Hemodynamic Deterioration of Trauma Patients Undergoing Interhospital Transfer.

INTRODUCTION: Organized trauma systems reduce morbidity and mortality after serious injury. Rapid transport to high-level trauma centers is ideal, but not always feasible. Thus, interhospital transfers are an important component of trauma systems. However, transferring a seriously injured patient carries the risk of worsening condition before reaching definitive care. In this study, we evaluated characteristics and outcomes of patients whose hemodynamic status worsened during the transfer process. METHODS: We conducted a retrospective cohort study using data from the Pennsylvania Trauma Outcomes Study database from 2011 to 2018. Patients were included if they had a heart rate ≤ 100 and systolic blood pressure ≥ 100 at presentation to the referring hospital and were transferred within 24 h. We defined hemodynamic deterioration (HDD) as admitting heart rate > 100 or systolic blood pressure < 100 at the receiving center. We compared demographics, mechanism of injury, injury severity, management, and outcomes between patients with and without HDD using descriptive statistics and multivariable regression analysis. RESULTS: Of 52,919 included patients, 5331 (10.1%) had HDD. HDD patients were more often moderately-severely injured (injury severity score 9-15; 40.4% versus 39.4%, P < 0.001) and injured via motor vehicle collision (23.2% versus 16.6%, P < 0.001) or gunshot wound (2.1% versus 1.3%, P < 0.001). HDD patients more often had extremity or torso injuries and after transfer were more likely to be transferred to the intensive care unit (35% versus 28.5%, P < 0.001), go directly to surgery (8.4% versus 5.9%, P < 0.001), or interventional radiology (0.8% versus 0.3%, P < 0.001). Overall mortality in the HDD group was 4.9% versus 2.1% in the group who remained stable. These results were confirmed using multivariable analysis. CONCLUSIONS: Interhospital transfers are essential in trauma, but one in 10 transferred patients deteriorated hemodynamically in that process. This high-risk component of the trauma system requires close attention to the important aspects of transfer such as patient selection, pretransfer management/stabilization, and communication between facilities.

Outcomes in Subfascial versus Subglandular Planes in Breast Augmentation: A Systematic Review and Meta-Analysis.

Breast augmentation is the most commonly performed aesthetic surgery procedure in women worldwide. The use of the subfascial plane has been suggested to decrease the incidence of capsular contracture compared to the subglandular plane, while simultaneously avoiding the complication of animation deformity in the subpectoral plane. The aim of this systematic review and meta-analysis was to compare the adverse outcomes of subfascial compared to subglandular planes in breast augmentation. This review was registered a priori on OSF (https://osf.io/pm92e/). A search from inception to June 2023 was performed on Medline, Embase, and CENTRAL. A hand search was also performed. All randomized and comparative cohort studies were included that assessed the use of the subfascial plane for breast augmentation. Outcomes evaluated included the incidences of seroma, hematoma, infection, rippling, capsular contracture, and revision surgery. Ten studies were included in this systematic review. Three randomized controlled trials and seven comparative cohort studies were used for quantitative synthesis. There was a significant difference favoring subfascial compared to subglandular planes in the incidence of hematoma, rippling, and capsular contracture. All included studies had high risk of bias. The current evidence suggests that the subfascial plane for breast augmentation decreases risk of capsular contracture, hematoma, and rippling compared to the subglandular plane. Further randomized evidence with high methodological rigor is still required to validate these findings.

Inhibition of mitochondrial translocase SLC25A5 and histone deacetylation is an effective combination therapy in neuroblastoma.

The mitochondrion is a gatekeeper of apoptotic processes, and mediates drug resistance to several chemotherapy agents used to treat cancer. Neuroblastoma is a common solid cancer in young children with poor clinical outcomes following conventional chemotherapy. We sought druggable mitochondrial protein targets in neuroblastoma cells. Among mitochondria-associated gene targets, we found that high expression of the mitochondrial adenine nucleotide translocase 2 (SLC25A5/ANT2), was a strong predictor of poor neuroblastoma patient prognosis and contributed to a more malignant phenotype in pre-clinical models. Inhibiting this transporter with PENAO reduced cell viability in a panel of neuroblastoma cell lines in a TP53-status-dependant manner. We identified the histone deacetylase inhibitor, suberanilohydroxamic acid (SAHA), as the most effective drug in clinical use against mutant TP53 neuroblastoma cells. SAHA and PENAO synergistically reduced cell viability, and induced apoptosis, in neuroblastoma cells independent of TP53-status. The SAHA and PENAO drug combination significantly delayed tumour progression in pre-clinical neuroblastoma mouse models, suggesting that these clinically advanced inhibitors may be effective in treating the disease.

