In Utero Diagnosis of Spinal Dermal Sinus.

INTRODUCTION: Congenital dermal sinus (CDS) is an open neural tube defect (NTD) that occurs in 1 in 2500 births a year and often goes undetected until patients present with complications like infection and neurological deficits. Early diagnosis and repair of CDS may prevent formation of these complications. In utero diagnosis of these lesions may improve long-term outcomes by enabling referral to specialty services and planned postnatal repair, however only two such cases have been reported in the literature. We present a third case of in utero diagnosis of CDS with a description and discussion of findings from surgical exploration and pathology. CASE PRESENTATION: Routine prenatal ultrasound scan detected a tethered cystic structure arising from the back of the fetus at 20 weeks gestation. Dedicated fetal ultrasound confirmed the presence of a cystic lesion protruding through a lamina defect while fetal magnetic resonance imaging (MRI) showed an intact spinal cord and meninges, suggesting a diagnosis of CDS. Neurosurgery followed along closely and took the child for surgical exploration on day 2 of life. A fibrous stalk with an intradural component and associated cord tethering was excised. Histology showed fibrous tissue without an epithelial-lined lumen. CONCLUSION: CDS is a form of NTD that occurs from nondisjunction of the cutaneous ectoderm and neuroectoderm during formation of the neural tube. Slight differences in how this error occurs can explain variations seen in this spectrum of disease, including CDS without an epithelial-lined lumen as seen in this case. Newborns with CDS can go undiagnosed for years and present with long-term complications. Fetal imaging can assist in early recognition and surgical excision of CDS in newborns.

Protocol for a scoping review to map health outcomes in individuals with inducible laryngeal obstruction.

BACKGROUND: Inducible laryngeal obstruction causes narrowing of the laryngeal aperture in response to external triggers. Outcomes are measured in inducible laryngeal obstruction to monitor changes in health status over time. METHODS: This study is a scoping review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The review will be guided by the following research question: 'What health outcomes are measured in studies including people with inducible laryngeal obstruction?' The research question was validated using the Population-Concept-Context framework according to the methodology for Joanna Briggs Institution Scoping Reviews. Relevant peer-reviewed studies and grey literature conducted over the last 40 years will be identified from electronic databases including AMED, CINAHL, Embase, EMCARE, MEDLINE, OVID, PubMed and PsycINFO. The search strings 'inducible laryngeal obstruction', 'ILO', 'vocal cord dysfunction', 'VCD', 'paradoxical vocal fold motion', 'PVFM', 'outcome', 'measure', 'measurement instrument', 'assessment', 'scale', 'questionnaire' will be combined using Boolean logic. An independent reviewer will conduct title screening; two independent reviewers will conduct abstract and full article screening, followed by data extraction by two reviewers. Analyses will be conducted appropriate to the findings. DISCUSSION: The review will document evidence of health outcomes measured in inducible laryngeal obstruction, identifying measurement characteristics and potential utility. Collating studies may identify gaps in coverage, the need for novel tools, and for standardisation for clinical and research purposes. WHAT THIS PAPER ADDS: What is already known on the subject Inducible laryngeal obstruction causes narrowing of the laryngeal aperture in response to external triggers. Outcomes are measured in inducible laryngeal obstruction to monitor changes in health status over time. Currently, there are no standardised outcome measures for measuring the effects of interventions in inducible laryngeal obstruction (ILO). What this paper adds to existing knowledge Assessment of health can be measured in a variety of ways. Physiological, radiological and biochemical measurements of impairment are more common historically but there are a lot of outcomes of other factors now including subjective measures of functional status and health-related quality of life, with data collected directly from patients. This study will allow us to scope the literature to see the health outcomes being measured in ILO to attempt to standardise and develop future health outcomes. What are the potential or actual clinical implications of this work? The review will document evidence of health outcomes measured in inducible laryngeal obstruction, identifying measurement characteristics and potential utility. Collating studies may identify gaps in coverage, the need for novel tools and for standardisation for clinical and research purposes.

Subdural hematoma, retinal hemorrhage, and fracture triad as a clinical predictor for the diagnosis of child abuse.

