a transdisciplinary manner which would potentially allow for even more innovation in the care of burn patients.

Development of the Preschool Life Impact Burn Recovery Evaluation (PS-LIBRE1-5) Profile.

Physical, social, and psychological outcomes have been identified as relevant to the rehabilitation process of children with burn injuries. Existing legacy measures are limited in item content and only cover a few constructs. Condition-specific outcomes are highly relevant to gauge early growth and development. Computerized adaptive tests (CATs) leveraging advanced psychometric technologies minimize respondent burden. This project developed PS-LIBRE1-5 Profile CAT (Preschool Life Impact Burn Recovery Evaluation) to measure relevant postburn outcomes in children aged one to five. Responses to the field-tested PS-LIBRE1-5 Profile (188 items) were measured on a scale of frequency or ability. Scores were coded from 0 to 4 where higher scores reflected better functioning. Factor analysis identified the items retained in the final item bank of each scale. CAT simulations were conducted to estimate the mean score of each scale. The simulated CAT score and full item bank scores were compared based upon the score range, ceiling and floor effects, and marginal reliabilities. The child mean age was 3.0 ± 1.5 years (n = 500). Average burn size and time since burn injury were 4.2% TBSA and 1.1 years, respectively. Psychometric analysis resulted in eight scales: Physical, Communication and Language, Emotional Wellbeing, Mood, Anxiety, Peer Acceptance, Play, and Peer Relations. Ceiling effects were acceptable at <13% for all scales. Marginal reliabilities of the CATs were credible. The PS-LIBRE1-5 Profile CAT contains 111 items, and is a comprehensive measure that captures physical, communication and language, psychological, and social functioning of preschool burn survivors.

Factors Associated with the Rehabilitation of the Older Adult Burn Patient.

The number of older people is increasing and as a result so will the number of older adult patients who present with a burn injury. There are distinct differences between older and younger burn patients, particularly with respect to skin anatomy and physiology and frailty. These are 2 important factors that influence the rehabilitation efforts with respect to older adult burn patients. There has been minimal work done studying the specific rehabilitation of older adult burn patients. More work is needed to fully understand the rehabilitation needs of older adult burn patients.

Evaluation of Outcomes Following Surgical Treatment of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS), a chronic disease of the apocrine bearing skin causing induration, pain, draining sinuses, and subcutaneous abscesses, significantly impairs patients' quality of life (QOL). Full-thickness excision followed by skin grafting of the involved area can be curative. Herein, we evaluated the impact of this surgical treatment on QOL and depression symptomatology. Adult patients (≥18 years) who consented to participate filled out the dermatology quality of life (DLQI) and the Patient History Questionnaire (PHQ-9) at consent and at 1, 6, and 12 months post-initial evaluation and surgery. Demographics, HS, admission, and operative information were collected. Sixteen patients were included. Subjects were mainly white (81.3 %) and female (56.3%) with a median age of 38.2 (Interquartile range: 34.2-54.5); 62.5% were obese (BMI= 39.7 [28.4-50.6]). Half of the subjects presented with HS in 2 or more areas. Six patients were still undergoing surgeries at 6 months. One-, six-, and 12-month follow-up surveys were obtained from 14, 11, and 8 subjects for DQLI and from 14, 9, and 5 subjects for PHQ9. DLQI scores significantly decreased at 6 months compared to baseline, which indicates QOL improvement (10 [4-20] vs 15.5 [12-21.8], P = .036). Although not significant, PHQ9 scores tended to decrease. For those with the worst disease, DLQI significantly decreased at both 6 (P = .049) and 12 months (P = .047) compared to baseline. Despite a small sample size, our data suggest that aggressive surgical treatment improves the QOL of HS patients. Further studies are warranted to confirm our findings.

Use of Cultured Epithelial Autograft in Conjunction with Biodegradable Temporizing Matrix in Massive Burns: A Case Series.

