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1.
  • Li, Peishun, 1988, et al. (författare)
  • Metabolic Alterations in Older Women With Low Bone Mineral Density Supplemented With Lactobacillus reuteri
  • 2021
  • Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 5:4
  • Tidskriftsartikel (refereegranskat)abstract
    • JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. Osteoporosis and its associated fractures are highly prevalent in older women. Recent studies have shown that gut microbiota play important roles in regulating bone metabolism. A previous randomized controlled trial (RCT) found that supplementation with Lactobacillus reuteri ATCC PTA 6475 (L.reuteri) led to substantially reduced bone loss in older women with low BMD. However, the total metabolic effects of L. reuteri supplementation on older women are still not clear. In this study, a post hoc analysis (not predefined) of serum metabolomic profiles of older women from the previous RCT was performed to investigate the metabolic dynamics over 1 year and to evaluate the effects of L. reuteri supplementation on human metabolism. Distinct segregation of the L. reuteri and placebo groups in response to the treatment was revealed by partial least squares-discriminant analysis. Although no individual metabolite was differentially and significantly associated with treatment after correction for multiple testing, 97 metabolites responded differentially at any one time point between L. reuteri and placebo groups (variable importance in projection score >1 and p value <0.05). These metabolites were involved in multiple processes, including amino acid, peptide, and lipid metabolism. Butyrylcarnitine was particularly increased at all investigated time points in the L. reuteri group compared with placebo, indicating that the effects of L. reuteri on bone loss are mediated through butyrate signaling. Furthermore, the metabolomic profiles in a case (low BMD) and control population (high BMD) of elderly women were analyzed to confirm the associations between BMD and the identified metabolites regulated by L. reuteri supplementation. The amino acids, especially branched-chain amino acids, showed association with L. reuteri treatment and with low BMD in older women, and may serve as potential therapeutic targets. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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2.
  • Grote, Ludger, 1964, et al. (författare)
  • National Knowledge-Driven Management of Obstructive Sleep Apnea-The Swedish Approach
  • 2023
  • Ingår i: Diagnostics. - : MDPI AG. - 2075-4418. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: This paper describes the development of "Swedish Guidelines for OSA treatment" and the underlying managed care process. The Apnea Hypopnea Index (AHI) is traditionally used as a single parameter for obstructive sleep apnea (OSA) severity classification, although poorly associated with symptomatology and outcome. We instead implement a novel matrix for shared treatment decisions based on available evidence. Methods: A national expert group including medical and dental specialists, nurses, and patient representatives developed the knowledge-driven management model. A Delphi round was performed amongst experts from all Swedish regions (N = 24). Evidence reflecting treatment effects was extracted from systematic reviews, meta-analyses, and randomized clinical trials. Results: The treatment decision in the process includes a matrix with five categories from a "very weak"" to "very strong" indication to treat, and it includes factors with potential influence on outcome, including (A) OSA-related symptoms, (B) cardiometabolic comorbidities, (C) frequency of respiratory events, and (D) age. OSA-related symptoms indicate a strong incitement to treat, whereas the absence of symptoms, age above 65 years, and no or well-controlled comorbidities indicate a weak treatment indication, irrespective of AHI. Conclusions: The novel treatment matrix is based on the effects of treatments rather than the actual frequency of respiratory events during sleep. A nationwide implementation of this matrix is ongoing, and the outcome is monitored in a prospective evaluation by means of the Swedish Sleep Apnea Registry (SESAR).
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3.