OBJECTIVE: Nonaccidental trauma (NAT) is a major cause of traumatic death during infancy and early childhood. Several findings are known to raise the index of clinical suspicion: subdural hematoma (SDH), retinal hemorrhage (RH), fracture, and external trauma. Combinations of certain injury types, determined via statistical frequency associations, may assist clinical diagnostic tools when child abuse is suspected. The present study sought to assess the statistical validity of the clinical triad (SDH + RH + fracture) in the diagnosis of child abuse and by extension pediatric NAT. METHODS: A retrospective review of The University of Arizona Trauma Database was performed. All patients were evaluated for the presence or absence of the components of the clinical triad according to specific International Classification of Diseases (ICD)-10 codes. Injury type combinations included some variation of SDH, RH, all fractures, noncranial fracture, and cranial fracture. Each injury type was then correlated with the ICD-10 codes for child abuse or injury comment keywords. Statistical analysis via contingency tables was then conducted for test characteristics such as sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: There were 3149 patients younger than 18 years of age included in the quantitative analysis, all of whom had at least one component of the clinical triad. From these, 372 patients (11.8%) had a diagnosis of child abuse. When compared to a single diagnosis of either SDH, RH, all fractures, noncranial fracture, or cranial fracture, the clinical triad had a significantly greater correlation with the diagnosis of child abuse (100% of cases) (p < 0.0001). The dyad of SDH + RH also had a significantly greater correlation with a child abuse diagnosis compared to single diagnoses (88.9%) (p < 0.0001). The clinical triad of SDH + RH + fracture had a sensitivity of 88.8% (95% CI 87.6%-89.9%), specificity of 100% (95% CI 83.9%-100%), and positive predictive value of 100% (95% CI 99.9%-100%). The dyad of SDH + RH had a sensitivity of 89.1% (95% CI 87.9%-90.1%), specificity of 88.9% (95% CI 74.7%-95.6%), and positive predictive value of 99.9% (95% CI 99.6%-100%). All patients with the clinical triad were younger than 3 years of age. CONCLUSIONS: When SDH, RH, and fracture were present together, child abuse and by extension pediatric NAT were highly likely to have occurred.

Study protocol for a randomized controlled trial of RealConsent2.0: a web-based intervention to promote prosocial alcohol-involved bystander behavior in young men.

BACKGROUND: Sexual violence (SV) is a significant, global public health problem, particularly among young adults. Promising interventions exist, including prosocial bystander intervention programs that train bystanders to intervene in situations at-risk for SV. However, these programs suffer from critical weaknesses: (1) they do not address the proximal effect of alcohol use on bystander decision-making and (2) they rely on self-report measures to evaluate outcomes. To overcome these limitations, we integrate new content specific to alcohol use within the context of prosocial bystander intervention into an existing, evidence-based program, RealConsent1.0. The resulting program, RealConsent2.0, aims to facilitate bystander behavior among sober and intoxicated bystanders and uses a virtual reality (VR) environment to assess bystander behavior in the context of acute alcohol use. METHODS: This protocol paper presents the design of a randomized controlled trial (RCT) in which we evaluate RealConsent2.0 for efficacy in increasing alcohol- and non-alcohol-involved bystander behavior compared to RealConsent1.0 or to an attention-control program ("Taking Charge"). The RCT is being implemented in Atlanta, GA, and Lincoln, NE. Participants will be 605, healthy men aged 21-25 years recruited through social media, community-based flyers, and university email lists. Eligible participants who provide informed consent and complete the baseline survey, which includes self-reported bystander behavior, are then randomized to one of six conditions: RealConsent2.0/alcohol, RealConsent2.0/placebo, RealConsent1.0/alcohol, RealConsent1.0/placebo, Taking Charge/alcohol, or Taking Charge/placebo. After completing their assigned program, participants complete a laboratory session in which they consume an alcohol (target BrAC: .08%) or placebo beverage and then engage in the Bystanders in Sexual Assault Virtual Environments (BSAVE), a virtual house party comprising situations in which participants have opportunities to intervene. Self-reported bystander behavior across alcohol and non-alcohol contexts is also assessed at 6- and 12-months post-intervention. Secondary outcomes include attitudes toward, outcome expectancies for, and self-efficacy for bystander behavior via self-report. DISCUSSION: RealConsent2.0 is the first web-based intervention for young men that encourages and teaches skills to engage in prosocial bystander behavior to prevent SV while intoxicated. This is also the first study to assess the proximal effect of alcohol on bystander behavior via a VR environment. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04912492. Registered on 05 February 2021.