A comparison of skin grafts versus local flaps for facial skin cancer from the patient perspective: protocol for a feasibility study.

BRIEF ABSTRACT: This is a protocol to assess feasibility of conducting a prospective cohort study comparing local flaps versus skin grafts for surgical excision of skin cancer from the face. INTRODUCTION: Skin cancer is the most common malignancy worldwide and the face is one of the most common locations of occurrence. Surgical excision is the most popular treatment for small lesions of the face. Defects can be reconstructed using local flaps or skin grafts. There is a paucity of literature evaluating outcomes after skin cancer surgery from the patient's perspective using valid measurement tools. The purpose of this study is to assess the feasibility of conducting a prospective observational cohort study. The primary outcomes include recruitment rates, eligibility rate, compliance of intervention and rate of completion of the primary outcome (FACE-Q scales) at 3 months. Secondary outcomes include examining patient characteristic and FACE-Q score differences between local flaps to skin grafts and adverse events. METHODS AND ANALYSIS: This study is a prospective cohort study consisting of an anticipated 30 patients aged ≥18 years. The study population will consist of a consecutive sample of non-melanoma facial skin cancer patients undergoing a skin graft or local flap. Patients will be followed and evaluated with the FACE-Q questionnaire at 2 weeks, 3 months, 6 months and 1 year post-operation. The following criteria will determine success: patients who meet eligibility criteria >70%; recruitment rate >70%; compliance with intervention >90%; rate of completion of full-scale prospective study primary outcome (FACE-Q at 3 months) >80%; retention rate at 6-month follow-up visit >70%. DISCUSSION: The findings of this study will be used to guide the sample size calculation for a future, large-scale prospective study.Trial registration: ClinicalTrials.gov (NCT04842279).

Learning curve for endoscopic posterior cervical foraminotomy.

PURPOSE: While anterior cervical discectomy and fusion as well as cervical disk arthroplasty are gold standard treatments for the surgical treatment of cervical radiculopathy, posterior endoscopic cervical foraminotomy (PECF) as a substitute procedure is gaining popularity. To date, studies investigating the number of surgeries needed to achieve proficiency in this procedure are lacking. The purpose of the study is to examine the learning curve for PECF. METHODS: The learning curve in operative time for two fellowship-trained spine surgeons at independent institutions was retrospectively assessed for 90 uniportal PECF procedures (PBD: n = 26, CPH: n = 64) performed from 2015 to 2022. Operative time was assessed across consecutive cases using a nonparametric monotone regression, and a plateau in operative time was used as a proxy to define the learning curve. Secondary outcomes assessing achievement of endoscopic prowess before and after the initial learning curve included number of fluoroscopy images, visual analog scale (VAS) for neck and arm, Neck Disability Index (NDI), and the need for reoperation. RESULTS: There was no significant difference in operative time between surgeons (p = 0.420). The start of a plateau for Surgeon 1 occurred at 9 cases and 111.6 min. The start of a plateau for Surgeon 2 occurred at 29 cases and 114.7 min. A second plateau for Surgeon 2 occurred at 49 cases and 91.8 min. Fluoroscopy use did not significantly change before and after surmounting the learning curve. The majority of patients achieved minimally clinically important differences in VAS and NDI after PECF, but postoperative VAS and NDI did not significantly differ before and after achieving the learning curve. There were no significant differences in revisions or postoperative cervical injections before and after reaching a steady state in the learning curve. CONCLUSION: PECF is an advanced endoscopic technique with an initial improvement in operative time that occurred after as few as 8 cases to as many as 28 cases in this series. A second learning curve may occur with additional cases. Patient-reported outcomes improve following surgery, and these outcomes are independent of the surgeon's position on the learning curve. Fluoroscopy use does not change significantly along the learning curve. PECF is a safe and effective technique that current and future spine surgeons should consider as part of their armamentarium.

