The Effect of 2019 Coronavirus Stay-at-Home Order on Geriatric Trauma Patients in Southern California.

BACKGROUND: California issued stay-at-home (SAH) orders to mitigate COVID-19 spread. Previous studies demonstrated a shift in mechanisms of injuries (MOIs) and decreased length of stay (LOS) for the general trauma population after SAH orders. This study aimed to evaluate the effects of SAH orders on geriatric trauma patients (GTPs), hypothesizing decreased motor vehicle collisions (MVCs) and LOS. METHODS: A post-hoc analysis of GTPs (≥65 years old) from 11 level-I/II trauma centers was performed, stratifying patients into 3 groups: before SAH (1/1/2020-3/18/2020) (PRE), after SAH (3/19/2020-6/30/2020) (POST), and a historical control (3/19/2019-6/30/2019) (CONTROL). Bivariate comparisons were performed. RESULTS: 5486 GTPs were included (PRE-1756; POST-1706; CONTROL-2024). POST had a decreased rate of MVCs (7.6% vs 10.6%, P = .001; vs 11.9%, P < .001) and pedestrian struck (3.4% vs 5.8%, P = .001; vs 5.2%, P = .006) compared with PRE and CONTROL. Other mechanisms of injury, LOS, mortality, and operations performed were similar between cohorts. However, POST had a lower rate of discharge to skilled nursing facility (SNF) (20% vs 24.5%, P = .001; and 20% vs 24.4%, P = .001). CONCLUSION: This retrospective multicenter study demonstrated lower rates of MVCs and pedestrian struck for GTPs, which may be explained by decreased population movement as a result of SAH orders. Contrary to previous studies on the generalized adult population, no differences in other MOIs and LOS were observed after SAH orders. However, there was a lower rate of discharge to SNF, which may be related to a lack of resources due to the COVID-19 pandemic, and thus potentially negatively impacted recovery of GTPs.Keywords.

Adolescent Trauma During the COVID Pandemic: Just Like Adults, Children, or Someone Else?

COVID-19 stay-at-home (SAH) orders were impactful on adolescence, when social interactions affect development. This has the potential to change adolescent trauma. A post-hoc multicenter retrospective analysis of adolescent (13-17 years-old) trauma patients (ATPs) at 11 trauma centers was performed. Patients were divided into 3 groups based on injury date: historical control (CONTROL:3/19/2019-6/30/2019, before SAH (PRE:1/1/2020-3/18/2020), and after SAH (POST:3/19/2020-6/30/2020). The POST group was compared to both PRE and CONTROL groups in separate analyses. 726 ATPs were identified across the 3 time periods. POST had a similar penetrating trauma rate compared to both PRE (15.8% vs 13.8%, P = .56) and CONTROL (15.8% vs 14.5%, P = .69). POST also had a similar rate of suicide attempts compared to both PRE (1.2% vs 1.5%, P = .83) and CONTROL (1.2% vs 2.1%, P = .43). However, POST had a higher rate of drug positivity compared to CONTROL (28.6% vs 20.6%, P = .032), but was similar in all other comparisons of alcohol and drugs to PRE and POST periods (all P > .05). Hence ATPs were affected differently than adults and children, as they had a similar rate of penetrating trauma, suicide attempts, and alcohol positivity after SAH orders. However, they had increased drug positivity compared to the CONTROL, but not PRE group.

Decreased hospital length of stay and intensive care unit admissions for non-COVID blunt trauma patients during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic overwhelmed hospitals, forcing adjustments including discharging patients earlier and limiting intensive care unit (ICU) utilization. This study aimed to evaluate ICU admissions and length of stay (LOS) for blunt trauma patients (BTPs). METHODS: A retrospective review of COVID (3/19/20-6/30/20) versus pre-COVID (3/19/19-6/30/19) BTPs at eleven trauma centers was performed. Multivariable analysis was used to identify risk factors for ICU admission. RESULTS: 12,744 BTPs were included (6942 pre-COVID vs. 5802 COVID). The COVID cohort had decreased mean LOS (3.9 vs. 4.4 days, p = 0.029), ICU LOS (0.9 vs. 1.1 days, p < 0.001), and rate of ICU admission (22.3% vs. 24.9%, p = 0.001) with no increase in complications or mortality compared to the pre-COVID cohort (all p > 0.05). On multivariable analysis, the COVID period was associated with decreased risk of ICU admission (OR = 0.82, CI 0.75-0.90, p < 0.001). CONCLUSIONS: BTPs had decreased LOS and associated risk of ICU admission during COVID, with no corresponding increase in complications or mortality.

