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Professional organizations, like most complex human entities in the world including companies and countries, undergo periodic changes. Sometimes, these changes happen in years, while others may take decades or more. This year is the 75th anniversary of the American Society of Maxillofacial Surgeons (ASMS), a society born of necessity after World War II, even though its inception goes further back several decades. This brief article commemorates this important landmark and summarizes some key events of the last 25 years from 1997 to 2022, as others have nicely summarized the earlier periods. In addition to changes in clinical, research, and education in the context of craniofacial surgery, the review also examines from the national and global perspectives within which exists ASMS. These historical comparisons allow for appreciation of changes and, more importantly, permits the educated forecast of the future. It is our hope that from the lessons learned from the past will emerge a brighter, better tomorrow.

“Ability and judgment” are the only terms that appeared twice in the Hippocratic Oath and are the pillars of medicine and surgery, as clinical decision making and treatments depend on physicians’ judgments and abilities. Sound judgment requires knowledge obtained and accumulated through individual and collective experience, but more importantly from studies employing scientific methods. In a compendium article to this current one, the death of George Washington within days of onset of respiratory infection in 1799 exemplified the futility of ineffective, if not dangerous and harmful, medical treatments. The key question is how can anyone know with certainty that a particular therapy is or is not effective? Since individual differences exist in responses to corrective procedures and medications, absolute certainty is uncommon. However, as the number of patients increases, so does the confidence, at times approaching certainty. Statistical testing allows for the extraction of valid, useful information from data collected and is a critical part of all surgical disciplines. While this mini-review will not replace the need for expert statistical inputs from statisticians, it will provide a deep appreciation of and a working knowledge for these tests. We focus on hypothesis testing, the foundation to synthesize knowledge to guide, improve new treatments, and confirm or repudiate existing ones. The primer begins with hypothesis testing and systematically examine parametric and non-parametric statistical tests, ending with Mendelian randomization.

Background Despite existing anthropometric data in the literature regarding the variation of female external genital anatomy, the ideal aesthetic characteristics have yet to be defined. Objectives The authors utilized crowdsourcing to better evaluate preferred anatomic characteristics of external female genitalia. Methods Fifty-six total images were digitally created by altering the proportions of the labia minora, labia majora, and clitoral hood. Images with differing ratios were presented in pairs to Amazon Mechanical Turk (Seattle, WA, USA) raters. Three different experiments were performed with each varying 2 of the 3 image characteristics to permit 2-factor modeling. The Bradley-Terry-Luce model was applied to the pairwise comparisons ratings to create a rank order for each image. Preferences for each anatomic variable were compared with chi-squared tests. Results A total of 5000 raters participated. Experiment 1 compared differing widths of the labia majora and labia minora and determined a significant preference for larger labia majora width and mid-range labia minora width (P = 0.007). Experiment 2 compared labia minora width vs clitoral hood length and showed a statistically significant preference for wider majoras (P Conclusions Raters preferred a labia majora to labia minora width ratio of 3:1 with minimal preference in clitoral hood length.

Aneuploidy is the hallmark of malignancy. Our previous study successfully detected nonhematogenic circulating aneuploidy cells (CACs) in types of gliomas. The current prospective clinical study aims to further precisely subcategorize aneuploid CACs, including CD31

Syndromic hypoplasia of the orbit and midface results in noticeable dysmorphology. Correction involves advancement of the orbito-facial complex either directly or by distraction osteogenesis. The surgery is challenging no matter where it is performed, however, the challenges are amplified on a surgical mission. Komedyplast Surgical Charity (Chicago, IL) has been performing complex craniofacial procedures, including midfacial advancement at the Monobloc level, for 13 years with safety and success. As such, key points need specific attention to avoid complications in a remote location, where staff and resources may be less than adequately equipped to handle them.

Background Three-dimensional printing (3DP) addresses distinct clinical challenges in pediatric care including: congenital variants, compact anatomy, high procedural risk, and growth over time. We hypothesized that patient-specific applications of 3DP in pediatrics could be categorized into concise, discrete categories of use. Methods Terms related to "three-dimensional printing" and "pediatrics" were searched on PubMed, Scopus, Ovid MEDLINE, Cochrane CENTRAL, and Web of Science. Initial search yielded 2122 unique articles; 139 articles characterizing 508 patients met full inclusion criteria. Results Four categories of patient-specific 3DP applications were identified: Teaching of families and medical staff (9.3%); Developing intervention strategies (33.9%); Procedural applications, including subtypes: contour models, guides, splints, and implants (43.0%); and Material manufacturing of shaping devices or prosthetics (14.0%). Procedural comparative studies found 3DP devices to be equivalent or better than conventional methods, with less operating time and fewer complications. Conclusion Patient-specific applications of Three-Dimensional Printing in Medicine can be elegantly classified into four major categories: Teaching, Developing, Procedures, and Materials, sharing the same TDPM acronym. Understanding this schema is important because it promotes further innovation and increased implementation of these devices to improve pediatric care. Impact This article classifies the pediatric applications of patient-specific three-dimensional printing. This is a first comprehensive review of patient-specific three-dimensional printing in both pediatric medical and surgical disciplines, incorporating previously described classification schema to create one unifying paradigm. Understanding these applications is important since three-dimensional printing addresses challenges that are uniquely pediatric including compact anatomy, unique congenital variants, greater procedural risk, and growth over time. We identified four classifications of patient-specific use: teaching, developing, procedural, and material uses. By classifying these applications, this review promotes understanding and incorporation of this expanding technology to improve the pediatric care.

