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Transesophageal echocardiography (TEE) can be utilized for hemodynamic monitoring and resuscitation. In order to study the pattern of TEE use in trauma patients, a multi-institutional retrospective cohort study was performed comparing adult trauma patients who underwent TEE or those who underwent traditional invasive hemodynamic monitoring (TIHM). TIHM was defined as the use of arterial line, central venous line, or pulmonary artery catheter without TEE. Mortality rates were obtained and multivariable logistic regression was used to risk adjust for age, gender, race, insurance status, Glasgow coma scale (GCS), ICD Injury severity score (ICISS). Compared to TIHM group, more patients in TEE group had a history of congestive heart failure (CHF) or chronic pulmonary disease (CPD). Mortality rate was lower in the TEE group 7 versus 23% ( P -value < .0001). After adjusting for GCS and ICISS in multivariable analysis, inpatient mortality was significantly lower in the TEE cohort.

Introduction: Hip fractures are one of the most common traumatic injuries in the United States, secondary to an aging population. Multiple comorbidities are found in patients who present to trauma centers (TCs) with isolated hip fractures (IHFs) including significant cardiac disease. Aortic stenosis (AS) among these patients has been recently shown to increase mortality. However, factors leading to death from AS are unknown. We hypothesize that pulmonary hypertension (PH) is a significant mechanism of death among IHF patients with AS., Methods: This is a multicenter retrospective cohort study examining IHF patients treated at Level I and II TCs within a large hospital system from 2015 to 2019. Patients who had IHFs and AS were compared to those who had IHFs, AS, and PH. Multivariable logistic regression was used to risk adjust by age, race, insurance status, and comorbidities. The primary outcome was inpatient mortality. The secondary outcomes were hospital-acquired complications., Results: A total of 1388 IHF patients with AS were included in the study. Eleven percent of these patients also had PH. The crude mortality rate was higher if IHF patients had both AS and PH compared to IHF with AS alone (9% vs 3.7%, P -value .003). After risk adjustment, a higher risk of mortality was still significant (aOR 2.56 [95% CI 1.28, 5.11]). In addition, IHF patients with both AS and PH had higher complication rates; the exposure group had higher percentage of pulmonary embolism (1.4% vs .2%, adjusted P -value .03), new-onset congestive heart failure (4.1% vs 1%, adjusted P -value .01), and sepsis/septicemia (3.5% vs 1.4%, adjusted P -value .05)., Conclusion: In patients with IHFs, PH and AS increase the likelihood of inpatient mortality by 2.5 times compared to AS alone. Pulmonary hypertension among IHF patients with AS is an important risk factor to identify in the preoperative period. Early identification may lead to better perioperative management and counseling of patients at higher risk of complications.