Effects of the COVID-19 pandemic on pediatric trauma in Southern California.

PURPOSE: The COVID-19 pandemic resulted in increased penetrating trauma and decreased length of stay (LOS) amongst the adult trauma population, findings important for resource allocation. Studies regarding the pediatric trauma population are sparse and mostly single-center. This multicenter study examined pediatric trauma patients, hypothesizing increased penetrating trauma and decreased LOS after the 3/19/2020 stay-at-home (SAH) orders. METHODS: A multicenter retrospective analysis of trauma patients ≤ 17 years old presenting to 11 centers in California was performed. Demographic data, injury characteristics, and outcomes were collected. Patients were divided into three groups based on injury date: 3/19/2019-6/30/2019 (CONTROL), 1/1/2020-3/18/2020 (PRE), 3/19/2020-6/30/2020 (POST). POST was compared to PRE and CONTROL in separate analyses. RESULTS: 1677 patients were identified across all time periods (CONTROL: 631, PRE: 479, POST: 567). POST penetrating trauma rates were not significantly different compared to both PRE (11.3 vs. 9.0%, p = 0.219) and CONTROL (11.3 vs. 8.2%, p = 0.075), respectively. POST had a shorter mean LOS compared to PRE (2.4 vs. 3.3 days, p = 0.002) and CONTROL (2.4 vs. 3.4 days, p = 0.002). POST was also not significantly different than either group regarding intensive care unit (ICU) LOS, ventilator days, and mortality (all p > 0.05). CONCLUSIONS: This multicenter retrospective study demonstrated no difference in penetrating trauma rates among pediatric patients after SAH orders but did identify a shorter LOS.

Does Gender Matter: A Multi-Institutional Analysis of Viscoelastic Profiles for 1565 Trauma Patients With Severe Hemorrhage.

BACKGROUND: Viscoelastic tests including thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are being used in patients with severe hemorrhage at trauma centers to guide resuscitation. Several recent studies demonstrated hypercoagulability in female trauma patients that was associated with a survival advantage. The objective of our study was to elucidate the effects of gender differences in TEG/ROTEM values on survival in trauma patients with severe hemorrhage. METHODS: A retrospective review of consecutive adult patients receiving massive transfusion protocol (MTP) at 7 Level I trauma centers was performed from 2013 to 2018. Data were stratified by gender and then further examined by TEG or ROTEM parameters. Results were analyzed using univariate and multi-variate analyses. RESULTS: A total of 1565 patients were included with 70.9% male gender (n = 1110/1565). Female trauma patients were older than male patients (43.5 ± .9 vs 41.1 ± .6 years, P = .01). On TEG, females had longer reaction times (6.1 ± .9 min vs 4.8 ± .2 min, P = .03), increased alpha angle (68.6 ± .8 vs 65.7 ± .4, P < .001), and higher maximum amplitude (59.8 ± .8 vs 56.3 ± .4, P < .001). On ROTEM, females had significantly longer clot time (99.2 ± 13.7 vs 75.1 ± 2.6 sec, P = .09) and clot formation time (153.6 ± 10.6 sec vs 106.9 ± 3.8 sec, P < .001). When comparing by gender, no difference for in-hospital mortality was found for patients in the TEG or ROTEM group (P > .05). Multivariate analysis showed no survival difference for female patients (OR 1.11, 95% CI .83-1.50, P = .48). CONCLUSIONS: Although a difference between male and females was found on TEG/ROTEM for certain clotting parameters, no difference in mortality was observed. Prospective multi-institutional studies are needed.

Drug and alcohol positivity of traumatically injured patients related to COVID-19 stay-at-home orders.

