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Andreas A Mueller,1,2 Nadeem Kalak,3 Katja Schwenzer-Zimmerer,1,2 Edith Holsboer-Trachsler,3 Serge Brand3,4 1Craniomaxillofacial Surgery, University of Basel and University Hospital of Basel, Basel, Switzerland; 2Hightech Research Center of Craniomaxillofacial Surgery, University of Basel, Basel, Switzerland; 3Psychiatric Clinics of the University of Basel, Center for Affective, Stress, and Sleep Disorders, Basel, Switzerland; 4Department of Sport and Health Science, Division of Sport Science, University of Basel, Basel, Switzerland Background: Traumatic events during early infancy might damage infants’ psychobiological functioning, such as sleep and cortisol secretion. Infants born with orofacial clefts (OFCs) undergo functional, anatomical, and aesthetic surgery. The aim of the present study was to determine whether infants with OFC and undergoing OFC surgery show deteriorated sleep and cortisol secretion compared with healthy controls and with their presurgery status.Methods: A total of 27 infants with OFC (mean age: 22 weeks) and 30 healthy controls (mean age: 23 weeks) took part in the study. For infants with OFC, sleep actigraphy was performed and saliva cortisol was analyzed 5 days before, during, and 5 days after surgery. For controls, sleep and saliva cortisol were assessed similarly, except for the period taken up with surgery.Results: Compared with healthy controls, infants with OFC undergoing OFC surgery did not differ in sleep and cortisol secretion. Their sleep and cortisol secretion did deteriorate during the perisurgical period but recovered 5 days postsurgery. Conclusion: In infants with OFC undergoing corrective surgery, the pattern of results for sleep and cortisol suggests that OFC surgery does not seem to constitute a traumatic event with long-term consequences. Keywords: cortisol, sleep, orofacial cleft, surgery, infants

We demonstrate pre-epiglottic baton plate as non-invasive treatment modality for initial airway management in newborns with Pierre Robin Sequence. A case example illustrates management of upper airway obstruction and feeding using digital technology to facilitate customization. Laryngoscope, 134:4766-4769, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To evaluate the performance of smartphone scanning applications (apps) in acquiring 3D meshes of cleft palate models. Secondarily, to validate a machine learning (ML) tool for computing automated presurgical plate (PSP)., Materials and Methods: We conducted a comparative analysis of two apps on 15 cleft palate models: five unilateral cleft lip and palate (UCLP), five bilateral cleft lip and palate (BCLP) and five isolated cleft palate (ICP). The scans were performed with and without a mirror to simulate intraoral acquisition. The 3D reconstructions were compared to control reconstructions acquired using a professional intraoral scanner using open-source software., Results: Thirty 3D scans were acquired by each app, totalling 60 scans. The main findings were in the UCLP sample, where the KIRI scans without a mirror (0.22 ± 0.03 mm) had a good performance with a deviation from the ground truth comparable to the control group (0.14 ± 0.13 mm) (p = .653). Scaniverse scans with a mirror showed the lowest accuracy of all the samples. The ML tool was able to predict the landmarks and automatically generate the plates, except in ICP models. KIRI scans' plates showed better performance with (0.22 ± 0.06 mm) and without mirror (0.18 ± 0.05 mm), being comparable with controls (0.16 ± 0.08 mm) (p = .954 and p = .439, respectively)., Conclusions: KIRI Engine performed better in scanning UCLP models without a mirror. The ML tool showed a high capability for morphology recognition and automated PSP generation., (© 2024 The Author(s). Orthodontics & Craniofacial Research published by John Wiley & Sons Ltd.)

The incomplete unilateral cleft lip shares many of the same phenotypic characteristics as a complete unilateral cleft lip, but key differences include an intact nasal sill, a relative excess of skin in the lateral lip element, and favorable skeletal support. Surgical techniques for incomplete unilateral cleft lips should be tailored to the specific anatomical characteristics, be simple and reliable to perform, and minimize the risk of secondary deformity. Here we describe the "preservation technique" for incomplete unilateral cleft lip reconstruction. The modified design from the anatomical subunit approximation technique uses a nasal sill flap and obviates the need for nasal sill and lateral lip excision. Tissues of the lip are opened out and reorientated to maximize the anatomical advantage., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Intraosseous myofibroma of the jaw is a rare neoplasm of mesenchymal origin with limited comprehensive understanding. It typically affects patients in the first two decades of life with a male predilection., Case Presentation: This study presents a rare case of myofibroma mimicking an odontogenic lesion in a 2-year-old boy. The patient presented with an incidental finding of a painless swelling of the right mandibular ramus of unknown etiology. Imaging analysis revealed a solid, expansile lesion adjacent to the germinal zone of the right mandibular first molar. Histopathologic analysis and immunohistochemistry after incisional biopsy suggested a possible central odontogenic fibroma, and the patient underwent total enucleation, leading to the final diagnosis of intraosseous myofibroma. Follow-up examinations showed no evidence of recurrence., Conclusions: This report contributes to the understanding of myofibroma in pediatric patients and underscores the critical role of meticulous histopathologic examination for effective surgical planning and optimal patient outcomes., (© 2024. The Author(s).)

