"Early results after initiation of a rib fixation programme: A propensity score matched analysis".

INTRODUCTION: Chest wall injuries are very common in blunt trauma and development of treatment protocols can significantly improve outcomes. Surgical stabilisation of rib fractures (SSRF) is an adjunct for the most severe chest injuries and can be used as a part of a comprehensive approach to chest injuries care. We hypothesized that implementation of a SSRF programme program would result in improved short-term outcomes. MATERIALS AND METHODS: The characteristics of the initial group of SSRF patients (Early-SSRF) were used to identify matching factors. Patients prior to SSRF protocol underwent a propensity score match, followed by screening for operative indications and contraindications. After exclusions, a non-operative (Non-Op) cohort was defined (n=36) resulting in an approximately 1:1 match. An overall operative cohort, inclusive of Early-SSRF and all subsequent operative patients, was defined (All- SSRF). A before-and-after analysis using chi-squared, Students T-tests, and Mann-Whitney U-tests were used to assess significance at the level of 0.05. RESULTS: Early-SSRF (n=22) and All-SSRF (n=45) were compared to Non-Op (n=36). The selection process resulted in well matched groups, and equally well-balanced operative indications between the groups. The Early-SSRF group demonstrated shortened duration of mechanical ventilation and a decreased frequency of being discharged a long-term acute care hospital. The All-SSRF group again demonstrated markedly shorter duration of mechanical ventilation compared to Non-Op (median 6 days vs 16 days, p < 0.01), more decrease discharge to a long-term acute care hospital (9% vs. 36%, p=0.01), and reduced risk for tracheostomy (8.9% vs. 33.3% respectively, p<0.01) CONCLUSION: The introduction of an operative rib fixation to a comprehensive chest wall injury protocol can produce improvements in clinical outcomes that decrease time on the ventilator and tracheostomy rates, and result in more patients being discharged to home. Creation and implementation of a chest wall injury protocol to include SSRF requires a multidisciplinary approach and thoughtful patient selection.

A method for identifying the learning curve for the surgical stabilization of rib fractures.

BACKGROUND: Surgical stabilization of rib fractures (SSRF) is an accepted efficacious treatment modality for patients with severe chest wall injuries. Despite increased adoption of SSRF, surgical learning curves are unknown. We hypothesized intraoperative duration could define individual SSRF learning curves. METHODS: Consecutive SSRF operations between January 2017 and December 2021 at a single institution were reviewed. Operative time, as measured from incision until skin closure, was evaluated by cumulative sum methodology using a range of acceptable "missteps" to determine the learning curves. Misstep was defined by extrapolation of accumulated operative time data. RESULTS: Eighty-three patients underwent SSRF by three surgeons during this retrospective review. Average operative times ranged from 135 minutes for two plates to 247 minutes for seven plates. Using polynomial regression of average operative times, 75 minutes for general procedural requirements plus 35 minutes per plate were derived as the anticipated operative times per procedure. Cumulative sum analyses using 5%, 10%, 15%, and 20% incident rates for not meeting expected operative times, or "missteps" were used. An institutional learning curve between 15 and 55 SSRF operations was identified assuming a 90% performance rate. An individual learning curve of 15 to 20 operations assuming a 90% performance rate was observed. After this period, operative times stabilized or decreased for surgeons A, B, and C. CONCLUSION: The institutional and individual surgeon learning curves for SSRF appears to steadily improve after 15 to 20 operations using operative time as a surrogate for performance. The implementation of SSRF programs by trauma/acute care surgeons is feasible with an attainable learning curve. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

The Association Between Pulmonary Contusion Severity and Respiratory Failure.