Background: COVID-19 related stay-at-home (SAH) orders created many economic and social stressors, possibly increasing the risk of drug/alcohol abuse in the community and trauma population.Objectives: Describe changes in alcohol/drug use in traumatically injured patients after SAH orders in California and evaluate demographic or injury pattern changes in alcohol or drug-positive patients.Methods: A retrospective analysis of 11 trauma centers in Southern California (1/1/2020-6/30/2020) was performed. Blood alcohol concentration, urine toxicology results, demographics, and injury characteristics were collected. Patients were grouped based on injury date - before SAH (PRE-SAH), immediately after SAH (POST-SAH), and a historical comparison (3/19/2019-6/30/2019) (CONTROL) - and compared in separate analyses. Groups were compared using chi-square tests for categorical variables and Mann-Whitney U tests for continuous variables.Results: 20,448 trauma patients (13,634 male, 6,814 female) were identified across three time-periods. The POST-SAH group had higher rates of any drug (26.2% vs. 21.6% and 24.7%, OR = 1.26 and 1.08, p < .001 and p = .035), amphetamine (10.4% vs. 7.5% and 9.3%, OR = 1.43 and 1.14, p < .001 and p = .023), tetrahydrocannabinol (THC) (13.8% vs. 11.0% and 11.4%, OR = 1.30 and 1.25, p < .001 and p < .001), and 3,4-methylenedioxy methamphetamine (MDMA) (0.8% vs. 0.4% and 0.2%, OR = 2.02 and 4.97, p = .003 and p < .001) positivity compared to PRE-SAH and CONTROL groups. Alcohol concentration and positivity were similar between groups (p > .05).Conclusion: This Southern California multicenter study demonstrated increased amphetamine, MDMA, and THC positivity in trauma patients after SAH, but no difference in alcohol positivity or blood concentration. Drug prevention strategies should continue to be adapted within and outside of hospitals during a pandemic.

COVID-19 in trauma: a propensity-matched analysis of COVID and non-COVID trauma patients.

PURPOSE: There is mounting evidence that surgical patients with COVID-19 have higher morbidity and mortality than patients without COVID-19. Infection is prevalent amongst the trauma population, but any effect of COVID-19 on trauma patients is unknown. We aimed to evaluate the effect of COVID-19 on a trauma population, hypothesizing increased mortality and pulmonary complications for COVID-19-positive (COVID) trauma patients compared to propensity-matched COVID-19-negative (non-COVID) patients. METHODS: A retrospective analysis of trauma patients presenting to 11 Level-I and II trauma centers in California between 1/1/2019-6/30/2019 and 1/1/2020-6/30/2020 was performed. A 1:2 propensity score model was used to match COVID to non-COVID trauma patients using age, blunt/penetrating mechanism, injury severity score, Glasgow Coma Scale score, systolic blood pressure, respiratory rate, and heart rate. Outcomes were compared between the two groups. RESULTS: A total of 20,448 trauma patients were identified during the study period. 53 COVID trauma patients were matched with 106 non-COVID trauma patients. COVID patients had higher rates of mortality (9.4% vs 1.9%, p = 0.029) and pneumonia (7.5% vs. 0.0%, p = 0.011), as well as a longer mean length of stay (LOS) (7.47 vs 3.28 days, p < 0.001) and intensive care unit LOS (1.40 vs 0.80 days, p = 0.008), compared to non-COVID patients. CONCLUSION: This multicenter retrospective study found increased rates of mortality and pneumonia, as well as a longer LOS, for COVID trauma patients compared to a propensity-matched cohort of non-COVID patients. Further studies are warranted to validate these findings and to elucidate the underlying pathways responsible for higher mortality in COVID trauma patients.

The coronavirus disease 2019 (COVID-19) stay-at-home order's unequal effects on trauma volume by insurance status in Southern California.

BACKGROUND: The rapid spread of coronavirus disease 2019 in the United States led to a variety of mandates intended to decrease population movement and "flatten the curve." However, there is evidence some are not able to stay-at-home due to certain disadvantages, thus remaining exposed to both coronavirus disease 2019 and trauma. We therefore sought to identify any unequal effects of the California stay-at-home orders between races and insurance statuses in a multicenter study utilizing trauma volume data. METHODS: A posthoc multicenter retrospective analysis of trauma patients presenting to 11 centers in Southern California between the dates of January 1, 2020, and June 30, 2020, and January 1, 2019, and June 30, 2019, was performed. The number of trauma patients of each race/insurance status was tabulated per day. We then calculated the changes in trauma volume related to stay-at-home orders for each race/insurance status and compared the magnitude of these changes using statistical resampling. RESULTS: Compared to baseline, there was a 40.1% drop in total trauma volume, which occurred 20 days after stay-at-home orders. During stay-at-home orders, the average daily trauma volume of patients with Medicaid increased by 13.7 ± 5.3%, whereas the volume of those with Medicare, private insurance, and no insurance decreased. The average daily trauma volume decreased for White, Black, Asian, and Latino patients with the volume of Black and Latino patients dropping to a similar degree compared to White patients. CONCLUSION: This retrospective multicenter study demonstrated that patients with Medicaid had a paradoxical increase in trauma volume during stay-at-home orders, suggesting that the most impoverished groups remain disproportionately exposed to trauma during a pandemic, further exacerbating existing health disparities.