Intimate Partner Violence and Mental Health Outcomes Among Hispanic Women in the United States: A Scoping Review.

Hispanic women in the United States experience disproportionate mental health impacts of intimate partner violence (IPV). Following the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews guidelines, we synthesized the existing knowledge based on IPV and mental health outcomes among Hispanic women in the United States. In May 2020, we searched five electronic databases (i.e., MEDLINE, PILOTS, PSYCInfo, PSYCArticles, and EMBASE). From the initial 1,180 results, 13 articles met inclusion criteria for this review (written in English, empirical study, focus on the experiences of victimization from an intimate partner, focus on mental health outcomes occurring in the person experiencing IPV, included women who identify as Hispanic, and included participants residing in the United States), representing 4,060 women. Findings highlighted significant positive associations between IPV (n = 13; 4,060 women) and general mental health outcomes (n = 4; 759 women) as well as the specific outcomes of depression (n = 12; 2,661 women), anxiety (n = 1; 274 women), post-traumatic stress disorder (n = 3; 515 women), and substance misuse (n = 2; 1,673 women) among Hispanic women in the United States. Limitations included heterogeneity across Hispanic populations and methodological differences between studies. Key avenues for future research were identified, including the need to examine mental health outcomes understudied in relation to IPV among Hispanic women (e.g., personality, obsessive-compulsive, and eating disorders) and to identify cultural and demographic factors (e.g., nativity status, level of acculturation) that may influence relations between IPV and mental health outcomes among Hispanic women. Such research can inform prevention and intervention efforts aimed at improving mental health among Hispanic women in the Untied States experiencing IPV.

Emotion malleability beliefs influence emotion regulation and emotion recovery among individuals with depressive symptoms.

Despite the centrality of emotion regulation in psychiatric disorders such as depression, there is a lack of experimental studies examining the psychological factors that influence emotion regulation in individuals with depressive symptoms. Participants with current depressive symptoms were randomly assigned to an experimental manipulation promoting more malleable emotion beliefs or the control condition. Participants underwent a negative emotion induction and reported on their affect and emotion regulation during the induction. Individuals who received the experimental manipulation reported greater cognitive reappraisal and greater emotion recovery. Experimental manipulations that can enhance emotion regulation and emotion recovery possess significant promise as a preliminary step in developing brief interventions that can overcome formal barriers to care.

Neoadjuvant relatlimab and nivolumab in resectable melanoma.

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3-4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P = 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial1, provide further confirmation of the efficacy and safety of this new immunotherapy regimen.

Preoccupation in bulimia nervosa, binge-eating disorder, anorexia nervosa, and higher weight.

OBJECTIVE: Preoccupation (excessive and constant thoughts) about shape/weight and food/eating is thought to be prominent in individuals with eating disorders but has received much less research than overt behavioral features. This study examined the significance and distinctiveness of different foci of preoccupation in individuals categorized with different forms of eating disorders and in individuals with higher weight. METHOD: Participants (N = 1,363) completed a web-based survey with established measures of eating-disorder psychopathology and depression. The current study compared preoccupation among individuals with core features of bulimia nervosa (BN; n = 144), binge-eating disorder (BED; n = 576), anorexia nervosa (AN; n = 48), and higher body weight (body mass index [BMI] ≥ 25) without eating-disorder features (higher weight [HW]; n = 595). Associations of each type of preoccupation with other eating-disorder psychopathology and depression were examined both between and within study groups. RESULTS: Preoccupation with shape/weight and with food/eating showed a graded pattern of statistically significant differences: AN and BN had higher preoccupation than BED, which was higher than HW. Within BN, BED, and AN study groups, correlation magnitudes of shape/weight and food/eating preoccupation with eating-disorder psychopathology and depression did not differ significantly. Within the HW group, shape/weight preoccupation was significantly more strongly correlated than food/eating preoccupation with overvaluation, body dissatisfaction, and depression. DISCUSSION: The preoccupation cognitive style, as well as focus, appears associated with other facets of eating-disorder psychopathology and depression. If results are confirmed among individuals with formal diagnoses, clinicians addressing maladaptive cognitions in cognitive-behavioral therapy should consider the role of preoccupation. Future research should investigate whether preoccupation predicts or moderates eating disorder treatment outcomes.

