Outcomes of laparoscopic and open ventriculoperitoneal shunt placement.

OBJECTIVE: Ventriculoperitoneal (VP) shunt placement requires a concurrent abdominal procedure. For peritoneal access laparoscopic or open approach may be utilized. Our aim was to compare patient/procedure characteristics and outcomes by peritoneal approach for VP shunts in children. METHODS: NSQIP-Pediatric procedure targeted cerebral spinal fluid shunt Participant Use Data Files from 2016 to 2020 were queried. Patients were grouped into laparoscopic vs open abdominal approach. Patient demographics, procedure characteristics and 30-day outcomes were compared. RESULTS: 7742 NSQIP-Pediatric patients underwent VP shunt placement. Patients undergoing laparoscopic approach were older and required less preoperative support. Mean operative time was longer with laparoscopy (mean(SD): 74.2(48.1) vs. 64.6(39) minutes, p â€‹< â€‹0.0001) but had shorter hospital LOS. There was no difference in SSI, readmissions, or reoperation rates. CONCLUSION: Patients undergoing laparoscopy for distal VP shunts are older with less support needs preoperatively. While laparoscopic approach had a shorter hospital LOS, there was no demonstratable difference in SSI, readmissions or reoperations between approaches. Further studies are needed to assess long-term outcomes.

Laparoscopic Co-surgeon Ventriculoperitoneal Shunt Placement Versus Single Surgeon Mini Laparotomy.

INTRODUCTION: Ventriculoperitoneal (VP) shunt placement is one of the most common treatments for pediatric hydrocephalus. However, device failures often occur, requiring operative revision of either the intraventricular or intraperitoneal shunt catheters. Historically, shunt placement was performed via laparotomy, but there has been a trend towards laparoscopic-assisted placement of the intraperitoneal portion of the shunt. We examined the outcomes of laparoscopic-assisted versus open VP shunt placement utilizing a local institutional retrospective review. METHODS: Single institution 2012-2017 retrospective review of all cases was performed. Patients were divided into two groups - laparoscopic and open. Thirty-day outcomes, patient age, surgery performed, surgical control time (SCT), length of stay (LOS), and readmission were analyzed.  Results: Cohort analysis inclusion criteria included 188 patients. The cohort analysis showed both decreased laparoscopic-assisted SCT (56.4 vs 32.1 min, p<0.0001) and postop complications (16.7% vs 7.1%, p<0.07). There was no significant difference in surgical site infection or readmission rates.  Conclusion: Local analysis show advantages for laparoscopic-assisted VP shunt placement over open single surgeon techniques with decreased SCT, LOS, and unplanned interventions.

Novel Way to Improve Satisfaction, Comprehension, and Anxiety in Caregivers: A Randomized Trial Exploring the Use of Comprehensive, Illustrated Children's Books for Pediatric Surgical Populations.

BACKGROUND: Surgery generates anxiety and stress, which can negatively impact informed consent and postoperative outcomes. This study assessed whether educational, illustrated children's books improve comprehension, satisfaction, and anxiety of caregivers in pediatric surgical populations. METHODS: A prospective randomized trial was initiated at a tertiary care children's hospital. All patients ≤ 18 years old with caregiver and diagnosis of 1) uncomplicated appendicitis (English or Spanish speaking); 2) ruptured appendicitis; 3) pyloric stenosis; 4) need for gastrostomy tube; or 5) umbilical hernia were eligible. Conventional consent was obtained followed by completion of 17 validated survey questions addressing apprehension, satisfaction, and comprehension. Randomization (2:1) occurred after consent and before operative intervention with the experimental group (EG) receiving an illustrated comprehensive children's book outlining anatomy, pathophysiology, hospital course, and postoperative care. A second identical survey was completed before discharge. Primary outcomes were caregiver apprehension, satisfaction, and comprehension. RESULTS: Eighty caregivers were included (55: EG, 25: control group [CG]). There were no significant differences in patient or caregiver demographics between groups. The baseline survey demonstrated no difference in comprehension, satisfaction, or apprehension between groups (all p values NS). After intervention, EG had significant improvement in 14 of 17 questions compared with CG (all p < 0.05). When tabulated by content, there was significant improvement in comprehension (p = 0.0009), satisfaction (p < 0.0001), and apprehension (p < 0.0001). CONCLUSION: The use of illustrated educational children's books to explain pathophysiology and surgical care is a novel method to improve comprehension, satisfaction, and anxiety of caregivers. This could benefit informed consent, understanding, and postoperative outcomes.