Changes in traumatic mechanisms of injury in Southern California related to COVID-19: Penetrating trauma as a second pandemic.

BACKGROUND: The COVID-19 pandemic resulted in a statewide stay-at-home (SAH) order in California beginning March 19, 2020, forcing large-scale behavioral changes and taking an emotional and economic toll. The effects of SAH orders on the trauma population remain unknown. We hypothesized an increase in rates of penetrating trauma, gunshot wounds, suicide attempts, and domestic violence in the Southern California trauma population after the SAH order. METHODS: A multicenter retrospective analysis of all trauma patients presenting to 11 American College of Surgeons levels I and II trauma centers spanning seven counties in California was performed. Demographic data, injury characteristics, clinical data, and outcomes were collected. Patients were divided into three groups based on injury date: before SAH from January 1, 2020, to March 18, 2020 (PRE), after SAH from March 19, 2020, to June 30, 2020 (POST), and a historical control from March 19, 2019, to June 30, 2019 (CONTROL). POST was compared with both PRE and CONTROL in two separate analyses. RESULTS: Across all periods, 20,448 trauma patients were identified (CONTROL, 7,707; PRE, 6,022; POST, 6,719). POST had a significantly increased rate of penetrating trauma (13.0% vs. 10.3%, p < 0.001 and 13.0% vs. 9.9%, p < 0.001) and gunshot wounds (4.5% vs. 2.4%, p = 0.002 and 4.5% vs. 3.7%, p = 0.025) compared with PRE and CONTROL, respectively. POST had a suicide attempt rate of 1.9% and a domestic violence rate of 0.7%, which were similar to PRE (p = 0.478, p = 0.514) and CONTROL (p = 0.160, p = 0.618). CONCLUSION: This multicenter Southern California study demonstrated an increased rate of penetrating trauma and gunshot wounds after the COVID-19 SAH orders but no difference in attempted suicide or domestic violence rates. These findings may provide useful information regarding resource utilization and a target for societal intervention during the current or future pandemic(s). LEVEL OF EVIDENCE: Epidemiological, level IV.

Into the wild and on to the table: A Western Trauma Association multicenter analysis and comparison of wilderness falls in rock climbers and nonclimbers.

BACKGROUND: Wilderness activities expose outdoor enthusiasts to austere environments with injury potential, including falls from height. The majority of published data on falls while climbing or hiking are from emergency departments. We sought to more accurately describe the injury pattern of wilderness falls that lead to serious injury requiring trauma center evaluation and to further distinguish climbing as a unique pattern of injury. METHODS: Data were collected from 17 centers in 11 states on all wilderness falls (fall from cliff: International Classification of Diseases, Ninth Revision, e884.1; International Classification of Diseases, 10th Revision, w15.xx) from 2006 to 2018 as a Western Trauma Association multicenter investigation. Demographics, injury characteristics, and care delivery were analyzed. Comparative analyses were performed for climbing versus nonclimbing mechanisms. RESULTS: Over the 13-year study period, 1,176 wilderness fall victims were analyzed (301 climbers, 875 nonclimbers). Fall victims were male (76%), young (33 years), and moderately injured (Injury Severity Score, 12.8). Average fall height was 48 ft, and average rescue/transport time was 4 hours. Nineteen percent were intoxicated. The most common injury regions were soft tissue (57%), lower extremity (47%), head (40%), and spine (36%). Nonclimbers had a higher incidence of severe head and facial injuries despite having equivalent overall Injury Severity Score. On multivariate analysis, climbing remained independently associated with increased need for surgery but lower odds of composite intensive care unit admission/death. Contrary to studies of urban falls, height of fall in wilderness falls was not independently associated with mortality or Injury Severity Score. CONCLUSION: Wilderness falls represent a unique population with distinct patterns of predominantly soft tissue, head, and lower extremity injury. Climbers are younger, usually male, more often discharged home, and require more surgery but less critical care. LEVEL OF EVIDENCE: Epidemiological, Level IV.

