Surgical Management in Isolated Squamosal Craniosynostosis: A Systematic Review.

BACKGROUND: Although craniosynostoses involving the major sutures have been well described, the frequency of isolated minor suture craniosynostoses is much lower. Squamosal craniosynostosis (SQS) is a rare form of cranial synostosis, and the paucity of literature has made the creation of a standardized treatment plan difficult. We present a systematic review of the literature on isolated SQS to identify disease characteristics that lead to a need for operative intervention and to delineate patterns in surgical management. METHODS: A systematic literature review was performed using the electronic databases of PubMed, Scopus, and MEDLINE and the key words "squamosal AND craniosynostosis," "squamous AND craniosynostosis," "squamosal craniosynostosis, "squamosal suture craniosynostosis," and "isolated squamosal craniosynostosis." Only human studies that described presentation and management of SQS were included. A blinded, 2-reviewer analysis of the articles was performed. Data collected included patient and disease characteristics, imaging workup, and treatment specifics, which were analyzed by descriptive statistics. RESULTS: A total of 19 studies examining 119 patients with SQS were reviewed, with 97 (82%) multisutural cases and 22 isolated cases (18%). Of the isolated cases, 6 (27%) required surgical craniosynostosis repair, of which 1 (17%) had unilateral sutural involvement and 5 (83%) had bilateral involvement. Of the patients with isolated SQS, 7 (32%) had a congenital syndrome and comprised 33% of patients who required surgical intervention. The nonsyndromic patients with isolated SQS who required surgery presented with a wide array of phenotypic findings; 3 patients underwent some form of cranial vault remodeling, whereas 1 patient underwent ventriculoperitoneal shunt only. Of the 4 nonsyndromic patients with isolated SQS who underwent surgical repair, half required operative intervention because of elevated intracranial pressure and the other half because of dysmorphic head shape. CONCLUSION: The findings of this updated systematic review suggest a trend toward surgical management in bilateral SQS versus unilateral SQS, and that patients with isolated SQS, previously considered to be a nonsurgical finding, should be carefully monitored, as there remains risk of increased intracranial pressure. Pooled systematic review data suggest isolated SQS has a 27% operative intervention rate, with the presence of coexisting syndromic diagnoses increasing that risk.

The Role of Postoperative Nasal Stents in Cleft Rhinoplasty: A Systematic Review.

OBJECTIVE: To evaluate the role of postoperative nasal stenting in preserving nasal shape and preventing nostril stenosis in cleft rhinoplasty, and to develop a classification system for postoperative nasal stents. DESIGN: Systematic review. METHODS: Electronic and manual searches of scientific literature were conducted from 3 databases (PubMed, SCOPUS, OVID). Primary evidence that described postoperative nasal stenting in cleft rhinoplasty were included. Exclusion criteria included secondary evidence, non-English articles, and studies focusing on preoperative nasal stents. PATIENTS AND PARTICIPANTS: Patients with cleft lip/nose of any type were included. MAIN OUTCOME MEASURE(S): Role in preservation of nasal shape & symmetry, role in prevention of nostril stenosis, complications with the use of postoperative nasal stent. RESULTS: Of the 13 articles, 9 papers described the preservation of nasal shape with nasal stents and three studies with a control group showed improved symmetry score. No studies evaluated the prevention of nostril stenosis; however, 2 studies reported improvement of nostril stenosis in secondary cleft rhinoplasty. The results of the included studies had significant heterogeneity. Nasal stents were classified into five types: Type I-spare parts assembled, Type II-prefabricated commercial, Type IIIa-patient specific 3D-printed static, Type IIIb-patient specific dynamic, and Type IV-internal absorbable. Total complications were 6.0%, including irritation (0.9%), infection (0.3%), and stent loss (4.6%). CONCLUSION: Despite the lack of consensus with postoperative nasal stents, this review suggests its safety and role in preserving shape and improving stenosis. Our classification system highlights variability and the need for better quality studies to determine the efficacy of nasal stents.