The impact of abnormal BMI on surgical complications after pediatric colorectal surgery.

BACKGROUND/PURPOSE: While childhood obesity is a growing problem, the implications of BMI on elective pediatric surgery remains poorly described. This study evaluates the impact of obesity on surgical outcomes after elective colorectal procedures. METHODS: Children ages 2-18 years undergoing elective colorectal surgery for IBD were identified from the NSQIP-Pediatric database. Patients were classified as underweight (UW), normal weight (NW), overweight (OW) and obese (OB) based on their age- and sex-adjusted BMI. Postoperative complications were compared between cohorts. RESULTS: 858 patients (14.8% UW, 64.3% NW, 13.1% OW, 7.8% OB) were identified, with overall complications occurring in 15.3% and SSI in 10.1%. Obese/overweight patients had higher rates of deep incisional SSI (4.5%OB, 4.5%OW, 0%NW, p=0.002) and superficial wound disruption (5.4%OB, 5.8%OW, 1.6%NW, p=0.04). Incremental increase in BMI by 1.0kg/m2 was associated with 4.3% increased likelihood of developing deep incisional SSI and 2.3% increase of superficial wound disruption. Obese/overweight children also had increased incidence of septic shock and UTI, as well as longer operative times, days of mechanical ventilation and LOS. CONCLUSIONS: Increasing BMI was associated with increased wound complications in IBD patients undergoing elective intestinal surgery. Preoperative optimization and weight loss strategies may potentially reduce SSI and other infectious complications. LEVEL OF EVIDENCE: III.

Home intravenous versus oral antibiotics following appendectomy for perforated appendicitis in children: a randomized controlled trial.

PURPOSE: To compare the effect of home intravenous (IV) versus oral antibiotic therapy on complication rates and resource utilization following appendectomy for perforated appendicitis. METHODS: This was a randomized controlled trial of patients aged 4-17 with surgically treated perforated appendicitis from January 2011 to November 2013. Perforation was defined intraoperatively and divided into three grades: I-contained perforation, II-localized contamination to right gutter/pelvis, and III-diffuse contamination. Patients were randomized to complete a ten-day course of home antibiotic therapy with either IV ertapenem or oral amoxicillin-clavulanate. Thirty-day postoperative complication rates including abscess, readmission, wound infection, and charges were compared. RESULTS: Eighty-two patients were enrolled. Forty four (54%) were randomized to the IV group and 38 (46%) to the oral group. IV patients were older (12.3 ± 3.6 versus 10.1 ± 3.6, p < 0.05) with higher BMI (20.9 ± 5.8 versus 17.9 ± 3.5, p < 0.05). There were no differences in gender, comorbidities, or perforation grade (I-20.4% vs. 26.3%, II-36.4% vs. 34.2%, III-43.2% vs. 39.5%, all p > 0.05). Comparing IV to oral, there was no difference in length of stay (4.4 ± 1.5 versus 4.4 ± 2.0 days, p > 0.05), postoperative abscess rate (11.6% vs. 8.1%, p > 0.05), or readmission rate (14.0% vs. 16.2%, p > 0.05). Hospital and outpatient charges were higher in the IV group (p < 0.0001). CONCLUSION: Oral antibiotics had equivalent outcomes and incurred fewer charges than IV antibiotics following appendectomy for perforated appendicitis.

Thoracoscopic Versus Open Congenital Diaphragmatic Hernia Repair: Single Tertiary Center Review.