Outcomes in patients with gunshot wounds to the brain.

INTRODUCTION: Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. METHODS: We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. RESULTS: 825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. CONCLUSION: We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. LEVEL OF EVIDENCE: Level II.

Global validation of the WSES Sepsis Severity Score for patients with complicated intra-abdominal infections: a prospective multicentre study (WISS Study).

BACKGROUND: To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression. METHODS: The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study. RESULTS: Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p < 0.0001). The multivariate logistic regression model was highly significant (p < 0.0001, R2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4. CONCLUSIONS: WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.

Venous thromboembolism in the elderly: the result of comorbid conditions or a consequence of injury?

BACKGROUND: Venous thromboembolism (VTE) is a common complication in trauma patients. Several risk factors have been identified that may place patients at in increased risk for VTE including preexisting medical conditions, iatrogenic factors, and injury-related factors. Advanced age has also been implicated as a risk factor for VTE. The purpose of this study was to determine the incidence and outcomes of VTE in geriatric trauma patients as well as to identify risk factors for VTE in this population. METHODS: We performed a 10-year retrospective review of all trauma patients aged 65 years or older discharged with a diagnosis of VTE. Demographic data, injuries, mechanism, Injury Severity Score, Abbreviated Injury Score, Glasgow Coma Scale, length of stay, and mortality were collected. RESULTS: : Of 2,521 trauma patients aged 65 years or older, 82 (3.2%) were diagnosed with VTE. Seventy-two of 82 patients were diagnosed with deep vein thrombosis, and pulmonary embolism was found in 8 patients. Two patients had both a deep vein thrombosis and pulmonary embolism. Independent predictors of VTE included traumatic brain injury (p < 0.05); chest Abbreviated Injury Score ≥ 3 (p < 0.001); mechanical ventilation (p < 0.001); major operation (p < 0.001); and history of VTE (p = 0.05). Other comorbid conditions were not significantly associated with VTE. Preinjury anticoagulation had a trend toward a protective effect. Although length of stay was longer in patients with VTE (adjusted mean difference 14.7 days, p < 0.001), mortality for patients with and without VTE was 8.5% and 7.0%, respectively (p = 0.59). CONCLUSION: VTE is associated with prolonged length of stay and duration of mechanical ventilation as well as continued medical dependence after discharge. Several risk factors place the elderly trauma patient at an increased risk for VTE, and trauma or injury-related risk factors seem to have a greater impact on the development of VTE in comparison to underlying conditions or increasing patient age (>65 years). LEVEL OF EVIDENCE: II, prognostic study.

Is contrast exposure safe among the highest risk trauma patients?

BACKGROUND: Despite improvements in the diagnosis and management of acute kidney injury (AKI), posttraumatic renal dysfunction continues to be associated with increased morbidity and mortality. Intravenous (IV) contrast is known to induce AKI in high-risk groups including the elderly and critically ill. We sought to determine whether IV contrast exposure among high-risk trauma patients resulted in renal dysfunction as defined by the Acute Kidney Injury Network criteria. METHODS: We performed a 3-year retrospective analysis of all patients admitted to our Level I trauma center surgical intensive care unit for >48 hours. Patients with preexisting chronic renal dysfunction were excluded. We performed univariate and bivariate analyses to identify risk factors for AKI. Multivariable logistic regression analysis identified independent predictors for AKI. Subgroup analysis was undertaken among high-risk groups to include elderly patients (aged ≥65 years) with admission hypotension (systolic blood pressure <90 mm Hg) and an Injury Severity Score (ISS) ≥25. RESULTS: Of the 6,317 patients, 571 (9.0%) patients met the inclusion criteria; 170 (29.8%) patients developed AKI. Age ≥65 years (odds ratio [OR] 2.26, 95% confidence interval [CI] = 1.06-4.80, p <0.034) and ISS ≥25 (OR 1.86, 95% CI = 1.12-3.07, p <0.015) were determined to be independent predictors of AKI. IV contrast was not identified to be a predictor of AKI. Upon subgroup analysis, IV contrast exposure was not a predictor of AKI among the elderly, hypotensive, or severely injured patients (ISS ≥25). CONCLUSION: A complete trauma workup including studies requiring IV contrast exposure should be considered safe even among high-risk trauma patients.