Nonhematogenic circulating aneuploid cells confer inferior prognosis and therapeutic resistance in gliomas.

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- circulating tumor cells (CTCs) and CD31+ circulating tumor endothelial cells, and thoroughly investigate the clinical utilities of these different subtypes of cells. Co-detection and analysis of CTCs and circulating tumor-derived endothelial cells (CTECs) expressing CD133, glial fibrillary acidic protein (GFAP), or epidermal growth factor receptor variant III (EGFR vIII) were performed by integrated subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) in 111 preoperative primary diffuse glioma patients. Aneuploid CACs could be detected in most de novo glioma patients. Among detected CACs, 45.6% were CD31- /CD45- aneuploid CTCs and the remaining 54.4% were CD31+ /CD45- aneuploid CTECs. Positive detection of CTECs significantly correlated with disruption of the blood-brain barrier. The median number of large CTCs (L CTCs, >5 µm, 2) in low-grade glioma (WHO grade 2) was less than high-grade glioma (WHO grades 3 and 4) (3, p = 0.044), but this difference was not observed in small CTCs (S CTCs, ≤5 µm), CTECs or CACs (CTCs + CTECs). The numbers of CTCs, CTECs, or CACs in patients with contrast-enhancing (CE) lesions considerably exceeded that of non-CE lesions (p < 0.05). Receiver operating characteristic curves demonstrated that CD31+ CTECs, especially L CTECs, exhibited a close positive relationship with CE lesions. Survival analysis revealed that the high number of CD31- CTCs could be an adverse factor for compromised progression-free survival and overall survival. Longitudinal surveillance of CD31- CTCs was suitable for evaluating the therapeutic response and for monitoring potential emerging treatment resistance.

Defining Ideal External Female Genital Anatomy via Crowdsourcing Analysis.

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 < 0.001) but no significant preference in clitoral hood length (P = 0.54). Experiment 3 compared clitoral hood length vs labia minora width and showed a statistically significant preference for mid-range labia minora widths (P < 0.001) but no significant preference in clitoral hood length (P = 0.78). CONCLUSIONS: Raters preferred a labia majora to labia minora width ratio of 3:1 with minimal preference in clitoral hood length.

Three-dimensional printing in medicine: a systematic review of pediatric applications.

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.

Yorkie is required to restrict the injury responses in planarians.

Regeneration requires the precise integration of cues that initiate proliferation, direct differentiation, and ultimately re-pattern tissues to the proper size and scale. Yet how these processes are integrated with wounding responses remains relatively unknown. The freshwater planarian, Schmidtea mediterranea, is an ideal model to study the stereotyped proliferative and transcriptional responses to injury due to its high capacity for regeneration. Here, we characterize the effector of the Hippo signalling cascade, yorkie, during planarian regeneration and its role in restricting early injury responses. In yki(RNAi) regenerating animals, wound responses are hyper-activated such that both stem cell proliferation and the transcriptional wound response program are heighted and prolonged. Using this observation, we also uncovered novel wound-induced genes by RNAseq that were de-repressed in yki(RNAi) animals compared with controls. Additionally, we show that yki(RNAi) animals have expanded epidermal and muscle cell populations, which we hypothesize are the increased sources of wound-induced genes. Finally, we show that in yki(RNAi) animals, the sensing of the size of an injury by eyes or the pharynx is not appropriate, and the brain, gut, and midline cannot remodel or scale correctly to the size of the regenerating fragment. Taken together, our results suggest that yki functions as a key molecule that can integrate multiple aspects of the injury response including proliferation, apoptosis, injury-induced transcription, and patterning.

Plastic Surgery Innovation with 3D Printing for Craniomaxillofacial Operations.

