Christian Minshall

Growth hormone, growth factors and hematopoiesis

Hypocellularity of primary lymphoid organs is a distinctive and reproducible characteristic of aged humans and animals. Similar changes have been reported in both hypophysectomized and dwarf rodents. In the bone marrow of these animals, there is an associated reduction in the number of erythroid, lymphoid and myeloid elements. Implantation of growth hormone (GH)-secreting GH3 pituitary cells or infusion of growth hormone into aged rodents dramatically improves cellularity of both the thymus gland and bone marrow. At present it is unknown whether these effects are due to direct effects of growth hormone on hematopoietic cells or if they are caused by the induction of insulin-like growth factor-1 (IGF-1) synthesis. We recently discovered that colony-stimulating factor-1 (CSF-1) and interleukin-3 (IL-3) induce expression and synthesis of the IGF-1 peptide in murine bone marrow cells. Transcripts for IGF-1 increase approximately 50-fold during differentiation over the negligible levels that are expressed in freshly isolated bone marrow cells. Two potential functions of macrophage-derived IGF-1 are to: (a) increase the proliferation of early or committed bone marrow progenitors and (b) reduce their rate of cell death. In support of the first possibility, IGF binding protein-3 significantly inhibits the proliferation of CSF-1-treated bone marrow cells and this inhibition can be reversed by addition of exogenous IGF-1. In support of the second possibility, we have induced apoptosis of both nonadherent bone marrow cells and a myeloid progenitor cell line by depriving these cells of CSFs. Preliminary results indicate that addition of IGF-1 to these cells reduces apoptotic cell death by 50%. These data establish that two different CSFs, CSF-1 and IL-3, induce abundant expression of IGF-1 as these cells differentiate into more mature hematopoietic cells. This model offers a novel approach for investigating the developmental expression of IGF-1 during defined differentiation pathways of hematopoietic cells. If IGF-1 is indeed proven to act as a survival factor for hematopoietic progenitors, these data would support the idea that the hypocellularity of primary lymphoid tissues in aged animals is related to the limited availability to these cells of either growth hormone or IGF-1.

Surgical rib fixation for flail chest deformity improves liberation from mechanical ventilation

PURPOSE The goal of this study was to determine the impact of surgical rib fixation (SRF) in a treatment protocol for severe blunt chest trauma. MATERIALS AND METHODS Patients with flail chest admitted between September 2009 and June 2010 to our level I trauma center who failed traditional management and underwent SRF were matched with an historical group. Outcome variables evaluated include age, injury severity score, intensive care unit length of stay (LOS), hospital LOS, ventilator days, total number of rib fractures, and total number of segmental rib fractures. RESULTS The 2 groups were similar in age, injury severity score, intensive care unit LOS, hospital LOS, total number of rib fractures, and total segmental rib fractures. The operative group demonstrated a significant reduction in total ventilator days as compared with the nonsurgical group (4.5 [0-30] vs 16.0 [4-40]; P = .040). Patients with SRF were permanently liberated from the ventilator within a median of 1.5 days (0-8 days). CONCLUSIONS Surgical rib fixation resulted in a significant decrease in ventilator days and may represent a novel approach to decreasing morbidity in flail chest patients when used as a rescue therapy in patients with declining pulmonary status. Larger studies are required to further identify these benefits.

Safety and efficacy of heparin or enoxaparin prophylaxis in blunt trauma patients with a head abbreviated injury severity score >2

BACKGROUND Timing and type of chemoprophylaxis (CP) that should be used in patients with traumatic brain injury (TBI) remains unclear. We reviewed our institutions experience with low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in TBI. METHODS The charts of all TBI patients with a head abbreviated injury severity score >2 (HAIS) and an intensive care unit length of stay >48 hours admitted during a 42-month period between 2006 and 2009 were reviewed. CP was initiated after intracranial hemorrhage was considered stable. We reviewed all operative notes and radiologic reports in these patients to analyze the rate of significant intracranial hemorrhagic complications, deep venous thrombosis, or pulmonary embolus. RESULTS A total of 386 patients with TBI were identified; 158 were treated with LMWH and 171 were treated with UFH. HAIS was significantly different between the LMWH (3.8 ± 0.7) and UFH (4.1 ± 0.7) groups; the time to initiation of CP was not. The UFH group had a significantly higher rate of deep venous thrombosis and pulmonary embolus. Progression of ICH that occurred after the initiation of CP was significantly higher in the UFH-treated patients (59%) when compared with those treated with LMWH (40%). Two patients in the UFH group required craniotomy after the initiation of CP. CONCLUSION LMWH is an effective method of CP in patients with TBI, providing a lower rate of venous thromboembolic and hemorrhagic complications when compared with UFH. A large, prospective, randomized study would better evaluate the safety and efficacy of LMWH in patients suffering blunt traumatic brain injury.