Evaluation of Cuprimine® and Syprine® for decorporation of radioisotopes of cesium, cobalt, iridium and strontium.

Cuprimine® and Syprine® are therapeutics approved by the USFDA to treat copper overload in Wilson Disease (a genetic defect in copper transport) by chelation and accelerated excretion of internally-deposited copper. These oral therapeutics are based on the respective active ingredients D-penicillamine (DPA) and N,N'-bis (2-aminoethyl) -1,2-ethanediamine dihydrochloride (Trien). Cuprimine is considered the primary treatment, although physicians are increasingly turning to Syprine as a first-line therapy. Both drugs exhibit oral systemic activity and low toxicity; their biological effects and safety are established. Previous in vivo studies using a rodent animal model established the decorporation potential of Cuprimine and Syprine for (60)Co and (210)Po. Currently these studies are being expanded to evaluate the in vivo decorporation efficacy of these drugs for several additional radionuclides. In this report, results of this investigation are discussed using the radionuclides (137)Cs, (60)Co, (192)Ir and (85)Sr. Short-term 48-h pilot studies were undertaken to evaluate DPA and Trien for their in vivo decorporation potential using male Wistar-Han rats. In these studies, a radionuclide solution was administered to the animals by intravenous (IV) injection, followed by a single IV dose of either DPA or Trien. Control animals received the radionuclide alone. Results show effective decorporation of (60)Co by DPA within the time frame evaluated. DPA and Trien were also modestly effective in decorporation of (137)Cs and (85)Sr, respectively. The study did not find DPA or Trien effective for decorporation of (192)Ir. Based on these encouraging findings, further studies to evaluate the dose-response profiles and timing of the chelator administration post exposure to radionuclides are warranted.

Biomaterials for the decorporation of (85)Sr in the rat.

Although four stable isotopes of strontium occur naturally, Sr is produced by nuclear fission and is present in surface soil around the world as a result of fallout from atmospheric nuclear weapons tests. It can easily transfer to humans in the event of a nuclear/radiological emergency or through the plant-animal-human food chain causing long-term exposures. Strontium is chemically and biologically similar to calcium, and is incorporated primarily into bone following internal deposition. Alginic acid (alginate) obtained from seaweed (kelp) extract selectively binds ingested strontium in the gastrointestinal tract blocking its systemic uptake and reducing distribution to bone in rats, while other natural polysaccharides including chitosan and hyaluronic acid had little in vivo affinity for strontium. Alginate exhibits the unique ability to discriminate between strontium and calcium and has been previously shown to reduce intestinal absorption and skeletal retention of strontium without changing calcium metabolism. In our studies, the effect of commercially available alginate on intestinal absorption of strontium was examined. One problem associated with alginate treatment is its limited solubility and gel formation in water. The aqueous solubility of sodium alginate was improved in a sodium chloride/sodium bicarbonate electrolyte solution containing low molecular weight polyethylene glycol (PEG). Furthermore, oral administration of the combined alginate/electrolyte/PEG solution accelerated removal of internal strontium in rats when compared to treatment with individual sodium alginate/electrolyte or electrolyte/PEG solutions. Importantly, both alginate and PEG are nontoxic, readily available materials that can be easily administered orally in case of a national emergency when potentially large numbers of the population may require medical treatment for internal depositions. Our results suggest further studies to optimize in vivo decorporation performance of engineered alginate material via modification of its chemical and physicochemical properties are warranted.

Evaluation of Cuprimine and Syprine for decorporation of (60)Co and (210)Po.