Background: Patients who require mechanical ventilation secondary to severe COVID-19 infection have poor survival. It is unknown if the benefit of tracheostomy extends to COVID-19 patients. If so, what is the optimal timing?, Methods: Retrospective cohort study within a large hospital system in the United States. The population included patients with COVID-19 from January 1, 2020 to September 30, 2020. In total, 93,918 cases were identified. They were excluded if no intubation or tracheostomy, underwent tracheostomy before intubation, <18 years old, hospice patients before admission, and bacterial pneumonia. In total, 5,911 patients met the criteria. Outcomes between patients who underwent endotracheal intubation only versus tracheostomy were compared. The primary outcome was inpatient mortality. All patients who underwent tracheostomy versus intubation only were compared. Three cohort analysis compared early (<10 days) versus late (>10 days) tracheostomy versus control. Eight cohort analysis compared days 0-2, days 3-6, days 7-10, days 11-14, days 15-18, days 19-22, and days 23+ to tracheostomy versus control., Results: There was an overall inpatient mortality rate of 37.5% in the tracheostomy cohort compared to 54.4% in the control group (P < .0001). There was an early tracheostomy group inpatient mortality rate of 44.7% (adjusted odds ratio 0.73, 95% confidence interval 0.52-1.01) compared to 33.1% (adjusted odds ratio 0.44, 95% confidence interval 0.34-0.58) in the late tracheostomy group., Conclusion: COVID-19 patients with tracheostomy had a significantly lower mortality rate compared to intubated only. Optimal timing for tracheostomy placement for COVID-19 patients is 11 days or later. Future studies should focus on early tracheostomy patients., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: Mucormycosis is a rare angioinvasive infection caused by filamentous fungi with a high lethality among the immunocompromised. In healthy people, the innate immune system is sufficient to prevent infection. The exception to this is deep tissue exposure seen during trauma. The purpose of this study is to evaluate the epidemiology of mucormycosis using a statewide population-based data set., Methods: This is a retrospective cohort study of all hospital admissions for mucormycosis within the state of Florida from 1997 through the beginning of 2020. A distribution map was created to evaluate for geographic variation. Botanical growth zones, based on plant hardiness, used by state environmental agencies and landscapers were also used to detect possible patterns based on climate conditions throughout Florida. A multivariable regression analysis was performed to account for confounders and limit bias., Results: A total of 1190 patients were identified for mucormycosis infection. Only 86 of these patients were admitted for trauma. Cutaneous infections were more prevalent among trauma patients while non-trauma patients had more pulmonary infections ( P = .04). Trauma patients with infection tended to be younger and less likely to suffer from comorbidities such as immunosuppression (36% vs 46%, P = .07) and diabetes (22.1% vs 47.1%, P ≤ .0001) as compared to their non-trauma counterparts. Mortality was similar with 17.8% for non-trauma patients and 15.1% for traumatized patients (AOR .80 [.42, 1.52]). Length of stay was longer for trauma patients (37.3 vs 23.0, P < .0001). Infections were less prominent in plant hardiness Zone 9 and Zone 10 as compared to Zone 8 (AOR .71 [.61, .82]; AOR .54 [.46, .64], respectively)., Conclusion: Trauma patients who develop infection from mucormycosis are at high risk of death despite being a younger and healthier population. Mucormycosis infections were primarily soft tissue based among trauma patients. These infections are more prevalent in colder regions within Florida.

Aims: This large cohort study aimed to assess the role of chronic statin use on COVID-19 disease severity., Methods: An observational retrospective study from electronic medical records of hospitalized patients (n = 43 950) with COVID-19 between January and September 2020 in 185 hospitals in the United States. A total of 38 875 patients met inclusion criteria; 23 066 were included in the propensity-matched sampling with replacement cohort; 11 533 were prehospital statin users. The primary outcome was all-cause death; secondary outcomes were death from COVID-19 and serious complications. Mean, standard deviation, chi-square test, Student's t-test, linear regression, and binary and multinomial logistic regressions were used for statistical analysis., Results: Among 38 875 patients, 30% were chronic statin users [mean age, 70.82 (±12.25); 47.1% women] and 70% were statin nonusers [mean age, 58.44 (±18.27); 48.5% women]. Key propensity-matched outcomes among 11 533 chronic statin users showed 20% lower risk of all-cause mortality (OR 0.80, 95% CI 0.74-0.86, P < 0.001), 23% lower risk of mortality from COVID-19 (OR 0.77, 95% CI 0.71-0.84, P < 0.001), 16% lower risk of ICU admission (OR 0.84, 95% CI 0.79-0.89, P < 0.001), 24% lower risk of critical acute respiratory distress syndrome with COVID-19 (OR 0.76, 95% CI 0.70-0.83, P < 0.001), 23% lower risk of mechanical ventilation (OR 0.77, 95% CI 0.71-0.82, P < 0.001), 20% lower risk of severe sepsis with septic shock (OR 0.80, 95% CI 0.67-0.93, P = 0.004), shorter hospital length of stay [9.87 (±8.94), P < 0.001] and brief duration of mechanical ventilation [8.90 (±8.94), P < 0.001]., Conclusion: Chronic use of statins is associated with reduced mortality and improved clinical outcomes in patients hospitalized for COVID-19., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Infections within intensive care unit (ICU) are a persistent problem among the critically ill. Viral pneumonias have already been established as having a season variations. We attempt to evaluate the seasonal variations of pneumonia among the traumatically injured and the critically ill., Materials and Methods: A retrospective cohort study among traumatized patients admitted from 1997 to 2017 to an ICU within the state of Florida was performed who were diagnosed with pneumonia. A multivariate regression analysis was performed to adjust for confounders. Time periods were divided into seasons: summer, winter, spring, and fall. A subset analysis of geriatric patients (>65 years) was also performed., Results: A total of 869 553 patients were identified. The most common viral infection was influenza with adenovirus the least. The most common bacterial pneumonia was Staphylococcus aureus with Bordetella pertussis the least. Pneumonias had a seasonal variation. Compared to summer, winter had a higher likelihood of pneumonia overall (Adjusted Odds Ratio (AOR)1.13). This was seen in the spring (AOR 1.04) but not in fall (AOR 1.00). Viral infections were more pronounced (AOR 3.79) in all other seasons, while bacterial showed increased likelihood during winter (AOR 1.05). In geriatrics, pneumonia was again more likely in the winter (AOR 1.22) with both viral and bacterial infections being more pronounced during winter (AOR 4.79, AOR 1.09)., Discussion: Pneumonias are seen more frequently within the ICU during the winter for the traumatized patient. This held true with the critically ill geriatric population as well. This effect was observed in both viral and bacterial pneumonias.