Simple Summary Circulating tumor cells (CTCs) and CD31+ circulating tumor endothelial cells (CTECs) constitute a unique pair of cellular circulating tumor biomarkers and play a crucial role in cancer metastasis and disease progression. Precise detection of live and necrotic aneuploid CTCs and CTECs in therapeutic cancer patients, though clinically highly demanded, has yet to be achieved in the field. The aim of this study is to develop a comprehensive strategy to effectively distinguish and co-detect viable and dead non-hematological cancer cells harboring aneuploid chromosomes and expressing various tumor markers. The innovative strategy developed in the present study will assist in an efficient assessment of therapy effectiveness, rapid detection of emerging treatment resistance and bringing in new insights into the comprehension of cancer cells in circulation. Abstract Aneuploid circulating tumor cells (CTCs, CD31−) and circulating tumor endothelial cells (CTECs, CD31+) exhibit an active interplay in peripheral blood, and play an essential role in tumorigenesis, neoangiogenesis, disease progression, therapy-resistant minimal residual disease (MRD), cancer metastasis and relapse. Currently, most CTC detection techniques are restricted to the indistinguishable quantification of circulating rare cells, including both necrotic and viable cells in cancer patients. Clinically imperative demands to distinguish and detect live and/or dead non-hematological aneuploid cancer cells in peripheral blood, which will assist in the rapid evaluation of therapeutic effects, real-time monitoring of treatment resistance longitudinally developed along with therapy and the effective detection of post-therapeutic MRD, have not yet been achieved. The integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH)-derived novel strategy was developed in this study, aiming to precisely identify and detect live and necrotic cancer cells (NC) enriched from carcinoma patients’ biofluids. The innovative SE-iFISH (NC) provides a meaningful and practical approach to co-detect various viable and necrotic aneuploid CTCs and CTECs. The detected circulating rare cells can be characterized and categorized into diverse subtypes based upon cell viability, morphology, multiple tumor markers’ expression, and the degree of aneuploidy relevant to both malignancy and therapeutic resistance. Each subtype of live or necrotic CTCs and CTECs possesses distinct utility in anti-cancer drug development, translational research, and clinical practice.

BACKGROUND Reduction mammaplasty relieves symptomatic macromastia. Pathologic specimens occasionally reveal unsuspected proliferative lesions or carcinoma. Few studies examine the incidence, risk factors, and outcomes in this population. METHODS A retrospective review was performed between 2000 and 2012. The pathologic condition was categorized as benign, proliferative, or cancer. RESULTS Five hundred seventy-two patients underwent 995 reduction mammaplasties. Cancer was detected in 23 specimens (2.3 percent) and proliferative lesions were detected in 137 (13.8 percent). Compared with patients with benign pathologic findings, patients with proliferative lesions or cancer were older (p < 0.001), had greater body mass index (p = 0.003), had increased unilateral procedures (p < 0.001), and more had history of cancer (p < 0.001). On multivariable regression analysis, age (OR, 1.058; 95 percent CI, 1.040 to 1.077; p < 0.001) and prior breast cancer (OR, 2.070; 95 percent CI, 1.328 to 3.227, p = 0.001) were independent risk factors for proliferative lesions, and age significantly predicted cancer (OR, 1.054; 95 percent CI, 1.012 to 1.097; p = 0.010). Forty-one percent of patients with proliferative lesions and no history of cancer had a change in management. If there was a history of cancer, 54 percent had a change in management. CONCLUSIONS Proliferative lesions of the breast may be more common than previously reported. Age and a history of breast cancer increase the risk for proliferative lesions. All should be referred to oncology, as nearly half of these patients will have a change in management. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, III.