The acknowledged risk of deliberate release of radionuclides into local environments by terrorist activities has prompted a drive to improve novel materials and methods for removing internally deposited radionuclides. These decorporation treatments will also benefit workers in the nuclear industry, should an exposure occur. Cuprimine and Syprine are oral therapeutics based on the active ingredients D-penicillamine and N,N'-bis-(2-aminoethyl)-1,2-ethanediamine dihydrochloride, respectively. These therapeutic drugs have been used for several decades to treat Wilson's disease, a genetic defect leading to copper overload, by chelation and accelerated excretion of internally deposited copper. Studies were undertaken to evaluate these FDA-approved drugs for the in vivo decorporation of radioactive cobalt (Co) and polonium (Po) using male Wistar-Han rats. In these studies, Co or Po was administered to animals by IV injection, followed by oral gavage doses of either Cuprimine or Syprine. Control animals received the radionuclide alone. For Co studies, animals received a single dose of Cuprimine or Syprine, while for Po studies animals were repeatedly dosed at 24-h intervals for a total of 5 doses. Results show that Syprine significantly increased urinary elimination and skeletal concentrations of Co compared to controls. While Cuprimine had little effect on total excretion of Co, the skeletal, kidney, liver, muscle, and stomach tissues had significantly lower radioactivity compared to control animals. The low overall excretion of Po made it difficult to reliably measure urinary or fecal radioactivity and draw a definitive conclusion on the effect of Cuprimine or Syprine treatment on excretion. However, Cuprimine treatment was effective at reducing spleen levels of Po compared to controls. Similarly, Syprine treatment produced statistically significant reductions of Po in the spleen and skeletal tissues compared to control animals. Based on these promising findings, further studies to evaluate the dose-response pharmacokinetic profiles for decorporation are warranted.

Aminothiol receptors for decorporation of intravenously administered (60)Co in the rat.

This report provides a comparison of the oral decorporation efficacy of L-glutathione (GSH), L-cysteine (Cys), and a liposomal GSH formulation (ReadiSorb) toward systemic (60)Co to that observed following intravenous administration of GSH and Cys in F344 rats. Aminoacid L-histidine (His) containing no thiol functionality was tested intravenously to compare in vivo efficacy of the aminothiol (GSH, Cys) chelators with that of the aminoimidazole (His) chelator. In these studies, (60)Co was administered to animals by intravenous injection, followed by intravenous or oral gavage doses of a chelator repeated at 24-h intervals for a total of 5 doses. The results suggest that GSH and Cys are potent decorporation agents for (60)Co in the rat model, although the efficacy of treatment depends largely on the systemic availability of the chelator. The intravenous route of administration of GSH or Cys was most effective in reducing tissue (60)Co levels and in increasing excretion of radioactivity compared to control animals. Liposomal encapsulation was found to markedly enhance the oral bioavailability of GSH compared to non-formulated GSH. The oral administration of liposomal GSH reduced (60)Co levels in nearly all tissues by 12-43% compared to that observed for non-formulated GSH. Efficacy of oral Cys was only slightly reduced in comparison with intravenous Cys. Further studies to optimize the dosing regimen in order to maximize decorporation efficiency are warranted.

Investigation of chitosan for decorporation of 60Co in the rat.

With the increased threat of terrorist release of radioactive materials, there is a need for non-toxic decorporation agents to treat internal contamination with radionuclides. In this study, low molecular weight chitosan was evaluated for decorporation of radioactive cobalt (60Co). The affinity of chitosan for Co(II) was tested in vitro using spectrophotometric and potentiometric titration techniques. For in vivo studies, the effect of chitosan on ingested 60Co was evaluated using F344 rats administered a single dose followed by oral chitosan. Chitosan was also evaluated for systemic decorporation of 60Co following intravenous injection with repeated chitosan administration over 5 d. Control animals received 60Co without chelation treatment. Excreta and tissues were collected for analysis using gamma-counting techniques. Results from in vitro experiments confirmed the binding of Co(II) to chitosan, with the postulated formation of a mixed cobalt-chitosan-hydroxide complex species; a stability constant was calculated for this complex. For in vivo studies, oral administration of chitosan significantly reduced systemic absorption of orally administered 60Co as evidenced by an increase in fecal elimination and decrease in urinary elimination. However, oral administration of chitosan lactate slightly decreased fecal excretion of 60Co. Further, oral administration of chitosan significantly reduced 60Co levels in kidney, liver, and skeleton compared to control animals receiving 60Co alone. By the i.v. route, chitosan slightly reduced levels of 60Co in tissues compared to controls, although statistically significant reductions were only observed for blood and kidney. Overall, this commercially available chitosan oligosaccharide exhibited promising potential; further studies are warranted to evaluate the optimal dosing regimen and chemical modifications to increase effectiveness.