A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections.

BACKGROUND: Biologic agents are emerging as an important treatment option for immune-mediated diseases. Injection site reactions following subcutaneous injection of biologic agents is not well described in the literature. OBJECTIVE: To summarize injection site reaction data in phase 3 trials of all biologic agents. METHODS: MEDLINE, Embase, and CENTRAL databases were systematically searched on February 8, 2022. Proportional meta-analysis was conducted to summarize injection site reaction prevalence for each biologic. RESULTS: There were 158 articles included in the review. The most common types of injection site reactions were erythema (42.8%), unspecified reaction (23.3%), pain (12.4%), and pruritus (5.7%). No patients discontinued their treatment due to injection site reactions in 39 of the 48 studies that reported on discontinuation data. There were 16 biologics included in meta-analysis across 80 eligible studies. The biologics with the highest point prevalence of patients reporting injection site reactions were Canakinumab (15.5%; 294 patients), Dupilumab (11.4%; 1888 patients), Etanercept (11.4%; 4363 patients), and Ixekizumab (11.2%; 2205 patients). The biologics with the lowest point prevalence of injection site reactions were Risankizumab (0.8%; 707 patients), Brodalumab (1.3%; 1365 patients), Guselkumab (1.3%; 1852 patients), Secukinumab (1.9%; 1277 patients). CONCLUSIONS: The prevalence of injection site reaction in response to biologics ranges from 0.08 to 15.5%. Canakinumab, Dupilumab, Etanercept, and Ixekizumab had the highest prevalence of injection site reactions. Risankizumab, Brodalumab, Guselkumab, and Secukinumab had the lowest prevalence of injection site reactions. Recommendations are made regarding the improvement of adverse event reporting to better understand the epidemiology of injection site reactions.

Characteristics and Outcomes of Squamous Cell Carcinoma and Other Cutaneous Malignancies in Epidermolysis Bullosa: A Systematic Review.

OBJECTIVE: To identify cases and summarize outcomes of cutaneous malignancies in patients with epidermolysis bullosa (EB). DATA SOURCES: MEDLINE and EMBASE databases were searched on February 8, 2022. STUDY SELECTION: Original observational or experimental studies with cases of cutaneous malignancy in patients with inherited EB were included. DATA EXTRACTION: Data were extracted by two reviewers in duplicate. DATA SYNTHESIS: A total of 87 articles with 367 patients were included in this systematic review. Squamous cell carcinomas were the most common malignancy (94.3%) with a median survival of 60 months. The presence of metastasis was investigated at diagnosis in 77 patients; 18.8% of patients had detectable metastasis. Patients with squamous cell carcinoma with metastasis at diagnosis had significantly shorter median survival (16.8 months) than those without (72 months; P = .027). The remission rate was 47.6%. At the end of follow-up, 15.1% were alive with disease, and 41.6% were deceased. Other malignancies included malignant melanoma and basal cell carcinoma. The most common initial modes of management were excisions (71.9%) and amputations (17.6%). Other modes included chemotherapy (4.6%), radiation (3.9%), and no treatment (2.6%). The overall rate of recurrence or new lesions was 38.8%, with a median time of 16 months to recurrence or new lesions. Immediate recurrence was lowest following amputation (4.3%). There were no statistically significant differences in median survival among initial excision, amputation, and all other modes combined ( P = .30). CONCLUSIONS: Squamous cell carcinomas in patients with EB have a high likelihood of metastasis and mortality. Surgical excision is the most common intervention. There are no significant differences in survival among different initial management options. There is a need for research that documents and monitors outcomes of the treatment options.

Best Practices for FACE-Q Aesthetics Research: A Systematic Review of Study Methodology.

