Abnormalities on Perfusion CT and Intervention for Intracranial Hypertension in Severe Traumatic Brain Injury.

The role of invasive intracranial pressure (ICP) monitoring in patients with severe traumatic brain injury (STBI) remain unclear. Perfusion computed tomography (CTP) provides crucial information about the cerebral perfusion status in these patients. We hypothesised that CTP abnormalities would be associated with the severity of intracranial hypertension (ICH). To investigate this hypothesis, twenty-eight patients with STBI and ICP monitors were investigated with CTP within 48 h from admission. Treating teams were blind to these results. Patients were divided into five groups based on increasing intervention required to control ICH and were compared. Group I required no intervention above routine sedation, group II required a single first tier intervention, group III required multiple different first-tier interventions, group IV required second-tier medical therapy and group V required second-tier surgical therapy. Analysis of the results showed demographics and injury severity did not differ among groups. In group I no patients showed CTP abnormality, while patients in all other groups had abnormal CTP (p = 0.003). Severe ischaemia observed on CTP was associated with increasing intervention for ICH. This study, although limited by small sample size, suggests that CTP abnormalities are associated with the need to intervene for ICH. Larger scale assessment of our results is warranted to potentially avoid unnecessary invasive procedures in head injury patients.

When a Slice Is Not Enough! Comparison of Whole-Brain versus Standard Limited-Slice Perfusion Computed Tomography in Patients with Severe Traumatic Brain Injury.

INTRODUCTION: Cerebral perfusion computed tomography (PCT) provides crucial information in acute stroke and has an increasing role in traumatic brain injury (TBI) management. Most studies on TBI patients utilize 64-slice scanners, which are limited to four brain slices (limited-brain PCT, LBPCT). Newer 320-slice scanners depict the whole brain perfusion status (WBPCT). We aimed to identify the additional information gained with WBPCT when compared to LBPCT. PATIENTS AND METHODS: Forty-nine patients with severe TBI were investigated within 48 h from admission with WBPCT. Findings from LBPCT were compared with findings from WBPCT. RESULTS: A perfusion abnormality was identified in 39 (80%) and 37 (76%) patients by WBPCT and LBPCT, respectively (p = 0.8). There were 90 and 68 perfusion abnormalities identified by WBPCT and LBPCT, respectively (p < 0.001). In the 39 patients with a perfusion abnormality detected by WBPCT, 15 (38%) had further perfusion abnormalities outside the LBPCT area of coverage. Thirty-six (92%) patients had a larger perfusion abnormality upon WBPCT compared with LBPCT. Additional information gained showed some statistically significant correlation with clinical outcome. CONCLUSIONS: In severe TBI patients, WBPCT provides extra information compared to LBPC. The limitations of LBPCT should be considered when evaluating studies reporting on PCT findings and their association with outcomes.

Which Emergency Medicine Milestone Sub-competencies are Identified Through Narrative Assessments?

INTRODUCTION: Evaluators use assessment data to make judgments on resident performance within the Accreditation Council for Graduate Medical Education (ACGME) milestones framework. While workplace-based narrative assessments (WBNA) offer advantages to rating scales, validity evidence for their use in assessing the milestone sub-competencies is lacking. This study aimed to determine the frequency of sub-competencies assessed through WBNAs in an emergency medicine (EM) residency program. METHODS: We performed a retrospective analysis of WBNAs of postgraduate year (PGY) 2-4 residents. A shared mental model was established by reading and discussing the milestones framework, and we created a guide for coding WBNAs to the milestone sub-competencies in an iterative process. Once inter-rater reliability was satisfactory, raters coded each WBNA to the 23 EM milestone sub-competencies. RESULTS: We analyzed 2517 WBNAs. An average of 2.04 sub-competencies were assessed per WBNA. The sub-competencies most frequently identified were multitasking, medical knowledge, practice-based performance improvement, patient-centered communication, and team management. The sub-competencies least frequently identified were pharmacotherapy, airway management, anesthesia and acute pain management, goal-directed focused ultrasound, wound management, and vascular access. Overall, the frequency with which WBNAs assessed individual sub-competencies was low, with 14 of the 23 sub-competencies being assessed in less than 5% of WBNAs. CONCLUSION: WBNAs identify few milestone sub-competencies. Faculty assessed similar sub-competencies related to interpersonal and communication skills, practice-based learning and improvement, and medical knowledge, while neglecting sub-competencies related to patient care and procedural skills. These findings can help shape faculty development programs designed to improve assessments of specific workplace behaviors and provide more robust data for the summative assessment of residents.