Background Speech is integral for human interaction and development. Speech assessments are critical in the growing child, especially in the surgical evaluation of patients undergoing cleft palate and speech surgeries. Online crowdsourcing enables layperson raters, allowing rapid and large-scale data collection. This systematic review analyzes the utility of online crowdsourcing to evaluate perceptual speech outcomes. Methods Terms related to “crowdsourcing” and “speech” were searched on PubMed, Scopus, CINAHL, Cochrane CENTRAL, and PsycINFO on August 16, 2017, returning 2812 unique articles. Inclusion and exclusion criteria concentrated on online crowdsourcing of perceptual speech outcomes: titles led to 140 abstracts that yielded 35 full-text articles, of which eight articles met criteria for analysis. Results All studies used Amazon Mechanical Turk for online crowd raters, and one used an additional crowdsourcing site (CrowdFlower). Disordered speech was provided by 376 speakers, for which 2203 crowd workers produced over 700,000 unique ratings. Five studies compared crowdsourced assessments to gold standards and found high concordances. Data collection time ranged from 59 min to 23 h, with worker payments ranging from $0.05 to $2.00 per task. Studies examined child pronunciation of the /r/ sound, dysarthria in Parkinson's speech, and articulation of English words produced by non-English speakers learning English. Conclusions Online crowdsourcing for perceptual speech outcomes provides high-quality data consistent with previous speech-assessment standards in a rapid, cost-effective manner. This novel methodology incorporates lay perspective of speech intelligibility and has the potential to revolutionize surgical speech outcome assessments, including cleft palate and speech surgery.

Existing goal-oriented dialogue datasets focus mainly on identifying slots and values. However, customer support interactions in reality often involve agents following multi-step procedures derived from explicitly-defined company policies as well. To study customer service dialogue systems in more realistic settings, we introduce the Action-Based Conversations Dataset (ABCD), a fully-labeled dataset with over 10K human-to-human dialogues containing 55 distinct user intents requiring unique sequences of actions constrained by policies to achieve task success. We propose two additional dialog tasks, Action State Tracking and Cascading Dialogue Success, and establish a series of baselines involving large-scale, pre-trained language models on this dataset. Empirical results demonstrate that while more sophisticated networks outperform simpler models, a considerable gap (50.8% absolute accuracy) still exists to reach human-level performance on ABCD., Comment: 16 pages, 5 figures. Accepted at NAACL 2021

The performance of autoregressive models on natural language generation tasks has dramatically improved due to the adoption of deep, self-attentive architectures. However, these gains have come at the cost of hindering inference speed, making state-of-the-art models cumbersome to deploy in real-world, time-sensitive settings. We develop a compression technique for autoregressive models that is driven by an imitation learning perspective on knowledge distillation. The algorithm is designed to address the exposure bias problem. On prototypical language generation tasks such as translation and summarization, our method consistently outperforms other distillation algorithms, such as sequence-level knowledge distillation. Student models trained with our method attain 1.4 to 4.8 BLEU/ROUGE points higher than those trained from scratch, while increasing inference speed by up to 14 times in comparison to the teacher model.

Objective Speech intelligibility is fundamental to social interactions and a critical surgical outcome in patients with cleft palate. Online crowdsourcing is a burgeoning technology, with potential to mitigate the burden of limited accessibility to speech-language-pathologists (SLPs). This pilot study investigates the concordance of online crowdsourced evaluations of hypernasality with SLP ratings of children with cleft palate. Methods Six audio-phrases each from children with cleft palate were assessed by online crowdsourcing using Amazon Mechanical Turk (MTurk), and compared to SLP’s gold-standard hypernasality score on the Pittsburgh Weighted Speech Score (PWSS). Phrases were presented to MTurk crowdsourced lay-raters to assess hypernasality on a Likert scale analogous to the PWSS. The survey included clickable reference audio samples for different levels of hypernasality. Results 1,088 unique online crowdsourced speech ratings were collected on 16 sentences of 3 children with cleft palate aged 4–8 years, with audio averaging 6.5 years follow-up after cleft palate surgery. Patient 1 crowd-mean was 2.62 (SLP rated 2–3); Patient 2 crowd-mean 2.66 (SLP rated 3); and Patient 3 crowd-mean 1.76 (SLP rated 2). Rounded for consistency with PWSS scale, all patients matched SLP ratings. Different sentences had different accuracies compared to the SLP gold standard scores. Conclusion Online crowdsourced ratings of hypernasal speech in children with cleft palate were concordant with SLP ratings, predicting SLP scores in all 3 patients. This novel technology has potential for translation in clinical speech assessments, and may serve as a valuable screening tool for non-experts to identify children requiring further assessment and intervention by a qualified speech language pathology expert.