Intimate Partner Violence and Posttraumatic Stress Symptoms: Indirect Effects Through Negative and Positive Emotion Dysregulation.

Women who experience intimate partner violence (IPV) are at heightened risk for developing posttraumatic stress (PTS). Emotion dysregulation has been linked to both IPV and PTS, separately, however, unknown is the role of emotion dysregulation in the relation of IPV to PTS among women who experience IPV. Moreover, existing investigations in this area have been limited in their focus on negative emotion dysregulation. Extending prior research, this study investigated whether physical, sexual, and psychological IPV were indirectly associated with PTS symptom severity through negative and positive emotion dysregulation. Participants were 354 women who reported a history of IPV recruited from Amazon's MTurk platform (Mage = 36.52, 79.9% white). Participants completed self-report measures assessing physical (Conflict Tactics Scale), sexual (Sexual Experiences Scale), and psychological (Psychological Maltreatment of Women) IPV; negative (Difficulties in Emotion Regulation Scale) and positive (Difficulties in Emotion Regulation Scale-Positive) emotion dysregulation; and PTS symptom severity (PTSD Checklist for DSM-5) via an online survey. Pearson's correlation coefficients examined intercorrelations among the primary study variables. Indirect effect analyses were conducted to determine if negative and positive emotion dysregulation explained the relations between physical, sexual, and psychological IPV and PTS symptom severity. Physical, sexual, and psychological IPV were significantly positively associated with both negative and positive emotion dysregulation as well as PTS symptom severity, with the exception that psychological IPV was not significantly associated with positive emotion dysregulation. Moreover, negative and positive emotion dysregulation accounted for the relationships between all three IPV types and PTS symptom severity, with the exception of positive emotion dysregulation and psychological IPV. Our findings provide support for the potential underlying role of both negative and positive emotion dysregulation in the associations of IPV types to PTS symptom severity. Negative and positive emotion dysregulation may be important factors to integrate into interventions for PTS among women who experience IPV.

Incidental Pituitary Cysts in Children: Does Growth Hormone Treatment Affect Cyst Size?

OBJECTIVE: To evaluate the response of incidentally discovered pituitary cysts to growth hormone (GH) treatment. METHODS: A retrospective chart review was performed of children with pituitary cysts on magnetic resonance imaging (MRI) over a 5-year period. Records and images were reviewed, and the results were analyzed using descriptive statistics. Children with pituitary cysts who received GH treatment were compared with those without. RESULTS: We identified 109 children with pituitary cysts, 24 were treated with GH therapy. The average age was 8.5 ± 5.1 years. Children whose initial MRI scan was to evaluate growth hormone deficiency were more commonly male and non-Hispanic White compared with those with scans for other indications (male, 18 of 24 vs 35 of 85, P = .003; White, 23 of 24 vs 58 of 85, P = .004). Among patients who received GH treatment, 12 had follow-up MRI. Six had no change in cyst size and 6 had a decrease in cyst size. We observed no difference in the likelihood of cyst growth between those who received GH and those who did not (0 of 12 cysts with GH vs 1 of 15 cysts without GH showed growth at follow-up). No patient had neurologic deficits attributable to the pituitary cyst at any time. CONCLUSION: In a single-institution, retrospective study, we find no evidence of growth in pituitary cysts in response to GH therapy.

Morphological changes of the dorsal contour of the corpus callosum during the first two years of life.