Outcome with Primary En-bloc Esophagectomy for Submucosal Esophageal Adenocarcinoma.

BACKGROUND: Intramucosal esophageal adenocarcinoma can be reliably treated endoscopically. Controversy exists about the use of endotherapy versus esophagectomy for submucosal tumors. Increasingly endotherapy is considered for submucosal tumors in part because of the presumed high mortality with esophagectomy and the perceived poor prognosis in patients with nodal disease. This study was designed to assess survival following primary en bloc esophagectomy (EBE) in patients with submucosal esophageal adenocarcinoma (EAC). METHODS: This is a retrospective review of all patients who underwent EBE for submucosal EAC between 1998 and 2015. No patient had neoadjuvant therapy. RESULTS: There were 32 patients (28M/4F; median age 64 years). The median tumor size was 1.5 cm (0.4-8.0), and the median number of resected nodes was 48 (23-85). There was one perioperative death. Lymph node metastases were present in 7 patients (22%). There was one involved node in four patients and 2, 3, and 31 nodes in one patient each. The one N3 patient received adjuvant therapy. The median follow-up was 87 months. Overall survival at 5 and 10 years was 84 and 70% respectively. Disease-specific survival at 10 years was 90%. Eight patients died, but only three deaths (9%) were related to EAC. Disease-specific survival at 10 years in node-positive patients was 71%. CONCLUSIONS: Survival after primary en bloc esophagectomy for submucosal adenocarcinoma was excellent even in node-positive patients. Mortality with esophagectomy was low and far less than the 22% risk of node metastases in patients with submucosal tumor invasion. Esophagectomy should remain the preferred treatment for T1b esophageal adenocarcinoma.

Perfusion Abnormalities are Frequently Detected by Early CT Perfusion and Predict Unfavourable Outcome Following Severe Traumatic Brain Injury.

BACKGROUND: In patients with severe traumatic brain injury (TBI), early CT perfusion (CTP) provides additional information beyond the non-contrast CT (NCCT) and may alter clinical management. We hypothesized that this information may prognosticate functional outcome. METHODS: Five-year prospective observational study was performed in a level-1 trauma centre on consecutive severe TBI patients. CTP (obtained in conjunction with first routine NCCT) was interpreted as: abnormal, area of altered perfusion more extensive than on NCCT, and the presence of ischaemia. Six months Glasgow Outcome Scale-Extended of four or less was considered an unfavourable outcome. Logistic regression analysis of CTP findings and core variables [preintubation Glasgow Coma Scale (GCS), Rotterdam score, base deficit, age] was conducted using Bayesian model averaging to identify the best predicting model for unfavourable outcome. RESULTS: Fifty patients were investigated with CTP (one excluded for the absence of TBI) [male: 80%, median age: 35 (23-55), prehospital intubation: 7 (14.2%); median GCS: 5 (3-7); median injury severity score: 29 (20-36); median head and neck abbreviated injury scale: 4 (4-5); median days in ICU: 10 (5-15)]. Thirty (50.8%) patients had an unfavourable outcome. GCS was a moderate predictor of unfavourable outcome (AUC = 0.74), while CTP variables showed greater predictive ability (AUC for abnormal CTP = 0.92; AUC for area of altered perfusion more extensive than NCCT = 0.83; AUC for the presence of ischaemia = 0.81). CONCLUSION: Following severe TBI, CTP performed at the time of the first follow-up NCCT, is a non-invasive and extremely valuable tool for early outcome prediction. The potential impact on management and its cost effectiveness deserves to be evaluated in large-scale studies. LEVEL OF EVIDENCE III: Prospective study.

Does Clubfoot Treatment Need to Begin As Soon As Possible?

INTRODUCTION: Parents of an infant with an idiopathic clubfoot deformity are often urged by their primary care physician to seek treatment as soon as possible. This advice frequently appears in many general pediatric and pediatric orthopaedic textbooks and monographs on the subject. This recommendation has not changed since the wide acceptance of the minimally invasive Ponseti method to treat clubfoot. We determined the correlations among patient-related variables, early treatment variables, and the age at which the patient was first seen to begin treatment. METHODS: Infants with moderate to very severe idiopathic clubfoot deformity were invited to participate. Age at which the patient presented to begin treatment was correlated against early treatment-related variables, including number of casts required, cast slippage, cast-related skin problems, brace-related skin problems, early noncompliance with brace wearing, and relapse before 1 year. Patient-related variables were also correlated against age at first visit. RESULTS: Over 7 years, 176 infants met the inclusion criteria. There were no significant differences in the aspects of the early management as a function of age at first visit, with the exception of cast slippage (P=0.05). CONCLUSIONS: The age at first visit influenced the incidence of cast slippage, but otherwise did not affect the early treatment of clubfoot. CLINICAL RELEVANCE: The treatment of idiopathic clubfoot deformity should not be considered an orthopaedic emergency, and parents whose infants are born with this deformity should be counseled accordingly.