Consensus statement: Surgical stabilization of rib fractures rib fracture colloquium clinical practice guidelines

Please cite this article as: Pieracci Fredric M, Majercik Sarah, Ali-Osman Francis, Ang Darwin, Doben Andrew, Edwards John G, French Bruce, Gasparri Mario, Marasco Silvana, Minshall Christian, Sarani Babak, Tisol William, VanBoerum Don H, White Thomas W.Consensus Statement: Surgical Stabilization of Rib Fractures Rib Fracture Colloquium Clinical Practice Guidelines.Injury http://dx.doi.org/10.1016/j.injury.2016.11.026

Competitive Reverse Transcriptase-Polymerase Chain Reaction Using a Synthetic Internal RNA Standard to Quantitate Transcripts for Leukocyte-Derived Hormones

Leukocytes synthesize a variety of hormones that were once thought to be unique products of endocrine tissues. Understanding the regulation of leukocyte-derived hormone synthesis requires an accurate means for measuring steady-state expression of specific mRNA transcripts. Here we describe a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) technique to accurately quantitate macrophage-derived insulin-like growth factor-I (IGF-I) mRNA, and demonstrate the utility of this approach for measuring expression of leukocyte-derived hormone transcripts. A riboprobe was constructed to generate approximately 1 kb of synthetic competitor IGF-I RNA (exons 1 and 3-6) that differed from cellular IGF-I RNA by insertion of 122 bp of beta-actin RNA. One set of oligonucleotide primers could thus be used to simultaneously reverse transcribe and amplify both 144 bp of cellular (exons 3 and 4) and 266 bp of competitor IGF-I RNA. Densitometric scanning of the PAGE-separated PCR products revealed that the ratio of competitor to cellular amplified DNA bore a linear relationship (r2 > or = 0.98) to the amount of competitor RNA for both rat liver and splenocytes. However, rat liver contained 104 x 10(6) IGF-I molecules per microgram of total cellular RNA compared to only 2 x 10(6) IGF-I molecules for splenocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Applicability of the National Healthcare Safety Network's surveillance definition of ventilator-associated events in the surgical intensive care unit: A 1-year review

BACKGROUND In 2012, the National Healthcare Safety Network presented a new surveillance definition for ventilator-associated events (VAEs) to objectively define worsening pulmonary status in ventilated patients. VAE subcategories, ventilator-associated condition (VAC), infection-related VAC, and probable ventilator-associated pneumonia (PrVAP), were vetted predominantly in medical intensive care units. Our goal was to evaluate how well VAE criteria characterize pulmonary complications in surgical intensive care unit (SICU) patients. METHODS Since September 2012, all intubated SICU patients were screened prospectively for VAE and monitored for sustained respiratory dysfunction that did not meet VAE criteria. We diagnosed ventilator-associated pneumonia (VAP) using a clinical definition: Clinical Pulmonary Infection Score (CPIS) greater than 6 and catheter-directed bronchoalveolar lavage cultures with 104 or more colony-forming units per milliliter of pathogenic organisms. RESULTS We admitted 704 intubated patients. A total of 437 were intubated for two or more days (mean [SD], age 46 [18] years; 65% male; median ventilator days, 4 [range, 2–9]; median Sequential Organ Failure Assessment [SOFA] score, 8 [range, 5–10]). Using VAE criteria, we identified 37 patients with VAC, 31 with infection-related VAC, and 22 with PrVAP. While the remaining 400 patients did not meet VAE criteria, we identified 111 patients (28%) with respiratory deterioration and diagnosed 99 additional pneumonias. Of the 111 patients, 85 (77%) never had a period of stable/decreasing oxygenation, requiring elevated vent settings upon initiation of ventilation preventing them from meeting VAE criteria. Of the 99 pneumonia patients, 10% had sustained respiratory deterioration treated with elevations in mean airway pressure; they did not meet VAE criteria as the positive end-expiratory pressure or FIO2 was not elevated. Twenty-seven percent never had a period of stable/decreasing oxygenation. Fifty-eight percent had less than 2 days of respiratory deterioration. Agreement between PrVAP and clinical VAP was 77.3% (&kgr; = 0.243, p < 0.001). CONCLUSION The applicability of the new National Healthcare Safety Network categories of VAE to critically ill surgery patients is limited. Agreement between PrVAP and clinical VAP in SICU patients is poor. Most surgical patients are not well categorized by this new definition; a better method of surveillance should be created for this patient population. LEVEL OF EVIDENCE Diagnostic study, level III.