Background: The epidemiology of Clostridium difficile-associated infection (CDI) has changed, and it is evident that susceptibility is related not only to exposures and bacterial potency, but host factors as well. Several small studies have suggested that CDI after trauma is associated with a different patient phenotype. The purpose of this study was to examine and describe the epidemiologic factors associated with C. difficile in blunt trauma patients without traumatic brain injury using the Trauma-Related Database as a part of the "Inflammation and Host Response to Injury" (Glue Grant) and the University of Florida Integrated Data Repository., Methods: Previously recorded baseline characteristics, clinical data, and outcomes were compared between groups (67 C. difficile and 384 uncomplicated, 813 intermediate, and 761 complicated non-C. difficile patients) as defined by the Glue Grant on admission and at days seven and 14., Results: The majority of CDI patients experienced complicated or intermediate clinical courses. The mean ages of all cohorts were less than 65 y and CDI patients were significantly older than uncomplicated patients without CDI. The CDI patients had increased days in the hospital and on the ventilator, as well as significantly higher new injury severity scores (NISS), and a greater percentage of patients with NISS >34 points compared with non-CDI patients. They also had greater Marshall and Denver multiple organ dysfunction scores than non-CDI uncomplicated patients, and greater creatinine, alkaline phosphatase, neutrophil count, lactic acid, and PiO2:FiO2 compared with all non-CDI cohorts on admission. In addition, the CDI patients had higher glucose concentrations and base deficit from uncomplicated patients and greater leukocytosis than complicated patients on admission. Several of these changes persisted to days seven and 14., Conclusion: Analysis of severe blunt trauma patients with C. difficile, as compared with non-CDI patients, reveals evidence of increased inflammation, immunosuppression, worse acute kidney injury, higher NISS, greater days in the hospital and on the ventilator, higher organ injury scores, and prolonged clinical courses. This supports reports of an increased prevalence of CDI in a younger population not believed previously to be at risk. This unique population may have specific genomic or inflammation-related risk factors that may play more important roles in disease susceptibility. Prospective analysis may allow early identification of at-risk patients, creation of novel therapeutics, and improved understanding of how and why C. difficile colonization transforms into infection after severe blunt trauma.

Background: Blood product transfusions are associated with increased morbidity and mortality. The purpose of this study was to determine if implementation of a restrictive protocol for packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusion safely reduces blood product utilization and costs in a surgical intensive care unit (SICU)., Study Design: We performed a retrospective, historical control analysis comparing before (PRE) and after (POST) implementation of a restrictive PRBC/FFP transfusion protocol for SICU patients. Univariate analysis was utilized to compare patient demographics and blood product transfusion totals between the PRE and POST cohorts. Multivariate logistic regression models were developed to determine if implementation of the restrictive transfusion protocol is an independent predictor of adverse outcomes after controlling for age, illness severity, and total blood products received., Results: 829 total patients were included in the analysis (PRE, n=372; POST, n=457). Despite higher mean age (56 vs. 52 years, p=0.01) and APACHE II scores (12.5 vs. 11.2, p=0.006), mean units transfused per patient were lower for both packed red blood cells (0.7 vs. 1.2, p=0.03) and fresh frozen plasma (0.3 vs. 1.2, p=0.007) in the POST compared to the PRE cohort, respectively. There was no difference in inpatient mortality between the PRE and POST cohorts (7.5% vs. 9.2%, p=0.39). There was a decreased risk of urinary tract infections (OR 0.47, 95%CI 0.28-0.80) in the POST cohort after controlling for age, illness severity and amount of blood products transfused., Conclusions: Implementation of a restrictive transfusion protocol can effectively reduce blood product utilization in critically ill surgical patients with no increase in morbidity or mortality.