Objective: T cells contribute to tissue injury in systemic sclerosis (SSc), yet the specific T cell subsets expanded in patients with SSc remain incompletely defined. Here we evaluated specific phenotypes and functions of peripheral helper T (Tph) and follicular helper T (Tfh) cells, which have been implicated in autoantibody production, and assessed their associations with clinical features in a well-characterized cohort of patients with SSc., Methods: Mass cytometry of T cells from peripheral blood mononuclear cells of patients with SSc and controls were evaluated using t-distributed stochastic neighbor embedding visualization, biaxial gating, and marker expression levels. Findings were validated with flow cytometry and in vitro assays., Results: The frequencies of PD-1 high CXCR5 + Tfh cells and PD-1 high CXCR5 - Tph cells were similar in patients with SSc and controls. t-distributed stochastic neighbor embedding visualization (tSNE) revealed distinct populations within the PD-1 high CXCR5 - cells distinguished by expression of HLA-DR and inducible costimulator (ICOS). Among PD-1 high CXCR5 - cells, only the HLA-DR + ICOS - cell population was expanded in patients with SSc. Cytometric and RNA sequencing analyses indicated that these cells expressed cytotoxic rather than B cell helper features. HLA-DR + ICOS - PD-1 high CXCR5 - cells were less potent in inducing B cell plasmablast differentiation and antibody production than comparator T helper cell populations. HLA-DR + ICOS - PD-1 high CXCR5 - cells were significantly associated with the presence and severity of interstitial lung disease among patients with SSc., Conclusion: Among PD-1 high CXCR5 - T cells, a subset of HLA-DR + ICOS - cells with cytotoxic features is specifically expanded in patients with SSc and is significantly associated with interstitial lung disease severity. This potential cytotoxicity appearing in the CD4 T cell population can be evaluated as a prognostic disease biomarker in patients with SSc., (© 2024 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Brainstem evoked response audiometry (BERA) is the most established and recommended objective audiometric method for the clinical diagnosis of hearing impairment in high-risk infants. It is unclear whether infants with orofacial clefts meet the criteria for the high-risk group. This retrospective cohort study evaluated the need for diagnostic BERA in infants with cleft palate with or without cleft lip by assessing the predisposition to and diagnosis of congenital hearing impairment. Data from 122 patients treated at a single cleft centre were evaluated. BERA was conducted at the time of palate repair at 4-6 months of age. Clinical follow-up was analysed up to 4 years. The presence of a syndrome was examined as a risk factor for congenital hearing impairment. Among the 122 patients, four had congenital sensorineural or mixed hearing loss requiring hearing aids. All affected patients had syndromes in addition to the cleft. Most patients with elevated hearing thresholds had transient conductive hearing loss. Most suspected sensorineural hearing loss initially diagnosed was refuted. However, a higher incidence of sensorineural hearing loss was found in patients with syndromic clefts, supporting the diagnostic use of BERA with initial surgery only in patients with syndromic clefts., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Presurgical plate therapy has been widely accepted as a treatment prior to palatal cleft closure. The effects of passive presurgical plate therapy on cleft morphology prior to single-stage unilateral cleft lip and palate (UCLP) repair were quantified., Patients and Methods: We compared the dimensions of cleft width and cleft area (true cleft and palatal cleft) measured preoperatively at 2 European cleft centers. Center A performed single-stage UCLP repair in 8-month-old infants without any presurgical orthopedic treatment. Center B initiated passive presurgical plate therapy immediately after the birth of the neonates, followed by single-stage UCLP repair at 8 months of age., Results: We included 28 patients with complete UCLP from Center A and 12 patients from Center B. The average anterior width of the true cleft before surgery was significantly smaller in infants at Center B than that in Center A (p = 0.001) with 95% confidence interval of (1.8, 5.7) mm, but the average posterior width was similar in the 2 groups. The mean presurgical true cleft area amounted to 106.8 mm 2 (SD = 42.4 mm 2 ) at Center A and 71.9 mm 2 (SD = 32.2 mm 2 ) at Center B, with a confidence interval for the difference being (9.8, 60.1) mm 2 . This corresponded to a 32.7% reduction of the true cleft area when passive presurgical plate therapy was used for the first 8 months of the infants' life., Conclusion: Passive presurgical plate therapy in UCLP significantly reduced the cleft area. Implications for the subsequent surgical outcome might depend on the surgical technique used., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the influence of collateral vascularization on surgical cleft palate closure and deformities., Materials and Methods: Corrosion casting was performed using red-colored acrylic resin in twelve fresh adult cadavers with a normal hard palate. Additionally, white-colored barium sulfate was injected into a fetus with a unilateral complete cleft palate, and layer-by-layer tissue dissection was performed. Both substances were injected into the external carotid arteries. Corrosion casting involved dissolving the soft and hard tissues of the orofacial area utilizing an enzymatic solution., Results: In normal palates, bilateral intraosseous infraorbital arteries formed a network in the premaxilla with the intraosseous nasopalatine- and greater palatine arteries (GPAs). The perforating GPAs anastomosed with the sphenopalatine artery sub-branches. Bilateral extraosseous GPA anastomoses penetrated the median palatine suture. Complex vascularization in the retrotuberal area was detected. In the cleft zone, anastomoses were omitted, whereas in the non-cleft zone, enlarged GPAs were distributed along the cleft edges and followed the anatomical course anteriorly to initiate the network with facial artery sub-branches., Conclusions: The anatomical subunits of the palate exhibited distinct anastomosis patterns. Despite omitted anastomoses with collateral circulation in the cleft zone, arteries maintained their anatomical pattern as seen in the normal specimen in the non-cleft zone., Clinical Relevance: Based on the findings in normal- and cleft palates, surgeons may expect developed anastomosis patterns in the non-cleft zone. Due to the lack of microcirculation in the cleft zone, the existent anastomoses should be maintained as much as possible by the surgical technique. This applies anteriorly in the incisive canal territory, alveolar ridges, and posteriorly in the retrotuberal area., (© 2024. The Author(s).)

Objective: Cleft lip and palate is the most common craniofacial birth anomaly and requires surgery in the first year of life. However, craniofacial surgery training opportunities are limited. The aim of this study was to present and evaluate an open-source cleft lip and palate hybrid (casting and three-dimensional (3D) printing) simulation model which can be replicated at low cost to facilitate the teaching and training of cleft surgery anatomy and techniques., Design: The soft tissue component of the cleft surgery training model was casted using a 3D printed 5-component mold and silicone. The bony structure was designed to simulate the facial anatomy and to hold the silicone soft tissue., Setting: Two groups, one group of trainees and one group of expert surgeons, at University Hospital Basel in Switzerland and Pontifical Catholic University of Chile in Santiago, Chile, tested the cleft lip and palate simulation model. Participants completed a Likert-based face and content validity questionnaire to assess the realism of the model and its usefulness in surgical training., Results: More than 70 % of the participants agreed that the model accurately simulated human tissues found in patients with unilateral cleft lip and palate. Over 60 % of the participants also agreed that the model realistically replicated surgical procedures. In addition, 80-90 % of the participants found the model to be a useful and appropriate tool for teaching the anatomy and surgical techniques involved in performing unilateral cleft lip and palate repair., Conclusion: This open-source protocol provides a cost-effective solution for surgeons to introduce the cleft morphology and surgical techniques to trainees on a regular basis. It addresses the current financial barrier that limits access to commercially available models during the early stages of surgeon training prior to specialization in the field., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Andreas A. Mueller reports financial support was provided by 10.13039/100009572University of St. Gallen., (© 2024 The Author(s).)

Summary: Documenting complex three-dimensional (3D) cleft lip and palate malformation with plaster casts based on maxillary impressions is standard care. Presurgical orthopedic treatment also requires an impression. Digital impression-taking in patients with cleft lip and palate is feasible, but procurement costs hinder clinical implementation. Individualized impression trays allow for a precise impression, limiting airway risk. The authors present an open-source impression tray library with scalable impression trays not requiring 3D modeling knowledge. The cleft lip and palate impression tray library is accessible on Open Science Framework. Different shapes are available, and the tray size is selected based on the tuber distance. This allows 3D printing with biocompatible material at the point of care complying with local regulations. The open-source cleft tray library presented offers a hybrid solution for cleft centers, pending the implementation of digital impression., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Purpose: Presurgical orthopedic plates are widely used for the treatment of cleft lip and palate, which is the most common craniofacial birth defect. For the traditional plate fabrication, an impression is taken under airway-endangering conditions, which recent digital alternatives overcome via intraoral scanners. However, these alternatives demand proficiency in 3D modeling software in addition to the generally required clinical knowledge of plate design., Methods: We address these limitations with a data-driven and fully automated digital pipeline, endowed with a graphical user interface. The pipeline adopts a deep learning model to landmark raw intraoral scans of arbitrary mesh topology and orientation, which guides the nonrigid surface registration subsequently employed to segment the scans. The plates that are individually fit to these segmented scans are 3D-printable and offer optional customization., Results: With the distance to the alveolar ridges closely centered around the targeted 0.1 mm, our pipeline computes tightly fitting plates in less than 3 min. The plates were approved in 12 out of 12 cases by two cleft care professionals in a printed-model-based evaluation. Moreover, since the pipeline was implemented in clinical routine in two hospitals, 19 patients have been undergoing treatment utilizing our automated designs., Conclusion: The results demonstrate that our automated pipeline meets the high precision requirements of the medical setting employed in cleft lip and palate care while substantially reducing the design time and required clinical expertise, which could facilitate access to this presurgical treatment, especially in low-income countries., (© 2023. The Author(s).)