  • Palmquist, Anders, 1977, et al. (författare)
  • Complex geometry and integrated macro-porosity: Clinical applications of electron beam melting to fabricate bespoke bone-anchored implants
  • 2023
  • Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 156, s. 125-145
  • Forskningsöversikt (refereegranskat)abstract
    • The last decade has witnessed rapid advancements in manufacturing technologies for biomedical implants. Additive manufacturing (or 3D printing) has broken down major barriers in the way of producing complex 3D geometries. Electron beam melting (EBM) is one such 3D printing process applicable to metals and alloys. EBM offers build rates up to two orders of magnitude greater than comparable laser-based technologies and a high vacuum environment to prevent accumulation of trace elements. These features make EBM particularly advantageous for materials susceptible to spontaneous oxidation and nitrogen pick-up when exposed to air (e.g., titanium and titanium-based alloys). For skeletal reconstruction(s), anatomical mimickry and integrated macro-porous architecture to facilitate bone ingrowth are undoubtedly the key features of EBM manufactured implants. Using finite element modelling of physiological loading conditions, the design of a prosthesis may be further personalised. This review looks at the many unique clinical applications of EBM in skeletal repair and the ground-breaking innovations in prosthetic rehabilitation. From a simple acetabular cup to the fifth toe, from the hand-wrist complex to the shoulder, and from vertebral replacement to cranio-maxillofacial reconstruction, EBM has experienced it all. While sternocostal reconstructions might be rare, the repair of long bones using EBM manufactured implants is becoming exceedingly frequent. Despite the various merits, several challenges remain yet untackled. Nevertheless, with the capability to produce osseointegrating implants of any conceivable shape/size, and permissive of bone ingrowth and functional loading, EBM can pave the way for numerous fascinating and novel applications in skeletal repair, regeneration, and rehabilitation. Statement of significance: Electron beam melting (EBM) offers unparalleled possibilities in producing contaminant-free, complex and intricate geometries from alloys of biomedical interest, including Ti6Al4V and CoCr. We review the diverse range of clinical applications of EBM in skeletal repair, both as mass produced off-the-shelf implants and personalised, patient-specific prostheses. From replacing large volumes of disease-affected bone to complex, multi-material reconstructions, almost every part of the human skeleton has been replaced with an EBM manufactured analog to achieve macroscopic anatomical-mimickry. However, various questions regarding long-term performance of patient-specific implants remain unaddressed. Directions for further development include designing personalised implants and prostheses based on simulated loading conditions and accounting for trabecular bone microstructure with respect to physiological factors such as patient's age and disease status.
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4.
  • Wilms, Torben, 1973- (författare)
  • Squamous cell carcinoma of the head and neck, focusing on Epstein-Barr-virus, programmed cell death ligand 1 and serum lipoproteins
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Squamous cell carcinoma of the head and neck (SCCHN)comprises a large group of tumours including the oral cavity and nasopharyngealarea, and typically affects older males in association with alcohol/tobacco usage.Within the oral cavity, the mobile tongue is the most common site for tumourdevelopment. The incidence of squamous cell carcinoma of the oral tongue(SCCOT) is increasing in younger people, which has been suggested to associatewith other than the traditional risk factors for this disease. Two common humanoncogenic viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV)are connected to certain types of SCCHN, in oropharynx and nasopharynxrespectively. The receptor programmed cell death 1 (PD)-1 and its ligandprogrammed cell death ligand 1 (PD-L1) are particularly relevant in immunecheckpoint control, and elevated levels have been seen in various cancer types. Alink between hyperlipidemia and cancer risk has previously been suggested. Theaim of this thesis was to investigate risk factors and prognostic features forSCCHN, by focusing on EBV, PD-L1 and serum lipoproteins.Materials and methods: Ninety-eight cases of SCCOT and 15 cases of tonsillarsquamous cell carcinoma were examined for the presence of EBV-encodedribonucleic acids (EBERs), EBV deoxyribonucleic acid (DNA) and the proteinEBV-encoded nuclear antigen-1 (EBNA-1), using in situ hybridisation,polymerase chain reaction (PCR) and immunohistochemistry respectively. Onehundred and one cases of SCCOT were examined for expression of PD-L1 intumour and surrounding immune cells using Ventana SP263immunohistochemistry assay and a QuickScore (QS) method. An estimation oftumour-infiltrating immune cells was also performed in 25 of the patients.Circulating levels of PD-L1 were measured using an electrochemiluminescenceassay platform in serum from 30 patients. Finally, serum samples from 106patients and 28 healthy controls were investigated for levels of total cholesterol,low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides andlipoprotein(a).Results: In the first study, using an in situ hybridisation kit no EBER transcriptswere detected. No EBV DNA was identified with PCR analysis, andimmunohistochemistry for EBNA-1 was also negative. In the second study, highertumour cell PD-L1 levels were found in females than males (p = 0.019). Forpatients with low PD-L1 in tumour cells, better survival was shown in males thanfemales (overall survival p = 0.021, disease-free survival p = 0.020). Tumourinfiltrating natural killer (NK) T cells, immature dendritic cells (DCs) and M1macrophages correlated positively with tumour cell PD-L1 (p < 0.05). In the laststudy, the only lipoprotein showing significant difference in concentration iiibetween healthy controls and patients was HDL (p = 0.012). Kaplan-Meiersurvival curves showed that patients with high levels of total cholesterol or LDLhad better survival than patients with normal levels (p = 0.028 and p = 0.007respectively). Adjusting for the effects of age at diagnosis, TNM stage and weightchange, multivariate Cox regression models showed LDL to be an independentprognostic factor for both overall (p = 0.010) and disease-free survival (p =0.018).Conclusion: We excluded EBV as a potential player in SCCOT in both old andyoung patients and highlight the importance of appropriate controls for EBVencoded RNA in-situ hybridization (EBER-ISH) when investigating EBV inhuman diseases. Regarding PD-L1, our data supported the significance of genderon tumour cell PD-L1 expression and demonstrated combined effects of genderand PD-L1 levels on clinical outcome in patients with SCCOT. Data also indicatedthe involvement of specific immune cell types in PD-L1-regulated immuneevasion. Looking at serum lipoproteins, we found high LDL levels to be beneficialfor survival outcome in patients with SCCHN. Furthermore, the use of cholesterollowering medicine for prevention or management of SCCHN needs to be carefullyevaluated.
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5.
  • Taneja, Pankaj, et al. (författare)
  • Reliability of orofacial quantitative sensory testing for pleasantness and unpleasantness
  • 2020
  • Ingår i: Cephalalgia. - : Sage Publications. - 0333-1024 .- 1468-2982. ; 40:11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Quantitative sensory testing protocols for perceptions of pleasantness and unpleasantness based on the German Research Network on Neuropathic Pain protocol were recently introduced. However, there are no reliability studies yet published.AIM: To evaluate the intra-examiner (test-retest) and inter-examiner reliability for orofacial pleasantness and unpleasantness quantitative sensory testing protocols.METHODS: Sixteen healthy participants from Aarhus University (11 women and five men, mean age 24, range 21-26 years) contributed. Two examiners were trained in performing the entire quantitative sensory testing protocols for pleasantness and unpleasantness, which included the additional dynamic tactile stimulation test using a goat-hair brush. Each participant underwent examination of both protocols by each examiner (inter-examiner reliability) on day 1. They returned at least 8 days following the testing to be re-examined by one examiner (intra-examiner reliability). All testing was performed on the skin of the right mandibular mental region. The intraclass correlation (ICC) was used to determine reliability.RESULTS: For the protocol investigating pleasantness, the majority of parameters had good to excellent intra-examiner (11/14: Intraclass correlation 0.67-0.87) and inter-examiner (13/14: Intraclass correlation 0.62-0.96) reliabilities. Similarly, the protocol investigating unpleasantness had good to excellent intra-examiner (intraclass correlation 0.63-0.99) and inter-examiner (intraclass correlation 0.65-0.98) reliabilities for most (13/15) of the parameters.CONCLUSION:Intra and inter-examiner reliabilities in the majority of quantitative sensory testing parameters (apart from the summation ratio) investigating pleasantness and unpleasantness are acceptable when assessing somatosensory function of the orofacial region.Trial registration: NA.
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6.