BACKGROUND: The FACE-Q Aesthetics module is a validated patient-reported outcome measure (PROM) that evaluates perspectives on facial aesthetic treatments. Improper administration and poor study methodology can compromise the validity and interpretation of this PROM. OBJECTIVES: This systematic review sought to evaluate the administration and scoring of the FACE-Q Aesthetics scales within the literature. METHODS: A search of Ovid Medline, Embase, Cochrane, and Web of Science was performed on December 20, 2022, with the assistance of a health-research librarian (CRD42022383676). Studies that examined facial aesthetic interventions using the FACE-Q Aesthetics module as a primary or secondary outcome measure were included for analysis. RESULTS: There were 114 studies included. The Face Overall (n = 52, 45.6%), Psychological (n = 45, 39.4%), and Social (n = 43, 37.7%) scales were most frequently reported. Errors in FACE-Q administration were identified in 30 (26.3%) studies. The most common error was the presentation of raw ordinal scores rather than the converted Q score (n = 23). Most studies reported a time horizon for their primary analysis (n = 76, 66.7%); however, only 4 studies provided a rationale for this selection. Sample size calculations for the primary outcome were rarely performed (n = 9, 7.9%). CONCLUSIONS: There continues to be limitations in PROM administration and the quality of articles that report FACE-Q Aesthetic scale data. The authors suggest that future investigators using the FACE-Q refer to the User's Guide regarding administration and scoring of this scale, report a rationale for the study time horizon, and provide an a priori sample size calculation for the primary outcome of interest.

Biologic Use in Pediatric Patients With Hidradenitis Suppurativa: A Systematic Review.

BACKGROUND: There is currently at least 1 biologic (adalimumab) approved in North America for treatment of Hidradenitis Suppurativa in the pediatric population. However, no reviews or clinical trials have specifically analyzed the effectiveness and safety data of biologic use in this population. The objective of this systematic review is to identify and summarize the outcomes of biologic therapy in pediatric patients with HS. METHODS: MEDLINE and EMBASE databases were used to conduct the search on Sept 18, 2020. RESULTS: The 15 included studies consisted of 26 patients, with the mean age of 15 ± 2.3 years. Females accounted for 53.8% (n = 14/26) of cases. The mean duration of HS prior to biologic initiation was 3.5 ± 2.9 years, with the majority having Hurley Stage II. The 26 patients received 34 biologics in total: 85.3% treated with TNF alpha inhibitors (adalimumab n = 17, infliximab n = 10, etanercept n = 1, unspecified n = 1), 5.9% with IL-12/23 inhibitors (ustekinumab n = 2), 5.9% with IL-1 inhibitors (i.e., anakinra n = 2) and 2.9% received IL-23 inhibitors (i.e., guselkumab n = 1) biologics. Of the 26 patients, 23.1% (n = 6/26) experienced complete resolution (CR), 73.1% (n = 19/26) experienced partial resolution (PR), and 3.8% (n = 1/26) had no resolution outcomes reported. The time to resolution of HS lesions after biologic initiation ranged from 10 days to 11.5 months (mean: 5.1 months). No adverse events were reported in the studies. CONCLUSION: Although anti-TNF alpha were the most common biologics used for HS in pediatric cases, large-scale trials specific to pediatric patients with HS are needed to confirm these findings.

Chronic Wound Telemedicine Models Before and During the COVID-19 Pandemic: A Scoping Review.