Intensive care for massively burn patients has increased survival and highlights the need for a solution to the problem of insufficient donor sites for autologous skin coverage. In this case series, we present 10 patients with average burn size of 81% TBSA and mean age of 24 years old, who underwent burn excision followed by either immediate or delayed biodegradable temporizing matrix (BTM) placement. After an integration period, the BTM was delaminated either the day before or immediately prior to placement of cultured epithelial autografts over a widely meshed (4:1 or 6:1) split thickness skin graft. One patient had cultured epithelial autografts alone, without split thickness skin graft, placed on integrated BTM and had successful take. Seven patients survived to discharge and had average 95% wound closure at 135 ± 35 days. The patients had on average 10.4 total operations and 8.7 excision and grafting operations. Five patients had complications related to the BTM requiring removal or replacement including three fungal infections, one bacterial infection and one with bleeding and a large clot burden. In conclusion, this surgical strategy is a viable option for patients with massive burns and insufficient donor for autologous skin grafting.

Frailty in mid-life predicts outcome following trauma.

PURPOSE: Midlife adults (50-64 y) are at risk for falls and subsequent injury; yet current guidance on fall screening only pertains to older adults (> 65 y). Herein, we evaluated whether frailty was predictive of readmission for falls in midlife trauma patients. STUDY DESIGN: This was a retrospective cohort study of trauma midlife patients admitted for traumatic injuries from 2010 to 2015. Demographics, injury data, fall history, and post-index readmission for falls were collected from medical records. Frailty scores were calculated retrospectively using the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS). The association between frailty and outcomes was assessed. p < 0.05 was considered significant. RESULTS: A total of 326 midlife patients were included, 54% were considered fit, 33.7% pre-frail, and 12.3% frail. Compared to their fit and pre-frail counterparts, frail patients were more likely to be female (67.5% vs. 46.3% vs. 36.3%, p < 0.001), have a history of fall (22.5% vs. 15.5% vs. 6.2%, p < 0.001), and to have suffered a ground level fall on index admission (52.5% vs. 20% vs. 5.7%, p < 0.001). Controlling for age, BMI, gender, race, and fall history, frailty was associated with readmission of midlife adults for falls (OR = 1.82 [1.23-2.69]; p = 0.003) and discharge to skilled nursing facilities (OR = 26.86 [8.03-89.81], p < 0.001). CONCLUSIONS: Pre-injury frailty may be an effective tool to predict risk of readmission for fall and discharge disposition in midlife trauma patients.

Poverty and Frailty Are Not Related to Each Other With Regard to Outcomes in Middle-Aged and Older Patients with Burn Injuries.

The purpose of this study was to determine the relationship between frailty and poverty in burn patients ≥50 years old, and their association with patient outcomes. This was a single-center retrospective chart review from 2009 to 2018 of patients ≥50 years old admitted with acute burn injuries. Frailty was assigned using the Canadian Study of Health and Aging Clinical Frailty Scale. Poverty was defined as a patient from a zip code that had >20% of people living in poverty. The relationship between frailty and poverty, as well as each variable independently on mortality, length of stay (LOS), and disposition location, was examined. Of 953 patients, the median age was 61 years, 70.8% were male, and the median total body surface area burn was 6.6%. Upon admission, 26.4% and 35.2% of patients were frail and from impoverished neighborhoods, respectively. The mortality rate was 8.8%. Univariate analysis demonstrated that nonsurvivors had significantly higher chances of living in poverty (P = .02) and were more likely to be frail compared to survivors. There was no significant correlation between poverty and frailty (P = .08). Multivariate logistic regression confirmed the relationship between lack of poverty and mortality (OR .47, 95% CI 0.25-0.89) and frailty and mortality (OR 1.62, 95% CI 1.24-2.12). Neither poverty (P = .26) nor frailty (P = .52) was associated with LOS. Both poverty and frailty were associated with a patient's discharge location (P = .03; P < .0001). Poverty and frailty each independently predict mortality and discharge destination in burn patients ≥50, but they are not associated with LOS nor each other.

Admission Frailty Score Are Associated With Increased Risk of Acute Respiratory Failure and Mortality in Burn Patients 50 and Older.