Plastic Surgery restores unique human qualities such as appearance, speech (palate), hands, to improve interaction with others and quality of life. Three-dimensional printing technology can be applied to Plastic Surgery craniomaxillofacial operations to change the bony skeleton of the skull, face, and jaws. Three-dimensional printing for patient-specific applications have four types: Type I contour models, Type II guides, Type III splints, Type IV implants. Plastic Surgery innovation in 3D printing clinical applications are described here and https://www.slucare.edu/newsroom/kmov-science-of-healing-faces-of-childhood.php.

Systematic Review: Online Crowdsourcing to Assess Perceptual Speech Outcomes.

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.

Demystifying the "Triple Point: " Technical Nuances of the Fronto-Orbital Advancement.

Removal of the fronto-orbital bandeau is one of the most critical components for procedures designed to correct anomalies of the craniofacial skeleton and remodel the anterior calvarial vault. It is also used to improve exposure of the anterior cranial fossa. It is arguably one of the more difficult portions of some craniofacial procedures. While the technique for fronto-orbito-sphenoid osteotomy has been frequently described, it has only been minimally detailed. Separation of bone in this region remains challenging due to the bone thickness, adjacent vital structures, and limited direct visibility. The present paper describes the anatomy of this particular region, which the authors have termed the "triple point", to facilitate successful osteotomy and avoid potential injury.

Planarian yorkie/YAP functions to integrate adult stem cell proliferation, organ homeostasis and maintenance of axial patterning.

During adult homeostasis and regeneration, the freshwater planarian must accomplish a constant balance between cell proliferation and cell death, while also maintaining proper tissue and organ size and patterning. How these ordered processes are precisely modulated remains relatively unknown. Here we show that planarians use the downstream effector of the Hippo signaling cascade, yorkie (yki; YAP in vertebrates) to control a diverse set of pleiotropic processes in organ homeostasis, stem cell regulation, regeneration and axial patterning. We show that yki functions to maintain the homeostasis of the planarian excretory (protonephridial) system and to limit stem cell proliferation, but does not affect the differentiation process or cell death. Finally, we show that Yki acts synergistically with WNT/ß-catenin signaling to repress head determination by limiting the expression domains of posterior WNT genes and that of the WNT-inhibitor notum. Together, our data show that yki is a key gene in planarians that integrates stem cell proliferation control, organ homeostasis, and the spatial patterning of tissues.

Squamosal Craniosynostosis: Defining the Phenotype and Indications for Surgical Management.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Plastic Surgery Match: A Quantitative Analysis of Applicant Impressions From the Interview Visit.

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 (<3).Hierarchical item cluster analysis and analysis of variance testing validated these groupings. Average summary scores were calculated for the items representing Interactions, Information, and Ancillaries. Correlation analysis between clusters yielded no significant correlations. A review of the literature yielded a paucity of data on analysis of the interview visit. CONCLUSIONS: The interview visit consists of a discrete hierarchy of perceived importance by applicants. The strongest independent factor in determining future program ranking is the quality of interactions between applicants and program constituents on the interview visit. This calls for further investigation and optimization of the interview visit experience.

Development of Volunteer International Craniofacial Surgery Missions: The Komedyplast Protocol.

Volunteer surgical missions to provide cleft care to patients in developing countries has been done successfully for a number of years. Similar missions that provide craniofacial surgery introduce a dramatic step up in complexity. While articles have addressed protocols for the safe delivery of cleft care around the world, little has been written on volunteer craniofacial surgical missions. Komedyplast was established in March 2001 as a 501c(3) nonprofit organization to provide craniofacial surgical care to underserved populations and educate local surgeons in craniofacial principles. During 9 annual missions, the organization has provided surgical care to more than 150 patients with various complex, congenital, craniofacial conditions. The article addresses important safeguards that have been implemented to maximize safety and minimize risk.

Biphasic co-detection of melanoma aneuploid tumor cells and tumor endothelial cells in guidance of specifying the field cancerized surgical excision margin and administering immunotherapy.