BACKGROUND Ivosidenib (AG-120, IVO) is a first-in-class oral inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), and vorasidenib (AG-881, VOR) is an oral, potent, brain-penetrant inhibitor of mIDH1/2. Both have been evaluated in glioma patients in ongoing phase 1 studies. In orthotopic glioma models, IVO and VOR reduced 2-hydroxyglutarate (2-HG) levels by 85% and 98%, respectively, despite different brain-to-plasma ratios (< 0.04 vs 1.33). METHODS Patients with recurrent, nonenhancing, WHO-2016 grade 2/3, mIDH1-R132H oligodendroglioma or astrocytoma undergoing craniotomy were randomized 2:2:1 to IVO 500mg QD, VOR 50mg QD, or no treatment (cohort 1), or 1:1 to IVO 250mg BID or VOR 10mg QD (cohort 2), for 4 weeks preoperatively. Postoperatively, patients continued receiving IVO or VOR (control patients were randomized 1:1 to IVO or VOR). Tumors were assessed for mIDH1 status, cellularity, and 2-HG and drug concentrations. Treated subjects were compared with controls and mIDH1/wild-type banked reference samples. Primary endpoint: tumor 2-HG concentration following IVO or VOR. RESULTS As of March 1, 2019, 27 patients (18 men; 25/2 grade 2/3) were randomized preoperatively in cohort 1 (IVO 10, VOR 12, untreated 5): 27 received drug (IVO 13, VOR 14); 1 discontinued VOR postoperatively due to disease progression. Of 26 tumors analyzed, 22 were evaluable. Mean brain-to-plasma ratios: 0.13 IVO, 1.59 VOR. Relative to untreated samples, IVO and VOR reduced tumor 2-HG by 92.0% (95% CI 73.2, 97.4) and 92.5% (95% CI 78.1, 97.7), respectively. Common (≥ 4 patients) TEAEs (all cohort 1 patients, all grades): diarrhea (37.0%), constipation, hypocalcemia, and nausea (each 18.5%), anemia, hyperglycemia, pruritus, headache, and fatigue (each 14.8%). Cohort 2 has completed accrual, with analyses ongoing. CONCLUSIONS In cohort 1 of this phase 1 perioperative study, IVO and VOR demonstrated brain penetrance and lowered 2-HG compared with controls. Updated data from both cohorts will be presented.

Orofacial clefts, which include cleft lip, palate, or both, are a common congenital malformation occurring in one in every 700 live births in the United States alone. Such a defect leads to impaired function in daily activities including normal face for communication and normal palatal function for speech. Tissue engineering techniques have very recently been explored to develop scaffolds as an alternative treatment method. Due to the differing geometries of the cleft lip and palate, varying scaffold materials and geometries are necessary to facilitate proper healing at the defect site. This review provides an overview of the anatomical structure and impaired function in orofacial clefts, current treatment options, and unique tissue engineering scaffolds as methods of treatment to improve patient outcome and quality of life.

Mutations in isocitrate dehydrogenase (mIDH) are common in lower-grade glioma (LGG; mIDH1, 80%; mIDH2, 4%) and lead to epigenetic and genetic changes that promote oncogenesis via production of the oncometabolite 2-hydroxyglutarate (2-HG). AG-120 (ivosidenib) is a first-in-class oral mIDH1 inhibitor associated with a favorable safety profile in an ongoing phase 1 study in 66 glioma patients. AG-881 is a brain-penetrant oral mIDH1/2 inhibitor with an acceptable safety profile at dose levels

The current gold standard treatment for oral clefts is autologous bone grafting. This treatment, however, presents another wound site for the patient, greater discomfort, and pediatric patients have less bone mass for bone grafting. A potential alternative treatment is the use of tissue engineered scaffolds. Hydrogels are well characterized nanoporous scaffolds and cryogels are mechanically durable, macroporous, sponge-like scaffolds. However, there has been limited research on these scaffolds for cleft craniofacial defects. 3D-printed molds can be combined with cryogel/hydrogel fabrication to create patient-specific tissue engineered scaffolds. By combining 3D-printing technology and scaffold fabrication, we were able to create scaffolds with the geometry of three cleft craniofacial defects. The scaffolds were then characterized to assess the effect of the mold on their physical properties. While the scaffolds were able to completely fill the mold, creating the desired geometry, the overall volumes were smaller than expected. The cryogels possessed porosities ranging from 79.7% to 87.2% and high interconnectivity. Additionally, the cryogels swelled from 400% to almost 1500% of their original dry weight while the hydrogel swelling did not reach 500%, demonstrating the ability to fill a defect site. Overall, despite the complex geometry, the cryogel scaffolds displayed ideal properties for bone reconstruction.