Herein, we assessed the utility of the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS) to predict burn-specific outcomes. We hypothesized that frail patients are at greater risk for burn-related complications and require increased healthcare support at discharge. Patients 50 years and older admitted to our institution for burn injuries between July 2009 and June 2019 were included. Demographics, comorbidities, pre-injury functional status, injury and hospitalization information, complications (graft loss, acute respiratory failure, and acute kidney disease [AKI]), mortality, and discharge disposition were collected. Multivariate analyses were performed to assess the association between admission frailty scored using the CSHA-CFS and outcomes. P < .05 was considered significant. Eight-hundred fifty-one patients were included, 697 were not frail and 154 were frail. Controlling for Baux scores, sex, race, mechanism of injury, 2nd and 3rd degree burn surface, and inhalation injury, frailty was associated with acute respiratory failure (OR = 2.599 [1.460-4.628], P = .001) and with mortality (OR = 6.080 [2.316-15.958]; P < .001). Frailty was also associated with discharge to skilled nursing facility, rehabilitation, or long-term acute care facilities (OR = 3.135 [1.784-5.508], P < .001), and to hospice (OR = 8.694 [1.646-45.938], P = .011) when compared to home without healthcare services. Frailty is associated with increased risk of acute respiratory failure, mortality, and requiring increased healthcare support post-discharge. Our data suggest that frailty can be used as a tool to predict morbidity and mortality and for goals of care discussions for the burn patient.

Modified Frailty Index is an Independent Predictor of Death in the Burn Population: A Secondary Analysis of the Transfusion Requirement in Burn Care Evaluation (TRIBE) Study.

Frailty can increase the risk of dying after suffering a severe injury. The Modified Frailty Index (MFI) was developed by the American College of Surgeons National Surgical Quality Improvement Program to determine the impact of frailty on outcomes. Our aim was to correlate frailty with survival following a burn injury using the 11-item and 5-item MFI. We performed a secondary analysis of the Transfusion Requirement in Burn Care Evaluation (TRIBE) study. Data including, age, gender, medical history, extent and severity of burn injury, inhalation injury and discharge disposition was collected from the TRIBE database. The 11-item MFI (MFI-11) and 5-item MFI (MFI-5) scores were calculated for all patients in the TRIBE database. The TRIBE database included 347 patients. The mean age of subjects was 43 ± 17 years. Mean total body surface area burn (TBSA) was 38 ± 18%, and 23% had inhalation injury. Multivariate logistic regression analysis determined that both MFI-5 (OR 1.86; 95% CI: 1.11-3.11; P-value .02) and MFI-11 (OR 1.83; 95% CI: 1.18-2.8; P-value .007) were independent predictors for mortality. Additionally, MFI-11 scores that are >1 were independently associated with a markedly increased risk of dying after a burn injury (OR 2.91; 95% CI: 1.1-7.7; P-value .03). The MFI can be used to identify vulnerable burn injured patients who are at high risk of dying.

Understanding Factors in Burn Patient Follow-up.

Follow-up rates are concerningly low among burn-injured patients. This study investigates the factors associated with low follow-up rates and missed appointments. We hypothesize that patients who are homeless, use illicit substances, and have psychiatric comorbidities will have lower rates of follow-up and more missed appointments. Data from a discharge-planning survey of 281 burn-injured patients discharged from September 2019 to July 2020 were analyzed and matched with patients' electronic medical records for a retrospective chart review. Data collected included general demographics, burn characteristics, hospitalization details, follow-up visits, missed appointments, homeless status, substance use, major psychiatric illness, and survey responses. Data analysis used chi-square, Fisher's exact test, Student's t-test, Wilcoxon rank sum test, and multivariate regression analysis. Overall, 37% of patients had no follow-up in clinic and 46% had one or more missed appointment. On multivariate regression analysis, homeless patients were more likely to never follow-up, odds ratio (OR) = 0.23 (95% confidence interval [CI] = 0.11-0.49), as were patients who anticipated experiencing transportation difficulties, OR = 0.28 (95% CI = 0.15-0.50). Homeless patients were more likely to have missed appointments, OR = 0.23 (95% CI = 0.1-0.54). On univariate analysis, patients with one or more documented major psychiatric illness had lower follow-up rates, with 50.62% having no follow-up (P < .01). Among patients who responded to the survey that they were current drug users, 52% had no follow-up as compared to 28% of patients who responded that they did not use drugs (P < .01).