GENERAL PURPOSE: To present the results of a scoping review exploring chronic wound care telemedicine before and during the pandemic, including the characteristics of the models implemented. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Identify the characteristics of the studies the authors examined for their scoping review of chronic wound care telemedicine.2. Choose the electronic methods commonly used for wound care telemedicine in the studies the authors examined.3. Recognize the implications for the patients who participated in chronic wound care telemedicine in the studies the authors examined. ABSTRACT: OBJECTIVETo explore different chronic wound telemedicine models and identify current research on this topic.METHODSThe authors searched the MEDLINE and EMBASE databases on August 10, 2021 and identified 58 articles included in the analysis.RESULTSIncluded studies were published between 1999 and 2021, with more than half of the studies published between 2015 to 2019 (25.9%, n = 15/58) and 2020 to 2021 (25.9%, n = 15/58). There were 57 models identified, of which 87.7% (n = 50/57) used a blended model of care. Image assessment was the most common element in blended care (66.0%, n = 33/50), followed by video consultation (46.0%, n = 23/50), text (44.0%, n = 22/50), and telephone consultation (22.0%, n = 11/50). Purely virtual care was used in 12.3% (n = 7/57) of models, 85.7% (n = 6/7) of which were implemented during the COVID-19 pandemic. Most studies conducted a quantitative analysis (62.1%, n = 36/58); 20.7% (n = 12/58) conducted a qualitative analysis, and 17.2% (n = 10/58) conducted both. The most frequently assessed results were wound outcomes (53.4%, n = 31/58) and patient opinions (25.9%, n = 15/58).CONCLUSIONSChronic wound care-related telemedicine has common elements: image assessment, video and telephone consultation, and text-based information that can be combined in a variety of ways with unique implementation barriers. Blended care models are more common than purely virtual alternatives. Heterogeneity among outcomes and reporting methods make the results difficult to synthesize.

Diagnostic Accuracy of Ankle-Brachial Pressure Index Compared with Doppler Arterial Waveforms for Detecting Peripheral Arterial Disease: A Systematic Review.

GENERAL PURPOSE: To present the results of a research study evaluating the diagnostic accuracy of the ankle-brachial pressure index (ABPI) compared with that of Doppler arterial waveforms (DAWs) to detect peripheral arterial disease (PAD). TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After completing this continuing education activity, the participant will:1. Summarize the evidence the authors considered when comparing the diagnostic accuracy of the ABPI with that of Doppler arterial waveforms to detect PAD.2. Select the characteristics of the participants in the studies the authors analyzed.3. Identify the results of the authors' study comparing the diagnostic accuracy of the ABPI with that of Doppler arterial waveforms to detect PAD.4. Distinguish the authors' conclusions about the advantages of using Doppler arterial waveforms to detect PAD.

Although the ankle-brachial pressure index (ABPI) is a useful tool for the noninvasive assessment of peripheral arterial disease (PAD), it has several limitations necessitating alternative noninvasive diagnostic tools. This study assesses the diagnostic accuracy of ABPI compared with Doppler arterial waveforms (DAWs) to detect PAD. The authors searched Embase and MEDLINE for original studies that reported sensitivities and specificities for both the ABPI and DAW. Four studies were included representing 657 patients (58.8% men) with a mean age of 63.4 years. The authors detected overall higher sensitivities using DAW compared with ABPI but higher specificities with ABPI compared with DAW. In conclusion, because of the higher sensitivity and lower specificity of DAW compared with ABPI, the authors recommend DAW as a potential screening tool for PAD. To confirm these results, larger sample sizes and comparative trials with homogeneous reference standards and patient populations are required. In addition, DAW is not easily documented for everyday bedside practice in the community. With COVID-19 restrictions, an audible handheld Doppler signal may act as a reproducible equivalent to DAW and thus facilitate timely, safe application of compression therapy at point-of-care.

Post mortem computed tomography is highly sensitive for pyelonephritis. A radiologic-pathologic correlation series.

Pyelonephritis is a potentially lethal disease occasionally encountered in the forensic setting. Post mortem computed tomography (PMCT) is an important investigative tool for the forensic pathologist. In particular, it may be used to document and screen disease prior to traditional autopsy methods. While the sensitivity and specificity of computed tomography for pyelonephritis is well studied in the antemortem clinical setting, the test characteristics of PMCT are not yet described in the forensic pathology literature. A series of all cases of fatal pyelonephritis identified at the Ontario Forensic Pathology Service, over the course of 1 year was studied. Radiologic, clinical and pathologic findings were reviewed. A fulsome autopsy, including histopathologic examination, was considered the gold standard for sensitivity and specificity calculations. A control group consisting of 16 cases without pyelonephritis (ex: opiate toxicity) in which both PMCT and histologic data were available by way of comparison. Sixteen cases of pyelonephritis were identified. Post mortem computed tomographical signs of pyelonephritis included asymmetric renal enlargement, perinephric fat stranding, and ectopic renal air. The most (57%) individually sensitive of these findings was perinephric fat stranding but sensitivity increased to 100% if any of the three signs were present. The control group analysis revealed the specificity of air asymmetry (81%), asymmetric renal enlargement (81%), and fat stranding (69%). PMCT findings may rule in a diagnosis of pyelonephritis, and should prompt the pathologist to grossly and microscopically examine the kidneys.