The Outcome of Surgical Treatment of Multidirectionally Unstable (Type IV) Pediatric Supracondylar Humerus Fractures.

BACKGROUND: The outcome of multidirectionally unstable (type IV) supracondylar humerus fractures (SCHF) has been rarely described. We aimed to describe several aspects related to the diagnosis, treatment, and outcome of this complex injury. METHODS: We analyzed the clinical and radiographic data on 130 completely displaced SCHF in children, which was collected prospectively over a 6-year period (2007 to 2013), as part of an IRB-approved study. A minimum follow-up of 6 weeks was required. We compared the outcome of type IV SCHF (n=12, group 1) with that of type III SCHF (n=118, group 2) by assessing the need for open reduction, length of operative time, recovery of range of motion (as compared with the normal, contralateral side), and rate of complications. RESULTS: An open reduction was required in 17% and 2% of fractures in groups 1 and 2, respectively (P=0.04). A medial pin was added to supplement the fixation in 42% and 17% of fractures in groups 1 and 2, respectively (P=0.05). An acceptable reduction was obtained in all fractures. Surgery was longer for fractures in group 1, by a mean of 22 minutes (P=0.0001). No patient in either group required a reoperation. There was no significant difference between groups with respect to the latest range of motion of the treated side, as compared with the normal contralateral side (98% vs. 97%, respectively, P=0.4). Satisfactory outcomes were found in 92% and 98% of patients in groups 1 and 2, respectively (P=0.6). CONCLUSIONS: The results of this study suggest that a satisfactory outcome can be expected when treating type IV SCHF in a child. Although these fractures are associated with increased levels of technical difficulty, given the increased need for open reduction, utilization of medial pins, and longer surgical times, adequate reductions and satisfactory mid-term to long-term outcomes can be achieved. LEVEL OF EVIDENCE: Level II.

Closed Reduction and Percutaneous Pinning of Displaced Pediatric Lateral Condyle Fractures of the Humerus: A Cohort Study.

BACKGROUND: In treating pediatric lateral condyle fractures (LCFs) of the humerus, closed reduction and percutaneous pinning (CRPP) is an attractive alternative to open reduction and internal fixation (ORIF) because of the potential decrease in tissue injury, shorter surgical times, and faster functional recovery. However, there is limited information available regarding its outcome. METHODS: The data on 191 pediatric LCFs [163 fractures (85%) treated with ORIF (group 1) and 28 fractures (15%) treated with CRPP (group 2)], who were followed for over 12 weeks, was included in the present analysis. We compared several aspects related to the outcome of CRPP (as compared with ORIF), including issues related to surgical time, recovery of range of motion, lateral spur formation, complications, and overall outcome. RESULTS: The surgical time was significantly shorter for patients in group 2 (mean: 25.4 min; range: 18 to 50 min), as compared with group 1 (mean: 52.6 min; range: 24 to 121 min). A nearly anatomic reduction (<2 mm of residual displacement) was obtained in all fractures. No intraoperative or immediate postoperative complications were observed. The recovery of range of motion was similar in both groups: during the latest follow-up appointment, elbows in group 1 and 2 had achieved a mean relative arc of motion of 99.2% and 99.7%, respectively (P=0.3). Lateral spur formation was seen in 75% of fractures in group 1 and in 68% of fractures in group 2 (P=0.2). The overall rate of complications was 6.3% and 3.6% for fractures is groups 1 and 2, respectively (P=0.5). A satisfactory outcome was observed in 88.3% of fractures in group 1 and in 89.3% of fractures in group 2 (P=0.6) (Table 1). CONCLUSIONS: CRPP is a viable alternative for the treatment of pediatric LCFs with limited initial displacement (between 2 and 4 mm). In addition to the obvious cosmetic advantage of avoiding an unsightly scar, it is associated with decreased surgical times and does not significantly increase the incidence of complications.

Elbow dislocation with an associated lateral condyle fracture of the humerus: a rare occurrence in the pediatric population.