Summary:. Infection of the temporomandibular joint (TMJ) is a rare pediatric condition resulting from the introduction of pathogens into the joint by hematogenous seeding, local extension, or trauma. Early recognition of the typical signs and symptoms including fever, trismus, preauricular swelling, and TMJ region tenderness are critical in order to initiate further evaluation and prevent feared complications of fibrosis, ankylosis, abnormal facial structure, or persistence of symptoms. Contrast-enhanced computed tomography with ancillary laboratory analysis including erythrocyte sedimentation rate, C-reactive protein, and white blood cell count are beneficial in confirming the suspected diagnosis and monitoring response to therapy. Initial intervention should include empiric parenteral antibiotics, early mandibular mobilization, and joint decompression to provide synovial fluid for analysis including cultures. This report describes a case of TMJ bacterial arthritis in a healthy 6-year-old male who was promptly treated nonsurgically with intravenous antibiotics and localized needle joint decompression with return to normal function after completion of oral antibiotics and physical therapy.

Bone defects are extremely common in children with cleft-craniofacial conditions, especially those with alveolar cleft defects and cranial defects. This study used patient-specific 3D-printed molds derived from computed tomography and cryogel scaffold fabrication as a proof of concept for the creation of site-specific implants for bone reconstruction. Cryogel scaffolds are unique tissue-engineered constructs formed at sub-zero temperatures. When thawed, the resulting structure is macroporous, sponge-like, and mechanically durable. Due to these unique properties, cryogels have excellent potential for the treatment of patient-specific bone defects; however, there is little literature on their use in cleft-craniofacial defects. While 3D-printing technology currently lacks the spatial resolution to print the microstructure necessary for bone regeneration, it can be used to create site-specific molds. Thus, it is ideal to integrate these techniques for the fabrication of scaffolds with patient-specific geometry. Overall, all cryogels possessed appropriate geometry to allow for cell infiltration after 28 days. Additionally, suitable mechanical durability was demonstrated where, despite mold geometry, all cryogels could be compressed without exhibiting crack propagation. Such a patient-specific scaffold would be ideal in pediatric cleft-craniofacial defects, as these are complex 3D defects and children have less donor bone availability.

Squamosal craniosynostosis is seldom reported in the craniofacial literature. Given that this is an uncommon diagnosis, phenotype and management remain unclear. The authors present a case series and review the literature to define the phenotype and management of these patients.We retrospectively reviewed 7 patients from our institution and systematically reviewed all published cases of squamosal craniosynostosis. Demographics, medical history, imaging, clinical presentation, subsequent workup, and treatment were examined and analyzed.A comprehensive review of the literature yielded a total of 31 cases (including our new series) of squamosal craniosynostosis. Average age of presentation was 25.3 months, 52% of female patients, 74% of cases with bilateral squamosal involvement, 44% syndromic, 39% isolated squamosal (vs 61% multisutural). Overall, 56% of cases were handled surgically, whereas 44% were managed conservatively. Thirty-three percent of surgical cases required multiple operations. One patient with isolated bilateral squamosal craniosynostosis developed elevated intracranial pressure, requiring cranial vault remodeling.Squamosal craniosynostosis frequently presents in a delayed fashion with nonsyndromic, bilateral involvement. In isolated bilateral squamosal cases, the associated phenotype is frontal prominence, occipital flattening, scaphocephalic tendency (low-end normocephalic cranial index), and superior parietal cornering. Evaluation of clinical signs and computed tomography imaging guides management, as evidence of increased intracranial pressure may indicate need for cranial vault expansion. Although previous literature suggests that nonsyndromic cases are nonsurgical, the majority of cases reviewed required surgical intervention, including our case of isolated bilateral squamosal craniosynostosis. We recommend vigilant management in patients with squamosal craniosynostosis, even those with isolated squamosal involvement.

Three-dimensional printing technology has been advancing in surgical applications. This systematic review examines its patient-specific applications in craniomaxillofacial surgery.Terms related to "three-dimensional printing" and "surgery" were searched on PubMed on May 4, 2015; 313 unique articles were returned. Inclusion and exclusion criteria concentrated on patient-specific surgical applications, yielding 141 full-text articles, of which 33 craniomaxillofacial articles were analyzed.Thirty-three articles included 315 patients who underwent three-dimensional printing-assisted operations. The most common modeling software was Mimics, the most common printing software was 3D Systems, the average time to create a printed object was 18.9 hours (range, 1.5 to 96 hours), and the average cost of a printed object was $1353.31 (range, $69.75 to $5500). Surgical procedures were divided among 203 craniofacial patients (205 three-dimensional printing objects) and 112 maxillofacial patients (137 objects). Printing technologies could be classified as contour models, guides, splints, and implants. For craniofacial patients, 173 contour models (84 percent), 13 guides (6 percent), two splints (1 percent), and 17 implants (8 percent) were made. For maxillofacial patients, 41 contour models (30 percent), 48 guides (35 percent), 40 splints (29 percent), and eight implants (6 percent) were made. These distributions were significantly different (p0.0001). Four studies compared three-dimensional printing techniques to conventional techniques; two of them found that three-dimensional printing produced improved outcomes.Three-dimensional printing technology in craniomaxillofacial surgery can be classified into contour models (type I), guides (type II), splints (type III), and implants (type IV). These four methods vary in their use between craniofacial and maxillofacial surgery, reflecting their different goals. This understanding may help advance and predict three-dimensional printing applications for other types of plastic surgery and beyond.