Outcome of Hypotensive Trauma Patients by Time and Day of Arrival.

BACKGROUND: Although most studies of trauma patients have not demonstrated a "weekend" or "night" effect on mortality, outcomes of hypotensive (systolic blood pressure <90 mm Hg) patients have not been studied. We sought to evaluate whether outcomes of hypotensive patients were associated with admission time and day. METHODS: We retrospectively analyzed patients from Pennsylvania Level 1 and Level 2 trauma centers with systolic blood pressure of <90 mm Hg over 5 y. Patients were stratified into four groups by arrival day and time: Group 1, weekday days; Group 2, weekday nights; Group 3, weekend days; and Group 4, weekend nights. Patient characteristics and outcomes were compared for the four groups. Adjusted mortality risks for Groups 2, 3, and 4 with Group 1 as the reference were determined using a generalized linear mixed effects model. RESULTS: After exclusions, 27 trauma centers with a total of 4937 patients were analyzed. Overall mortality was 44%. Compared with patients arriving during the day (Groups 1 and 3), those arriving at night (Groups 2 and 4) were more likely to be younger, to be male, to have lower Glasgow Coma Scale scores and blood pressures, to have penetrating injuries, and to die in the emergency room. Controlled for admission variables, odds ratios (95% confidence intervals) for Groups 2, 3, and 4 were 0.92 (0.72-1.17), 0.89 (0.65-1.23), and 0.76 (0.56-1.02), respectively, for mortality with Group 1 as reference. CONCLUSIONS: Patients arriving in shock to Pennsylvania Level 1 and Level 2 trauma centers at night or weekends had no increased mortality risk compared with weekday daytime arrivals.

Correlations among metamorphopsia test scores, optical coherence tomography findings and multifocal electroretinogram responses in epiretinal membrane patients.

PURPOSE: To quantify metamorphopsia with a novel objective method in patients with epiretinal membrane (ERM) and to compare the relationships among metamorphopsia scores, spectral-domain optical coherence tomography (OCT) findings, and multifocal electroretinogram (mfERG) results. METHODS: This study included 52 eyes of 52 patients with idiopathic ERM who underwent comprehensive ophthalmologic examinations, including measurement of best-corrected visual acuity (BCVA), OCT, and mfERG. The degree of metamorphopsia was quantified using MonPack One® (Metrovision, Perenchies, France). On the topographic map of the early treatment diabetic retinopathy (ETDRS) grid, retinal thickness in the central, superior, inferior, nasal, and temporal subfields were measured, and metamorphopsia scores for each corresponding subfield were also obtained. The amplitudes and implicit times of mERG were elicited from each subfield. Then, the correlations among metamorphopsia scores, OCT findings, and mfERG responses were analyzed. RESULTS: The mean age of the patients was 65.3 ± 18.5 y, and the average metamorphopsia score of the individual subfields was 2.03 ± 1.18. Initial BCVA was 0.50 ± 0.12 logMAR, but there was no significant correlation between metamorphopsia scores and BCVA. The metamorphopsia scores from the central subfields showed significant correlations with central retinal thickness (CRT) (p = 0.001). The mean metamorphopsia scores in the central subfield showed a significant relationship with the mean N1 and P1 amplitudes (p = 0.001, p = 0.048, respectively), while no relationship was observed between metamorphopsia scores and mfERG amplitudes in other subfields. CONCLUSIONS: The degree of metamorphopsia in patients with ERM could be objectively quantified in each subfield using a novel metamorphopsia test. The metamorphopsia scores were significantly correlated with retinal thickness, especially at the central subfields, and the scores in the central subfields were significantly correlated with the N1 and P1 amplitudes of mfERG. Thus, the metamorphopsia test can be a useful method to evaluate metamorphopsia symptoms for patients with ERM.