The emphasis on high-quality care has spawned the development of quality programs, most of which focus on broad outcome measures across a diverse group of providers. Our aim was to investigate the clinical outcomes for a department of surgery with multiple service lines of patient care using a relational database. Mortality, length of stay (LOS), patient safety indicators (PSIs), and hospital-acquired conditions were examined for each service line. Expected values for mortality and LOS were derived from University HealthSystem Consortium regression models, whereas expected values for PSIs were derived from Agency for Healthcare Research and Quality regression models. Overall, 5200 patients were evaluated from the months of January through May of both 2011 (n = 2550) and 2012 (n = 2650). The overall observed-to-expected (O/E) ratio of mortality improved from 1.03 to 0.92. The overall O/E ratio for LOS improved from 0.92 to 0.89. PSIs that predicted mortality included postoperative sepsis (O/E:1.89), postoperative respiratory failure (O/E:1.83), postoperative metabolic derangement (O/E:1.81), and postoperative deep vein thrombosis or pulmonary embolus (O/E:1.8). Mortality and LOS can be improved by using a relational database with outcomes reported to specific service lines. Service line quality can be influenced by distribution of frequent reports, group meetings, and service line-directed interventions.

Background: Necrotizing fasciitis (NF) most often is caused by bacterial infection while a fungal source has been reported in immunosuppressed patients. Early wide surgical resection remains the mainstay of treatment. Split thickness skin grafts are both versatile and easy to harvest, thus making them a long-established option for soft tissue reconstruction., Case Report: A 55-year-old man was admitted for gunshot wounds. Purulence was noted at the central catheter site. Cultures grew Candida albicans. Antifungal therapy was initiated and debridement for NF of the neck and upper chest was performed. The patient underwent reconstruction using a split thickness skin graft obtained from the anterolateral thigh., Conclusions: Necrotizing fasciitis secondary to Candida species infection is exceedingly rare. We report an unusual case of candidal NF in a patient with no past medical history of immunocompromise. Patients with this type of infection can be successfully treated with aggressive surgical debridement and intravenous anidulafungin.

Objective: To develop a novel polytrauma model that better recapitulates the immunologic response of the severely injured patient by combining long-bone fracture, muscle tissue damage, and cecectomy with hemorrhagic shock, resulting in an equivalent Injury Severity Score of greater than 15. We compared this new polytrauma/shock model to historically used murine trauma-hemorrhage models., Design: Pre-clinical controlled in vivo laboratory study., Setting: Laboratory of Inflammation Biology and Surgical Science., Subjects: Six- to 10-week-old C57BL/6 (B6) mice., Interventions: Mice underwent 90 minutes of shock (mean arterial pressure 30 mm Hg) and resuscitation via femoral artery cannulation followed by laparotomy (trauma-hemorrhage), hemorrhage with laparotomy and femur fracture, or laparotomy with cecetomy and femur fracture with muscle tissue damage (polytrauma). Mice were euthanized at 2 hours, 1 day, and 3 days postinjury., Measurements and Main Results: The spleen, bone marrow, blood, and serum were collected from mice for analysis at the above time points. None of the models were lethal. Mice undergoing polytrauma exhibited a more robust inflammatory response with significant elevations in cytokine/chemokine concentrations when compared with traditional models. Polytrauma was the only model to induce neutrophilia (Ly6G (+)CD11b(+) cells) on days 1 and 3 (p<0.05). Polytrauma, as compared to trauma-hemorrhage and hemorrhage with laparotomy and femur fracture, induced a loss of circulating CD4(+) T cell with simultaneous increased cell activation (CD69(+) and CD25(+)), similar to human trauma. There was a prolonged loss of major histocompatibility complex class II expression on monocytes in the polytrauma model (p<0.05). Results were confirmed by genome-wide expression analysis that revealed a greater magnitude and duration of blood leukocyte gene expression changes in the polytrauma model than the trauma-hemorrhage and sham models., Conclusions: This novel polytrauma model better replicates the human leukocyte, cytokine, and overall inflammatory response following injury and hemorrhagic shock.