BACKGROUND: Pulmonary contusions (PCs) have historically been viewed as a serious complicating factor in thoracic injury. Recently, there has been conflicting evidence regarding the influence of PCs on outcomes; however, many studies do not stratify contusions by severity and may miss clinical associations. We sought to identify if contusion severity is associated with worse outcomes. METHODS: A previously published chest wall injury database at an urban Level I trauma center was retrospectively reviewed. All severely injured subjects (defined as Injury Severity Score [ISS] ≥ 15) with moderate to severe thoracic injury (defined as a chest wall Abbreviated Injury Scale [AIS] ≥ 3) who required mechanical ventilation for > 24 h were stratified by contusion severity. Moderate to severe contusions were defined as AIS contusion ≥ 3 and Blunt Pulmonary Contusion 18 (BPC18) score ≥ 3. RESULTS: Over 5 y, 3,836 patients presented with chest wall injuries, of which 1,176 (30.6%) had concomitant contusions. When screened for inclusion criteria, 339 subjects with contusions and 211 subjects without contusions (no-PC) were identified. Of these, 234 had moderate to severe contusions defined by AIS contusion ≥ 3 (PC-A) and 230 had moderate to severe contusions by BPC18 ≥ 3 (PC-B). Compared to no-PC, both PC-A and PC-B groups had significantly lower mortality (17.9% and 17.4%, respectively, vs 28.9%); however, PC-A and PC-B groups had longer durations of mechanical ventilation (6 and 7 d, respectively, vs 5 d), longer ICU length of stay (10 and 10 vs 8 d), and longer overall hospital length of stay (15 and 15 vs 13 d). CONCLUSIONS: In severely injured polytrauma patients, PCs are seen with more severe chest injuries. Furthermore, moderate to severe contusions are associated with longer durations of mechanical ventilation, ICU length of stay, and hospital length of stay. Despite practice pattern changes, contusions appear to contribute significantly to the clinical course of the blunt chest wall injured patients.

Does chest wall Organ Injury Scale (OIS) or Abbreviated Injury Scale (AIS) predict outcomes? An analysis of 16,000 consecutive rib fractures.

BACKGROUND: Chest wall injuries have serious clinical consequences. It is presumed a higher severity of injury correlates with worse outcomes. The 2 most common chest wall injury severity scores, the Organ Injury Scale and the Abbreviated Injury Scale, are based on expert opinion with unknown clinical endpoints. Our aim was to determine if either the Organ Injury Scale or the Abbreviated Injury Scale are associated with clinical outcomes. METHODS: A single institution, 4-year retrospective study of all patients with rib or sternal fractures was conducted. All patients were assessed for both Organ Injury Scale and Abbreviated Injury Scale scores. Outcomes assessed included mortality, complications, tracheostomy, and readmissions. Receiver operating characteristic areas under the curve were calculated to measure discriminatory accuracy of scoring systems for outcomes in chest wall injury. RESULTS: Overall, 3,033 patients presented with a total of 16,055 rib fractures. The median chest wall scores were 2 for Organ Injury Scale and 3 for Abbreviated Injury Scale. Abbreviated Injury Scale scores for the same patients were greater than the Organ Injury Scale in 48.7%, equivalent in 46.7%, and lower in 4.6%. The receiver operating characteristic areas under the curve for in-hospital outcomes were weakly predictive for the Organ Injury Scale over the Abbreviated Injury Scale. The receiver operating characteristic areas under the curve for readmissions were very weakly predictive for the Abbreviated Injury Scale over the Organ Injury Scale. CONCLUSION: There is a very weak association between chest wall Organ Injury Scale score and in-hospital outcomes. The Abbreviated Injury Scale score outperformed the Organ Injury Scale, only being weakly predictive of readmission. Chest wall injury scoring systems may need revision for future outcomes-based research and practice improvements.

A signal-anchor sequence selective for the mitochondrial outer membrane.

pOMD29 is a hybrid protein containing the NH2-terminal topogenic sequence of a bitopic, integral protein of the outer mitochondrial membrane in yeast, OMM70, fused to dihydrofolate reductase. The topogenic sequence consists of two structural domains: an NH2-terminal basic region (amino acids 1-10) and an apolar region which is the predicted transmembrane segment (amino acids 11-29). The transmembrane segment alone was capable of targeting and inserting the hybrid protein into the outer membrane of intact mitochondria from rat heart in vitro. The presence of amino acids 1-10 enhanced the rate of import, and this increased rate depended, in part, on the basic amino acids located at positions 2, 7, and 9. Deletion of a large portion of the transmembrane segment (amino acids 16-29) resulted in a protein that exhibited negligible import in vitro. Insertion of pOMD29 into the outer membrane was not competed by import of excess precursor protein destined for the mitochondrial matrix, indicating that the two proteins may have different rate-limiting steps during import. We propose that the structural domains within amino acids 1-29 of pOMD29 cooperate to form a signal-anchor sequence, the characteristics of which suggest a model for proper sorting to the mitochondrial outer membrane.