BACKGROUND: Congenital diaphragmatic hernia (CDH) can be repaired open or through thoracoscopy. Thoracoscopic CDH repair could improve cosmesis and avoid the complications of laparotomy, but may have higher recurrence rates. The purpose of this study was to examine the outcomes of thoracoscopic versus open CDH repair, with regard to recurrence, perioperative parameters, and postoperative complications. METHODS: We performed a retrospective review of open versus thoracoscopic CDH repairs over an 8.5-year period. The primary outcome was hernia recurrence. Secondary outcomes included intraoperative partial pressure of carbon dioxide (pCO2) levels, length of stay, and postoperative complications. All statistical analyses were performed using standard statistical methods. RESULTS: A total of 54 infants underwent CDH repair during the study period, of whom 25 underwent successful thoracoscopic repair. Two patients who had undergone open repair developed recurrent diaphragmatic hernias (recurrence rate 3.7%). Operative time and intraoperative pCO2 levels did not differ between groups. Length of stay was shorter in the thoracoscopic cohort. Four patients in the open cohort developed ventral hernias and five developed bowel obstructions during follow-up. No long-term complications were identified in the thoracoscopic cohort. The median follow-up was 27 months. CONCLUSIONS: In our experience, thoracoscopic CDH repair was performed safely and with similar outcomes compared to open repair. In addition to improved cosmesis, thoracoscopic repair may avoid some of the long-term complications of laparotomy. In our series, none of the thoracoscopic CDH repairs recurred. We conclude that thoracoscopic CDH repair is a safe and appropriate technique for select neonates.

Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies.

Chimeric antigen receptor T (CAR-T) cell therapy has produced impressive results in clinical trials for B-cell malignancies. However, safety concerns related to the inability to control CAR-T cells once infused into the patient remain a significant challenge. Here we report the engineering of recombinant antibody-based bifunctional switches that consist of a tumor antigen-specific Fab molecule engrafted with a peptide neo-epitope, which is bound exclusively by a peptide-specific switchable CAR-T cell (sCAR-T). The switch redirects the activity of the bio-orthogonal sCAR-T cells through the selective formation of immunological synapses, in which the sCAR-T cell, switch, and target cell interact in a structurally defined and temporally controlled manner. Optimized switches specific for CD19 controlled the activity, tissue-homing, cytokine release, and phenotype of sCAR-T cells in a dose-titratable manner in a Nalm-6 xenograft rodent model of B-cell leukemia. The sCAR-T-cell dosing regimen could be tuned to provide efficacy comparable to the corresponding conventional CART-19, but with lower cytokine levels, thereby offering a method of mitigating cytokine release syndrome in clinical translation. Furthermore, we demonstrate that this methodology is readily adaptable to targeting CD20 on cancer cells using the same sCAR-T cell, suggesting that this approach may be broadly applicable to heterogeneous and resistant tumor populations, as well as other liquid and solid tumor antigens.

National Trends in the Surgical Treatment of Ovarian Torsion in Children: An Analysis of 2041 Pediatric Patients Utilizing the Nationwide Inpatient Sample.

The aim of this study was to evaluate the national trends in surgical management of ovarian torsion (OT) in children. The Nationwide Inpatient Sample was queried from 1998 to 2011 for females less than 18 years of age with OT. Patients were stratified into three treatment groups: oophorectomy (OO), oophoropexy, or release of torsion (RT) alone. There were 2041 patients with OT, of which 1598 (78%) underwent OO, 126 (6%) oophoropexy, and 317 (15%) RT. RT significantly increased from 1998 to 2011 (9% vs 25%; P < 0.05). At nonteaching hospitals, there were higher rates of OO (89.3% vs 79.5%; P < 0.05) and lower rates of RT (10.7% vs 20.5%; P < 0.05) compared with teaching hospitals. RT was performed at a higher rate in Northeast United States compared with the South (22.7% vs 14.2%; P < 0.05). Girls presenting at nonteaching hospitals and the South had increased odds of undergoing OO compared with those presenting at teaching hospitals and the Northeast (P < 0.05). Although ovarian conservation for OT in children is more often performed in the Northeast United States and at teaching hospitals, this large population-based study demonstrates OO remains the most common surgical management for OT in the United States.

An anti-B cell maturation antigen bispecific antibody for multiple myeloma.