An optimum safety excision margin (EM) delineated by precise demarcation of field cancerization along with reliable biomarkers that enable predicting and timely evaluating patients' response to immunotherapy significantly impact effective management of melanoma. In this study, optimized biphasic "immunofluorescence staining integrated with fluorescence insitu hybridization" (iFISH) was conducted along the diagnosis-metastasis-treatment-cellular MRD axis to longitudinally co-detect a full spectrum of intact CD31- aneuploid tumor cells (TCs), CD31+ aneuploid tumor endothelial cells (TECs), viable and necrotic circulating TCs (CTCs) and circulating TECs (CTECs) expressing PD-L1, Ki67, p16 and Vimentin in unsliced specimens of the resected primary tumor, EM, dissected sentinel lymph nodes (SLNs) and peripheral blood in an early-stage melanoma patient. Numerous PD-L1+ aneuploid TCs and TECs were detected at the conventional safety EM (2 cm), quantitatively indicating the existence of a field cancerized EM for the first time. Contrary to highly heterogeneous PD-L1 expression and degrees of Chr8 aneuploidy in TCs and TECs in the primary lesions as well as CTCs and CTECs in peripheral blood, almost all TCs and TECs in SLNs and EM were homogeneously PD-L1+ haploid cells. Dynamic monitoring and cellular MRD assessment revealed that, in contrast to PD-L1+ CTCs being responsive to the immune checkpoint inhibitor (ICI-anti-PD-1), multiploid (≥pentasomy 8) PD-L1+ and Ki67+ CTECs were respectively resistant to ICI-sensitized T cells. In therapeutically stressed lymphatic and hematogenous metastatic cascades, stratified phenotypic and karyotypic profiling of iFISH tissue and liquid biopsied TCs, TECs, CTCs and CTECs in future large-cohort studies will enable appropriate re-specification of the optimal safety EM and distribution mapping of in-depth characterized, subcategorized target cells to help illustrate their metastatic relevance, ultimately improving risk stratification and clinical intervention of tumor progression, metastases, therapy resistance and cancer relapse.

Aortic aneurysm generation in mice with targeted deletion of integrin-linked kinase in vascular smooth muscle cells.

RATIONALE: Integrin-linked kinase (ILK) is located at focal adhesions and links the extracellular matrix (ECM) to the actin cytoskeleton via ß1- and ß3-integrins. ILK plays a role in the activation of kinases including protein kinase B/Akt and glycogen synthase kinase 3ß 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.

Seeing Cleft Lip from a New Angle: Crowdsourcing to Determine whether Scar Severity or Lip Angle Matters More to the General Public.

BACKGROUND: Modern cleft lip surgery aims to restore symmetry and create a level, normal-appearing Cupid's bow. However, families' concerns often center on the degree of scarring. The authors hypothesized that the lip angle would be less influential than scar severity in layperson ratings. METHODS: The authors received institutional review board approval for modifying patients' postoperative photographs to create systematic variations displaying different levels of scarring and lip angle. Each child's resulting composite images were presented in pairs to internet raters using Amazon Mechanical Turk. Users selected the simulated postoperative result they felt to be most normal. The Bradley-Terry model was used to determine raters' preferences between different levels of scarring and lip angle. RESULTS: Four children with primary unilateral cleft lip repair had their postoperative photographs modified (mean age, 1.4 years; mean follow-up, 1.0 years). Twelve-hundred crowdsourced pairwise ratings were collected for each patient (4800 combined ratings). For all four children, raters preferred images with more severe scarring than those with a greater lip angle, suggesting uneven lip angle has a more negative effect on perceived appearance. CONCLUSIONS: Online crowdsourcing postoperative lip angle had a significantly greater influence on ratings of normal appearance than does the severity of scarring. Although patients may ask about scars more often, clinically, this study suggests perceptions of a cleft lip repair result may be more likely influenced by the angle of the cleft lip repair.

Custom porous polyethylene implants for large-scale pediatric skull reconstruction: early outcomes.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

GLI3 regulates muscle stem cell entry into GAlert and self-renewal.

