Identification of circulating miRNAs as fracture-related biomarkers.

Fracture non-unions affect many patients worldwide, however, known risk factors alone do not predict individual risk. The identification of novel biomarkers is crucial for early diagnosis and timely patient treatment. This study focused on the identification of microRNA (miRNA) related to the process of fracture healing. Serum of fracture patients and healthy volunteers was screened by RNA sequencing to identify differentially expressed miRNA at various times after injury. The results were correlated to miRNA in the conditioned medium of human bone marrow mesenchymal stromal cells (BMSCs) during in vitro osteogenic differentiation. hsa-miR-1246, hsa-miR-335-5p, and miR-193a-5p were identified both in vitro and in fracture patients and their functional role in direct BMSC osteogenic differentiation was assessed. The results showed no influence of the downregulation of the three miRNAs during in vitro osteogenesis. However, miR-1246 may be involved in cell proliferation and recruitment of progenitor cells. Further studies should be performed to assess the role of these miRNA in other processes relevant to fracture healing.

[Rare differential diagnosis of an osteolytic lesion of the mandible in a young adult]. / Seltene Differenzialdiagnose bei osteolytischer Läsion des Unterkiefers einer jungen Erwachsenen.

We report a rarely occurring hematologic neoplasm in a young adult. Hematologic neoplasms were first described in 2008 and are now included in both accepted tumor classification systems, i.e., International Consensus Classification and World Health Organization. This hematologic neoplasm shows a characteristic ALK positivity in immunohistochemical examination and correspondingly, ALK fusion genes in the molecular analysis. Pathologists should be aware of this entity, particularly as it is challenging to differentiate from other more frequent neoplasms of the same disease group or mesenchymal neoplasm with ALK aberration.

Three-Dimensionally Cultured Jaw Periosteal Cells Attenuate Macrophage Activation of CD4+ T Cells and Inhibit Osteoclastogenesis.

The implementation of a successful therapeutic approach that includes tissue-engineered grafts requires detailed analyses of graft-immune cell interactions in order to predict possible immune reactions after implantation. The phenotypic plasticity of macrophages plays a central role in immune cell chemotaxis, inflammatory regulation and bone regeneration. The present study addresses effects emanating from JPC-seeded ß-TCP constructs (3DJPCs) co-cultivated with THP-1 derived M1/M2 macrophages within a horizontal co-culture system. After five days of co-culture, macrophage phenotype and chemokine secretion were analyzed by flow cytometry, quantitative PCR and proteome arrays. The results showed that pro-inflammatory factors in M1 macrophages were inhibited by 3DJPCs, while anti-inflammatory factors were activated, possibly affected by the multiple chemokines secreted by 3D-cultured JPCs. In addition, osteoclast markers of polarized macrophages were inhibited by osteogenically induced 3DJPCs. Functional assays revealed a significantly lower percentage of proliferating CD4+ T cells in the groups treated with secretomes from M1/M2 macrophages previously co-cultured with 3DJPCs compared to controls without secretomes. Quantifications of pit area resorption assays showed evidence that supernatants from 3DJPCs co-cultured with M1/M2 macrophages were able to completely suppress osteoclast maturation, compared to the control group without secretomes. These findings demonstrate the ability of 3D cultured JPCs to modulate macrophage plasticity.

Antibiotic prophylaxis and surgical site infections in orthognathic surgery - a retrospective analysis.

BACKGROUND: This study was conducted to determine surgical site infection (SSI) rates and potential risk factors as well as to evaluate antibiotic prophylaxis in orthognathic surgery. METHODS: This retrospective observational study included patients who received orthognathic surgery. SSIs and their management were assessed for up to one year post-operatively. The applied antibiotic regime and other possible influencing factors (smoking, age, site of infection, drainage, duration of surgery, displacement distances, craniofacial malformations) were assessed. RESULTS: In total 291 patient met the inclusion criteria (56.7% female). The mean age at surgery was 25.5 ± 8.5 years. Fifty-four patients (18.6%) were diagnosed with a craniofacial malformation. Relevant previous surgeries were documented in about one quarter of included patients (n = 75). Ninety-two percent of patients (n = 267) received intraoperative single-dose antibiotic prophylaxis. Surgical site infections occurred in 12.4% (n = 36) of patients. There was a significant association between postoperative infections and type of surgery (P = .037) as well as type of drainage (P = .002). Statistical analyses also revealed a higher prevalence of smokers (P = .036) and previous surgically assisted rapid palatal expansion (SARPE) (P = .018) in the infection group. Furthermore, no significant relationships were observed between postoperative infections and various co-factors (i.e. antibiotic regime, age at surgery, gender, associated craniofacial malformations, surgery duration, displacement distances, mandibular setback vs. advancement). CONCLUSION: Low rates of SSIs occurred following an intraoperative single-dose antibiotic regime. None of the SSIs had a significant effect on the final surgical outcome. Present data do not warrant escalation of the antibiotic regimen. Postoperative smoking and capillary drainage should be avoided.