Suicide by self-inflicted burns - A persistent psychiatric problem.

Self-inflicted burns are a relatively uncommon but profound attempt at suicide. Twenty years ago, we first reviewed our experience with self-inflicted burns. With this current study, we sought to determine whether there had been any change in the incidence or outcomes of self-inflicted burns. All burn patients admitted between January 1, 2012, and December 31, 2021, with self-inflicted burns were compared with all other admissions. The frequency of self-inflicted burns and confounding risk factors of patients with self-inflicted burns remained unchanged. A large proportion (87.4 %) of the patients had psychiatric disease. They also had larger burns and higher mortality than accidental burns. Unexpectedly, logistic regression analysis that controlled for age, total percent total body surface area (TBSA) burn, sex, and inhalation injury revealed that those patients with self-inflicted burns had 72 % lower odds of dying than the general population. In conclusion, there has been no improvement in the incidence of self-inflicted burns. They result in very severe injuries, but when age, burn size, gender, and inhalation injury are controlled for, they have at least as good a chance for survival as the general burn population.

Clinical Practice Guideline: Early Mobilization and Rehabilitation of Critically Ill Burn Patients.

This Clinical Practice Guideline addresses early mobilization and rehabilitation (EMR) of critically ill adult burn patients in an intensive care unit (ICU) setting. We defined EMR as any systematic or protocolized intervention that could include muscle activation, active exercises in bed, active resistance exercises, active side-to-side turning, or mobilization to sitting at the bedside, standing, or walking, including mobilization using assistance with hoists or tilt tables, which was initiated within at least 14 days of injury, while the patient was still in an ICU setting. After developing relevant PICO (Population, Intervention, Comparator, Outcomes) questions, a comprehensive literature search was conducted with the help of a professional medical librarian. Available literature was reviewed and systematically evaluated. Recommendations were formulated through the consensus of a multidisciplinary committee, which included burn nurses, physicians, and rehabilitation therapists, based on the available scientific evidence. No recommendation could be formed on the use of EMR to reduce the duration of mechanical ventilation in the burn ICU, but we conditionally recommend the use of EMR to reduce ICU-acquired weakness in critically ill burn patients. No recommendation could be made regarding EMR's effects on the development of hospital-acquired pressure injuries or disruption or damage to the skin grafts and skin substitutes. We conditionally recommend the use of EMR to reduce delirium in critically ill burn patients in the ICU.

Red death in Caenorhabditis elegans caused by Pseudomonas aeruginosa PAO1.

During host injury, Pseudomonas aeruginosa can be cued to express a lethal phenotype within the intestinal tract reservoir-a hostile, nutrient scarce environment depleted of inorganic phosphate. Here we determined if phosphate depletion activates a lethal phenotype in P. aeruginosa during intestinal colonization. To test this, we allowed Caenorhabditis elegans to feed on lawns of P. aeruginosa PAO1 grown on high and low phosphate media. Phosphate depletion caused PAO1 to kill 60% of nematodes whereas no worms died on high phosphate media. Unexpectedly, intense redness was observed in digestive tubes of worms before death. Using a combination of transcriptome analyses, mutants, and reporter constructs, we identified 3 global virulence systems that were involved in the "red death" response of P. aeruginosa during phosphate depletion; they included phosphate signaling (PhoB), the MvfR-PQS pathway of quorum sensing, and the pyoverdin iron acquisition system. Activation of all 3 systems was required to form a red colored PQS+Fe(3+) complex which conferred a lethal phenotype in this model. When pyoverdin production was inhibited in P. aeruginosa by providing excess iron, red death was attenuated in C. elegans and mortality was decreased in mice intestinally inoculated with P. aeruginosa. Introduction of the red colored PQS+Fe(3+) complex into the digestive tube of C. elegans or mouse intestine caused mortality associated with epithelial disruption and apoptosis. In summary, red death in C. elegans reveals a triangulated response between PhoB, MvfR-PQS, and pyoverdin in response to phosphate depletion that activates a lethal phenotype in P. aeruginosa.

Wound healing in older adults with severe burns: Clinical treatment considerations and challenges.