BACKGROUND: In the medicolegal literature, focal concavities or notching of the corpus callosum has been thought to be associated with fetal alcohol spectrum disorders. Recent work suggests corpus callosum notching is a dynamic and normal anatomical feature, although it has not yet been defined in early life or infancy. OBJECTIVE: Our purpose was to characterize the dorsal contour of the corpus callosum during the first 2 years of life by defining the prevalence, onset and trajectory of notching on midsagittal T1-weighted images. MATERIALS AND METHODS: We reviewed retrospectively 1,157 consecutive patients between birth and 2 years of age. Corpus callosum morphology was evaluated and described. A notch was defined as a dorsal concavity of at least 1 mm in depth along the dorsal surface of the corpus callosum. Patient age as well as notch depth, location, number and presence of the pericallosal artery in the notch were noted. RESULTS: Two hundred thirty-three notches were identified in 549 patients: 36 anterior, 194 posterior and 3 patients with undulations. A statistically significant (R2=0.53, Beta=0.021, P=0.002) positive correlation between posterior notch prevalence and age in months was noted. A positive correlation between age and depth of the posterior notch was also statistically significant (r=0.32, n=179, P≤0.001). A trend for increased anterior notch prevalence with age was identified with significant correlation between visualized pericallosal artery indentation and anterior notching (r=0.20, n=138, P=0.016). Sub-analysis of the first month of life showed corpus callosum notching was not present. CONCLUSION: The presence of posterior notching increased significantly with age and was more frequent than that of anterior notching. Corpus callosum notching was absent in the first week of life, building on prior studies suggesting corpus callosum notching is acquired. This study provides baseline data on normative corpus callosum notching trajectories by age group during early life, a helpful correlate when associating corpus callosum morphology with disease.

Biosensors to Monitor Water Quality Utilizing Insect Odorant-Binding Proteins as Detector Elements.

In the developing world, the identification of clean, potable water continues to pose a pervasive challenge, and waterborne diseases due to fecal contamination of water supplies significantly threaten public health. The ability to efficiently monitor local water supplies is key to water safety, yet no low-cost, reliable method exists to detect contamination quickly. We developed an in vitro assay utilizing an odorant-binding protein (OBP), AgamOBP1, from the mosquito, Anopheles gambiae, to test for the presence of a characteristic metabolite, indole, from harmful coliform bacteria. We demonstrated that recombinantly expressed AgamOBP1 binds indole with high sensitivity. Our proof-of-concept assay is fluorescence-based and demonstrates the usefulness of insect OBPs as detector elements in novel biosensors that rapidly detect the presence of bacterial metabolic markers, and thus of coliform bacteria. We further demonstrated that rAgamOBP1 is suitable for use in portable, inexpensive "dipstick" biosensors that improve upon lateral flow technology since insect OBPs are robust, easily obtainable via recombinant expression, and resist detector "fouling." Moreover, due to their wide diversity and ligand selectivity, insect chemosensory proteins have other biosensor applications for various analytes. The techniques presented here therefore represent platform technologies applicable to various future devices.

The role of wearables in spinal posture analysis: a systematic review.

BACKGROUND: Wearables consist of numerous technologies that are worn on the body and measure parameters such as step count, distance travelled, heart rate and sleep quantity. Recently, various wearable systems have been designed capable of detecting spinal posture and providing live biofeedback when poor posture is sustained. It is hypothesised that long-term use of these wearables may improve spinal posture. RESEARCH QUESTIONS: To (1) examine the capabilities of current devices assessing spine posture, (2) to identify studies implementing such devices in the clinical setting and (3) comment on the clinical practicality of integration of such devices into routine care where appropriate. METHODS: A comprehensive systematic review was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA) across the following databases: PubMed; MEDLINE; EMBASE; Cochrane; and Scopus. Articles related to wearables systems able to measure spinal posture were selected amongst all published studies dated from 1980 onwards. Extracted data was collected as per a predetermined checklist including device types, study objectives, findings and limitations. RESULTS: A total of 37 articles were extensively reviewed and analysed in the final review. The proposed wearables most commonly used Inertial Measurement Units (IMUs) as the underlying technology. Wearables measuring spinal posture have been proposed to be used in the following settings: post-operative rehabilitation; treatment of musculoskeletal disorders; diagnosis of pathological spinal posture; monitoring of progression of Parkinson's Disease; detection of falls; workplace occupational health and safety; comparison of interventions. CONCLUSIONS: This is the first and only study to specifically review wearable devices that monitor spinal posture. Our findings suggest that currently available devices are capable of assessing spinal posture with good accuracy in the clinical setting. However, further validation regarding the long-term use of these technologies and improvements regarding practicality is required for commercialisation.

Author Correction: Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma.