Accuracy of full-guided vs. pilot-guided implant insertion - A prospective laboratory study in fifth-year dental students.

BACKGROUND: Education of undergraduates in implant dentistry has been extended. In order to assess the correct implant position, the accuracy of implant insertion using templates for pilot-drill guided and full-guided implant insertion was examined in a laboratory set-up in a cohort of undergraduates. METHODS: After three-dimensional planning of the implant position in partially edentulous mandibular models, individual templates for the pilot-drill guided or full-guided implant insertion in the region of the first premolar were produced. A total of 108 dental implants were inserted. The results of the radiographic evaluation of the three-dimensional accuracy were statistically analyzed. Furthermore, the participants completed a questionnaire. RESULTS: The deviation of the three-dimensional angle of the implants inserted fully guided was 2.74 ± 1.49 degrees compared to 4.59 ± 2.70 degrees for pilot-drill guided. The difference was statistically significant (p < 0.01). The returned questionnaires revealed a high interest in oral implantology and a positive evaluation of the hands-on course. CONCLUSIONS: In this study, the undergraduates benefited from applying full-guided implant insertion considering the accuracy in this laboratory examination. However, the clinical effects are not clear as the differences are within a small range. Based on the returned questionnaires, the implementation of practical courses in the undergraduate curriculum should be encouraged.

How osteogenic is dexamethasone?-effect of the corticosteroid on the osteogenesis, extracellular matrix, and secretion of osteoclastogenic factors of jaw periosteum-derived mesenchymal stem/stromal cells.

Dexamethasone (dexa) is commonly used to stimulate osteogenic differentiation of mesenchymal stem/stromal cells (MSCs) in vitro. However, it is paradoxical that glucocorticoids (GCs) such as dexa lead to bone loss and increased fracture risk in patients undergoing glucocorticoid therapy, causing glucocorticoid-induced osteoporosis (GIOP). In a recent publication, we demonstrated that osteogenic differentiation of progenitor cells isolated from jaw periosteal tissue (JPCs) does not depend on dexa, if the medium is supplemented with human platelet lysate (hPL) instead of fetal bovine serum (FBS). This allows the in vitro conditions to be much closer to the natural situation in vivo and enables us to compare osteogenic differentiation with and without dexa. In the present study, we demonstrate that the absence of dexa did not reduce mineralization capacity, but instead slightly improved the osteogenic differentiation of jaw periosteal cells. On the other hand, we show that dexa supplementation strongly alters the gene expression, extracellular matrix (ECM), and cellular communication of jaw periosteal cells. The secretome of periosteal cells previously treated with an osteogenic medium with and without dexa was used to investigate the changes in paracrine secretion caused by dexa. Dexa altered the secretion of several cytokines by jaw periosteal cells and strongly induced osteoclast differentiation of peripheral blood mononuclear cells (PBMCs). This study demonstrates how dexa supplementation can influence the outcome of in vitro studies and highlights a possible role of periosteal cells in the pathogenesis of glucocorticoid-induced osteoporosis. The methods used here can serve as a model for studying bone formation, fracture healing, and various pathological conditions such as (glucocorticoid-induced) osteoporosis, osteoarthritis, bone cancer, and others, in which the interactions of osteoblasts with surrounding cells play a key role.

Speech Development in Cleft Palate with and without Robin Sequence.