Satellite cells are required for the growth, maintenance, and regeneration of skeletal muscle. Quiescent satellite cells possess a primary cilium, a structure that regulates the processing of the GLI family of transcription factors. Here we find that GLI3 processing by the primary cilium plays a critical role for satellite cell function. GLI3 is required to maintain satellite cells in a G0 dormant state. Strikingly, satellite cells lacking GLI3 enter the GAlert state in the absence of injury. Furthermore, GLI3 depletion stimulates expansion of the stem cell pool. As a result, satellite cells lacking GLI3 display rapid cell-cycle entry, increased proliferation and augmented self-renewal, and markedly enhanced regenerative capacity. At the molecular level, we establish that the loss of GLI3 induces mTORC1 signaling activation. Therefore, our results provide a mechanism by which GLI3 controls mTORC1 signaling, consequently regulating muscle stem cell activation and fate.

Case report: Post-therapeutic laryngeal carcinoma patient possessing a high ratio of aneuploid CTECs to CTCs rapidly developed de novo malignancy in pancreas.

Effectively evaluating therapeutic efficacy, detecting minimal residual disease (MRD) after therapy completion, and predicting early occurrence of malignancy in cancer patients remain as unmet imperative clinical demands. This article presents a case of a laryngeal carcinoma patient who had a surgical resection and complete post-operative chemoradiotherapy in combination with the targeted therapy, then rapidly developed pancreatic adenocarcinoma. Detected by SE-iFISH, the patient had a substantial amount of 107 non-hematological aneuploid circulating rare cells including 14 circulating tumor cells (CTCs, CD31-/CD45-) and 93 circulating tumor endothelial cells (CTECs, CD31+/CD45-) with a high ratio of CTECs/CTCs > 5 upon finishing post-surgical combination regimens. Positive detection of those aneuploid non-hematological circulating rare cells was five months prior to subsequent plasma CA19-9 increasing and ten months before the de novo pancreatic cancer was diagnosed by medical imaging modalities. Besides previously reported clinical utilities of co-detection of aneuploid CD31- CTCs and CD31+ CTECs in real-time evaluation of therapeutic efficacy, longitudinal monitoring of emerging treatment resistance and adequate detection of MRD, a large cohort study is necessary to further investigate whether, and how, a high ratio of MRD CTECs to CTCs may function as an appropriate index forecasting either occurrence or metastatic distant recurrence of malignancy in post-therapeutic cancer patients.

Nasal strips for evaluating and classifying valvular nasal obstruction.

BACKGROUND: A normal-appearing upper lateral cartilage (ULC) or lower lateral cartilage (LLC) may be functionally abnormal. The Cottle sign estimates obstruction but not its exact location. A test is needed that evaluates the ULC and LLC separately. METHODS: The study included 30 patients with airway obstruction symptoms and signs referable only to the nasal valves. They received a Cottle test and a Breathe-Rite nasal strip to the middle third of the nose and again to the lower third (the rims). The patients were asked whether the strip made their inspiration better, worse, or no different and classified as BR 0 (no airway obstruction due to ULC/LLC dysfunction), BR I (improvement with the strip on the ULC), BR II (improvement with the strip on the LLC), or BR III (improvement with strips on both the ULC and the LLC, independently). All the patients underwent surgery involving spreader grafts, lateral crural struts, suture techniques, and the like. Correlations were sought between the BR classification, Cottle sign, and physical integrity of the ULC/LLC. RESULTS: A total of 12 patients required internal valve correction, whereas 8 required external valve correction, and 10 required correction of both. The Cottle test was nonspecific because most patients in all the groups exhibited a positive Cottle. However, the BR classification was specific, correlating with functional outcomes for 27 of the 30 patients. The McNemar test showed a significant correlation (Χ(2) = 9.09091; P = 0.00257) between physical finding and BR score. CONCLUSIONS: Inspiratory nasal function (related to ULC/LLC cartilages) is easily classified using nasal strips. The BR test is more specific and powerful than the Cottle test.