In the version of this article originally published, there was an error in Fig. 2b. RECIST ORR and pCR were both listed as 25%. RECIST ORR was actually 73%, and pCR was 45%. Also, an author's name was incorrect in the author list. Danny K. Wells should have been listed as Daniel K. Wells. The errors have been corrected in the print, HTML and PDF versions of this article.

Publisher Correction: Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma.

In the version of this article originally published, there was an error in Fig. 1. In the neoadjuvant phase column, the n values for arms A and B were both reported to be 20. The n values for arms A and B were actually 12 and 11, respectively. Also, the URL underlying the accession code in the data availability section was incorrect. The URL was originally https://www.ebi.ac.uk/ega/studies/EGAS00001002698. It should have been https://www.ebi.ac.uk/ega/studies/EGAS00001003178. The errors have been corrected in the print, HTML and PDF versions of this article.

Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma.

Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses compared with adjuvant treatment1; however, optimal regimens have not been defined. Here we report results from a randomized phase 2 study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma ( NCT02519322 ). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs) and immune correlates of response were assessed. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%) but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8% grade 3 trAEs). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. These results describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma and emphasize the need for additional studies to optimize treatment regimens and to validate putative biomarkers.

Combined Laminoplasty and Posterior Fusion for Cervical Spondylotic Myelopathy Treatment: A Literature Review.

STUDY DESIGN: A literature review. PURPOSE: To explore the utility of laminoplasty in combination with instrumented fusion, with a focus on neurological outcomes and changes in kyphotic deformity. OVERVIEW OF LITERATURE: Management of cervical spondylotic myelopathy (CSM) to reduce morbidity within the neurosurgical population. METHODS: A US National Library of Medicine PubMed search was conducted for manuscripts pertaining to cervical laminoplasty and fusion for the management of CSM. Several relevant studies were shortlisted for review, and the bibliographies of the articles were searched for additional references. The search was limited to human studies, English-language literature, and reports on more than one patient. RESULTS: Combined laminoplasty and fusion was found to provide at least comparable, if not superior, neurological outcomes in specific patient populations with CSM. The Japanese Orthopedic Association scores, local kyphosis, and C2-C7 angle have been reviewed in several manuscripts, and improvement in each of these categories was found with laminoplasty and fusion. CONCLUSIONS: The treatment of CSM necessitates an individualized approach based on the pathoanatomical variation. Laminoplasty and fusion can be appropriately used for patients with CSM in a setting of local kyphotic deformity, ossification of the posterior longitudinal ligament, associated segmental instability, and the need for strong stabilization.

Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial.

BACKGROUND: Dual BRAF and MEK inhibition produces a response in a large number of patients with stage IV BRAF-mutant melanoma. The existing standard of care for patients with clinical stage III melanoma is upfront surgery and consideration for adjuvant therapy, which is insufficient to cure most patients. Neoadjuvant targeted therapy with BRAF and MEK inhibitors (such as dabrafenib and trametinib) might provide clinical benefit in this high-risk p opulation. METHODS: We undertook this single-centre, open-label, randomised phase 2 trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible participants were adult patients (aged ≥18 years) with histologically or cytologically confirmed surgically resectable clinical stage III or oligometastatic stage IV BRAFV600E or BRAFV600K (ie, Val600Glu or Val600Lys)-mutated melanoma. Eligible patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, a life expectancy of more than 3 years, and no previous exposure to BRAF or MEK inhibitors. Exclusion criteria included metastases to bone, brain, or other sites where complete surgical excision was in doubt. We randomly assigned patients (1:2) to either upfront surgery and consideration for adjuvant therapy (standard of care group) or neoadjuvant plus adjuvant dabrafenib and trametinib (8 weeks of neoadjuvant oral dabrafenib 150 mg twice per day and oral trametinib 2 mg per day followed by surgery, then up to 44 weeks of adjuvant dabrafenib plus trametinib starting 1 week after surgery for a total of 52 weeks of treatment). Randomisation was not masked and was implemented by the clinical trial conduct website maintained by the trial centre. Patients were stratified by disease stage. The primary endpoint was investigator-assessed event-free survival (ie, patients who were alive without disease progression) at 12 months in the intent-to-treat population. This trial is registered at ClinicalTrials.gov, number NCT02231775. FINDINGS: Between Oct 23, 2014, and April 13, 2016, we randomly assigned seven patients to standard of care, and 14 to neoadjuvant plus adjuvant dabrafenib and trametinib. The trial was stopped early after a prespecified interim safety analysis that occurred after a quarter of the participants had been accrued revealed significantly longer event-free survival with neoadjuvant plus adjuvant dabrafenib and trametinib than with standard of care. After a median follow-up of 18·6 months (IQR 14·6-23·1), significantly more patients receiving neoadjuvant plus adjuvant dabrafenib and trametinib were alive without disease progression than those receiving standard of care (ten [71%] of 14 patients vs none of seven in the standard of care group; median event-free survival was 19·7 months [16·2-not estimable] vs 2·9 months [95% CI 1·7-not estimable]; hazard ratio 0·016, 95% CI 0·00012-0·14, p<0·0001). Neoadjuvant plus adjuvant dabrafenib and trametinib were well tolerated with no occurrence of grade 4 adverse events or treatment-related deaths. The most common adverse events in the neoadjuvant plus adjuvant dabrafenib and trametinib group were expected grade 1-2 toxicities including chills (12 patients [92%]), headache (12 [92%]), and pyrexia (ten [77%]). The most common grade 3 adverse event was diarrhoea (two patients [15%]). INTERPRETATION: Neoadjuvant plus adjuvant dabrafenib and trametinib significantly improved event-free survival versus standard of care in patients with high-risk, surgically resectable, clinical stage III-IV melanoma. Although the trial finished early, limiting generalisability of the results, the findings provide proof-of-concept and support the rationale for further investigation of neoadjuvant approaches in this disease. This trial is currently continuing accrual as a single-arm study of neoadjuvant plus adjuvant dabrafenib and trametinib. FUNDING: Novartis Pharmaceuticals Corporation.