BACKGROUND: Robin sequence is defined as the triad of micrognathia, glossoptosis, and upper airway obstruction. In up to 85 percent, it is associated with cleft palate. Many studies have reported worse speech development in Robin sequence children after cleft palate repair. The authors investigated speech development in isolated Robin sequence with cleft palate versus children with cleft palate only at the age of 5 to 6 years. METHODS: All Robin sequence children were treated with the Tübingen palatal plate after birth. Data were collected using the German version of the Great Ormond Street Speech Assessment. Audio and video recordings were reviewed and analyzed separately by two blinded senior phoniatricians based on the German version of the Universal Reporting Parameters for Cleft Palate Speech, and scored to enable comparability of speech outcomes. RESULTS: Forty-four children (Robin sequence, n = 22; cleft palate only, n = 22) were included. Robin sequence children were significantly older at surgery (11.8 months versus 7.1 months; p < 0.001) but younger at study (70.5 months versus 75.2 months; p = 0.035). They also had more severe cleft of the palate (p = 0.006). All children studied showed good to very good speech development without serious impairment. None of the reported parameters on the German version of the Universal Reporting Parameters for Cleft Palate Speech showed significant group differences; the median total score in the Robin sequence group was 23 (interquartile range, 16.5 to 27.5) versus 19 (interquartile range, 17 to 23) in the cleft palate-only group. Statistical analysis revealed no significant effect of group (Z = -1.47; p = 0.14). CONCLUSIONS: No group differences in speech development were found at age 5 to 6 years. Isolated Robin sequence does not necessarily represent a risk for impaired speech development. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Three-Dimensional Quantification of Facial Asymmetry in Children with Positional Cranial Deformity.

BACKGROUND: The extent of facial involvement in positional plagiocephaly is only little investigated so far. Investigation methods that take into account the challenging anatomical conditions and growth of infants' faces are desirable. In this study, the authors established a new three-dimensional photogrammetry quantification method evaluating pretherapeutic and posttherapeutic facial asymmetry in positional plagiocephaly. Furthermore, a facial asymmetry index was established and evaluated. METHODS: Three-dimensional photographs of 100 children undergoing treatment with head orthoses were analyzed by constructing a standardized interindividual coordinate system. Defining landmarks, section planes, and point coordinates with a computer-aided design software, both sides of the faces were compared. Facial asymmetry was quantified by measuring differences between left and right sides and pretherapeutic and posttherapeutic changes in each patient. The facial asymmetry index was calculated by putting the absolute differences in relation with the coordinates of the nonaffected side. RESULTS: Present results indicate that positional plagiocephaly results in a distinct facial asymmetry (range, -3.8 to 9.6 mm) in nearly all spatial directions and facial regions. Helmet therapy led to a significant reduction (p < 0.05) of intraindividual facial asymmetry (median change in facial asymmetry index, -1.9 to 3.1 percent). However, no correlation of the Cranial Vault Asymmetry Index and facial asymmetry (Spearman rank correlation coefficient, ρ = -0.09 to 0.47) has been seen. According to these results, severe occipital deformation does not necessarily provoke distinct facial asymmetry. CONCLUSIONS: Present three-dimensional photogrammetry method allows the longitudinal quantification of facial involvement in positional plagiocephaly. Asymmetry has been determined in all facial regions. The facial asymmetry decreased through helmet therapy but was not eliminated completely.

Perioperative complications in cleft palate repair with Robin sequence following Tuebingen palatal plate treatment.

Our study aimed to evaluate perioperative complications following our institutional pre- and intraoperative management in cleft palate repair with Robin sequence (RS). RS patients who underwent cleft palate repair between 2000 and 2020 were retrospectively analysed. RS children with complete documentation and whose initial treatment involved the Tuebingen palatal plate (TPP) were included. Clinical records and operative charts were reviewed with regard to clinical characteristics as well as the neonatal and perioperative course. Results before and after adjustment of the anesthesiology protocol in 2014 were compared. 143 RS patients (41% male, 59% female) were included. Median pretherapeutic mixed-obstructive apnea index (MOAI) after birth was 9.4/hour (IQR 20.0). TPP treatment was associated with normalisation of the MOAI and adequate weight gain until surgery. At surgery, median age was 10 months (IQR 3), MOAI 0.1/h (IQR 0.5), and weight 8.7 kg (IQR 1.7). In 93% of cases (n = 133), the postoperative course was uneventful. Refinement of the anesthesiology protocol showed positive effects on the perioperative course and led to a reduction in perioperative events (10.7% vs. 2.9%). No severe perioperative complications occurred. We recommend the adoption of TPP treatment in the therapy of RS children. Our favourable results show that early TPP treatment minimizes perioperative complications in cleft palate repair by effectively and sustainably correcting upper airway obstruction.

Fungus Ball of the Maxillary Sinus-Modern Treatment by Osteoplastic Approach and Functional Endoscopic Sinus Surgery.