Background: Documenting cleft lip and palate morphology prior to surgery is standard care. Presurgical orthopedic treatment also requires a 3D cleft model. Endangering the airway, conventional impressions require additional safety measures and resources. We investigate the implementation and risks of digital impressions for the youngest patients with orofacial clefts., Methods: We report a retrospective cohort study of patients with cleft lip and palate, aged up to 6 years, treated at two cleft centers in Europe (Basel (A), Warsaw (B)). We scanned with the Medit i500 (Medit Corp, Seoul, South Korea). Center A for presurgical orthopedics and prior surgery from June 2020 to March 2022. Center B prior surgery from December 2020 to May 2021. Scanning data were analyzed for adverse events and adverse device effects, scanning duration, and number of images according to cleft type and age., Results: We analyzed 342 digital impressions in 190 patients (center A: 71, B: 119). The median age was 8.7 months with a range from the first day of birth (presurgical orthopedics) to six years of life (early alveolar bone grafting). No adverse events or adverse device effects were observed. The median scan duration was 85.5 s for cleft palate and 50 s for cleft lip and nose (IQR 56 s and 39 s, respectively)., Conclusion: Digital impressions with intraoral scanners are safe in patients with cleft lip and palate from newborn to preschool age. Given the funding to purchase an intraoral scanner, interfaces to electronic patient records, and point-of-care 3D printing, cleft centers can successfully implement this technology., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cleft lip and palate are one of the most common congenital craniofacial malformations. As an initial treatment, presurgical orthopedics is considered standard treatment at many cleft centers. Digital impressions are becoming feasible in cleft care. Computer-aided design (CAD) and three-dimensional (3D) printing are manufacturing standards in dentistry. The assimilation of these technologies has the potential to alter the traditional workflow for the fabrication of customized presurgical orthopedic plates. We present a digital workflow comprising three steps: 3D digital image acquisition with an intraoral scanner, open-source CAD modeling, and point-of-care 3D printing for the fabrication of personalized passive presurgical plates for newborns with cleft lip and palate. The digital workflow resulted in patient-related benefits, such as no risk of airway obstruction with quicker data acquisition (range 1-2.5 min). Throughput time was higher in the digital workflow 260-350 min compared to 135 min in the conventional workflow. The manual and personal intervention time was reduced from 135 min to 60 min. We show a clinically useful digital workflow for presurgical plates in cleft treatment. Once care providers overcome procurement costs, digital impressions, and point-of-care 3D printing will simplify these workflows and have the potential to become standard for cleft care.

Background: Primary alveolar bone grafting inhibits craniofacial growth. However, its effect on craniofacial growth in one-stage cleft lip and palate protocols is unknown. This study investigated whether primary alveolar bone grafting performed during one-stage unilateral cleft lip and palate repair negatively affects growth up to 6-11 years old., Methods: The craniofacial growth, dental arch relationship and palatal morphology at 6-11 years old in children with unilateral cleft lip and palate were compared retrospectively. Two cohorts after a one-stage protocol without (Group A) and with (Group B) primary bone grafting at the same center were compared. Further, cephalometric measurements for growth were compared with an external cohort of a one-stage protocol and a heathy control., Results: Group A comprised 16 patients assessed at 6.8 years (SD 0.83), and Group B comprised 15 patients assessed at 9 years (SD 2.0). Cephalometric measurements indicated similar sagittal maxillary growth deficits and a significant deviation in maxillary inclination in both groups compared to the healthy group. Moderate to severe changes in palatal morphology were observed in 70% of the members in both groups., Conclusion: Omitting primary alveolar bone grafting under the one-stage protocol with two-flap palatoplasty studied did not improve growth at 6-11 years. The results implicate two-flap palatoplasty with secondary healing as having greater adverse effects on growth than primary alveolar bone grafting. Dental and palatal morphology was considerably compromised regardless of primary alveolar bone grafting.

Background: Common surgical techniques aim to turn the entire vomerine mucosa with vomer flaps either to the oral side or to the nasal side. The latter approach is widely performed due to the similarity in color to the nasal mucosa. However, we lack a histologic description of the curved vomerine mucosa in cleft lip and palate malformations., Methods: We histologically examined an excess of curved vomerine mucosa in 8 patients using hematoxylin-eosin, periodic acid-Schiff, Elastin van Gieson, and Alcian blue stains. Tissue samples were obtained during surgery at 8 months of age., Results: Our histological analysis of the mucoperiosteum overlying the curved vomer revealed characteristics consistent with those of an oral mucosa or a squamous metaplasia of the nasal mucosa, as exhibited by a stratified squamous epithelium containing numerous seromucous glands. Some areas showed a palisaded arrangement of the basal cells compatible with metaplasia of respiratory epithelium, but no goblet cells or respiratory cilia were identified. Abundant fibrosis and rich vascularity were present., Conclusion: The vomer mucosa showed no specific signs of nasal mucosa. These findings should be considered in presurgical cleft orthopedics and palatal surgery for further refinement. Shifting the vomer mucosa according to a fixed physiologic belief should not overrule other important aspects of cleft repair such as primary healing and establishing optimal form and function of palatal roof and nasal floor.