BACKGROUND: Plagiocephaly, involving positional deformity of the calvarium in infants, is one of the most common reasons for pediatric neurosurgical consultation. OBJECTIVE: To answer the question: “what is the evidence for the effectiveness of repositioning for positional plagiocephaly?” Treatment recommendations are provided based on the available evidence. METHODS: The National Library of Medicine MEDLINE database and the Cochrane Library were queried using MeSH headings and key words relevant to repositioning as a means to treat plagiocephaly and brachycephaly. Abstracts were reviewed to identify which studies met the inclusion criteria. An evidentiary table was assembled summarizing the studies and the quality of evidence (Classes I-III). Based on the quality of the literature, a recommendation was rendered (Level I, II, or III). RESULTS: There were 3 randomized trials (Class I), 1 prospective cohort study (Class II), and 6 retrospective cohort studies (Class III). Repositioning education was found to be equal to a repositioning device and inferior to a physical therapy program. Five of the 7 cohort studies comparing repositioning with a helmet reported helmets to be better and take less time. CONCLUSION: Within the limits of this systematic review, repositioning education is effective in affording some degree of correction in virtually all infants with positional plagiocephaly or brachycephaly. Most studies suggest that a molding helmet corrects asymmetry more rapidly and to a greater degree than repositioning education. In a Class I study, repositioning education was as effective as repositioning education in conjunction with a repositioning wrap/device. Another Class I study demonstrated that a bedding pillow was superior to physical therapy for some infants. However, in keeping with the American Academy of Pediatrics' warning against the use of soft positioning pillows in the sleeping environment, the Task Force recommends physical therapy over any positioning device. The full guidelines document can be located at https://www.cns.org/guidelines/guidelines-management-patients-positional-plagiocephaly/Chapter_3.

Background Plagiocephaly, involving positional deformity of the calvarium in infants, is one of the most common reasons for pediatric neurosurgical consultation. Objective To answer the question: "what is the evidence for the effectiveness of repositioning for positional plagiocephaly?" Treatment recommendations are provided based on the available evidence. Methods The National Library of Medicine MEDLINE database and the Cochrane Library were queried using MeSH headings and key words relevant to repositioning as a means to treat plagiocephaly and brachycephaly. Abstracts were reviewed to identify which studies met the inclusion criteria. An evidentiary table was assembled summarizing the studies and the quality of evidence (Classes I-III). Based on the quality of the literature, a recommendation was rendered (Level I, II, or III). Results There were 3 randomized trials (Class I), 1 prospective cohort study (Class II), and 6 retrospective cohort studies (Class III). Repositioning education was found to be equal to a repositioning device and inferior to a physical therapy program. Five of the 7 cohort studies comparing repositioning with a helmet reported helmets to be better and take less time. Conclusion Within the limits of this systematic review, repositioning education is effective in affording some degree of correction in virtually all infants with positional plagiocephaly or brachycephaly. Most studies suggest that a molding helmet corrects asymmetry more rapidly and to a greater degree than repositioning education. In a Class I study, repositioning education was as effective as repositioning education in conjunction with a repositioning wrap/device. Another Class I study demonstrated that a bedding pillow was superior to physical therapy for some infants. However, in keeping with the American Academy of Pediatrics' warning against the use of soft positioning pillows in the sleeping environment, the Task Force recommends physical therapy over any positioning device. The full guidelines document can be located at https://www.cns.org/guidelines/guidelines-management-patients-positional-plagiocephaly/Chapter_3.

BACKGROUND Positional plagiocephaly is a common problem seen by pediatricians, pediatric neurologists, and pediatric neurosurgeons. OBJECTIVE To create evidence-based guidelines for the treatment of pediatric positional plagiocephaly. METHODS This guideline was prepared by the Plagiocephaly Guideline Task Force, a multidisciplinary team made up of physician volunteers (clinical experts), medical librarians, and clinical guidelines specialists. The task force conducted a series of systematic literature searches of PubMed and the Cochrane Library, according to standard protocols for each topic addressed in subsequent chapters of this guideline. RESULTS The systematic literature searches returned 396 abstracts relative to the 4 main topics addressed in this guideline. The results were analyzed and are described in detail in each subsequent chapter included in this guideline. CONCLUSION Evidence-based guidelines for the management of infants with positional plagiocephaly will help practitioners manage this common disorder. The full guidelines documents can be located at https://www.cns.org/guidelines/guidelines-management-patients-positional-plagiocephaly.