The development of immunotherapies for multiple myeloma is critical to provide new treatment strategies to combat drug resistance. We report a bispecific antibody against B cell maturation antigen (BiFab-BCMA), which potently and specifically redirects T cells to lyse malignant multiple myeloma cells. BiFab-BCMA lysed target BCMA-positive cell lines up to 20-fold more potently than a CS1-targeting bispecific antibody (BiFab-CS1) developed in an analogous fashion. Further, BiFab-BCMA robustly activated T cells in vitro and mediated rapid tumor regression in an orthotopic xenograft model of multiple myeloma. The in vitro and in vivo activities of BiFab-BCMA are comparable to those of anti-BCMA chimeric antigen receptor T cell therapy (CAR-T-BCMA), for which two clinical trials have recently been initiated. A BCMA-targeted bispecific antibody presents a promising treatment option for multiple myeloma.

Oscillatory spatial profile of alcohol's effects on the resting state: anatomically-constrained MEG.

It has been firmly established that opening and closing the eyes strongly modulate the electro- and magnetoencephalography (EEG and MEG) signals acquired during wakeful rest. Certain features of the resting EEG are altered in chronic alcoholics and their offspring, and have been proposed as biomarkers for alcoholism. Spontaneous brain oscillations are also affected by pharmacological manipulations, but the spectral and spatial characteristics of these changes are not clear. This study examined effects of the eyes-open (EO) and eyes-closed (EC) resting paradigm and alcohol challenge on the spatial profile of spontaneous MEG and EEG oscillations. Whole-head MEG and scalp EEG signals were acquired simultaneously from healthy social drinkers (n = 17) who participated in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. Power of the signal was calculated with Fast Fourier Transform and was decomposed into its constituent theta (4-7 Hz), alpha (8-12 Hz), and beta (15-20 Hz) frequency bands. High-resolution structural MRI images were additionally obtained from all participants and used to constrain distributed minimum norm inverse source power estimates. The spatial estimates of the main generator nodes were in agreement with studies using a combined fMRI-EEG approach. Alpha band oscillations dominated the spectral profile and their source was estimated to the medial parieto-occipital area. Power in theta and beta bands was weaker overall and their sources were estimated to a more focal medial prefrontal area. EO and EC manipulation most strongly modulated power in the alpha band, but a wide-band power increase was observed during the EC condition. Alcohol intoxication increased alpha power, particularly during the EC condition. Application of this methodology to cohorts of chronic alcoholics or individuals at risk could potentially provide insight into the neural basis of oscillatory differences that may be predictive of the vulnerability to alcoholism.

Adenosine A2A receptor agonist improves cardiac dysfunction from pulmonary ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion (IR) injury negatively impacts patient outcome in lung transplantation. Clinically, we observed that lung transplant patients with ischemia-reperfusion injury tend to have cardiac dysfunction. Previous studies have shown that ATL-146e (4-{3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester), a selective adenosine A2A receptor agonist, reduces lung inflammation after ischemia-reperfusion. We hypothesized that pulmonary ischemia-reperfusion causes secondary heart dysfunction and ATL-146e will improve this dysfunction. METHODS: We utilized an in vivo rabbit lung ischemia-reperfusion model. The Sham group underwent 120 minutes single lung ventilation. The IR and ATL groups underwent 90 minutes right lung ischemia with 30 minutes right lung reperfusion. The ATL-146e was given intravenously to the ATL group during reperfusion. Cardiac output and arterial blood gases were monitored, and neutrophil sequestration was measured by myeloperoxidase activity. RESULTS: Upon reperfusion, cardiac output (mL/min) significantly dropped in the IR and ATL groups. By 15 minutes reperfusion, cardiac output in the ATL group improved significantly over the IR group and remained significant thereafter. Lung myeloperoxidase activity was significantly reduced by ATL-146e. Although never hypoxemic, arterial oxygenation was lower in the IR and ATL groups while central venous pressures and mean arterial pressures were similar among groups. A separate experiment demonstrated that reperfusion with the antioxidant N-(2-mercaptopropionyl)glycine prevented cardiac dysfunction. CONCLUSIONS: Pulmonary ischemia-reperfusion causes cardiac dysfunction independent of preload, afterload, and oxygenation. The ATL-146e improves this dysfunction presumably by the antiinflammatory effects of adenosine A2A receptor activation on neutrophils. One likely mechanism involves the release of oxidants from the ischemic lung upon reperfusion, which has immediate negative effects on the heart.