PURPOSE: Functional endoscopic sinus surgery (FESS) is considered standard surgical therapy for fungus ball of the maxillary sinus. However, recent findings have indicated an odontogenic etiology, which requires simultaneous treatment of the dental origin. This study presents the authors' treatment results of fungus ball of the maxillary sinus using a combination of FESS and an endoscopically assisted osteoplastic approach through the anterior wall of the maxillary sinus, enabling simultaneous treatment of the dental origin. MATERIALS AND METHODS: A cohort of 22 patients with histopathologically confirmed fungus ball of the maxillary sinus was retrospectively analyzed. Clinical records and medical imaging data were reviewed to evaluate the etiology, clinical and radiologic findings, and postoperative outcome. RESULTS: Only 15 patients presented nonspecific clinical symptoms compatible with chronic unilateral maxillary sinusitis. Computed tomography visualized complete opacity of the maxillary sinus in 11 patients and intralesional hyperdensity in 12 patients. An odontogenic association was verified in 18 patients. Twenty-one patients underwent endoscopically assisted osteoplastic surgery through the anterior maxillary sinus wall. In 12 cases, the assumed persistent odontogenic source was treated simultaneously. Depending on the patency of the ostiomeatal complex, the accompanying chronic sinusitis was treated by FESS. CONCLUSIONS: The present data support the assumption of an odontogenic etiology of fungus ball of the maxillary sinus. Hence, surgical management requires simultaneous treatment of the fungal mass, the odontogenic origin of the disease, and the accompanying chronic sinusitis. To properly treat fungus ball, the authors present a modern treatment concept, using a minimally invasive endoscopically assisted osteoplastic approach through the anterior maxillary wall, for sufficient and necessary surgical treatment.

Isolated gluteal metastasis 3 years after sufficiently treated oral squamous cell carcinoma: Case report and literature review.

Metastases from oral squamous cell carcinoma usually occur in the cervical lymph nodes. Distant skeletal muscle metastases are exceedingly rare and have been reported only in sporadic cases. A 70-year-old male patient was diagnosed with nonmetastatic oral squamous cell carcinoma (pT4a, N0, M0). The patient underwent successful surgical treatment involving tumor resection and selective neck dissection of both sides, including adjuvant radiotherapy. After 3 years of uneventful course, with no clinical or radiographic evidence for local recurrence or metastasis, an isolated distant metastasis in the gluteal muscles was diagnosed. The patient died 7 months after diagnosis despite further surgical resection and adjuvant chemotherapy. Distant metastases are mostly accompanied by systemic spread of tumor cells. Thus, the prognosis is generally very poor. The therapeutic concept of surgical tumor resection and adjuvant chemotherapy failed to significantly improve the patient's prognosis in the present case.

A prospective histomorphometric and cephalometric comparison of bovine bone substitute and autogenous bone grafting in Le Fort I osteotomies.

PURPOSE: The aim of the present study was the histomorphometric and cephalometric comparison of autogenous bone grafting of the anterior iliac crest and the application of bovine bone substitute concerning new bone formation and postoperative stability in patients undergoing orthognathic Le Fort I osteotomy. PATIENTS AND METHODS: Twenty-five patients requiring orthognathic surgery with Le Fort I osteotomy were included in this study. Patients were randomly divided into three groups receiving either autogenous iliac crest BONE grafting (BONE; n = 8) or xenogenic bovine bone grafting (Bio-Oss®) in INTER (n = 12) or in ONLAY (n = 5) position. Histomorphometric analysis was performed using trephine bone biopsies from the autogenous, respectively xenogenic bone grafting region. Postoperative stability was evaluated using teleradiographies of three different timepoints. RESULTS: All groups showed comparable mineralized fractions in bone biopsies of 50.2% (±13.2%) INTER, 46.48% (±12.3%) ONLAY and 57.1% (±20.6%) BONE as well as comparable percentage of connective tissue. Patients in the INTER-group revealed the lowest relapse rate of 20.5% (INTER) compared to 30.3% (ONLAY) and 33.0% (BONE). All groups underwent comparable maxillary advancement and healing time. CONCLUSIONS: Present results indicate that block shaped bovine bone substitute is a promising alternative to autogenous bone grafting to bridge the Le Fort I osteotomy gap in orthognathic surgery.

Three-dimensional accuracy of mandibular reconstruction by patient-specific pre-bent reconstruction plates using an "in-house" 3D-printer.