Background: Evidence demonstrates that susceptibility to Clostridium difficile infection is related to host risk factors as much as bacterial potency. Using blood leukocyte genome-wide expression patterns of severe blunt trauma patients obtained by the National Institute of General Medical Sciences-sponsored Glue Grant Inflammation and the Host Response to Injury, we examined leukocyte genomic profiles of patients with C. difficile infection to determine preinfection and postinfection gene expression changes., Methods: The genomic responses of 21 severe trauma patients were analyzed (5 C. difficile, 16 controls matched for age and severity of injury). After elimination of probe sets whose expression was below baseline or were unchanged, remaining probe sets underwent hierarchical clustering and principal component analysis. Molecular pathways were generated through Ingenuity Pathways Analysis., Results: Supervised analysis demonstrated 118 genes whose expression in patients with C. difficile infection varied before and after their infection. Supervised analysis comparing patients with C. difficile infection with matched non-C. difficile patients before infection suggested that the expression of 501 genes were different in the two groups with up to 87% class prediction (p < 0.05). Many of these genes are related to cell-mediated immune responses, signaling, and interaction., Conclusion: Genomic analysis of severe blunt trauma patients reveals a distinct leukocyte expression profile of C. difficile both before and after infection. We conclude that an association may exist between a severe trauma patient's leukocyte genomic expression profile and subsequent susceptibility to C. difficile infection. Further prospective expression analysis of this C. difficile population may reveal potential therapeutic interventions and allow early identification of C. difficile-susceptible patients., Level of Evidence: Prognostic/diagnostic study, level III.

Background: Census predictions for Florida suggest a 3-fold increase in the 65 and older population within 20 years. We predict resource utilization for burn patients in this age group., Methods: Using the Florida Agency for Healthcare Administration admission dataset, we evaluated the effect of age on length of stay, hospital charges, and discharge disposition while adjusting for clinical and demographic factors. Using US Census Bureau data and burn incidence rates from this dataset, we estimated future resource use., Results: Elderly patients were discharged to home less often and were discharged to short-term general hospitals, intermediate-care facilities, and skilled nursing facilities more often than the other age groups (P < .05). They also required home health care and intravenous medications significantly more often (P < .05). Their length of stay was longer, and total hospital charges were greater (P < .05) after adjusting for sex, race, Charleson comorbidity index, payer, total body surface area burned, and burn center treatment., Conclusions: Our data show an age-dependent increase in the use of posthospitalization resources, the length of stay, and the total charges for elderly burn patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Blood transfusion is a well-established risk factor for adverse outcomes during sepsis. The specific mechanisms responsible for this effect remain elusive, and few studies have investigated this phenomenon in a model that reflects not only the clinical circumstances in which blood is transfused, but also how packed red blood cells (PRBCs) are created and stored. Using a cecal ligation and puncture model of polymicrobial sepsis as well as creating murine allogeneic and stored PRBCs in a manner that replicates the clinical process, we have demonstrated that transfusion of PRBCs induces numerous effects on leukocyte subpopulations. In polymicrobial sepsis, these responses are profoundly dissimilar to the proinflammatory effects of PRBC transfusion observed in the healthy mouse. Transfused septic mice, as opposed to mice receiving crystalloid resuscitation, had a significant loss of blood, spleen, and bone marrow lymphocytes, especially those with an activated phenotype. Myeloid cells behaved similarly, although they were able to produce more reactive oxygen species. Overall, transfusion in the septic mouse may contribute to the persistent immune dysfunction known to be associated with this process, rather than simply promote proinflammatory or anti-inflammatory effects on the host. Thus, it is possible that blood transfusion contributes to the multiple known effects of sepsis on leukocyte populations that have been shown to result in increased morbidity and mortality.

