Improving material properties of a poloxamer P407 hydrogel-based hydroxyapatite bone substitute material by adding silica-A comparative in vivo study.

The structure and handling properties of a P407 hydrogel-based bone substitute material (BSM) might be affected by different poloxamer P407 and silicon dioxide (SiO2) concentrations. The study aimed to compare the mechanical properties and biological parameters (bone remodeling, BSM degradation) of a hydroxyapatite: silica (HA)-based BSM with various P407 hydrogels in vitro and in an in vivo rat model. Rheological analyses for mechanical properties were performed on one BSM with an SiO2-enriched hydrogel (SPH25) as well on two BSMs with unaltered hydrogels in different gel concentrations (PH25 and PH30). Furthermore, the solubility of all BSMs were tested. In addition, 30 male Wistar rats underwent surgical creation of a well-defined bone defect in the tibia. Defects were filled randomly with PH30 (n = 15) or SPH25 (n = 15). Animals were sacrificed after 12 (n = 5 each), 21 (n = 5 each), and 63 days (n = 5 each). Histological evaluation and histomorphometrical quantification of new bone formation (NB;%), residual BSM (rBSM;%), and soft tissue (ST;%) was conducted. Rheological tests showed an increased viscosity and lower solubility of SPH when compared with the other hydrogels. Histomorphometric analyses in cancellous bone showed a decrease of ST in PH30 (p = .003) and an increase of NB (PH30: p = .001; SPH: p = .014) over time. A comparison of both BSMs revealed no significant differences. The addition of SiO2 to a P407 hydrogel-based hydroxyapatite BSM improves its mechanical stability (viscosity, solubility) while showing similar in vivo healing properties compared to PH30. Additionally, the SiO2-enrichment allows a reduction of poloxamer ratio in the hydrogel without impairing the material properties.

[Surgical emergencies during the COVID-19 pandemic]. / Chirurgische Notfälle während der COVID-19-Pandemie.

BACKGROUND: Within a few months coronavirus disease 2019 (COVID-19) spread around the world. Some studies showed a significant reduction in medical consultations. Due to new discussions about restrictions in the case of rising COVID-19 case numbers, this study investigated the consequences of the COVID-19 pandemic on surgical emergencies at the Rostock University Medical Center and compared the results to the years before. MATERIAL AND METHODS: The aim of the study was to compare the case numbers of the surgical emergency department of the Rostock University Medical Center from the period 2020 and 2021 to the years before (2018, 2019). Furthermore, the consequences of COVID-19 case numbers for the case numbers of the surgical emergency department were investigated. RESULTS: A total of 74,936 patient cases could be included in this study. The results showed a significant reduction of surgical emergencies during the COVID-19 pandemic (p < 0.001). There was a significant negative correlation with the COVID-19 case numbers (p < 0.001). The restrictions of the government showed a direct influence on COVID-19 case numbers and emergency visits. CONCLUSION: The results showed a correlation of COVID-19 case numbers with the case numbers of the surgical emergency department. Due to difficult workforce planning during a pandemic, this can be important information for workforce management in similar future events.

Combining Electrostimulation with Impedance Sensing to Promote and Track Osteogenesis within a Titanium Implant.

(1) Background: Electrical stimulation is a promising alternative to promote bone fracture healing but with the limitation of tracking the osteogenesis progress in vivo. To overcome this issue, we present an opportunity to combine the electrical stimulation of a commercial titanium implant, which promotes osteogenesis within the fracture, with a real-time readout of the osteogenic progress by impedance sensing. This makes it possible to adjust the electrical stimulation modalities to the individual patient's fracture healing process. (2) Methods: In detail, osteogenic differentiation of several cell types was monitored under continuous or pulsatile electrical stimulation at 0.7 V AC/20 Hz for at least seven days on a titanium implant by electric cell-substrate impedance sensing (ECIS). For control, chemical induction of osteogenic differentiation was induced. (3) Results: The most significant challenge was to discriminate impedance changes caused by proliferation events from those initiated by osteogenic differentiation. This discrimination was achieved by remodeling the impedance parameter Alpha (α), which increases over time for pulsatile electrically stimulated stem cells. Boosted α-values were accompanied by an increased formation of actin stress fibers and a reduced expression of the focal adhesion kinase in the cell periphery; morphological alterations known to occur during osteogenesis. (4) Conclusions: This work provided the basis for developing an effective fracture therapy device, which can induce osteogenesis on the one hand, and would allow us to monitor the induction process on the other hand.

Adjuvant Radiotherapy in Patients with Squamous Cell Carcinoma of the Oral Cavity or Oropharynx and Solitary Ipsilateral Lymph Node Metastasis (pN1)-A Prospective Multicentric Cohort Study.