Examination with Next-Generation Sequencing Technology of the Bacterial Microbiota in Bronchoalveolar Lavage Samples after Traumatic Injury

BACKGROUND We examined the microbiota of bronchoalveolar lavage (BAL) samples with next-generation sequencing (NGS) technology to determine whether its results correlate with those of standard culture methods or affect patient outcome or both. METHODS We collected BAL samples in the surgical intensive care unit (SICU) as part of the standard of care for intubated individuals who had a Clinical Pulmonary Infection Score (CPIS)≥6 points. A portion of the BAL fluid was sequenced for the 16S region of ribosomal deoxyribonucleic acid (rDNA) with the Roche 454 FLX Titanium sequencer. Sequences were analyzed through a data-analysis pipeline to identify the appropriate taxonomic designation (∼species) of each 16s sequence. The bacterial microbiota of each BAL sample was compared with the bacteria identified in the sample through standard culture methods. Correlations between the taxonomic diversity of the microbiota and clinical outcome were examined through linear regression and Pearson correlation. RESULTS Bronchoalveolar lavage samples from 12 individuals in the SICU who had a CPIS≥6 points were examined through 454 pyrosequencing. The number of phylotypes (∼species) in the samples ranged from 15 to 129. The number of phyla in the BAL samples ranged from 3 to 14. There was little correlation between the bacteria identified by NGS and those identified with standard culture methods. The same predominant bacterial strain was identified by both culture and sequencing in only a single sample. The correlation between patient days on a ventilator and the number of species in BAL samples was significant (r=0.7435, p=0.0056; r2=0.5528). CONCLUSIONS Increasing diversity of the bacterial microbiota in BAL samples correlates with the duration of mechanical ventilation. Bacteria identified through standard culture methods were not well correlated with the findings of NGS.

Cervical Spine Injuries and Helmet Laws: A Population-Based Study

BACKGROUND: To assess the incidence of cervical spine (C-spine) injuries in patients admitted after motorcycle crash in states with mandatory helmet laws (MHL) compared with states without helmet laws or selective helmet laws. METHODS: The Nationwide Inpatient Sample from the Healthcare and Utilization Project for the year 2008 was analyzed. International Classification of Diseases and Health Related Problems, Ninth Edition codes were used to identify patients with a diagnosis of motorcycle crash and C-spine injuries. National estimates were generated based on weighted analysis of the data. Outcome variables investigated were as follows: length of stay (LOS), in-hospital mortality, hospital teaching status, and discharge disposition. States were then stratified into states with MHL or selective helmet laws. RESULTS: A total of 30,117 discharges were identified. Of these, 2,041 (6.7%) patients had a C-spine injury. Patients in MHL states had a lower incidence of C-spine injuries (5.6 vs. 6.4%; p = 0.003) and less in-hospital mortality (1.8 vs. 2.6%; p = 0.0001). Patients older than 55 years were less likely to be discharged home (57.5% vs. 72.5%; p = 0.0001), more likely to die in-hospital (3.0% vs. 2.1%; p = 0.0001), and more likely to have a hospital LOS more than 21 days (7.7% vs. 6.2%; p = 0.0001). CONCLUSION: Patients admitted to the hospital in states with MHLs have decreased rate of C-spine injuries than those patients admitted in states with more flexible helmet laws. Patients older than 55 years are more likely to die in the hospital, have a prolonged LOS, and require services after discharge. LEVEL OF EVIDENCE: III.

Cervical Spinal Clearance: A Prospective Western Trauma Association Multi-Institutional Trial.