Background No evidence-based guidelines exist on the role of cranial-molding orthosis (helmet) therapy for patients with positional plagiocephaly. Objective To address the clinical question: "Does helmet therapy provide effective treatment for positional plagiocephaly?" and to make treatment recommendations based on the available evidence. Methods The US National Library of Medicine Medline database and the Cochrane Library were queried by using MeSH headings and key words relevant to the objective of this systematic review. Abstracts were reviewed, after which studies meeting the inclusion criteria were selected and graded according to their quality of evidence (Classes I-III). Evidentiary tables were constructed that summarized pertinent study results, and, based on the quality of the literature, recommendations were made (Levels I-III). Results Fifteen articles met criteria for inclusion into the evidence tables. There was 1 prospective randomized controlled trial (Class II), 5 prospective comparative studies (Class II), and 9 retrospective comparative studies (Class II). Conclusion There is a fairly substantive body of nonrandomized evidence that demonstrates more significant and faster improvement of cranial shape in infants with positional plagiocephaly treated with a helmet in comparison with conservative therapy, especially if the deformity is severe, provided that helmet therapy is applied during the appropriate period of infancy. Specific criteria regarding the measurement and quantification of deformity and the most appropriate time window in infancy for treatment of positional plagiocephaly with a helmet remains elusive. In general, infants with a more severe presenting deformity and infants who are helmeted early in infancy tend to have more significant correction (and even normalization) of head shape. The full guidelines document can be located at https://www.cns.org/guidelines/guidelines-management-patients-positional-plagiocephaly/Chapter_5.

BACKGROUND The integrated plastic surgery match is a competitive process not only for applicants but also for programs vying for highly qualified candidates. Interactions between applicants and program constituents are limited to a single interview visit. The authors aimed to identify components of the interview visit that influence applicant decision making when determining a final program rank list. METHODS Thirty-six applicants who were interviewed (100% response) completed the survey. Applicants rated the importance of 20 elements of the interview visit regarding future ranking of the program on a 1 to 5 Likert scale. Data were analyzed using descriptive statistics, hierarchical cluster analysis, analysis of variance, and Pearson correlations. A literature review was performed regarding the plastic surgery integrated residency interview process. RESULTS Survey questions were categorized into four groups based on mean survey responses:1. Interactions with faculty and residents (mean response > 4),2. Information about the program (3.5-4),3. Ancillaries (food, amenities, stipends) (3-3.5),4. Hospital tour, hotel (

Some of the most problematic craniofacial injuries in pediatric plastic surgery are large calvarial defects in children who have passed the age of maximal dural osteogenic potential and yet are too young to yield split calvarial grafts. Porous polyethylene (Medpor; Porex) is an alloplastic material that can be customized to precisely match a cranial defect. We present a clinical series that demonstrates successful use of porous polyethylene cranioplasties in large pediatric cranial defects.From 2007 to 2009, 9 pediatric patients underwent custom-made porous polyethylene cranioplasties for large calvarial defects. Descriptive statistical analyses were performed on the cause of the defects, time to cranioplasty, size of defect, reconstruction technique, and postoperative healing.A total of 5 boys and 4 girls, with a mean age of 6.8 years, underwent 9 cranioplasties incorporating custom porous polyethylene implants. Initial pathologic findings included 7 patients with traumatic brain injuries, 1 patient with intractable seizures, and 1 patient with brain cancer. Initially, each patient had a craniectomy followed by replacement of the frozen bone "flap." All patients experienced either infection or resorption of the bone leading to a permanent defect. The mean defect size was 152 cm. The mean delay between the removal of failed bone "flap" and the final implant cranioplasty was 6.8 months. At the last follow-up, which averaged 3.6 months, all patients had stable wounds with acceptable cranial contour.For pediatric large-scale calvarial defects, custom-made porous polyethylene implants can be safely used for cranioplasty. Tissue expansion and acellular dermal matrix were useful tools to help augment the soft tissues of the scalp before cranioplasty to prevent complications of implant extrusion and wound breakdown.

Rationale: Integrin-linked kinase (ILK) is located at focal adhesions and links the extracellular matrix (ECM) to the actin cytoskeleton via β1- and β3-integrins. ILK plays a role in the activation of kinases including protein kinase B/Akt and glycogen synthase kinase 3β and regulates cell proliferation, motility, and survival. Objective: To determine the function of ILK in vascular smooth muscle cells (SMCs) in vivo. Methods and Results: SM22Cre + Ilk Fl/Fl conditional mutant mice were generated in which the Ilk gene was selectively ablated in SMCs. SM22Cre + Ilk Fl/Fl conditional mutant mice survive to birth but die in the perinatal period exhibiting multiple vascular pathologies including aneurysmal dilatation of the aorta and patent ductus arteriosus (PDA). Defects in morphogenetic development of the aorta were observed as early as E12.5 in SM22Cre + Ilk Fl/Fl mutant embryos. By late gestation (E16.5 to 18.5), striking expansion of the thoracic aorta was observed in ILK mutant embryos. Histological analyses revealed that the structural organization of the arterial tunica media is severely disrupted with profound derangements in SMC morphology, cell-cell, and cell-matrix relationships, including disruption of the elastic lamellae. ILK deletion in primary aortic SMCs results in alterations of RhoA/cytoskeletal signaling transduced through aberrant localization of myocardin-related transcription factor (MRTF)-A repressing the transcription and expression of SMC genes, which are required for the maintenance of the contractile SMC phenotype. Conclusions: These data identify a molecular pathway linking ILK signaling to the contractile SMC gene program. Activation of this pathway is required for morphogenetic development of the aorta and ductus arteriosus during embryonic and postnatal survival.