Intestinal diffusion barrier: unstirred water layer or membrane surface mucous coat?

The dimensions of the small intestinal diffusion barrier interposed between luminal nutrients and their membrane receptors were determined from kinetic analysis of substrate hydrolysis by integral surface membrane enzymes. The calculated equivalent thickness of the unstirred water layer was too large to be compatible with the known dimensions of rat intestine. The discrepancy could be reconciled by consideration of the mucous coat overlying the intestinal surface membrane. Integral surface membrane proteins could not be labeled by an iodine-125 probe unless the surface coat was first removed. The mucoprotein surface coat appears to constitute an important diffusion barrier for nutrients seeking their digestive and transport sites on the outer intestinal membrane.

DNA base composition of rickettsiae.

There is a small but distinct difference in DNA base composition between the typhus and spotted fever groups of rickettsiae. The molar percentages of guanine plus cytosine for Rickettsia prowazeki, R. typhi, and R. canada are approximately 30, for R. rickettsi, R. conori, and R. akari they are about 32.5. The percentage for trench fever rickettsia, Rochalimaea quintana, is 38.6.

Acridine araphanes: a new class of probe molecules for biological systems.

The bis-acridine ring system forms the basis for new biophysical probes of novel stereochemistry. Spectral data indicate that certain alkylene bridged bis-9-aminoacridines have a parallel plane conformation of predictable interplane distance. The parallel plane conformation is independent of solvent and thus is different from nucleic acid systems. This stable conformation allows these compounds to be used as sensitive "rulers" for describing binding site geometry in cholinergic enzymes and in the delineation of the mechanism of allosteric control in acetylcholinesterase.

Blue-fluorescent antibodies.

The forte of catalytic antibodies has resided in the control of the ground-state reaction coordinate. A principle and method are now described in which antibodies can direct the outcome of photophysical and photochemical events that take place on excited-state potential energy surfaces. The key component is a chemically reactive optical sensor that provides a direct report of the dynamic interplay between protein and ligand at the active site. To illustrate the concept, we used a trans-stilbene hapten to elicit a panel of monoclonal antibodies that displayed a range of fluorescent spectral behavior when bound to a trans-stilbene substrate. Several antibodies yielded a blue fluorescence indicative of an excited-state complex or "exciplex" between trans-stilbene and the antibody. The antibodies controlled the isomerization coordinate of trans-stilbene and dynamically coupled this manifold with an active-site residue. A step was taken toward the use of antibody-based photochemical sensors for diagnostic and clinical applications.

Readmission rates and associated factors following rib cage injury.

BACKGROUND: There remains a lack of knowledge about readmission characteristics after sustaining rib fractures. We aimed to determine rates, characteristics, and predictive/protective factors associated with unexpected reevaluation and readmission after rib cage injury. METHODS: A retrospective review was performed based on trauma patients evaluated at an urban Level I trauma center from January 2014 to December 2016. Adult patients sustaining blunt trauma with more than one rib fracture or a sternomanubrial fracture were defined as having moderate to severe rib cage injury. Exclusion criteria included penetrating injury, death during initial hospitalization, and only one rib fracture. Reevaluation was defined as presenting at a hospital within 90 days of discharge urgently or emergently. Demographics, injury characteristics, comorbidities, complications, imaging, and readmission data were collected. Univariate and multivariate analysis was performed with a significance of p less than 0.05. RESULTS: During the study period, 11,667 patients underwent trauma evaluation, of which 1,717 patients were found to have a moderate to severe rib cage injury. Within 90 days, 397 (23.1%) of patients underwent reevaluation, while 177 (10.3%) required readmission. One hundred forty-two (8.3%) patients were reevaluated specifically for chest-related complaints, and 55 (3.2%) required readmission. On univariate analysis, Injury Severity Score greater than 15, hospital length of stay longer than 7 days, intensive care unit (ICU) length of stay longer than 3 days, a worsened chest x-ray at discharge, a psychiatric comorbidity, a smoking comorbidity, deep vein thrombosis, unplanned readmission to the ICU, and unplanned intubation were higher in the overall reevaluation cohort. On multivariate analysis, age of 15 years to 35 years, Risk Assessment Profile score greater than 8, hypertension, psychiatric comorbidity, current smoker, and unplanned return to the ICU on index admission were predictive of reevaluation of overall reevaluation. CONCLUSION: Moderate to severe rib cage injury is associated with high rates of reevaluation and readmission. Younger patients who smoke and required a return to the ICU are at greater risk for readmission. LEVEL OF EVIDENCE: Level IV, Prognostic and Epidemiologic.