Predictors of patients who will develop prolonged occult hypoperfusion following blunt trauma.

BACKGROUND: Prolonged occult hypoperfusion or POH (serum lactate >2.4 mmol/L persisting >12 hours from admission) represents a reversible risk factor for adverse outcomes following traumatic injury. We hypothesized that patients at increased risk for POH could be identified at the time of admission. METHODS: Prospective data from adult trauma admissions between January 1, 1998 and December 31, 2000 were analyzed. Potential risk factors for POH were determined by univariate analysis (p < or =0.10= significant). Significant factors were tested in a logistic regression model (LR) (p < or =0.05= significant). The predictive ability of the LR was tested by receiver operating curve (ROC) analysis (p < or =0.05= significant). RESULTS: Three hundred seventy-eight patients were analyzed, 129 with POH. Injury Severity Score (ISS), emergency department Glasgow Coma Scale score, hypotension, and the individual Abbreviated Injury Scale score (AIS) for Head (H), Abdominal/Pelvic Viscera (A) and Pelvis/Bony Extremity (P) were significantly associated with POH. LR demonstrated that ISS, A-AIS > or =3 and P-AIS > or =3 were independent predictors of POH (p <0.05). ROC analysis of the LR equation was statistically significant (Area=0.69, p <0.001). CONCLUSIONS: We identified factors at admission that placed patients at higher risk for developing POH. Select patients may benefit from rapid, aggressive monitoring and resuscitation, possibly preventing POH and its associated morbidity and mortality.

A hierarchical modeling approach for estimating national distributions of chemicals in public drinking water systems.

Water quality studies often include the analytical challenge of incorporating censored data and quantifying error of estimation. Many analytical methods exist for estimating distribution parameters when censored data are present. This paper presents a Bayesian-based hierarchical model for estimating the national distribution of the mean concentrations of chemicals occurring in U.S. public drinking water systems using fluoride and thallium as examples. The data used are Safe Drinking Water Act compliance monitoring data (with a significant proportion of left-censored data). The model, which assumes log-normality, was evaluated using simulated data sets generated from a series of Weibull distributions to illustrate the robustness of the model. The hierarchical model is easily implemented using the Markov chain Monte Carlo simulation method. In addition, the Bayesian method is able to quantify the uncertainty in the estimated cumulative density function. The estimated fluoride and thallium national distributions are presented. Results from this study can be used to develop prior distributions for future U.S. drinking water regulatory studies of contaminant occurrence.

Differential local and systemic tumor necrosis factor-alpha responses to a second hit of lipopolysaccharide after hemorrhagic shock.

BACKGROUND: The immune response to subsequent stressors after traumatic hemorrhage and resuscitation (HR) may be dependent on timing and counterinflammatory cytokine expression. Our hypothesis was that the timing of the second hit would influence the immune response, and we investigated whether an early second stimulus after HR would result in worse acute lung injury. METHODS: One hour after HR or sham shock (Sham), mice were given intraperitoneal (IP) injections of lipopolysaccharide (LPS) or saline (Sal). Mortality, pulmonary function (PF), bronchoalveolar lavage neutrophil infiltration, and bronchoalveolar lavage (BAL), in addition to serum interleukin (IL)-10, IL-6, and tumor necrosis factor-alpha (TNF-alpha), were assessed. RESULTS: HR blunted serum TNF-alpha expression to LPS (HR+LPS, 424.8 pg/mL; Sham+LPS, 2,248.8 pg/mL; p < 0.05), but primed for increased bronchoalveolar lavage TNF-alpha (HR+LPS, 259.5 pg/mL; Sham+LPS, 23.5 pg/mL; p < 0.05). Elevated serum TNF-alpha corresponded with greater bronchoalveolar lavage neutrophil infiltration (HR+LPS, 0.93%; Sham+LPS, 17.5%; p < 0.05). IL-10 expression was similar in HR and Sham. There were no significant differences in mortality or PF between HR+LPS and Sham+LPS. CONCLUSION: Priming and blunting of the LPS-induced TNF-alpha response occurred concomitantly in two-hit mice, corresponding to an altered pattern of pulmonary inflammation, but no change in PF.