(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55-1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15-0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19-0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.

CT imaging-based approaches to cochlear duct length estimation-a human temporal bone study.

OBJECTIVES: Knowledge about cochlear duct length (CDL) may assist electrode choice in cochlear implantation (CI). However, no gold standard for clinical applicable estimation of CDL exists. The aim of this study is (1) to determine the most reliable radiological imaging method and imaging processing software for measuring CDL from clinical routine imaging and (2) to accurately predict the insertion depth of the CI electrode. METHODS: Twenty human temporal bones were examined using different sectional imaging techniques (high-resolution computed tomography [HRCT] and cone beam computed tomography [CBCT]). CDL was measured using three methods: length estimation using (1) a dedicated preclinical 3D reconstruction software, (2) the established A-value method, and (3) a clinically approved otosurgical planning software. Temporal bones were implanted with a 31.5-mm CI electrode and measurements were compared to a reference based on the CI electrode insertion angle measured by radiographs in Stenvers projection (CDLreference). RESULTS: A mean cochlear coverage of 74% (SD 7.4%) was found. The CDLreference showed significant differences to each other method (p < 0.001). The strongest correlation to the CDLreference was found for the otosurgical planning software-based method obtained from HRCT (CDLSW-HRCT; r = 0.87, p < 0.001) and from CBCT (CDLSW-CBCT; r = 0.76, p < 0.001). Overall, CDL was underestimated by each applied method. The inter-rater reliability was fair for the CDL estimation based on 3D reconstruction from CBCT (CDL3D-CBCT; intra-class correlation coefficient [ICC] = 0.43), good for CDL estimation based on 3D reconstruction from HRCT (CDL3D-HRCT; ICC = 0.71), poor for CDL estimation based on the A-value method from HRCT (CDLA-HRCT; ICC = 0.29), and excellent for CDL estimation based on the A-value method from CBCT (CDLA-CBCT; ICC = 0.87) as well as for the CDLSW-HRCT (ICC = 0.94), CDLSW-CBCT (ICC = 0.94) and CDLreference (ICC = 0.87). CONCLUSIONS: All approaches would have led to an electrode choice of rather too short electrodes. Concerning treatment decisions based on CDL measurements, the otosurgical planning software-based method has to be recommended. The best inter-rater reliability was found for CDLA-CBCT, for CDLSW-HRCT, for CDLSW-CBCT, and for CDLreference. KEY POINTS: • Clinically applicable calculations using high-resolution CT and cone beam CT underestimate the cochlear size. • Ten percent of cochlear duct length need to be added to current calculations in order to predict the postoperative CI electrode position. • The clinically approved otosurgical planning software-based method software is the most suitable to estimate the cochlear duct length and shows an excellent inter-rater reliability.

Lips and noses in 10-year old patients with repaired complete unilateral clefts of lip, alveolus, and palate. A prospective three-centre study of the Baltic Cleft Network.

This multicenter study aimed at comparing different techniques of lip and nose repair with or without NAM and primary anterior rhinoplasty in pre-adolescent children. Patients with unilateral clefts of lip, alveolus, and palate who had undergone cleft lip and nose repair were evaluated in a prospective three-centre study using standardized monochromatic, cropped photographs. Four cleft surgeons evaluated the aesthetics of the central part of the face when the patients had reached age ten years. Seventy-six sets of photographs out of 87 patients were evaluated. The overall ratings of lips and noses did not differ much between centres. However, noses of centres 1 (mean 0.74; SD 0.57) and 2 (mean 0.76; SD 0.60) had been rated better than centre 3 (mean 1.32; SD 0.78; p = 0.0078), especially "Deformation of upper part of nostril rim or poor position of alar cartilage". Centre 3 had produced better looking scars (mean 0.33; SD 0.48); p = 0.0036. Within the limitations of the study it seems that NAM and primary anterior rhinoplasty including postoperative nasal stents should be performed whenever possible in order to achieve a favorable shape of the nose and to reduce the need for secondary corrective surgery.

An optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications.