The study aims at assessing wound healing and safety of single-stage two-layers continuous closure in patients with unilateral cleft lip and palate (UCLP). In this retrospective, descriptive cohort study, we assessed wound healing without fistula formation at 1, 3, and 6 months after a single-stage two-layer UCLP repair, in which the midline suture is continuously circular all along the oral and nasal sides. We examined lengths of hospital stay and the incidence of intra- and postoperative adverse events. Furthermore, we compared the cleft width at birth and on the day of surgery, after presurgical orthopaedics. Eleven UCLP patients underwent one cleft surgery between July 2016 and June 2018 at the age of 8-9 months. Full primary healing occurred in all patients without fistulas. Median length of post-operative hospital stay was 5 days (range = 4-9 days). No intra- or postoperative adverse events above Grade I (according to ClassIntra and Clavien-Dindo, respectively) occurred. Median and interquartile range (IQR) of the palatal cleft width decreased significantly from birth to surgery, i.e., from 12.0 mm (10.8-13.6 mm) to 5.0 mm (4.0-7.5 mm) anteriorly and from 14.0 mm (11.5-15.0 mm) to 7.3 mm (6.0-8.5 mm) posteriorly (p = 0.0033 in both cases). Given these preliminary results, the concept of single-stage continuous circular closure in UCLP has potential for further investigation. However, it remains to be proven that there are no relevant adverse effects such as inhibition of maxillary growth. Registered in clinicaltrials.gov:NCT04108416., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: COVID-19 can induce a hyperinflammatory state, which might lead to poor clinical outcomes. We aimed to assess whether patients with a systemic rheumatic disease might be at increased risk for hyperinflammation and respiratory failure from COVID-19., Methods: We did a retrospective, comparative cohort study of patients aged 18 years or older admitted to hospital with PCR-confirmed COVID-19 at Mass General Brigham (Boston, USA). We identified patients by a search of electronic health records and matched patients with a systemic rheumatic disease 1:5 to comparators. We compared individual laboratory results by case status and extracted laboratory results and COVID-19 outcomes for each participant. We calculated the COVID-19-associated hyperinflammation score (cHIS), a composite of six domains (a score of ≥2 indicating hyperinflammation) and used logistic regression to estimate odds ratios (ORs) for COVID-19 outcomes by hyperinflammation and case status., Findings: We identified 57 patients with a systemic rheumatic disease and 232 matched comparators who were admitted to hospital with COVID-19 between Jan 30 and July 7, 2020; 38 (67%) patients with a rheumatic disease were female compared with 158 (68%) matched comparators. Patients with a systemic rheumatic disease had higher peak median neutrophil-to-lymphocyte ratio (9·6 [IQR 6·4-22·2] vs 7·8 [4·5-16·5]; p=0·021), lactate dehydrogenase concentration (421 U/L [297-528] vs 345 U/L [254-479]; p=0·044), creatinine concentration (1·2 mg/dL [0·9-2·0] vs 1·0 mg/dL [0·8-1·4], p=0·014), and blood urea nitrogen concentration (31 mg/dL [15-61] vs 23 mg/dL [13-37]; p=0·033) than comparators, but median C-reactive protein concentration (149·4 mg/L [76·4-275·3] vs 116·3 mg/L [58·8-225·9]; p=0·11) was not significantly different. Patients with a systemic rheumatic disease had higher peak median cHIS than comparators (3 [1-5] vs 2 [1-4]; p=0·013). All patients with a peak cHIS of 2 or more had higher odds of admission to intensive care (OR 3·45 [95% CI 1·98-5·99]), mechanical ventilation (66·20 [8·98-487·80]), and in-hospital mortality (16·37 [4·75-56·38]) than patients with a peak cHIS of less than 2. In adjusted analyses, patients with a rheumatic disease had higher odds of admission to intensive care (2·08 [1·09-3·96]) and mechanical ventilation (2·60 [1·32-5·12]) than comparators, but not in-hospital mortality (1.78 [0·79-4·02]). Among patients who were discharged from hospital, risk of rehospitalisation (1·08 [0·37-3·16]) and mortality within 60 days (1·20 [0·58-2·47]) was similar in patients and comparators., Interpretation: Patients with a systemic rheumatic disease who were admitted to hospital for COVID-19 had increased risk for hyperinflammation, kidney injury, admission to intensive care, and mechanical ventilation compared with matched comparators. However, among patients who survived, post-discharge outcomes were not significantly different. The cHIS identified patients with hyperinflammation, which was strongly associated with poor COVID-19 outcomes in both patients with a rheumatic disease and comparators. Clinicians should be aware that patients with systemic rheumatic diseases and COVID-19 could be susceptible to hyperinflammation and poor hospital outcomes., Funding: None., Competing Interests: HKC has received research support from AstraZeneca and consultancy fees from Takeda, Selecta, GlaxoSmithKline, and Horizon. EMG has an editor position at New England Journal of Medicine and has received royalties from the textbook Rheumatology. ZSW has received research support from Bristol-Myers Squibb and Principia and consulting fees from Viela Bio and MedPace. JAS has received research support from Amgen and Bristol-Myers Squibb and consultancy fees from Bristol-Myers Squibb, Gilead, Inova, Janssen, Optum, and Pfizer. All other authors declare no competing interests., (© 2021 Elsevier Ltd. All rights reserved.)

This protocol aids both new and experienced researchers in designing retrospective clinical and translational studies of acute respiratory decline in hospitalized patients. This protocol addresses (1) the basics of respiratory failure and electronic health record research, (2) defining patient cohorts as "mild, progressive, or severe" instead of "ICU versus non-ICU", (3) adapting physiological indices, and (4) using biomarker trends. We apply these approaches to inflammatory biomarkers in COVID-19, but this protocol can be applied to any progressive respiratory failure study. For complete details on the use and execution of this protocol, please refer to Mueller et al. (2020)., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Background: In order to overcome the geometrical and physical limitations of conventional rotating and piezosurgery instruments used to perform bone osteotomies, as well as the difficulties in translating digital planning to the operating room, a stand-alone robot-guided laser system has been developed by Advanced Osteotomy Tools, a Swiss start-up company. We present our experiences of the first-in-man use of the Cold Ablation Robot-guided Laser Osteotome (CARLO ® )., Methods: The CARLO ® device employs a stand-alone 2.94-µm erbium-doped yttrium aluminum garnet (Er:YAG) laser mounted on a robotic arm. A 19-year-old patient provided informed consent to undergo bimaxillary orthognathic surgery. A linear Le Fort I midface osteotomy was digitally planned and transferred to the CARLO ® device. The linear part of the Le Fort I osteotomy was performed autonomously by the CARLO ® device under direct visual control. All pre-, intra-, and postoperative technical difficulties and safety issues were documented. Accuracy was analyzed by superimposing pre- and postoperative computed tomography images., Results: The CARLO ® device performed the linear osteotomy without any technical or safety issues. There was a maximum difference of 0.8 mm between the planned and performed osteotomies, with a root-mean-square error of 1.0 mm. The patient showed normal postoperative healing with no complications., Conclusion: The newly developed stand-alone CARLO ® device could be a useful alternative to conventional burs, drills, and piezosurgery instruments for performing osteotomies. However, the technical workflow concerning the positioning and fixation of the target marker and the implementation of active depth control still need to be improved. Further research to assess safety and accuracy is also necessary, especially at osteotomy sites where direct visual control is not possible. Finally, cost-effectiveness analysis comparing the use of the CARLO ® device with gold-standard surgery protocols will help to define the role of the CARLO ® device in the surgical landscape.