Factor VIIa administration in traumatic brain injury: an AAST-MITC propensity score analysis.

BACKGROUND: Recombinant factor VIIa (rFVIIa) has been used off-label as an adjunct in the reversal of warfarin therapy and management of hemorrhage after trauma. Only a handful of these reports are rigorous studies, from which results regarding safety and effectiveness have been mixed. There remains no clear consensus as to the role of rFVIIa in traumatic brain injury (TBI). METHODS: Eleven level 1 trauma centers provided clinical data and head CT scans of patients with a Glasgow Coma Scale (GCS) score of ≤13 and radiographic evidence of TBI. A propensity score (PS) to receive rFVIIa in those surviving ≥2 days was calculated for each patient based on patient demographics, comorbidities, physiology, Injury Severity Score, admission GCS score, and treatment center. Patients receiving rFVIIa within 24 hours of admission were matched to patients who did not receive rFVIIa for outcomes assessment. Subgroup analysis evaluated patients with primary head injury with PS matching. RESULTS: There were 4284 patient observations; 129 received rFVIIa. Groups were comparable after matching. No differences in mortality or morbidity were found. Improvement in GCS score from admission to discharge was less among those receiving rFVIIa (5.5 vs. 2.4; P value 0.001); however, there was no difference in average GCS score at discharge. No significant differences in outcomes were identified in patients with isolated TBI receiving rFVIIa. DISCUSSION: rFVIIa in early management of TBI is not associated with a decreased risk of mortality or morbidity, and may negatively impact recovery and functional status at discharge in the severely injured patient with polytrauma. LEVEL OF EVIDENCE: Level III. STUDY TYPE: Therapeutic/care management.

Safety and efficacy of brain injury guidelines at a Level III trauma center.

BACKGROUND: Patients with mild to moderate traumatic brain injury (TBI) are often primarily managed by emergency medicine and trauma/acute care physicians. The Brain Injury Guidelines (BIG) were developed at an American College of Surgeons-accredited Level 1 trauma center to triage mild to moderate TBI patients and help identify patients who warrant neurosurgical consultation. The BIG have not been validated at a Level III trauma center. We hypothesized that BIG criteria can be safely adapted to an American College of Surgeons-accredited Level III trauma center to guide transfers to a higher echelon of care. METHODS: We reviewed the trauma registry at a Level III trauma center to identify TBI patients who presented with an Abbreviated Injury Severity-Head score greater than zero. Demographic data, injury details, and clinical outcomes were abstracted with primary outcome measures of worsening on second computed tomography of the head, neurosurgical intervention, transfer to a Level I trauma center, and in-hospital mortality. Patients were classified using the BIG criteria. After validating the BIG in our cohort, we reclassified patients using updated BIG criteria. Updated criteria included mechanism of injury, reclassification of anticoagulation or antiplatelet use, and replacement of the neurologic examination component with stratification by admission Glasgow Coma Scale (GCS) score. RESULTS: From July 2013 to June 2016, 332 TBI patients were identified: 115 BIG-1, 25 BIG-2, and 192 BIG-3. Patients requiring neurosurgical intervention (n = 30) or who died (n = 29) were BIG-3 with one exception. Patients with GCS score of less than 12 had worse outcomes than those with a GCS score of 12 or greater, regardless of BIG classification. Anticoagulant or antiplatelet use was not associated with worsened outcomes in patients not meeting other BIG-3 criteria. The updated BIG resulted in more patients in BIG-1 (n = 109) and BIG-2 (n = 100) without negatively affecting outcomes. CONCLUSION: The BIG can be applied in the Level III trauma center setting. Updated BIG criteria can aid triage of mild to moderate TBI patients to a Level I trauma center and may reduce secondary overtriage. LEVEL OF EVIDENCE: Care management, level IV.