A clinical implementation of cell-based bone regeneration in combination with scaffold materials requires the development of efficient, controlled and reproducible seeding procedures and a tailor-made bioreactor design. A perfusion system for efficient, homogeneous, and rapid seeding with human adipogenic stem cells in bone substitute scaffolds was designed. Variants concerning medium inlet and outlet port geometry, i.e. cylindrical or conical diffuser, cell concentration, perfusion mode and perfusion rates were simulated in silico. Cell distribution during perfusion was monitored by dynamic [18F]FDG micro-PET/CT and validated by laser scanning microscopy with three-dimensional image reconstruction. By iterative feedback of the in silico and in vitro experiments, the homogeneity of cell distribution throughout the scaffold was optimized with adjustment of flow rates, cell density and perfusion properties. Finally, a bioreactor with a conical diffusor geometry was developed, that allows a homogeneous cell seeding (hoover coefficient: 0.24) in less than 60 min with an oscillating perfusion mode. During this short period of time, the cells initially adhere within the entire scaffold and stay viable. After two weeks, the formation of several cell layers was observed, which was associated with an osteogenic differentiation process. This newly designed bioreactor may be considered as a prototype for chairside application.

Prospective clinical implementation of optional implant treatment into pregraduate dental education-mini implants for retention and support of mandibular overdentures.

BACKGROUND: The primary aim of the study was to evaluate mini implant (MDI) survival, prosthodontic maintenance, and patient-reported outcome measures after conducting an optional pregraduate academic course on patients with mandibular edentulism including fabrication of overdentures and MDI planning and placement as well as chair-side incorporation of the respective restauration. In a prospective clinical study, 20 patients received 80 MDIs that were restored with mandibular overdentures. All treatment steps including placement of 40 MDIs were conducted by undergraduate students under strict guidance of a consultant. Next to students' perceptions after participation, survival of MDIs, and prosthodontic maintenance, patients' perceptions as well as peri-implant parameters were assessed after 4 weeks and 3 and 12 months. RESULTS: Three MDIs fractured (two during insertion and one after 3 months; total survival 96.25%). Two overdentures fractured and a total of 23 cases of minor prosthodontic maintenance were required. Over time, patients' satisfaction significantly increased. Besides, questionnaires showed a high rate of students' positive perception and high self-confidence to include MDI therapy into own practice. CONCLUSIONS: The results are in accordance to those reported by postgraduate dentists. In accordance, therapy with MDI-retained mandibular overdentures seems to be feasible and successful at pregraduate level if the students receive guidance.

Establishment and characterization of patient-derived head and neck cancer models from surgical specimens and endoscopic biopsies.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is heterogeneous in etiology, phenotype and biology. Patient-derived xenografts (PDX) maintain morphology and molecular profiling of the original tumors and have become a standard "Avatar" model for human cancer research. However, restricted availability of tumor samples hindered the widespread use of PDX. Most PDX-projects include only surgical specimens because reliable engraftment from biopsies is missing. Therefore, sample collection is limited and excludes recurrent and metastatic, non-resectable cancer from preclinical models as well as future personalized medicine. METHODS: This study compares the PDX-take rate, -growth, histopathology, and molecular characteristics of endoscopic specimens with surgical specimens. HNSCC samples (n = 55) were collected ad hoc, fresh frozen and implanted into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice. RESULTS: Engraftment was successful in both sample types. However, engraftment rate was lower (21 vs. 52%) and growth delayed (11.2 vs. 6.7 weeks) for endoscopic biopsies. Following engraftment, growth kinetic was similar. Comparisons of primary tumors and corresponding PDX models confirmed preservation of histomorphology (HE histology) and molecular profile (Illumina Cancer Hotspot Panel) of the patients' tumors. Accompanying flow cytometry on primary tumor specimens revealed a heterogeneous tumor microenvironment among individual cases and identified M2-like macrophages as positive predictors for engraftment. Vice versa, a high PD-L1 expression (combined positive score on tumor/immune cells) predicted PDX rejection. CONCLUSION: Including biopsy samples from locally advanced or metastatic lesions from patients with non-surgical treatment strategies, increases the availability of PDX for basic and translational research. This facilitates (pre-) clinical studies for individual response prediction based on immunological biomarkers.

Sustainable Surface Modification of Polyetheretherketone (PEEK) Implants by Hydroxyapatite/Silica Coating-An In Vivo Animal Study.