In this single-center, retrospective cohort analysis of hospitalized coronavirus disease 2019 (COVID-19) patients, we investigate whether inflammatory biomarker levels predict respiratory decline in patients who initially present with stable disease. Examination of C-reactive protein (CRP) trends reveals that a rapid rise in CRP levels precedes respiratory deterioration and intubation, although CRP levels plateau in patients who remain stable. Increasing CRP during the first 48 h of hospitalization is a better predictor (with higher sensitivity) of respiratory decline than initial CRP levels or ROX indices (a physiological score of respiratory function). CRP, the proinflammatory cytokine interleukin-6 (IL-6), and physiological measures of hypoxemic respiratory failure are correlated, which suggests a mechanistic link. Our work shows that rising CRP predicts subsequent respiratory deterioration in COVID-19 and may suggest mechanistic insight and a potential role for targeted immunomodulation in a subset of patients early during hospitalization., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)

This study examined the potential for dental magnets to act as a driving force for osteogenesis in the palate of newborns with a unilateral cleft lip and palate. In the first part of the study dental magnets were arranged in a set up mimicking a distraction device and the curves of the magnetic attraction force versus gap distance curves generated, with and without the presence of palatal rugae tissue in between both sides of the distraction device. The attraction forces ranged from 1 to 12 N depending on the gap distance and the presence of soft tissue in the gap. In the second part of the study these forces were used as input for a 3D finite element model of the palate of a newborn affected by unilateral cleft lip and palate. In the analysis of load transfer, it was found that the strains generated by a magnetically induced distraction exceed 1,500 µstrain suggesting that bone locally is submitted to mild overload leading to bone apposition.

The aim of this cohort study was to quantify the morphological changes in the palatal cleft and true cleft areas with passive plate therapy using a new analysis method based on three-dimensional standardized reproducible landmarks. Forty-five casts of 15 consecutive patients with complete unilateral cleft lip and palate were laser scanned and investigated retrospectively. The landmarks and the coordinate system were defined, and the interrater and intrarater measurement errors were within 1.0 mm. The morphological changes of the cleft palate area after a period of 8 months of passive plate therapy without prior lip surgery are presented graphically. The median decrease in cleft width was 38.0% for the palatal cleft, whereas it was 44.5% for the true cleft. The width of the true and palatal cleft decreased significantly over a period of 8 months. The true cleft area decreased by 34.7% from a median of 185.4 mm 2 (interquartile range, IQR = 151.5-220.1) to 121.1 mm 2 (IQR = 100.2-144.6). The palatal cleft area decreased by 31.5% from a median of 334 mm 2 (IQR = 294.9-349.8) to 228.8 mm 2 . The most important clinical considerations are the reproducibility and reliability of the anatomical points, as well as the associated morphological changes. We propose using the vomer edge to establish a validated measuring method for the width, area, and height of the true cleft.

A major challenge in bone tissue engineering is the lack of post-implantation vascular growth into biomaterials. In the skeletal system, blood vessel growth appears to be coupled to osteogenesis-suggesting the existence of molecular crosstalk between endothelial cells (ECs) and osteoblastic cells. The present study (performed in two murine ectopic models) was designed to determine whether co-transplantation of human Wharton's jelly mesenchymal stem cell-derived osteoblasts (WJMSC-OBs) and human differentiated ECs enhances bone regeneration and stimulates angiogenesis, relative to the seeding of WJMSC-OBs alone. Human WJMSC-OBs and human ECs were loaded into a silicate-substituted calcium phosphate (SiCaP) scaffold and then ectopically implanted at subcutaneous or intramuscular sites in nude mice. At both subcutaneous and intramuscular implantation sites, we observed ectopic bone formation and osteoids composed of host cells when WJMSC-OBs were seeded into the scaffold. However, the addition of ECs was associated with a lower level of osteogenesis, and we did not observe stimulation of blood vessel ingrowth. in vitro studies demonstrated that WJMSC-OBs lost their ability to secrete vascular endothelial growth factor and stromal cell-derived factor 1-including when ECs were present. In these two murine ectopic models, our cell-matrix environment combination did not seem to be optimal for inducing vascularized bone reconstruction., (© 2019 John Wiley & Sons, Ltd.)

Introduction: Chronic undernutrition affects over 150 million children worldwide and has serious consequences. The causes are complex and include insufficient dietary diversity and poor hygiene practices. Systematic reviews of nutrition-sensitive agricultural interventions concluded that while these hold promise, there is insufficient evidence for their impact on child growth. The Food and Agricultural Approaches to Reducing Malnutrition (FAARM) project is a 1:1 cluster-randomised trial aiming to evaluate the impact of a Homestead Food Production (HFP) programme implemented by Helen Keller International on women's and children's undernutrition., Methods and Analysis: The HFP intervention comprises training of women's groups and asset distribution to support year-round home gardening, poultry rearing and improved nutrition and hygiene practices. Formal trainings are supplemented by behaviour change communication during household visits, and facilitated links between producer groups and market actors. The FAARM trial will examine if and how this complex intervention reduces undernutrition. In 2015, FAARM enrolled married women and their children (0-3 years) in 96 rural settlements of Habiganj district in Sylhet division, Bangladesh. Covariate-constrained randomisation was used to assign 48 settlements to receive a 3-year HFP intervention, with the other 48 acting as controls, targeting over 2700 women. To study impact pathways, a surveillance system collects data on all participants every 2 months. In late 2019, children 0-3 years of age (born during the intervention period) will be surveyed, thus capturing impact during the critical first 1000 days of life. Children's length/height-for-age z-scores will be compared between intervention and control arms using mixed-effects linear regression. Secondary outcomes include women's and children's micronutrient status, dietary intake, dietary diversity and other indicators of child growth, development and morbidity., Ethics and Dissemination: Ethical approval was received in Bangladesh and Germany. Results will be disseminated through peer-reviewed publications and presentations in Bangladesh and internationally., Trial Registration Number: NCT02505711; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Microvascular surgery following tumor resection has become an important field of oral and maxillofacial surgery (OMFS). Following the results from management of T1/T2 floor-of-mouth and tongue squamous cell carcinoma (SCC) in German-speaking countries, Europe, and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T3/T4 SCC of the maxillary and mandibular alveolar process and tongue., Methods: The DÖSAK questionnaire was distributed in three different phases to a growing number of maxillofacial units worldwide. Within this survey, clinical patient settings were presented to participants and center-specific treatment strategies were evaluated., Results: A total of 188 OMFS units from 36 different countries documented their treatment strategies for T3/T4 maxillary and mandibular alveolar process and tongue SCC. The extent of surgical resections and subsequent reconstructions is more consistent than with T1/T2 tumors, although the controversy surrounding continuity resections and mandible-sparing procedures remains. For continuity resection of the mandible the fibula free flap is the most frequently used bone replacement, whereas maxilla reconstruction concepts are less consistent, ranging from locoregional coverage concepts and different microvascular reconstruction options to treatment via obturator prosthesis., Conclusion: Results from treatment strategies for T3/T4 tumors underline the limited evidence for the appropriate amount of resection and subsequent reconstruction process, especially in cases involving the mandible. Prospective randomized trials will be necessary in the long term to establish valid treatment guidelines., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: We aimed to test if EEG responses to novel events reliably dissociated individuals with Parkinson's disease and controls, and if this dissociation was sensitive and specific enough to be a candidate biomarker of cognitive dysfunction in Parkinson's disease., Methods: Participants included N = 25 individuals with Parkinson's disease and an equal number of well-matched controls. EEG was recorded during a three-stimulus auditory oddball paradigm both ON and OFF medication., Results: While control participants showed reliable EEG habituation to novel events over time, individuals with Parkinson's did not. In the OFF condition, individual differences in habituation correlated with years since diagnosis. Pattern classifiers achieved high sensitivity and specificity in discriminating patients from controls, with a maximum accuracy of 82%. Most importantly, the confidence of the classifier was related to years since diagnosis, and this correlation increased as the time course of differential habituation increasingly distinguished the groups., Conclusions: These findings identify systemic alteration in an obligatory neural mechanism that may contribute to higher-level cognitive dysfunction in Parkinson's disease., Significance: These findings suggest that EEG responses to novel events in this rapid, simple, and inexpensive test have tremendous promise for tracking individual trajectories of cognitive dysfunction in Parkinson's disease., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Introduction: Microvascular surgery following tumor resection has become an important field of oral maxillofacial surgery (OMFS). Following the results on general aspects of current reconstructive practice in German-speaking countries, Europe and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T1/T2 squamous cell carcinoma (SCC) of the anterior floor of the mouth and tongue., Methods: The DOESAK questionnaire was distributed in three different phases to a growing number of maxillofacial units worldwide. Within this survey, clinical patient settings were presented to participants and center-specific treatment strategies were evaluated., Results: A total of 188 OMFS units from 36 different countries documented their treatment strategies for T1/T2 anterior floor of the mouth squamous cell carcinoma and tongue carcinoma. For floor of mouth carcinoma close to the mandible, a wide variety of concepts are presented: subperiosteal removal of the tumor versus continuity resection of the mandible and reconstruction ranging from locoregional closure to microvascular bony reconstruction. For T2 tongue carcinoma, concepts are more uniform., Conclusion: These results demonstrate the lack of evidence and the controversy of different guidelines for the extent of safety margins and underline the crucial need of global prospective randomized trials on this topic to finally obtain evidence for a common guideline based on a strong community of OMFS units., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. All rights reserved.)