Is there an upper limit of intracranial pressure in patients with severe head injury if cerebral perfusion pressure is maintained?

Authors of recent studies have championed the importance of maintaining cerebral perfusion pressure (CPP) to prevent secondary brain injury following traumatic head injury. Data from these studies have provided little information regarding outcome following severe head injury in patients with an intracranial pressure (ICP) greater than 40 mm Hg, however, in July 1997 the authors instituted a protocol for the management of severe head injury in patients with a Glasgow Coma Scale score lower than 9. The protocol was focused on resuscitation from acidosis, maintenance of a CPP greater than 60 mm Hg through whatever means necessary as well as elevation of the head of the bed, mannitol infusion, and ventriculostomy with cerebrospinal fluid drainage for control of ICP. Since the institution of this protocol, nine patients had a sustained ICP greater than 40 mm Hg for 2 or more hours, and five of these had an ICP greater than 75 mm Hg on insertion of the ICP monitor and later experienced herniation and expired within 24 hours. Because of the severe nature of the injuries demonstrated on computerized tomography scans and their physical examinations, these patients were not aggressively treated under this protocol. The authors vigorously attempted to maintain a CPP greater than 60 mm Hg with intensive fluid resuscitation and the administration of pressor agents in the four remaining patients who had developed an ICP higher than 40 mm Hg after placement of the ICP monitor. Two patients had an episodic ICP greater than 40 mm Hg for more than 36 hours, the third patient had an episodic ICP greater than of 50 mm Hg for more than 36 hours, and the fourth patient had an episodic ICP greater than 50 mm Hg for more than 48 hours. On discharge, all four patients were able to perform normal activities of daily living with minimal assistance and experience ongoing improvement. Data from this preliminary study indicate that intense, aggressive management of CPP can lead to good neurological outcomes despite extremely high ICP. Aggressive CPP therapy should be performed and maintained even though apparently lethal ICP levels may be present. Further study is needed to support these encouraging results.

Young versus old: factors affecting mortality after blunt traumatic injury.

Advanced age predicts poor outcome after trauma. We have previously demonstrated that prolonged occult hypoperfusion (POH), defined as serum lactic acid >2.4 mmol/L persisting for >12 hours, is also associated with worse outcomes. We hypothesized that older patients--a group with potentially less physiologic reserve--would be at greater risk from POH. Prospective data from adult blunt trauma patients admitted to a surgical/trauma intensive care unit from January 1, 1998 through December 31, 1999 were analyzed. Mortality, POH, Injury Severity Score (ISS), chronic health designation (CH) from the Acute Physiology and Chronic Health Evaluation, emergency department Glasgow Coma Scale score (EDGCS), emergency department systolic blood pressure (EDSBP), and gender were compared between older (>55 years) and younger (<56 years) patients and then between nonsurvivors and survivors within age cohorts. Two hundred sixty-four patients were analyzed: 195 younger and 69 older. Mortality was 8.3 per cent (22/264). Older patients had higher mortality (20.3% vs 4.1%, P < 0.05), higher CH (42.9% +/- 1.3 vs 8.4% +/- 0.6), lower ISS (22.6 +/- 1.5 vs 25.6 +/- 0.8, P < 0.05), higher EDGCS (12.9 +/- 0.5 vs 10.7 +/- 0.4, P < 0.05), and higher EDSBP (141.5 +/- 4.1 vs 129.3 +/- 2.2). There were no differences in incidence of POH and gender. Within both age cohorts nonsurvivors had higher ISS, lower EDGCS, and higher CH. Older patients with POH had 34.6 per cent mortality as compared with 11.6 per cent for no POH (P < 0.05). Mortality in younger patients was no different in the presence of POH, and all non-survivors were male. Despite lower ISS and higher EDGCS and EDSBP older patients had five times the mortality of younger patients. Age-specific mortality was influenced by POH and gender. POH was associated with higher mortality only in older patients. With less physiologic reserve older patients may not have been able to adequately compensate for POH; this emphasizes the importance of rapidly correcting serum lactic acid as an endpoint in resuscitation in this population.