  • Sjöström, Mats, et al. (författare)
  • Starting a Swedish national quality registry for orthognathic surgery: a tool for auditing fundamentals of care
  • 2022
  • Ingår i: Bmc Oral Health. - : Springer Science and Business Media LLC. - 1472-6831. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: National quality registries (NQRs) provide open data for user-directed acquisition. National Quality Registry (NQR) data are often used to analyze the rates of treatment success and adverse events for studies that aim to improve treatment quality and patient satisfaction. Thus, NQRs promote the goal of achieving evidence-based therapies. However, the scientific literature seldom focuses on the complex process of initiating, designing, and implementing an NQR. Starting an NQR may be particularly challenging in a setting where specialized care is decentralized, such as orthognathic surgery in Sweden. The present study describes the initiation and early phases of a new NQR for orthognathic surgery in Sweden. Methods: The initial inventory phase included gaining knowledge on regulations, creating economic plans, and identifying pitfalls in existing NQRs. Next, a crude framework for the registry was achieved. Outcome measures were selected with a nation-wide questionnaire, followed by a Delphi-like process for selecting parameters to include in the NQR. Our inclusive process comprised a stepwise introduction, feedback-based modifications, and preparatory educational efforts. Descriptive data were collected, based on the first 2 years (2018–2019) of registry operation. Results: Two years after implementation, 862 patients that underwent 1320 procedures were registered. This number corresponded to a 91% coverage rate. Bimaxillary treatments predominated, and the most common were a Le Fort I osteotomy combined with a bilateral sagittal split osteotomy (n = 275). Reoperations were conducted in 32 patients (3.6%), and the rate of patient satisfaction was 95%. Conclusions: A National Quality Registry should preferentially be started and maintained by an appointed task force of active clinicians. A collaborative, transparent, inclusive process may be an important factor for achieving credibility and high coverage, particularly in a decentralized setting.
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7.
  • Holy, Marek, 1981-, et al. (författare)
  • A Novel Treatment of Pediatric Atlanto-Occipital Dislocation with Nonfusion Using Muscle-Preserving Temporary Internal Fixation of C0-C2 : Case Series and Technical Note
  • 2023
  • Ingår i: Journal of Neurological Surgery Reports. - : Georg Thieme Verlag KG. - 2193-6358 .- 2193-6366. ; 84:01, s. E11-E16
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Design: Case series with surgical technical note.Objectives: This article reports experiences and results of muscle-preserving temporary C0-C2 fixation for the treatment of atlanto-occipital dislocation (AOD).Methods: AOD is a rare injury caused by high-energy trauma, occurring in less than 1% of pediatric trauma patients. Recommended treatment is C0-C2 fusion which, however, will result in significant loss of mobility in the craniocervical junction (CCJ), especially C1-C2 rotation. An alternative approach, with the ability of preserving mobility in the C1-C2 segment, is a temporary fixation that allows the ligaments to heal, after which the implants can be removed to regain function in the CCJ joints. By using a muscle-preserving approach and navigation for the C2 screws, a relatively atraumatic fixation of the CCJ can be achieved with motion recovery after implant removal.Results: We present two cases of AOD treated with temporary fixation. A 12-year-old boy involved in a frontal car collision, as a strapped back seat passenger, was treated with temporary C0-C2 fixation for 10 months. Follow-up at 11 months after implant removal included clinical evaluation, computed tomography, magnetic resonance imaging (MRI), and flexion-extension X-rays. He was free of symptoms at follow-up. The CCJ was radiographically stable and he had 45 degrees of C1-C2 rotation.A 7-year-old girl was hit by a car as she got off a bus. She was treated with temporary fixation for 4 months after which the implant was removed. Follow-up at 8 years included clinical evaluation and MRI in rotation. She was free of symptoms. The ligaments of the CCJ appeared normal and her C1-C2 rotation was 30 degrees.Conclusion: C0-C2 fixation without fusion allows the CCJ ligaments to heal in pediatric AOD. By removing the implants after ligament healing, rotation in the C1-C2 segment can be regained without subsequent instability. Both our patients tolerated the treatment well and were free of symptoms at follow-up.By using minimally invasive muscle-preserving technique and navigation, temporary fixation of the CCJ can be achieved with minimal damage to the soft tissues allowing recovery of almost normal function after implant removal.
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8.