Coordinated activation of muscle stem cells (known as satellite cells) is critical for postnatal muscle growth and regeneration. The muscle stem cell niche is central for regulating the activation state of satellite cells, but the specific extracellular signals that coordinate this regulation are poorly understood. Here we show that macrophages at sites of muscle injury induce activation of satellite cells via expression of Adamts1. Overexpression of Adamts1 in macrophages in vivo is sufficient to increase satellite cell activation and improve muscle regeneration in young mice. We demonstrate that NOTCH1 is a target of ADAMTS1 metalloproteinase activity, which reduces Notch signaling, leading to increased satellite cell activation. These results identify Adamts1 as a potent extracellular regulator of satellite cell activation and have significant implications for understanding the regulation of satellite cell activity and regeneration after muscle injury.Satellite cells are crucial for growth and regeneration of skeletal muscle. Here the authors show that in response to muscle injury, macrophages secrete Adamts1, which induces satellite cell activation by modulating Notch1 signaling.

Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson's patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson's patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson's patients. In this report we tested the influence of two high-level cognitive states (cost of conflict and value of volition) that have recently been shown to cause predictable learning biases in healthy young adults as a function of dopamine receptor subtype and dopaminergic challenge. It was hypothesized that Parkinson's patients OFF medication would have an enhanced cost of conflict and a decreased value of volition, and that these effects would be remediated or reversed ON medication. Participants included N = 28 Parkinson's disease patients who were each tested ON and OFF dopaminergic medication and 28 age- and sex-matched controls. The expected cost of conflict effect was observed in Parkinson's patients OFF versus ON medication, but only in those that were more recently diagnosed (<5 years). We found an unexpected effect in the value of volition task: medication compromised the ability to learn from difficult a-volitional (instructed) choices. This novel finding was also enhanced in recently diagnosed patients. The difference in learning biases ON versus OFF medication between these two tasks was strongly correlated, bolstering the idea that they tapped into a common underlying imbalance in dopaminergic tone that is particularly variable in earlier stage Parkinsonism. The finding that these decision biases are specific to earlier but not later stage disease may offer a chance for future studies to quantify phenotypic expressions of idiosyncratic disease progression., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Platelet-derived growth factor receptor α (PDGFRα) exhibits divergent effects in skeletal muscle. At physiological levels, signalling through this receptor promotes muscle development in growing embryos and angiogenesis in regenerating adult muscle. However, both increased PDGF ligand abundance and enhanced PDGFRα pathway activity cause pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFRα in fibrosis, little is known about the cells through which this pathway acts. Here we show in mice that PDGFRα signalling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. We found that FAPs produce multiple transcriptional variants of Pdgfra with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signalling and to prevent FAP over-activation. Moreover, increasing the expression of this isoform limits fibrosis in vivo in mice, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem-cell populations.

Background: Bisphosphonate-associated osteonecrosis of the jaws (MRONJ/BP-ONJ/BRONJ) is a commonly seen disease. During recent decades, major advances in diagnostics have occurred. Once the clinical picture shows typical MRONJ features, imaging is necessary to determine the size of the lesion. Exposed bone is not always painful, therefore a thorough clinical examination and radiological imaging are essential when MRONJ is suspected., Methods: In this paper we will present the latest clinical update on the imaging options in regard to MRONJ: X-ray/Panoramic Radiograph, Cone Beam Computed Tomography (CBCT) and Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Nuclear Imaging, Fluorescence-Guided Bone Resection., Conclusion: Which image modality is chosen depends not only on the surgeon's/practitioner's preference but also on the available imaging modalities. A three-dimensional imaging modality is desirable, and in severe cases necessary, for extended resections and planning of reconstruction.