BACKGROUND: In the pediatric population, reports of a concomitant lateral condyle fracture (LCF) of the humerus and an elbow dislocation are rare. METHODS: From 2007 to 2013, we identified a group of 12 children who presented to our institution with a concomitant LCF and an elbow dislocation. This subset of fractures (group 1), all of which were managed surgically, is the subject of the present report. Their outcome was compared with that of all LCFs that were treated surgically at our institution during the study period (group 2, n=179). The length of surgery, recovery of range of motion (ROM), lateral spur formation, and the presence or absence of neurological or vascular complications, pin-tract infection, loss of fixation, and avascular necrosis or nonunion of the lateral condyle were used to describe the outcome of the fracture. RESULTS: A concomitant elbow dislocation and LCF of the humerus was observed in 12 patients with a mean age of 5.5 years (range, 2 to 8), and a mean follow-up of 51 weeks. A posteromedial dislocation of the elbow was observed in most patients. The recovery of ROM appeared to be slower for patients with an associated elbow dislocation, but a full recovery of ROM was obtained in the long term. Lateral spur formation was seen in all fractures in group 1 and only in 72% of fractures in group 2 (P=0.02). A satisfactory outcome was observed in 92% of fractures in group 1 and in 88% of fractures in group 2 (P=0.58). CONCLUSIONS: Concomitant LCF of the humerus and an elbow dislocation are rare. Satisfactory outcomes can be expected when prompt reduction of the elbow dislocation and timely anatomic reduction and fixation of the fracture is obtained. A delayed recovery of elbow motion is common among this population, but a full recovery of ROM can be expected in the long term. LEVEL OF EVIDENCE: Level II-retrospective.

Comparison between Freeze-dried and Ready-to-use AlloDerm in Alloplastic Breast Reconstruction.

BACKGROUND: AlloDerm, a brand of acellular dermal matrix, is commonly used as an internal hammock to support the tissue expander or permanent implant in breast reconstruction. The aim of our study is to evaluate the complication rates associated with the freeze-dried (FD) AlloDerm and the ready-to-use (RTU) AlloDerm. METHODS: This institutional review board-approved retrospective study involved 103 patients who underwent immediate postmastectomy breast reconstructions from June 2011 to August 2012. The first 51 patients underwent 96 immediate breast reconstructions with FD AlloDerm. The subsequent 52 patients underwent 100 immediate breast reconstructions with RTU AlloDerm. Patient demographics, postoperative complication rates in study cohort, and complication rates stratified by body mass index (BMI) were analyzed. RESULTS: Multiple patient demographics in the 2 cohorts are closely matched (P > 0.05). RTU AlloDerm was associated with higher rates of seroma and cellulitis compared with FD AlloDerm (22.0% vs 18.8%, P = 0.599 and 21.0% vs 12.5%, P = 0.129, respectively). Significantly higher rates of seroma and cellulitis were found in patients with BMI ≥ 30 compared with BMI < 30 (34.5% vs 9.2%, P < 0.001 and 29.9% vs 6.4%, P < 0.001, respectively). A generalized linear mixed model shows that obesity and RTU AlloDerm are statistically significant predictors of cellulitis (adjusted odds ratio = 10.413, P < 0.001 and adjusted odds ratio = 3.712, P = 0.011, respectively). CONCLUSIONS: Our study demonstrates a clinically higher postoperative complication rate in immediate breast reconstruction with RTU AlloDerm compared with FD AlloDerm and highlights the unfavorable risk factor correlation with significant obesity.

Walking age of infants with idiopathic clubfoot treated using the ponseti method.

BACKGROUND: The Ponseti method is an established approach to treating idiopathic clubfoot in infants. The method involves a period of cast immobilization and postcorrective bracing that potentially interferes with normal movements of the lower extremities. In the present study, we investigated the age at which infants who had idiopathic clubfoot treated using the Ponseti method achieved independent walking. METHODS: We prospectively evaluated patients of a single surgeon. Included in the study were all patients with idiopathic clubfoot who were full term at birth, were no more than twelve weeks of age at the start of treatment, had received no prior outside treatment, and were followed for a minimum of twenty-four months. RESULTS: Ninety-four patients were included. The mean age at which patients began walking independently was 14.5 ± 2.6 months (range, ten to twenty-two months). By eighteen months, 90% of the patients were walking without assistance. Patients with moderate or severe clubfoot deformity began walking earlier than did patients with very severe deformity (a mean of 14.2 months compared with 15.8 months; p = 0.03). Patients who experienced a relapse before learning to walk began walking later than those who did not relapse (a mean of 15.9 months compared with 14.2 months; p = 0.04). Other patient and treatment-related variables had no significant influence on the onset of walking. CONCLUSIONS: On the basis of our findings, parents of infants with idiopathic clubfoot treated using the Ponseti method may expect their child to achieve independent walking approximately two months later than infants without clubfoot deformity. A greater delay may be expected for those patients who have a very severe deformity or those who experience a deformity relapse. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Cluster M mycobacteriophages Bongo, PegLeg, and Rey with unusually large repertoires of tRNA isotypes.