Natural History of Nonoperative Management of Grade II Blunt Thoracic Aortic Injury.

BACKGROUND: The morbidity and mortality of thoracic blunt aortic injury (BAI) has been both diminished and revolutionized by the advent of endovascular repair. Nevertheless, the question remains as to what severity of injury requires endovascular repair. We therefore conducted a retrospective analysis of our experience with nonoperative grade II BAI of the thoracic aorta. METHODS: The records of patients with BAI from 2007 to 2017 at a Level I trauma center were retrospectively reviewed. Images were reviewed and graded by a radiologist according to the Society of Vascular Surgery Guidelines (grade I-IV). Demographics, injury severity, and outcomes were recorded. RESULTS: We identified 111 patients with BAI. Of these, 15 were deemed grade II injuries and were managed nonoperatively. Mean patient age was 45 ± 21 years; 60% of patients were male. The mean injury severity scale was 36 ± 13. No patients had progression of BAI to a more severe grade requiring intervention. Until now, the survival rate is 86.7% with a mean follow-up of 69 months (range 7-138). CONCLUSIONS: Within the grade II BAI cohort, injury progression did not occur, nor were any operative interventions performed. We conclude that grade II BAI can be managed nonoperatively. However, given that progression of the BAI is possible, follow-up aortic imaging is encouraged as well as appropriate blood pressure control and exercise restriction.

Is the Risk of Infection Lower with Sutures than with Staples for Skin Closure After Orthopaedic Surgery? A Meta-analysis of Randomized Trials.

BACKGROUND: Two previous meta-analyses comparing staples versus sutures have led to conflicting relative risks for surgical site infection between skin closure methods after orthopaedic surgery. Consequently, the choice of sutures or staples for skin closure continues to be a subject of conversation. Recently, additional randomized trials have been published, and an updated meta-analysis is needed to inform this debate. QUESTIONS/PURPOSES: To determine using a meta-analysis of randomized trials (1) whether there is a difference in surgical site infection (SSI) between staples and sutures for skin closure after orthopaedic surgery, and (2) whether that finding remains the same when the analysis is limited to randomized trials with a low risk of bias. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing staples with sutures for skin closure after orthopaedic surgery was conducted. We excluded barbed sutures, surgical zippers, and skin adhesives from this meta-analysis. Medline, Embase, CINAHL, Cochrane Library, and Global Index Medicus were searched from date of inception to October 18, 2017. The sole outcome of interest was SSI as defined by the original study authors, with preference given to Center for Disease Control and Prevention (CDC) definitions whenever possible, recognizing that this may result in the pooling of more common minor events with rarer, more severe events, and in so doing, overestimate between-group differences. Because of this, subgroup analysis was planned based on severity of infection. Relative risk was calculated using a random-effects model (relative risk [RR], 95% confidence interval [CI]). Heterogeneity was estimated using I. Publication bias was explored using visual inspection of the funnel plot and Egger's test. Subgroup analysis was planned for type of orthopaedic surgery, suture material, SSI category, and country development index. Subgroup interaction p values were calculated. The Cochrane risk of bias tool was used to assess study quality. Sensitivity analysis was planned to assess whether the results changed when the analysis was limited to studies with low risk of bias. In total, 17 RCTs (2446 patients) were eligible, of which five RCTs (501 patients) were at low risk of bias. RESULTS: In the primary analysis, patients randomized to staples had a higher risk of SSI versus those who received sutures for skin closure (RR, 2.05; 95% CI,1.38-3.06; I = 0%). However, most of the events were driven by superficial SSI, and only two deep infections were explicitly reported in total (one in each group). After a post-hoc sensitivity analysis excluded a highly influential trial with high risk of bias, the results were highly fragile, relying on a difference of only four additional events in the staples group. When we limited the analysis to RCTs with low risk of bias, no difference was found between sutures and staples in terms of SSI (RR, 1.45; 95% CI, 0.31-6.79; I = 46%). Effect sizes were consistent across subgroups (p value for subgroup interaction was not significant for elective versus trauma; hip versus knee arthroplasty; suture material; high versus middle- versus low-income settings). CONCLUSIONS: Even in this relatively large meta-analysis, existing RCTs do not provide definitive evidence of a difference in SSI risk when staples are used instead of sutures for skin closure after orthopaedic surgery. Currently, the total body of evidence remains weak and, even when limiting to only low risk of bias studies, it is not possible to rule in or rule out clinically important differences between staples and sutures. Until randomized studies of adequate power and followup duration are performed to definitively inform this issue, the choice between staples versus sutures should be based on other factors such as local availability, surgeon preference, and cost. LEVEL OF EVIDENCE: Level I, therapeutic study.