Objective: The state of Florida has some of the most dangerous highways in the USA. In 2006, Florida averaged 1.65 fatalities per 100 million vehicle miles travelled (VMT) compared with the national average of 1.42. A study was undertaken to find a method of identifying counties that contributed to the most driver fatalities after a motor vehicle collision (MVC). By regionalising interventions unique to this subset of counties, the use of resources would have the greatest potential of improving statewide driver death., Methods: The Florida Highway Safety Motor Vehicle database 2000-2006 was used to calculate driver VMT-weighted deaths by county. A total of 3,468,326 motor vehicle crashes were evaluated. Counties that had driver death rates higher than the state average were sorted by a weighted averages method. Multivariate regression was used to calculate the likelihood of death for various risk factors., Results: VMT-weighted death rates identified 12 out of 67 counties that contributed up to 50% of overall driver fatalities. These counties were primarily clustered in central and south Florida. The strongest independent risk factors for driver death attributable to MVC in these high-risk counties were alcohol/drug use, rural roads, speed limit ≥45 mph, adverse weather conditions, divided highways, vehicle type, vehicle defects and roadway location., Conclusions: Using the weighted averages method, a small subset of counties contributing to the majority of statewide driver fatalities was identified. Regionalised interventions on specific risk factors in these counties may have the greatest impact on reducing driver-related MVC fatalities.

Background: Percutaneous needle biopsy, also known as minimally invasive breast biopsy (MIBB), has become the gold standard for the initial assessment of suspicious breast lesions. The purpose of this study is to determine modern rates of MIBB and open breast biopsy., Methods: The Florida Agency for Health Care Administration outpatient surgery and procedure database was queried for patients undergoing open surgical biopsy and MIBB between 2003 and 2008., Results: Although there was an increase in the use of MIBB, the overall rate of open surgical biopsy remained high (∼30%). A reduction in the open biopsy rate from 30% to 10% could be associated with a charge reduction of >$37.2 million per year., Conclusions: The current rate of open surgical breast biopsy remains high. Interventions and quality initiatives are warranted, which could lead to a reduction in unnecessary operations for women, improved patient care, and a reduction in breast health care costs., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The goal of this study was to examine the association between patient complications and admission to Level I trauma centers (TC) compared with nontrauma centers (NTC)., Study Design: This was a retrospective cohort study of data derived from the National Study on the Costs and Outcomes of Trauma (NSCOT). Patients were recruited from 18 Level I TCs and 51 NTCs in 15 regions encompassing 14 states. Trained study nurses, using standardized forms, abstracted the medical records of the patients. The overall number of complications per patient was identified, as was the presence or absence of 13 specific complications., Results: Patients treated in TCs were more likely to have any complication compared with patients in NTCs, with an adjusted relative risk (RR) of 1.34 (95% CI, 1.03, 1.74). For individual complications, only the urinary tract infection RR of 1.94 (95% CI, 1.07, 3.17) was significantly higher in TCs. TC patients were more likely to have 3 or more complications (RR, 1.83; 95% CI, 1.16, 2.90). Treatment variables that are surrogates for markers of injury severity, such as use of pulmonary artery catheters, multiple operations, massive transfusions (> 2,500 mL packed red blood cells), and invasive brain catheters, occurred significantly more often in TCs., Conclusions: Trauma centers have a slightly higher incidence rate of complications, even after adjusting for patient case mix. Aggressive treatment may account for a significant portion of TC-associated complications. Pulmonary artery catheter use and intubation had the most influence on overall TC complication rates. Additional study is needed to provide accurate benchmark measures of complication rates and to determine their causes.

Impalement injuries are relatively uncommon during vehicular trauma. We present a dual case report of patients sustaining simultaneous impalement injuries during a high-speed motor vehicle collision in a rural (austere) environment. After Institutional Review Board approval, we performed a review of the patients' medical records. Two young men were traveling in an automobile at high speed when the driver lost control of the vehicle, causing it to strike a wooden fence. Portions of the fence were dislodged, penetrated the windshield, and impaled both the driver and passenger. Both patients were extricated rapidly and transported to our trauma center. Multidisciplinary teams consisting of trauma, thoracic, plastic, and hepatobiliary surgeons addressed the injuries of both patients. Both survived their injuries and have since returned to their homes. This case of dual impalements highlights three key points: first, the principles of management of thoracoabdominal impalement injuries; second, the importance of rapid action of first responders in complex traumas; and finally, the value of using a multidisciplinary surgical team in complicated trauma cases.