Background Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on an absorbable collagen sponge is a U.S. Food and Drug Administration-approved therapy shown to be an effective means of generating bone formation in multiple clinical settings. However, the optimum dose and delivery of rhBMP-2 to the calvaria are undetermined. The aim of the authors' study was to investigate the use of rhBMP-2 in addressing calvarial defects in a large-animal model through a variety of modifications to this U.S. Food and Drug Administration-approved therapy. Methods Twenty-three adult canines underwent the creation of a standard calvarial defect and received either no treatment, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with corticocancellous chips, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with MasterGraft Granules, or 0.4 mg/ml rhBMP-2 in a compression-resistant matrix carrier. Direct comparisons of defect radiopacity were performed at 0, 8, 16, and 24 weeks postoperatively before the animals were euthanized. All specimens were evaluated qualitatively with histology. Results Surgical control animals had an average defect radiopacity of 32.7 percent at study completion compared with an average of 99.95 percent across all treatment groups. Ectopic bone formation was found consistently in all treatment groups with varying degrees of severity. Regenerated bone thickness, compactness, and organization varied qualitatively between groups. Conclusions Treatment with 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with MasterGraft Granules showed the least amount of ectopic bone formation and the most compact bone formation within the defect, and produced reasonably consistent bony thickness across the defect. Future studies should focus on spatial regulation of rhBMP-2 to minimize unwanted bone formation.

Leukotriene B(4) (LTB(4)) is a pro-inflammatory lipid mediator generated by the enzymes 5-lipoxygenase (5-LO) and LTA(4)-hydrolase. LTB(4) signals primarily through its G protein-coupled receptor BLT1, which is highly expressed on specific leukocyte subsets. Recent genetic studies in humans as well as knockout studies in mice have implicated the leukotriene synthesis pathway in several vascular pathologies. Here we tested the hypothesis that pharmacological inhibition of BLT1 diminishes abdominal aortic aneurysm (AAA) formation, a major complication associated with atherosclerotic vascular disease. Chow-fed Apoe(-/-) mice were treated with a 4-week infusion of Angiotensin II (AngII, 1000 ng/(kg min)) beginning at 10 weeks of age, in a well-established murine AAA model. Administration of the selective BLT1 antagonist CP-105,696 beginning simultaneously with AngII infusion reduced the incidence of AAA formation from 82% to 40% (p

Leukotriene B4 is a proinflammatory lipid mediator generated by the enzymes 5-lipoxygenase and leukotriene A4 hydrolase. Leukotriene B4 signals primarily through its high-affinity G protein-coupled receptor, BLT1, which is highly expressed on specific leukocyte subsets. Recent genetic studies in humans as well as knockout studies in mice have implicated the leukotriene synthesis pathway in several vascular pathologies. In this study, we tested the hypothesis that BLT1 is necessary for abdominal aortic aneurysm (AAA) formation, a major complication of atherosclerotic vascular disease. Chow-fed Apoe−/− and Apoe−/−/Blt1−/− mice were treated with a 4-wk infusion of angiotensin II (1000 ng/min/kg) beginning at 20 wk of age, in a well-established murine AAA model. We found a reduced incidence of AAA formation as well as concordant reductions in the maximum suprarenal/infrarenal diameter and total suprarenal/infrarenal area in the angiotensin II-treated Apoe−/−/Blt1−/− mice as compared with the Apoe−/− controls. Diminished AAA formation in BLT1-deficient mice was associated with significant reductions in mononuclear cell chemoattractants and leukocyte accumulation in the vessel wall, as well as striking reductions in the production of matrix metalloproteinases-2 and -9. Thus, we have shown that BLT1 contributes to the frequency and size of abdominal aortic aneurysms in mice and that BLT1 deletion in turn inhibits proinflammatory circuits and enzymes that modulate vessel wall integrity. These findings extend the role of BLT1 to a critical complication of vascular disease and underscore its potential as a target for intervention in modulating multiple pathologies related to atherosclerosis.