UNLABELLED: Genomic analysis of a large set of phages infecting the common host Mycobacterium smegmatis mc(2)155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode. IMPORTANCE: The bacteriophage population is vast, dynamic, and old and plays a central role in bacterial pathogenicity. We know surprisingly little about the genetic diversity of the phage population, although metagenomic and phage genome sequencing indicates that it is great. Probing the depth of genetic diversity of phages of a common host, Mycobacterium smegmatis, provides a higher resolution of the phage population and how it has evolved. Three new phages constituting a new cluster M further expand the diversity of the mycobacteriophages and introduce novel features. As such, they provide insights into phage genome architecture, virion structure, and gene regulation at the transcriptional and translational levels.

Dopamine efflux in the rat striatum evoked by electrical stimulation of the subthalamic nucleus: potential mechanism of action in Parkinson's disease.

The precise mechanism whereby continuous high-frequency electrical stimulation of the subthalamic nucleus ameliorates motor symptoms of Parkinson's disease is unknown. We examined the effects of high-frequency stimulation of regions dorsal to and within the subthalamic nucleus on dopamine efflux in the striatum of urethane-anaesthetized rats using constant potential amperometry. Complementary extracellular electrophysiological studies determined the activity of subthalamic nucleus neurons in response to similar electrical stimulation of the subthalamic nucleus. High-frequency stimulation of the subthalamic nucleus increased action potential firing in the subthalamic nucleus only during the initial stimulation period and was followed by a cessation of firing over the remainder of stimulation. Electrical stimulation of the subthalamic nucleus with 15 pulses elicited stimulus-time-locked increases in striatal dopamine efflux with maximal peak effects occurring at 50 Hz frequency and 300 microA intensity. Extended subthalamic nucleus stimulation (1000 pulses at 50 Hz; 300 microA) elicited a similar peak increase in striatal dopamine efflux that was followed by a relatively lower steady-state elevation in extracellular dopamine over the course of stimulation. In contrast, extended stimulation immediately adjacent and dorsal to the subthalamic nucleus resulted in an 11-fold greater increase in dopamine efflux that remained elevated over the course of the stimulation. Immunohistochemical staining for tyrosine hydroxylase revealed catecholaminergic fibers running immediately dorsal to and through the subthalamic nucleus. Taken together, these results suggest that enhanced dopamine release within the basal ganglia may be an important mechanism whereby high-frequency stimulation of the subthalamic nucleus improves motor symptoms of Parkinson's disease.

Ligand-dependent complex formation between the Angiotensin II receptor subtype AT2 and Na+/H+ exchanger NHE6 in mammalian cells.

Involvement of Angiotensin II (Ang II) in the regulation of sodium levels by modulating the Na+/H+ exchangers is demonstrated in many tissues. Screening of a mouse 17-day fetus cDNA library with the Angiotensin II receptor AT2 as the bait in yeast two-hybrid assay led us to identify an AT2-interacting mouse fetus peptide that shared 98% amino acid identity with the corresponding region of the human NHE6. NCBI Blast search showed that the clone 6430520C02 (GenBank Accession # AK032326) of the mouse genome project carried the complete sequence of this new mouse NHE6 isoform. The human and mouse NHE6 peptides share 97% overall homology. Further analysis showed that the region spanning the third intracellular loop and C-terminal cytoplasmic tail of the AT2 directly interacted with a 182 amino acid region that spans the predicted 5th intracellular loop and the initial part of the C-terminus of the mouse NHE6 in yeast two-hybrid assay. This 182-amino acid region that interacted with the AT2 also shares 98% homology with the corresponding region of rat NHE6 and therefore is highly conserved across species. We detected widespread expression of this NHE6 isoform in several rat tissues including 10-day fetus, 17-day fetus, and 30-day post-natal tissues of heart, brain, kidney and muscle. Moreover, the AT2 co-immunoiprecipitated with a hemagglutinin tagged NHE6 when expressed in human cell line MCF-7, and activated by AngII. This ligand-dependent complex formation between the AT2 and NHE6 suggests that the hormone Ang II may act as a regulator of NHE6, and Ang II-mediated direct protein-protein interaction between AT2 and NHE6 could be a mechanism for modulating the functions of the ubiquitously expressed NHE6 in different tissues.