Improved resuscitation minimizes respiratory dysfunction and blunts interleukin-6 and nuclear factor-kappa B activation after traumatic hemorrhage.

OBJECTIVE: We hypothesized that modifying resuscitation would alter hemorrhagic shock-induced respiratory dysfunction and correlate with nuclear factor-kappa B and cytokine expression. DESIGN: Randomized, controlled, prospective study. SETTING: University hospital trauma research laboratory. SUBJECTS: Female, Swiss Webster mice, 8-12 wks old. INTERVENTIONS: Hemorrhagic shock was induced by removing 0.025 mL of blood/g of body weight via a carotid catheter. Animals were resuscitated 30 mins later. Mice were randomized into four groups: group I was cannulated but not bled (sham); group II received normal saline to three times their shed blood volume; group III received their shed blood; and group IV received shed blood + normal saline at two times shed blood volume. MEASUREMENTS AND MAIN RESULTS: We measured the following: serum lactates at the end of shock and after resuscitation, pulmonary function before any instrumentation and after 24 hrs, cytokine concentrations by enzyme-linked immunosorbent assay, and nuclear factor-kappa B activity by electrophoretic mobility shift assay. Groups that were hemorrhaged had significant hypotension and a significant increase in serum lactates over 30 mins. Resuscitation returned the blood pressure to baseline in all groups, and lactates improved in all groups except group II. Group II also demonstrated a significant decrease in pulmonary function characterized by increased airway resistance and decreases in minute volume, lung compliance, and alveolar function. Bronchoalveolar fluid and serum interleukin-6 and whole lung nuclear factor-kappa B activity also were elevated significantly in group II. CONCLUSIONS: Group II demonstrated the least improvement in serum lactate after resuscitation, the most significant acute lung injury, and the greatest interleukin-6 and nuclear factor-kappa B response. Group IV mice had the least acute lung injury, with no detectable interleukin-6 response. Improved resuscitation with crystalloid and shed blood minimized acute lung injury. The reduction in pulmonary dysfunction after improved resuscitation may be attributable to a blunting of the nuclear factor-kappa B and interleukin-6 responses to hemorrhage.

Blood transfusions correlate with infections in trauma patients in a dose-dependent manner.

Infections are a common and significant sequela of major traumatic injury. The objective of this study was to evaluate the relationship between infections in trauma patients and the transfusion of packed red blood cells (pRBCs) within the first 48 hours of admission. We hypothesized that transfusions of pRBCs were associated with an increased risk of infection in a dose-dependent manner. All adult patients admitted to the trauma service of a Level I trauma center from November 1996 to December 1999 were studied. Secondary analysis was performed on prospectively collected data. One thousand five hundred ninety-three consecutive patients were studied; of these 12.6 per cent developed at least one infection. The overall transfusion rate was 19.4 per cent. The infection rate in patients who received at least one transfusion was significantly higher (P < 0.0001) at 33.0 versus 7.6 per cent in patients receiving no pRBCs. Transfusions per patient ranged from 0 to 46 units. There was a clear exponential correlation in patients receiving between 0 and 15 transfusions (R2 = 0.757). Multivariate logistic regression, which was used to identify risk factors for the development of infection, demonstrated the odds ratio of receiving pRBCs to be 1.084, with a 95 per cent confidence interval of 1.028 to 1.142 (P = 0.0028). In summary there is a clear dose-dependent correlation between transfusions of pRBCs and the development of infection in trauma patients. Multivariate analysis further demonstrated that pRBCs were an independent risk factor for the development of infections. Although transfusions are frequently indicated, they should be administered appropriately and with no more pRBCs than absolutely necessary.