Multicenter retrospective evaluation of the validity of the Thoracolumbar Injury Classification and Severity Score system in children.

OBJECTIVE The Thoracolumbar Injury Classification and Severity Score (TLICS) system was developed to streamline injury assessment and guide surgical decision making. To the best of the authors' knowledge, external validation in the pediatric age group has not been undertaken prior to this report. METHODS This study evaluated the use of the TLICS in a large retrospective series of children and adolescents treated at 4 pediatric medical centers (Texas Children's Hospital, Children's Healthcare of Atlanta, Riley Children's Hospital, and Doernbecher Children's Hospital). A total of 147 patients treated for traumatic thoracic or lumbar spine trauma between February 1, 2002, and September 1, 2015, were included in this study. Clinical and radiographic data were evaluated. Injuries were classified using American Spinal Injury Association (ASIA) status, Denis classification, and TLICS. RESULTS A total of 102 patients (69%) were treated conservatively, and 45 patients (31%) were treated surgically. All patients but one in the conservative group were classified as ASIA E. In this group, 86/102 patients (84%) had Denis type compression injuries. The TLICS in the conservative group ranged from 1 to 10 (mean 1.6). Overall, 93% of patients matched TLICS conservative treatment recommendations (score ≤ 3). No patients crossed over to the surgical group in delayed fashion. In the surgical group, 26/45 (58%) were ASIA E, whereas 19/45 (42%) had neurological deficits (ASIA A, B, C, or D). One of 45 (2%) patients was classified with Denis type compression injuries; 25/45 (56%) were classified with Denis type burst injuries; 14/45 (31%) were classified with Denis type seat belt injuries; and 5/45 (11%) were classified with Denis type fracture-dislocation injuries. The TLICS ranged from 2 to 10 (mean 6.4). Eighty-two percent of patients matched TLICS surgical treatment recommendations (score ≥ 5). No patients crossed over to the conservative management group. Eight patients (8/147, 5%) had a calculated TLICS of 4, which meant they were candidates for surgery or conservative therapy by TLICS criteria. Excluding these patients, the degree of agreement between TLICS and surgeon decision was deemed to be very good (κ = 0.878). CONCLUSIONS The TLICS results and recommendations matched treatment in 96% of conservative group cases. In the surgical group, TLICS recommendations matched treatment in 93% of cases. The TLICS recommendations and surgeon decision making displayed very good concordance. The TLICS appears to be effective in the classification of thoracic and lumbar spine injuries and in guiding treatment in the pediatric age group.