Polyetheretherketone (PEEK) has the potential to overcome some of the disadvantages of titanium interbody implants in anterior cervical and discectomy and fusion (ACDF). However, PEEK shows an inferior biological behavior regarding osseointegration and bioactivity. Therefore, the aim of the study was to create a bioactive surface coating on PEEK implants with a unique nanopore structure enabling the generation of a long-lasting interfacial composite layer between coating material and implant. Seventy-two PEEK implants-each thirty-six pure PEEK implants (PI) and thirty-six PEEK implants with a sprayed coating consisting of nanocrystalline hydroxyapatite (ncHA) embedded in a silica matrix and interfacial composite layer (SPI)-were inserted in the femoral condyles of adult rats using a split-side model. After 2, 4 and 8 weeks, the femur bones were harvested. Half of the femur bones were used in histological and histomorphometrical analyses. Additionally, pull-out tests were performed in the second half. Postoperative healing was uneventful for all animals, and no postoperative complications were observed. Considerable crestal and medullary bone remodeling could be found around all implants, with faster bone formation around the SPI and fewer regions with fibrous tissue barriers between implant and bone. Histomorphometrical analyses showed a higher bone to implant contact (BIC) in SPI after 4 and 8 weeks (p < 0.05). Pull-out tests revealed higher pull-out forces in SPI at all time points (p < 0.01). The presented findings demonstrate that a combination of a bioactive coating and the permanent chemical and structural modified interfacial composite layer can improve bone formation at the implant surface by creating a sustainable bone-implant interface. This might be a promising way to overcome the bioinert surface property of PEEK-based implants.

Mechanical Characterization of Human Trabecular and Formed Granulate Bone Cylinders Processed by High Hydrostatic Pressure.

One main disadvantage of commercially available allogenic bone substitute materials is the altered mechanical behavior due to applied material processing, including sterilization methods like thermal processing or gamma irradiation. The use of high hydrostatic pressure (HHP) might be a gentle alternative to avoid mechanical alteration. Therefore, we compressed ground trabecular human bone to granules and, afterwards, treated them with 250 and 300 MPa for 20 and 30 min respectively. We characterized the formed bone granule cylinders (BGC) with respect to their biomechanical properties by evaluating stiffness and stress at 15% strain. Furthermore, the stiffness and yield strength of HHP-treated and native human trabecular bone cylinders (TBC) as control were evaluated. The mechanical properties of native vs. HHP-treated TBCs as well as HHP-treated vs. untreated BGCs did not differ, independent of the applied HHP magnitude and duration. Our study suggests HHP treatment as a suitable alternative to current processing techniques for allogenic bone substitutes since no negative effects on mechanical properties occurred.

Complications or rather side effects? Quantification of patient satisfaction and complications after orthognathic surgery-a retrospective, cross-sectional long-term analysis.

OBJECTIVES: The aim of this clinical analysis was to evaluate intraoperative and early postoperative complications as well as late findings and the overall patient satisfaction following orthognathic surgery. MATERIALS AND METHODS: In a retrospective, cross-sectional study, 119 patients after orthognathic surgery were included. Surgical approaches were single bilateral sagittal split osteotomy (BSSO (n = 52)), single LeFort-I osteotomy (n = 5) and bimaxillary osteotomy (LeFort-I + BSSO (n = 62)). Intraoperative and early (0-4 weeks postoperative) complications were investigated retrospectively (n = 119), whereas late findings and quality of life were assessed via clinical follow-up and survey (mean: 59 months postoperative) on 48 patients. RESULTS: Bad split (n = 4/114) was the most common intraoperative complication followed by one case of severe bleeding. Regarding early postoperative complications, temporary damage of the inferior alveolar nerve after BSSO was most common (n = 33/114), followed by facial nerve dysfunction (n = 3), failed osteosynthesis (n = 2) and one case of postoperative dyspnoea. Permanent hypaesthesia of the lower lip was the most prevalent (n = 28/45(BSSO and LeFort-I + BSSO)) late finding with varying extent, followed by temporomandibular dysfunction (TMD) (n = 25/48). Skeletal relapse mostly occurred after class II treatment, followed by class III, posterior crossbite and open bite. Overall, the surgery improved the patients' self-perception (85.4%), with 60.4% of patients opting for surgery again. CONCLUSIONS: Long-term complications after orthognathic surgery occurred more frequently than commonly described in the literature, and analyses of the quality of life show the need for more comprehensive preoperative patient education. CLINICAL RELEVANCE: Hypaesthesia of the lower lip presented less as complication but rather as side effect following BSSO. As orthognathic surgery is mostly elective, preoperative patient education is of pivotal importance and should include proactive risk stratification.

Continuous Electrical Stimulation Affects Initial Growth and Proliferation of Adipose-Derived Stem Cells.