Salmonella Typhimurium (S.Tm) causes acute enteropathy resolving after 4-7 days. Strikingly, antibiotic therapy does not accelerate disease resolution. We screened for factors blocking remission using a S.Tm enterocolitis model. The antibiotic ciprofloxacin clears pathogen stool loads within 3-24 hr, while gut pathology resolves more slowly (ψ50: ∼48 hr, remission: 6-9 days). This delayed resolution is mediated by an interferon-γ (IFN-γ)-dependent response that is triggered during acute infection and continues throughout therapy. Specifically, IFN-γ production by mucosal T and NK cells retards disease resolution by maintaining signaling through the transcriptional regulator STAT1 and boosting expression of inflammatory mediators like IL-1β, TNF, and iNOS. Additionally, sustained IFN-γ fosters phagocyte accumulation and hampers antimicrobial defense mediated by IL-22 and the lectin REGIIIβ. These findings reveal a role for IFN-γ in delaying resolution of intestinal inflammation and may inform therapies for acute Salmonella enteropathy, chronic inflammatory bowel diseases, or disease resolution during antibiotic treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Microvascular surgery following tumor resection has become an important field of oral maxillofacial surgery (OMFS). Following the surveys on current reconstructive practice in German-speaking countries and Europe, this paper presents the third phase of the project when the survey was conducted globally., Methods: The DOESAK questionnaire has been developed via a multicenter approach with maxillofacial surgeons from 19 different hospitals in Germany, Austria and Switzerland. It was distributed in three different phases to a growing number of maxillofacial units in German-speaking clinics, over Europe and then worldwide., Results: Thirty-eight units from Germany, Austria and Switzerland, 65 remaining European OMFS-departments and 226 units worldwide responded to the survey. There is wide agreement on the most commonly used flaps, intraoperative rapid sections and a trend towards primary bony reconstruction. No uniform concepts can be identified concerning osteosynthesis of bone transplants, microsurgical techniques, administration of supportive medication and postoperative monitoring protocols. Microsurgical reconstruction is the gold standard for the majority of oncologic cases in Europe, but worldwide, only every second unit has access to this technique., Conclusion: The DOESAK questionnaire has proven to be a valid and well accepted tool for gathering information about current practice in reconstructive OMFS surgery. The questionnaire has been able to demonstrate similarities, differences and global inequalities., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

This study examines the associations between objective and subjective measurements and impressions of body shape and cold pressor pain reporting in healthy adults. On the basis of sexual selection theory (SST), we hypothesized that body characteristics that are universally preferred by the opposite sex-specifically, lower waist-to-hip ratios (WHR) in women and higher shoulder-to-hip ratios (SHR) in men-and characteristics (e.g., proportion of body fat in women) that infer attractiveness differently across cultures will correspond to higher experimental pain reporting in women and lower pain reporting in males. A convenience sample of young adults (n = 96, 58 females, 18-24 years; mean age = 19.4) was measured for body mass index (BMI), WHR, SHR, and subjective body impressions (SBI), along with cold pressor pain reporting. The findings showed that BMI was positively associated with WHR and less-positive SBI in both sexes. Consistent with SST, however, only BMI and WHR predicted variability in pain expression in women, whereas only SHR predicted variability in men. Subjective body impressions were positively associated with SHR among males and unrelated to WHR among females, yet only females showed a positive association between SBI and higher pain reporting. The findings suggest that sexually selected physical characteristics (WHR and SHR) and culturally influenced somatic (BMI) and psychological (SBI) indicators of attractiveness correspond with variability in pain reporting, potentially reflecting the general tendency for people to express clusters of sexually selected and culturally influenced traits that may include differential pain perception.

Background: This multicentre study aimed to investigate long-term radiographic and functional results following the treatment of condylar fractures using an angulated screwdriver system and open rigid internal fixation with an intraoral surgical approach., Methods: Twenty-nine patients with a total of 32 condylar fractures were evaluated. The patients were investigated prospectively based on the following variables: age, sex, aetiology, side, location and classification of the fracture, degree of displacement, associated fractures, surgical approach, oral health status, type of osteosynthesis plate, duration of surgery, mouth-opening, complications, and duration of follow-up., Results: The fractures were classified as subcondylar (n = 25) or condylar neck (n = 7). Mean patient age was 36.38 ± 16.60 years. The median duration of postoperative follow-up was 24.39 ± 13.94 months. No joint noise, weakness of the facial nerve, joint pain, or muscle pain was observed. An additional retromandibular approach was necessary to enable the treatment of one subcondylar fracture with medial displacement., Conclusion: Subcondylar or condylar neck fractures with medial or lateral displacement can be treated using an intraoral approach with satisfactory results with the advantages of the absence of visible scarring, the avoidance of facial nerve injury, and the ability to obtain rapid access to the fracture., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background. Separate lines of research have shown that menstrual cycling and contextual factors such as the gender of research personnel influence experimental pain reporting. Objectives. This study examines how brief, procedural interactions with female and male experimenters can affect experimentally reported pain (cold pressor task, CPT) across the menstrual cycle. Methods. Based on the menstrual calendars 94 naturally cycling women and 38 women using hormonal contraceptives (M age = 19.83,  SD = 3.09) were assigned to low and high fertility groups. This assignment was based on estimates of their probability of conception given their current cycle day. Experimenters (12 males, 7 females) engaged in minimal procedural interactions with participants before the CPT was performed in solitude. Results. Naturally cycling women in the high fertility group showed significantly higher pain tolerance (81 sec, d = .79) following interactions with a male but not a female experimenter. Differences were not found for women in the low fertility or contraceptive groups. Discussion. The findings illustrate that menstrual functioning moderates the effect that experimenter gender has on pain reporting in women. Conclusion. These findings have implications for standardizing pain measurement protocols and understanding how basic biopsychosocial mechanisms (e.g., person-perception systems) can modulate pain experiences.

Introduction: Microvascular surgery following tumour resection has become an important field of oral maxillofacial surgery (OMFS). This paper aims to evaluate current microsurgical practice in Europe., Methods: The questionnaire of the DOESAK collaborative group for Microsurgical Reconstruction was translated into English, transformed into an online based survey and distributed to 200 OMFS units with the aid of the European Association for Cranio-Maxillo-Facial Surgery (EACMFS)., Results: 65 complete and 72 incomplete questionnaires were returned. Hospitals from the United Kingdom, France, Italy, the Netherlands, Spain, Belgium, Greece, Slovenia and Lithuania participated. 71% of contributing centres were university hospitals, 87% out of these perform microvascular tumour surgery at least on a two-weekly base. Overall complication rate was at around five percent. Most frequently used transplants were the radial forearm flap and the fibular flap. The perioperative management varied widely. Success factors for flap survival, however, were uniformly rated, with the surgical skill being the most important factor, followed by the quality of postoperative management. Medication seems to play a less important role., Conclusion: Within Europe microvascular surgery is a common and safe procedure for maxillofacial reconstructive surgery in the field of OMFS. While there is a major accordance for the surgical procedure itself and the most frequently used flaps, perioperative management shows a wide variety of protocols with low presumed impact on surgical outcome., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Cleft lip and cleft palate are increasingly being detected by prenatal ultrasound, which raises the opportunity of using the patient's own osteogenicity from umbilical cord mesenchymal cells for bony repair. The authors address the growth of the cells under a fully defined and regulated protocol., Methods: Wharton jelly-derived mesenchymal stromal cells were isolated and expanded as a monolayer with defined serum-free medium. Osteoblastic differentiation was tested in the cells and in the entire Wharton jelly biopsy specimens. The serum-free-cultured cells were included in hydroxyapatite granule-fibrin constructs and, without predifferentiation, subcutaneously implanted into immunoincompetent mice., Results: Isolation and expansion of Wharton jelly-derived mesenchymal stromal cells were consistently successful under serum-free conditions, and the cells expressed standard mesenchymal stromal cell markers. The serum-free-cultivated cells produced a mineralized extracellular matrix under osteogenic differentiation, with a significant increase of osteoblastic lineage gene expression (Hox-A10 and Runx2) and an up-regulation of downstream osteogenic genes (OSX, OCN, ALPL, and BSP2). In vivo, they formed a dense matrix adjacent to the granules after 8 weeks, but no lamellar bone. serum-free-cultivated entire Wharton jelly biopsy specimens produced a mineralized extracellular matrix within the collagen matrix of the Wharton jelly., Conclusions: The osteogenic differentiation potential of Wharton jelly-derived mesenchymal stromal cells was maintained under serum-free isolation and expansion techniques. The cells without predifferentiation form a dense collagen matrix but not bone in vivo. Moreover, entire Wharton jelly biopsy specimens showed periosteal-like mineralization under osteogenic differentiation, which offers new options for autologous bone tissue engineering, including cleft palate surgery.