Background: The older adult population continues to rapidly expand in number, with a projection by the United States (US) Census Bureau that there will be more individuals older than > 65 years (77.0 million) than those younger than < 18 years (76.5 million) by 2034. This review provides an overview of aging as it relates to wound healing and burn injuries in older adult patients, summarizes current treatment practices, and addresses the key challenges and considerations for treating severe burn injuries in this specific patient population. Materials and methods: A narrative literature search was conducted, focusing on recent primary literature on burns and wound healing in elderly patients. Results: Studies showed that the aging process results in both physiologic (eg, nutritional and metabolic status) and anatomic changes (eg, thinning dermis) that contribute to a reduced capacity to recover from burn-injury trauma compared with younger patients. Owing to impaired vision, decreased coordination, comorbidities, and medication-induced side effects, older adults (ie, > 65 years) are susceptible to severe burn injury (deep-partial thickness and full-thickness), which is associated with significant morbidity and mortality. Conclusion: A better understanding of the effects of age-related changes regarding wound healing in older adult patients who incur severe burn injuries may provide insight into clinical strategies to improve outcomes among this population.

The human microbiome and surgical disease.

OBJECTIVE: The purpose of this review article is to summarize what is currently known about microbes associated with the human body and to provide examples of how this knowledge impacts the care of surgical patients. BACKGROUND: Pioneering research over the past decade has demonstrated that human beings live in close, constant contact with dynamic communities of microbial organisms. This new reality has wide-ranging implications for the care of surgical patients. METHODS AND RESULTS: Recent advances in the culture-independent study of the human microbiome are reviewed. To illustrate the translational relevance of these studies to surgical disease, we discuss in detail what is known about the role of microbes in the pathogenesis of obesity, gastrointestinal malignancies, Crohn disease, and perioperative complications including surgical site infections and sepsis. The topics of mechanical bowel preparation and perioperative antibiotics are also discussed. CONCLUSIONS: Heightened understanding of the microbiome in coming years will likely offer opportunities to refine the prevention and treatment of a wide variety of surgical conditions.

Prevention of siderophore- mediated gut-derived sepsis due to P. aeruginosa can be achieved without iron provision by maintaining local phosphate abundance: role of pH.

BACKGROUND: During extreme physiological stress, the intestinal tract can be transformed into a harsh environment characterized by regio- spatial alterations in oxygen, pH, and phosphate concentration. When the human intestine is exposed to extreme medical interventions, the normal flora becomes replaced by pathogenic species whose virulence can be triggered by various physico-chemical cues leading to lethal sepsis. We previously demonstrated that phosphate depletion develops in the mouse intestine following surgical injury and triggers intestinal P. aeruginosa to express a lethal phenotype that can be prevented by oral phosphate ([Pi]) supplementation. RESULTS: In this study we examined the role of pH in the protective effect of [Pi] supplementation as it has been shown to be increased in the distal gut following surgical injury. Surgically injured mice drinking 25 mM [Pi] at pH 7.5 and intestinally inoculated with P. aeruginosa had increased mortality compared to mice drinking 25 mM [Pi] at pH 6.0 (p < 0.05). This finding was confirmed in C. elegans. Transcriptional analysis of P. aeruginosa demonstrated enhanced expression of various genes involved in media alkalization at pH 6.0 and a global increase in the expression of all iron-related genes at pH 7.5. Maintaining the pH at 6.0 via phosphate supplementation led to significant attenuation of iron-related genes as demonstrated by microarray and confirmed by QRT-PCR analyses. CONCLUSION: Taken together, these data demonstrate that increase in pH in distal intestine of physiologically stressed host colonized by P. aeruginosa can lead to the expression of siderophore-related virulence in bacteria that can be prevented without providing iron by maintaining local phosphate abundance at pH 6.0. This finding is particularly important as provision of exogenous iron has been shown to have untoward effects when administered to critically ill and septic patients. Given that phosphate, pH, and iron are near universal cues that dictate the virulence status of a broad range of microorganisms relevant to serious gut origin infection and sepsis in critically ill patients, the maintenance of phosphate and pH at appropriate physiologic levels to prevent virulence activation in a site specific manner can be considered as a novel anti-infective therapy in at risk patients.