Lkb1 regulates granule cell migration and cortical folding of the cerebellar cortex.

Cerebellar growth and foliation require the Hedgehog-driven proliferation of granule cell precursors (GCPs) in the external granule layer (EGL). However, that increased or extended GCP proliferation generally does not elicit ectopic folds suggests that additional determinants control cortical expansion and foliation during cerebellar development. Here, we find that genetic loss of the serine-threonine kinase Liver Kinase B1 (Lkb1) in GCPs increased cerebellar cortical size and foliation independent of changes in proliferation or Hedgehog signaling. This finding is unexpected given that Lkb1 has previously shown to be critical for Hedgehog pathway activation in cultured cells. Consistent with unchanged proliferation rate of GCPs, the cortical expansion of Lkb1 mutants is accompanied by thinning of the EGL. The plane of cell division, which has been implicated in diverse processes from epithelial surface expansions to gyrification of the human cortex, remains unchanged in the mutants when compared to wild-type controls. However, we find that Lkb1 mutants display delayed radial migration of post-mitotic GCPs that coincides with increased cortical size, suggesting that aberrant cell migration may contribute to the cortical expansion and increase foliation. Taken together, our results reveal an important role for Lkb1 in regulating cerebellar cortical size and foliation in a Hedgehog-independent manner.

Unusual Rearrangement of an N-Donor-Functionalized N-Heterocyclic Carbene Ligand on Group 8 Metals.

We report an unexpected rearrangement of a deprotonated picolyl-functionalized N-heterocyclic carbene (NHC) ligand from N,C-chelate to N,N-chelate in three-legged piano-stool Fe(II) and Ru(II) complexes. The reaction mechanism has been explored for one of the Fe(II) complexes. Experimental and computational studies suggest an unusual intermediate featuring a four-membered chelate ring, where the NHC and the α-carbon of one of the N-substituents coordinate to the Fe(II) center. A possible Fe-alkylidene intermediate has also been predicted by computations.

Blastema formation and periosteal ossification in the regenerating adult mouse digit.

While mammals cannot regenerate amputated limbs, mice and humans have regenerative ability restricted to amputations transecting the digit tip, including the terminal phalanx (P3). In mice, the regeneration process is epimorphic and mediated by the formation of a blastema comprised of undifferentiated proliferating cells that differentiate to regenerate the amputated structures. Blastema formation distinguishes the regenerative response from a scar-forming healing response. The mouse digit tip serves as a preclinical model to investigate mammalian blastema formation and endogenous regenerative capabilities. We report that P3 blastema formation initiates prior to epidermal closure and concurrent with the bone histolytic response. In this early healing response, proliferation and cells entering the early stages of osteogenesis are localized to the periosteal and endosteal bone compartments. After the completion of stump bone histolysis, epidermal closure is completed and cells associated with the periosteal and endosteal compartments blend to form the blastema proper. Osteogenesis associated with the periosteum occurs as a polarized progressive wave of new bone formation that extends from the amputated stump and restores skeletal length. Bone patterning is restored along the proximal-distal and medial digit axes, but is imperfect in the dorsal-ventral axis with the regeneration of excessive new bone that accounts for the enhanced regenerated bone volume noted in previous studies. Periosteum depletion studies show that this compartment is required for the regeneration of new bone distal to the original amputation plane. These studies provide evidence that blastema formation initiates early in the healing response and that the periosteum is an essential tissue for successful epimorphic regeneration in mammals.