Fluorescence studies of DNA and RNA structure and dynamics.

Fluorescence spectroscopy is increasingly being used as a technique for probing the structure and dynamics of nucleic acids. Recently, fluorescence methods have been used to elucidate the three-dimensional arrangement of complex DNA and RNA structures, characterize structural perturbations resulting from base bulges in helices and junctions, determine helical handedness in solution, and analyze the protein-induced melting of DNA.

Time-resolved fluorescence spectroscopy.

Time-resolved fluorescence spectroscopy is used to monitor molecular interactions and motions that occur in the picosecond-nanosecond time range, and is especially useful in the analysis of biomolecular structure and dynamics. Recent advances in the application of time-resolved fluorescence spectroscopy to biological systems have led to a better understanding of the origin of nonexponential fluorescence decay in proteins, the use of tryptophan analogs as unique spectroscopic probes of protein-protein interactions, the detailed characterization of protein-folding processes and intermediates, and the development of new approaches to the study of DNA-protein interactions.

Prospective economic evaluation alongside the non-invasive ventilation trial.

OBJECTIVE: To determine the cost-effectiveness of nasal continuous positive pressure (nCPAP) compared with nasal intermittent positive pressure ventilation (NIPPV) in the context of the reported randomized clinical trial. STUDY DESIGN: Using patient-level data from the clinical trial, we undertook a prospectively planned economic evaluation. We measured costs, from a third-party payer perspective in all patients, and from a societal perspective in a subgroup with a time horizon through the earlier of discharge, death or 44 weeks post-menstrual age. RESULTS: From the third-party payer perspective, the mean cost of hospitalization per infant was statistically similar, $143 745 in the NIPPV group compared to $140 403 in the nCPAP group. Cost-effectiveness evaluation revealed a 61% probability that NIPPV is more expensive and less effective than nCPAP. Similar results were found in subgroup analysis from a societal perspective. CONCLUSION: In addition to being clinically equivalent, economic evaluation confirms that NIPPV, as employed in this trial, is also not economically favorable.

Antithrombin for respiratory distress syndrome in preterm infants.

BACKGROUND: Acquired Antithrombin (AT) deficiency is a common and prognostically important finding in sick preterm infants with respiratory distress syndrome (RDS). It has been hypothesised that AT concentrate may improve clinical outcomes in preterm infants with RDS. OBJECTIVES: To determine whether the administration of AT concentrate decreases mortality in preterm infants with RDS compared with placebo or no treatment. SEARCH STRATEGY: An electronic literature search in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE in August 2006 was performed. No language restriction was applied. References from identified studies were cross-checked for possible additional studies. Experts in the field and pharmaceutical companies were contacted for unpublished data. Abstracts of the American Society of Pediatric Research and European Society of Pediatric Research meetings (1983-2005) were searched and authors of relevant studies were contacted to obtain additional information. SELECTION CRITERIA: Randomized controlled trials comparing any dose and duration of AT therapy with placebo or no treatment in preterm infants with RDS. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data from included studies regarding mortality, intraventricular hemorrhage, mechanical ventilation, and other reported events in the clinical course of the patients. Data for similar outcomes were combined where appropriate, using a fixed-effects model in MetaView 4.2 (Update Software). MAIN RESULTS: Two trials consisting of 182 preterm infants, fulfilled the inclusion criteria. Mean gestational age of patients included was 28 weeks. In one trial, patients had to be intubated and ventilated for RDS to be eligible for the study. In the other trial, RDS was not mentioned as an inclusion criteria, however the vast majority of infants in the study received surfactant. No individual trial showed a significant difference in mortality. One of the trials was stopped early because of an increase in deaths in the AT group. The pooled analysis for mortality within the first week of life showed a typical relative risk of 2.67 (95% CI 0.72-9.83) in favour of the control group. Only the trial that was stopped early followed the infants long enough to report neonatal mortality. This trial reported 7 deaths (11.5%) in the AT group and two deaths (3.3%) in the placebo group within 28 days of life. Secondary outcomes included days of mechanical ventilation and supplemental oxygen which were only reported in 1 trial. Both outcomes were in favour of the control group and statistically significant (p < 0.05). AUTHORS' CONCLUSIONS: Preterm infants with RDS are unlikely to benefit from AT treatment and may be harmed.