PURPOSE: The purpose of this study was to compare the three-dimensional accuracy of mandibular reconstruction following mandible continuity resection in patients treated with patient-specific, pre-bent reconstruction plates, using an 'in-house' 3D printer, with that in patients treated with conventional, intraoperatively bent plates. PATIENTS AND METHODS: We retrospectively analyzed 42 alloplastic mandibular reconstructions following continuity resection. 21 patients received patient-specific, pre-bent reconstruction plates using an in-house 3D printer. The control group consisted of 21 patients provided with intraoperatively bent reconstruction plates. Distances between corresponding anatomical landmarks on the mandibular angle and condyle (A-A', BB', CC', BC'), as well as the intercondylar angle (ICA), were measured and compared on the pre- and postoperative CT scans. RESULTS: Multivariate analysis of variance (MANOVA) showed significant multivariate main effect of group (F(5, 36) = 5.58, p = 0.001; Wilks lambda 0.564; partial η2 = 0.436), indicating more accurate postoperative results for the pre-bent group. Post-hoc comparison revealed significantly larger postoperative deviation in the distances between the mandibular angle and the intercondylar angle (ICA) for the intraoperatively bent group in comparison with the pre-bent group. However, there was no significant effect on the distance between the condyles. CONCLUSIONS: Mandibular reconstructions employing patient-specific, pre-bent reconstruction plates made using an in-house 3D printer show significantly better three-dimensional accuracy compared with intraoperatively bent plates. The described method prevents rotational error of the mandibular angle and improves restoration of the physiological intercondylar angle in mandible reconstruction after continuity resection.

Health-related quality of life in cleft lip and/or palate patients - A cross-sectional study from preschool age until adolescence.

PURPOSE: Cleft lip and/or palate (CLP) is the most common congenital craniofacial anomaly. Multiple operations, long-lasting supplementary treatments, as well as impaired functional and esthetic outcome might have a negative impact on patients' social-emotional functioning and self-esteem, resulting in a lower health-related quality of life (HRQoL). PATIENTS AND METHODS: This cross-sectional study aimed to evaluated CLP patients' HRQoL from preschool age (4 years) until adolescence (18 years) using the age-specific German KINDLR questionnaire. We compared self-reports and parent proxy-reports, as well as reference values from an age-matched German norm population. Multivariate analysis was applied to identify mediating factors, e.g. cleft type, age, and gender. Additionally, a KINDSCREEN-10 questionnaire was used to implement a screening tool in the clinical routine. RESULTS: In total, 134 participants (average age 9.0 ± 3.8 years; 47.8% female) were included. Compared with German normative data, the evaluation revealed a significantly higher 'total QoL' in all self-report groups (Kiddy-, Kid-, Kiddo-KINDLR) and a significantly higher proxy rating for children aged 7-13 years. Multivariate analysis verified a significant disparity between self-reports and parents' conceptions of HRQoL, as well as a deterioration of the ratings with increasing age. No significant effects of other contributing factors, e.g. cleft type and gender, were found. The KIDSCREEN-10 questionnaire successfully confirmed these findings. CONCLUSIONS: Surprisingly, our survey revealed a higher HRQoL in cleft patients compared with normative data from healthy controls. But because the return rate of the forwarded questionnaire was low, this may have contributed to bias. Keeping this in mind, we may conclude at least that the HRQoL in our cleft patients was not significantly lower than in healthy children. On the other hand, it can be assumed that the special attention of the parents and the support from speech therapy and other medical professionals may have contributed to a positive effect on family interaction, communication skills, and self-esteem.

Donor site morbidity of the anterolateral thigh flap.

INTRODUCTION: The purpose of this study was to investigate donor site morbidity after reconstruction of defects in the head and neck region with an anterolateral thigh (ALT) flap. METHODS: From 07/2006 to 12/2015 the anterolateral thigh flap was used for reconstruction of large intra- or extraoral defects in 138 patients. The donor sites were available to examine for morbidity in 51 patients (36.7%). All patients completed a standardized questionnaire, received a physical examination, and underwent isokinetic muscle exercises of the lower extremity with a Dynamometer. RESULTS: The average postoperative follow-up was 29 months and showed significant donor site morbidity in the form of sensory disturbance as well as revealing significant differences in extension and flexion between donor and normal thighs in the isokinetic power test. Range of motion at the hip and knee was moderately compromised. CONCLUSION: The results of this study suggest that dissection of the musculocutaneous perforators can compromise the function of vastus lateralis, which is the largest compartment of the quadriceps group. This could also affect the antagonistic muscles such as the semitendinosus, semimembranosus and biceps femoris. Because of its versatility, adequate tissue stock, possibility of simultaneous two-team approach large and long pedicle and minimal donor site morbidity, the ALT flap has become one of the most preferred transplants for soft tissue reconstruction in the head and neck region. Most authors described the donor site morbidity as minimal (Song et al. 1984; Wolff et al., 2006; Xu et al., 1988; Kimata et al., 1997; Kuo et al., 2001; Collins et al., 2012). In summary, the study shows that functional impairment of the donor thigh can occur but does not affect the patients in their daily life.