Hyaluronate carboxymethylcellulose (Seprafilm; Genzyme Corp., Cambridge, MA) has been demonstrated to be safe and efficacious for the prevention of abdominal and pelvic adhesions; however, information is scarce regarding its use in children and adolescents. We wanted to characterize our experience with Seprafilm in a pediatric surgical population. After Institutional Review Board approval, we searched our hospital and pediatric surgery database for cases in which Seprafilm was used and retrospectively reviewed medical records for demographic and clinical information. Between July 2000 and October 2005, 18 patients had Seprafilm placed. Patients ranged in age from 0.25 to 18 years. Seven patients had not undergone any previous operations. Of patients having undergone prior surgery, the most common preceding intervention was a Ladd's procedure. Seprafilm was applied in a variety of scenarios, the most frequently being adhesiolysis for bowel obstruction. No patient required reoperation for obstruction. Two patients underwent subsequent operations for unrelated reasons; one was noted to have no significant adhesions, but the other had extensive adhesions. No patient demonstrated signs or symptoms of small bowel obstruction, intraperitoneal abscess, or localized inflammatory reaction to Seprafilm. Seprafilm was successfully used in our pediatric surgical population without complications.

In vitro selections performed in the presence of Mg(2+) generated DNA sequences capable of cleaving an internal ribonucleoside linkage. Several of these, surprisingly, displayed intermolecular catalysis and catalysis independent of Mg(2+), features that the selection protocol was not explicitly designed to select. A detailed physical organic analysis was applied to one of these DNAzymes, termed 614. First, the progress curve for the reaction was dissected to identify factors that prevented the molecule from displaying clean first-order transformation kinetics and 100% conversion. Several factors were identified and quantitated, including (a) competitive intra- and intermolecular rate processes, (b) alternative reactive and unreactive conformations, and (c) mutations within the catalyst. Other factors were excluded, including "approach to equilibrium" kinetics and product inhibition. The possibility of complementary strand inhibition was demonstrated but was shown to not be a factor under the conditions of these experiments. The rates of the intra- and intermolecular processes were compared, and saturation models for the intermolecular process were built. The rate-limiting step for the intermolecular reaction was found to be the association/folding of the enzyme with the substrate and not the cleavage step. The DNAzyme 614 is more active in trans than in cis and more active at temperatures below the selection temperature than at the selection temperature. Many of these properties have not been reported in similar systems; these results therefore expand the phenomenology known for this class of DNA-based catalysts. A brief survey of other catalysts arising from this selection found other Mg(2+)-independent DNAzymes and provided a preliminary view of the ruggedness of the landscape, relating function to structure in sequence space. Hypotheses are suggested to account for the fact that a selection in the presence of Mg(2+) did not exploit this Mg(2+). This study of a specific catalytically active DNAzyme is an example of studies that will be necessary generally to permit in vitro selection to help us understand the distribution of function in sequence space.

5-(3"-Aminopropynyl)-2'-deoxyuridine (dJ), a modified nucleoside with a side chain carrying a cationic functional group, was incorporated into an oligonucleotide library, which was amplified using the Vent DNA polymerase in a polymerase chain reaction (PCR). When coupled to an in vitro selection procedure, PCR amplification generated receptors that bind ATP. This is the first example of an in vitro selection generating oligonucleotide receptors where the oligonucleotide library has incorporated a cationic nucleotide functionality. The selection yielded functionalized receptors having sequences differing from a motif known to arise in a standard selection experiment using only natural nucleotides. Surprisingly, both the natural and the functionalized motifs convergently evolved to bind not one, but two ATP molecules cooperatively. Likewise, the affinity of the receptors for ATP had converged; in both cases, the receptors are half saturated at the 3 mM concentrations of ATP presented during the selection. The convergence of phenotype suggests that the outcome of this selection experiment was determined by features of the environment during which selection occurs, in particular, a highly loaded affinity resin used in the selection step. Further, the convergence of phenotype suggests that the optimal molecular phenotype has been achieved by both selections for the selection conditions. This interplay between environmental conditions demanding a function of a biopolymer and the ability of the biopolymer to deliver that function is strictly analogous to that observed during natural selection, illustrating the nature of life as a self-sustaining chemical system capable of Darwinian evolution.