Extensive DNA methylation spanning the Rb promoter in retinoblastoma tumors.

The retinoblastoma gene (Rb) is one of the best characterized tumor suppressor genes, and its inactivation is associated with a number of cancers. Previous studies have shown, by restriction enzyme analysis, that the promoter region of the Rb gene is methylated in a significant proportion of primary retinoblastoma tumors. We now report the first detailed methylation sequence analysis of the CpG island spanning the retinoblastoma promoter from hypermethylated retinoblastoma tumors. Our results show methylation is not confined to a specific CpG site, as detected by restriction enzyme studies, but extends to essentially all 27 CpG dinucleotides spanning the retinoblastoma CpG island, including the core promoter. The methylation pattern from each tumor DNA sample is different, ranging from densely to sparsely methylated profiles. Single CpG sites, in particular the E2F transcription factor binding site, as well as blocks of CpGs, were undermethylated in some tumor samples. Possible interference of methylation could be due to the binding of sequence-specific protein factors at these sites in the tumor cells. This study highlights that the dynamics of DNA methylation in cancer cells are clearly different from normal cells and gives an insight into the mechanism of abnormal methylation of CpG islands in cancer cells.

Loss of annexin II heavy and light chains in prostate cancer and its precursors.

Annexin II mRNA coding for a calcium binding protein was found to be absent in prostate cancer by subtractive hybridization and Northern analysis. In contrast to high expression in normal and benign hyperplastic glandular and basal epithelium, Annexin II heavy (p36) and light (p11) chains in 31/31 prostate cancer specimens were lost immunohistochemically. In glands involved by prostate intraepithelial neoplasia, 65% lost both chains in glandular epithelial cells, whereas basal cells were all positively stained. Southern analysis of cancer DNA showed no noticeable deletion in p36 gene. LNCaP cells treated with 5-azacytidine re-expressed p36, suggesting methylation could be responsible for the silencing.

Detailed methylation analysis of the glutathione S-transferase pi (GSTP1) gene in prostate cancer.

Glutathione-S-Transferases (GSTs) comprise a family of isoenzymes that provide protection to mammalian cells against electrophilic metabolites of carcinogens and reactive oxygen species. Previous studies have shown that the CpG-rich promoter region of the pi-class gene GSTP1 is methylated at single restriction sites in the majority of prostate cancers. In order to understand the nature of abnormal methylation of the GSTP1 gene in prostate cancer we undertook a detailed analysis of methylation at 131 CpG sites spanning the promoter and body of the gene. Our results show that DNA methylation is not confined to specific CpG sites in the promoter region of the GSTP1 gene but is extensive throughout the CpG island in prostate cancer cells. Furthermore we found that both alleles are abnormally methylated in this region. In normal prostate tissue, the entire CpG island was unmethylated, but extensive methylation was found outside the island in the body of the gene. Loss of GSTP1 expression correlated with DNA methylation of the CpG island in both prostate cancer cell lines and cancer tissues whereas methylation outside the CpG island in normal prostate tissue appeared to have no effect on gene expression.

On the homogeneity of 11-S acetylcholinesterase.

11-S acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) purified by affinity chromatography of trypsin-digested homogenates was shown to be contaminated with three other active forms of enzyme. The initial purification used an affinity column of the inhibitor, N-methylacridinium ion. Chromatography of the "affinity-pure" sample on hydroxyapatite resulted in two peaks of acetylcholinesterase activity. One peak contained only a form sedimenting at 11-S (approx. 85% of the recovered activity). The other peak consisted of a 9.5-S form, in addition to 14-S and 18-S forms. The 9.5-S form (approx. 7% of the activity) co-electrophoresed with 11-S in 6% polyacrylamide gels and co-sedimented with the same form in sucrose density gradients containing 0.1 M NaCl. The purified 11-S enzyme was shown to be homogeneous by sucrose density gradient centrifugation and electrophoresis. These results indicate that 11-S acetylcholinesterase may be unsuitable for some characterization studies due to undetected contamination by the 9.5-S form.