The aim of the study was to establish electrical stimulation parameters in order to improve cell growth and viability of human adipose-derived stem cells (hADSC) when compared to non-stimulated cells in vitro. hADSC were exposed to continuous electrical stimulation with 1.7 V AC/20 Hz. After 24, 72 h and 7 days, cell number, cellular surface coverage and cell proliferation were assessed. In addition, cell cycle analysis was carried out after 3 and 7 days. After 24 h, no significant alterations were observed for stimulated cells. At day 3, stimulated cells showed a 4.5-fold increase in cell numbers, a 2.7-fold increase in cellular surface coverage and a significantly increased proliferation. Via cell cycle analysis, a significant increase in the G2/M phase was monitored for stimulated cells. Contrastingly, after 7 days, the non-stimulated group exhibited a 11-fold increase in cell numbers and a 4-fold increase in cellular surface coverage as well as a significant increase in cell proliferation. Moreover, the stimulated cells displayed a shift to the G1 and sub-G1 phase, indicating for metabolic arrest and apoptosis initiation. In accordance, continuous electrical stimulation of hADSC led to a significantly increased cell growth and proliferation after 3 days. However, longer stimulation periods such as 7 days caused an opposite result indicating initiation of apoptosis.

Collagen membranes of dermal and pericardial origin-In vivo evolvement of vascularization over time.

Aim of the study was to compare the evolvement of vascularization over time of collagen membranes (CMs) of dermal and pericardial origin in an in vivo animal study. Twenty-eight mice underwent implantation of three commercially available CM derived from porcine dermis (homogenous structure: CM1 (Control 1) and bilayer structure: CM2 [Control 2]), from porcine pericardium (CM3; Test 1) as well as CM3 sprayed with silica-enhanced nanostructured hydroxyapatite (CM4, Test 2). After 3, 6, 9, and 12 days, intravital fluorescence microscopy was conducted for determination of capillary diameter, density, flow, and length. At Day 12, samples were examined immunohistologically for expression of fibroblast growth factor receptor 4 (FGFR4), CD11b, CD68, αSMA, and CD34. In all CM, intravital fluorescence microscopy over time showed increasing values for all parameters with the highest levels in CM4 and the lowest values in CM1. Significant lower amounts of FGFR4, CD11b, and CD68 were detected in CM4 when compared to CM2 (p < .05). In contrast to CM3, lower values of αSMA and higher numbers of CD34 positive-marked vessels were observed in CM4 (p < .05). In conclusion, dermal bilayer as well as pericardial CM seem to have a higher vascularization rate than dermal homogenous CM. Additional coating of pericardial CM with a silica-enhanced hydroxyapatite increases the speed of vascularization as well as biological remodeling processes.

S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - update 2018.

Merkel cell carcinoma (MCC, ICD-O M8247 / 3) is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. The neoplastic cells share many morphological, immunohistochemical and ultrastructural characteristics with Merkel cells of the skin. The diagnosis of MCC is rarely made on clinical grounds. Histological and immunohistochemical studies are usually required to confirm the clinical suspicion. Given the frequent occurrence of occult lymph node metastasis, sentinel lymph node biopsy should be performed once distant metastasis has been ruled out by cross-sectional imaging. Primary tumors without evidence of organ metastases are treated with complete surgical excision with appropriate surgical margins. Radiation therapy should be considered at all stages of the disease. For advanced MCC that is no longer amenable to curative treatment by surgery or radiation therapy, there is currently no established systemic therapy for which an improvement in recurrence-free survival or overall survival has been demonstrated in a prospective randomized trial. However, immunotherapy using PD-1/PD-L1 blockade seems to be superior to chemotherapy. Various factors warrant that further diagnostic and therapeutic interventions be determined by an interdisciplinary tumor board. These factors include the tumor's aggressiveness, the frequent indication for sentinel lymph node biopsy along with the frequent occurrence in the head and neck region, the potential indication for adjuvant radiation therapy as well as the complexity of the required diagnostic workup.

Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer.

BACKGROUND: The eighth international symposium for sentinel node biopsy (SNB) in head and neck cancer was held in 2018. This consensus conference aimed to deliver current multidisciplinary guidelines. This document focuses on the surgical aspects of SNB for oral cancer. METHOD: Invited expert faculty selected topics requiring guidelines. Topics were reviewed and evidence evaluated where available. Data were presented at the consensus meeting, with live debate from panels comprising expert, nonexpert, and patient representatives followed by voting to assess the level of support for proposed recommendations. Evidence review, debate, and voting results were all considered in constructing these guidelines. RESULTS/CONCLUSION: A range of topics were considered, from patient selection to surgical technique and follow-up schedule. Consensus was not achieved in all areas, highlighting potential issues that would benefit from prospective studies. Nevertheless these guidelines represent an up-to-date pragmatic recommendation based on current evidence and expert opinion.

S2k Guidelines for Cutaneous Basal Cell Carcinoma - Part 2: Treatment, Prevention and Follow-up.

Basal cell carcinoma (BCC) is the most common malignant tumor among fair-skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow-up of patients with basal cell carcinoma.