  • Klintö, Kristina, et al. (författare)
  • Coverage, reporting degree and design of the Swedish quality registry for patients born with cleft lip and/or palate
  • 2020
  • Ingår i: BMC Health Services Research. - : BMJ Publishing Group Ltd. - 1472-6963. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The objective of the Swedish cleft lip and palate (CLP) registry is to promote quality control, research and improvement of treatment, by comparison of the long-term results of surgery, orthodontics and speech from all six Swedish CLP centres. The purpose of the study was to investigate the coverage and reporting degree of the Swedish CLP registry, and to describe the design of the registry and discuss questions of reliability and validity of the data included.Methods: All six Swedish CLP centres participate in the registry. All children in Sweden with cleft lip and/or cleft palate, born from 2009 onwards, are included in the registry. Baseline data such as cleft type (ICD-10 diagnosis), heredity, birth weight and additional deformities and/or syndromes, as well as pre-surgical treatment, are recorded at first visit. Data on surgical treatment are recorded continuously. Treatment outcome regarding dentofacial development and speech are recorded at follow-ups at 5, 10, 16 and 19 years of age. Data on dentofacial development are also recorded 1 year after orthognathic surgery. In addition, data on babbling and speech are recorded at 18 months of age. Coverage degree and reporting degree of surgery was assessed by comparison with registrations in the Swedish Central patient registry. Reporting degree of orthodontic and speech registrations at 5 years of age was assessed by comparison with registrations at baseline.Results: The average coverage degree for children born 2009 to 2018 was 95.1%. For cleft-related surgeries, the average reporting degree was 92.4%. Average reporting degree of orthodontic registrations and speech registrations at age 5 years was 92 and 97.5% respectively.Conclusion: In order to achieve valid and reliable data in a healthcare quality registry, the degree of coverage and reporting needs to be high, the variables included should be limited and checked for reliability, and the professionals must calibrate themselves regularly. The Swedish CLP registry fulfils these requirements.
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9.
  • Meyer, Simon, et al. (författare)
  • Fibula Graft Cutting Devices : Are 3D-Printed Cutting Guides More Precise than a Universal, Reusable Osteotomy Jig?
  • 2020
  • Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 9:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Individual cutting guides for the reconstruction of lower jaw defects with fibular grafts are often used. However, the application of these osteotomy tools is costly and time intensive. The aim of this study was to compare the precision of osteotomies using a 3D-printed guide with those using a universal, reusable, and more cost-efficient Multi-Use Cutting Jig (MUC-Jig). In this non-blinded experimental study, 10 cranio-maxillofacial surgeons performed four graft removals each in a randomized order using the same osteotomy angle, both proximally (sagittal cut) and distally (coronal cut), of a graft (45°, 30°, 15°, or 0°), first with the MUC-Jig then with the 3D-printed cutting guide. The 40 fibula transplants (Tx) of each method (n = 80) were then analyzed concerning their Tx length and osteotomy angles and compared to the original planning data. Furthermore, the surgeons' subjective perception and the duration of the two procedures were analyzed. The mean relative length and mean relative angle deviation between the MUC-Jig (-0.08 ± 1.12 mm; -0.69° ± 3.15°) and the template (0.22 ± 0.90 mm; 0.36° ± 2.56°) group differed significantly (p = 0.002; p = < 0.001), but the absolute deviations did not (p = 0.206; p = 0.980). Consequently, clinically comparable osteotomy results can be achieved with both methods, but from an economic point of view the MUC-Jig is a more cost-efficient solution.
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10.
  • Sundell, Anna Lena, et al. (författare)
  • Body Mass Index and Association With Caries in School-Aged Children With Orofacial Cleft : A Case-Control Study.
  • 2020
  • Ingår i: The Cleft Palate-Craniofacial Journal. - : Sage Publications. - 1055-6656 .- 1545-1569. ; 57:2, s. 169-176
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Data on the association between body mass index (BMI) and dental caries in children with orofacial clefts are sparse. Therefore, studies on the impact of BMI on caries frequency in children with cleft lip and/or palate (CL/P) are of importance. The aim of the current study was to investigate the association between BMI and frequency of dental caries in children with and without CL/P. Height, weight, and BMI in children with CL/P were also compared to controls.DESIGN: This study used a cross-sectional case-control design.PARTICIPANTS: One hundred and thirty-nine 5- and 10-year-old children with CL/P and 299 age-matched controls.MAIN OUTCOME MEASURES: Caries was recorded according to the International Caries Detection and Assessment System. Height and weight were recorded, and BMI was calculated as weight/height2.RESULTS: There was no correlation between BMI and caries frequency. Weight, height, and BMI were significantly lower in all children with CL/P compared to controls. After adjustment for international adoption, only BMI was significantly lower in CL/P children compared to controls. Non-adopted children with CL/P were significantly heavier and longer than adopted children with CL/P.CONCLUSIONS: Five- and 10-year-old children with corrected CL/P seemed to have a lower BMI than controls, but there was no association between BMI and caries frequency. Internationally adopted children with CL/P were lighter and shorter than non-adopted CL/P children and controls.
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