BACKGROUND For blunt trauma patients who have failed the NEXUS (National Emergency X-Radiography Utilization Study) low-risk criteria, the adequacy of computed tomography (CT) as the definitive imaging modality for clearance remains controversial. The purpose of this study was to prospectively evaluate the accuracy of CT for the detection of clinically significant cervical spine (C-spine) injury. METHODS This was a prospective multicenter observational study (September 2013 to March 2015) at 18 North American trauma centers. All adult (≥18 years old) blunt trauma patients underwent a structured clinical examination. NEXUS failures underwent a CT of the C-spine with clinical follow-up to discharge. The primary outcome measure was sensitivity and specificity of CT for clinically significant injuries requiring surgical stabilization, halo, or cervical-thoracic orthotic placement using the criterion standard of final diagnosis at the time of discharge, incorporating all imaging and operative findings. RESULTS Ten thousand seven hundred sixty-five patients met inclusion criteria, 489 (4.5%) were excluded (previous spinal instrumentation or outside hospital transfer); 10,276 patients (4,660 [45.3%] unevaluable/distracting injuries, 5,040 [49.0%] midline C-spine tenderness, 576 [5.6%] neurologic symptoms) were prospectively enrolled: mean age, 48.1 years (range, 18–110 years); systolic blood pressure 138 (SD, 26) mm Hg; median, Glasgow Coma Scale score, 15 (IQR, 14–15); Injury Severity Score, 9 (IQR, 4–16). Overall, 198 (1.9%) had a clinically significant C-spine injury requiring surgery (153 [1.5%]) or halo (25 [0.2%]) or cervical-thoracic orthotic placement (20 [0.2%]). The sensitivity and specificity for clinically significant injury were 98.5% and 91.0% with a negative predictive value of 99.97%. There were three (0.03%) false-negative CT scans that missed a clinically significant injury, all had a focal neurologic abnormality on their index clinical examination consistent with central cord syndrome, and two of three scans showed severe degenerative disease. CONCLUSIONS For patients requiring acute imaging for their C-spine after blunt trauma, CT was effective for ruling out clinically significant injury with a sensitivity of 98.5%. For patients with an abnormal neurologic examination as the trigger for imaging, there is a small but clinically significant incidence of a missed injury, and further imaging with magnetic resonance imaging is warranted. LEVEL OF EVIDENCE Diagnostic tests, level II.

Early nonbronchoscopic bronchoalveolar lavage: predictor of ventilator-associated pneumonia?

BACKGROUND Ventilator-associated pneumonia is a problem in trauma and emergency general surgery patients. Our hospital-acquired infection prevention committee approved the use of early nonbronchoscopic bronchoalveolar lavage (screening-BAL) in the surgical intensive care unit (SICU) to identify ventilated patients with bronchiolar bacteria before 48 hours. We reviewed the results of this quality improvement initiative. METHODS All ventilated patients in the SICU (March 2011 to June 2012) underwent a screening-BAL 36 hours to 48 hours after intubation; quantitative culture results (>5 × 104 colony-forming unit per milliliter) were used to identify positive specimens. Clinical pneumonia was defined as clinical pulmonary infection score greater than 6 with a subsequent positive diagnostic-BAL result. Sequential organ failure assessment scores were averaged for the first 48 hours in the SICU. Continuous and dichotomous data were compared, and a multivariate regression analysis was performed on the screening-BAL and pneumonia results. RESULTS Screening-BALs were performed in 150 patients (99 trauma and 51 emergency general surgery patients), 72 of these specimens had positive findings. Fifty-three clinical pneumonias were diagnosed, and 45 (positive predictive value, 0.85) identified the same organism as the screening-BAL. Clinical pneumonia developed in eight patients with a negative screening-BAL (negative predictive value, 0.85). Antibiotic therapy at the time of the screening-BAL was associated with a negative screen (odds ratio, 0.44; p = 0.026). Pneumonia developed on median postintubation Day 4 (2–15 days) in patients with a positive screening-BAL results as compared with day 7.5 in the patients with a negative screening-BAL results (3.5–15 days; p = 0.007). Field intubation is an independent risk factor (odds ratio, 3.5; p = 0.004). CONCLUSION Positive screening-BAL results in trauma and emergency general surgery patients are associated with the development of ventilator-associated pneumonia by the same organism and may play a role in identifying patients at risk for pneumonia. Further studies must be conducted to evaluate the role of screening-BAL in this patient population. LEVEL OF EVIDENCE Diagnostic/prognostic study, level III.