In vertebrates, activation of innate immunity is an early response to injury, implicating it in the regenerative process. However, the mechanisms by which innate signals might regulate stem cell functionality are unknown. Here, we demonstrate that type 2 innate immunity is required for regeneration of skeletal muscle after injury. Muscle damage results in rapid recruitment of eosinophils, which secrete IL-4 to activate the regenerative actions of muscle resident fibro/adipocyte progenitors (FAPs). In FAPs, IL-4/IL-13 signaling serves as a key switch to control their fate and functions. Activation of IL-4/IL-13 signaling promotes proliferation of FAPs to support myogenesis while inhibiting their differentiation into adipocytes. Surprisingly, type 2 cytokine signaling is also required in FAPs, but not in myeloid cells, for rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Stem cell quiescence, activation, and differentiation are governed by a complex network of molecular pathways. There has been a growing recognition that posttranscriptional modifications, such as alternative polyadenylation (APA) of transcripts, play an important role in regulating gene expression and function. Recent analyses of stem cell populations have suggested that APA controls stem cell fate and behavior. Here, we review recent developments that have shaped our understanding of the control of stem cell behavior by APA and we highlight promising areas for future investigation., (Published by Elsevier Ltd.)

The optimisation of the relation between quality of outcome and burden of care is difficult in the treatment of cleft lip and palate. We analysed long-term outcome after one-stage repair of clefts to assess the benefits and limitations of this form of treatment. Thirty-three patients aged 6-18 years who had had lip repair, two-flap palatoplasty, and corticocancellous alveolar bone grafts at 6 months of age were divided into three age groups (6-11, 12-14, and 15-18 years) and compared with mean outcome data from the Eurocleft centres and with cephalometric standards of healthy people. Fifteen of the 33 patients were assessed for nasalance. Maxillary protrusion (SNA) and intermaxillary relation (ANB) in the one-stage groups differed significantly from those of healthy people, but not from corresponding means in the Eurocleft study. In 61% the Bergland score for alveolar ossification was grade I or II, and in 15% it was grade III; 24% had secondary alveolar bone grafting. No palatal fistulas occurred and nasalance did not differ significantly from that of healthy controls. As each patient generally had a primary operation and one secondary procedure, they benefited from half the number of surgical steps of multistage procedures. However, one-stage procedures led to significant disturbance in growth, but the degree of this was similar to mean values of multistage procedures in the Eurocleft study. Primary alveolar bone grafting led to inconsistent alveolar ossification and was suspected to interfere with anterior maxillary growth so it has been abandoned., (Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Cleft lip repair aims to normalize the disturbed anatomy and function. The authors determined whether normalization of blood circulation is achieved., Methods: The authors measured the microcirculatory flow, oxygen saturation, and hemoglobin level in the lip and nose of controls (n = 22) and in patients with unilateral and bilateral cleft lip-cleft palate. The authors measured these parameters before lip repair (n = 29 and n = 11, respectively), at the end of lip repair (n = 27 and 10, respectively), and in the late postoperative period (n = 33 and n = 20, respectively). The arterial flow velocity was measured in unilateral groups at the same time points (n = 13, n = 11, and n = 12, respectively). Statistical differences were determined using analysis of variance., Results: Before surgery, the arterial flow velocities and microcirculation values were similar on each side of the face and between groups. The microcirculatory flow was significantly higher in the prolabium of bilateral patients than in the philtrum of controls. All circulation values in unilateral and bilateral patients in the late postoperative period were within the range of controls and of those before surgery. Intraoperatively, the authors consistently found a perforating artery on the superficial side of the transverse nasalis muscle., Conclusions: There appears to be no intrinsic circulatory deficit in unilateral and bilateral cleft lip-cleft palate patients. The increased flow in the prolabium indicates a strong hemodynamic need in this territory, compelling its vascular preservation. Whether surgical preservation of the nasalis perforator artery is of long-term benefit should be addressed in future studies., Clinical Question/level of Evidence: Therapeutic, V.

Mirroring of missing facial parts and rapid prototyping of templates have become widely used in the manufacture of prostheses. However, mirroring is not applicable for central facial defects, and the manufacture of a template still requires labour-intensive transformation into the final facial prosthesis. We have explored innovative techniques to meet these remaining challenges. We used a morphable model of a face for the reconstruction of missing facial parts that did not have mirror images, and skin-coloured polyamide laser sintering for direct manufacture of the prosthesis. From the knowledge gleaned from a data set of 200 coloured, three-dimensional scans, we generated a missing nose that was statistically compatible with the remaining parts of the patient's face. The planned prosthesis was manufactured directly from biocompatible skin-coloured polyamide powder by selective laser sintering, and the prosthesis planning system produced a normal-looking reconstruction. The polyamide will need adjustable colouring, and we must be able to combine it with a self-curing resin to fulfil the requirements of realistic permanent use., (Copyright © 2011 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: Bacterial cultures from nontraumatic brain abscesses (BAs) frequently contain oral bacteria. We assessed bacterial cultures from BAs and oral infective sources for a bacterial match., Study Design: Bacterial samples from brain abscesses and oral abscesses, and at sites with probing depths >or=3.5 mm were taken from 11 nontraumatic BA patients and analyzed., Results: Brain abscess bacterial cultures were obtained in 9 of the 11 cases, which revealed 5 cases of Streptococcus milleri group bacteria and 4 cases of subgingival flora. The bacteriologic results were interpreted taking all medical and bacteriologic findings into account, which made an oral origin of the BAs most likely in 6 of the 11 cases: from an oral abscess and from the subgingival flora in 3 cases each., Conclusions: Early collaboration between neurosurgeons, infectious disease specialists, and oral-maxillofacial surgeons will aid the identification and treatment of suspected oral sources of nontraumatic BAs.