Aims/hypothesis
Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct ...factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. Therefore, we asked the question of whether treatment with rivaroxaban could influence endothelial function, arterial stiffness and platelet activation.
Methods
We conducted a multi-centre, prospective, randomised, open-label trial in 179 participants with type 2 diabetes (duration 2–20 years), subclinical inflammation (high-sensitivity C-reactive protein 2–10 mg/l) and at least two traits of the metabolic syndrome to compare the effects of the direct factor Xa inhibitor rivaroxaban (5 mg twice daily) vs aspirin (100 mg every day) on endothelial function (assessed by forearm occlusion plethysmography), skin blood flow (assessed by laser-Doppler fluxmetry), arterial stiffness (assessed by pulse wave velocity) and serum biomarkers of endothelial function and inflammation. Furthermore, we investigated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in platelets, the concentration of platelet-derived microparticles (PMPs) and the effects of isolated PMPs on HUVEC proliferation in vitro.
Results
Rivaroxaban treatment for 20 weeks (
n
= 89) resulted in a significant improvement of post-ischaemic forearm blood flow (3.6 ± 4.7 vs 1.0 ± 5.2 ml/100 ml,
p
= 0.004), a numerically increased skin blood flow and reduced soluble P-Selectin plasma level vs aspirin. We did not find significant differences of arterial stiffness or further biomarkers. Neither rivaroxaban nor aspirin influenced VASP phosphorylation of platelets. The number of PMPs increased significantly with both rivaroxaban (365.2 ± 372.1 vs 237.4 ± 157.1 μl
−1
,
p
= 0.005) and aspirin (266.0 ± 212.7 vs 201.7 ± 162.7 μl
−1
,
p
= 0.021). PMPs of rivaroxaban-treated participants stimulated HUVEC proliferation in vitro compared with aspirin. Rivaroxaban was associated with a higher number of bleeding events.
Conclusions/interpretation
Our findings indicate that the direct factor Xa inhibitor rivaroxaban improved endothelial function in participants with type 2 diabetes and subclinical inflammation but also increased the risk of bleeding.
Trial registration:
ClinicalTrials.gov
NCT02164578.
Funding
The study was supported by a research grant from Bayer Vital AG, Germany.
Graphical abstract
Xerostomia is the phenomenon of dry mouth and is mostly caused by hypofunction of the salivary glands. This hypofunction can be caused by tumors, head and neck irradiation, hormonal changes, ...inflammation or autoimmune disease such as Sjögren's syndrome. It is associated with a tremendous decrease in health-related quality of life due to impairment of articulation, ingestion and oral immune defenses. Current treatment concepts mainly consist of saliva substitutes and parasympathomimetic drugs, but the outcome of these therapies is deficient. Regenerative medicine is a promising approach for the treatment of compromised tissue. For this purpose, stem cells can be utilized due to their ability to differentiate into various cell types. Dental pulp stem cells are adult stem cells that can be easily harvested from extracted teeth. They can form tissues of all three germ layers and are therefore becoming more and more popular for tissue engineering. Another potential benefit of these cells is their immunomodulatory effect. They suppress proinflammatory pathways of lymphocytes and could therefore probably be used for the treatment of chronic inflammation and autoimmune disease. These attributes make dental pulp stem cells an interesting tool for the regeneration of salivary glands and the treatment of xerostomia. Nevertheless, clinical studies are still missing. This review will highlight the current strategies for using dental pulp stem cells in the regeneration of salivary gland tissue.
The free flap transfer of a latissimus dorsi flap (LDF) for the closure of sacral wound defects after pelvic exenteration and radiation therapy offers a successful tool of the plastic surgeon. This ...case report shows the successful coverage using an upstream arterio-venous (AV) loop in combination with an LDF.
We describe the case of a patient who underwent a pelvic exenteration and radiation therapy due to a local recurrence of rectal cancer. The initially used VRAM flap could not ensure a satisfactorily wound closure. An interdisciplinary approach first yielded an AV loop using both greater saphenous veins and was connected to the arteria and vena femoris followed by a free LDF transfer, which was performed 11 days later. The result was an excellent reconstructive and plastic coverage of the sacral wound defect with a well-perfused LDF. The long-term result showed a perfectly integrated flap in the sacral region.
We recommend the free LDF for the coverage of large wound defects in irradiated areas after the failure of VRAM flap. If an AV loop is necessary within the flap transfer, we recommend conducting two procedures to guarantee the perfusion of the AV loop.
Background
Even though mandibular condyle fractures have a high clinical relevance, their treatment remains somewhat challenging. Open reduction and internal fixation are difficult due to narrow ...surgical approaches, poor overview during reduction, and a possible risk of facial nerve damage. In times of technical endeavors in surgery, there is a trend towards the usage of stable CAD-CAM-implants from additive manufacturing or titanium laser sintering. Up until now, there have not been any reports of fracture treatment of the mandibular condyle using this technique.
Results and conclusion
We present a workflow for virtual repositioning of the fractured mandibular condyle, to manufacture patient-specific implants for osteosynthesis with the intention of use of resorbable metal alloys in the future.
Objective
In many countries the access to high quality medical service depends on socioeconomic factors. Therefore, these factors are associated with the treatment and prognosis of many diseases. In ...Germany health care is claimed to be independent from such factors due to obligatory health insurance and a well-developed medical infrastructure. Thus, socioeconomically caused health disparities should be absent. The aim of this study was to analyze the association between socioeconomic factors and the survival of oral cavity cancer in Germany.
Patients and methods
In this descriptive cohort study socioeconomic status related factors as well as demographic, tumor-specific, and comorbidity factors of 500 patients treated for oral cavity cancer were obtained in the university hospital of Dresden. Pearson correlation was used to describe associations between continuous variables. Associations between categorical variables were assessed using the chi-square test. Overall and recurrence-free survival were studied using the Kaplan-Meier method. Log-rank test was carried out to test between-group differences. Cox proportional hazard models were used to estimate the risk of death and the risk of recurrence.
Results
Significant differences in overall survival were found between the different educational levels and sex. Seventy-nine percent of the patients did not have a university degree or master craftsman/craftswoman. Less discrepancy was observed according to the marital status (49.4% married/engaged vs. 47.8% single, divorced, or widowed). In the multivariable analysis only sex, age at diagnosis, the Charlson score, the number of positive lymph nodes, and the nodal status were identified as independent predictors for overall survival whereas sex and the age at diagnosis were identified as independent predictors for recurrence-free survival.
Conclusion
Despite the equitable health system in Germany, significant associations between overall survival of oral cavity cancer and different socioeconomic factors could be found. For elimination of these disparities, health education programs should be established in socially deprived areas. Furthermore, clinicians should keep these factors in mind when determining recall periods for dental check-ups.
Digit replantation under wide-awake local anesthesia is a challenging method, and there are only a few works of literature on this procedure. This article describes the authors' clinical experience ...in finger replantation under wide-awake local anesthesia compared to general anesthesia.
Fifty-one patients who received single finger replantation after initial sharp amputation were included in the study, of whom 16 received wide-awake local anesthesia and 35 general anesthesia treatment. The indications for wide-awake local anesthesia were sharp amputation injury, estimated operation time less than 3 hours, and cooperative patients. The wide-awake local anesthesia was performed with 1% or 2% lidocaine infiltrated at the volar midpoint of the metacarpophalangeal joint of the affected digit without sedation medications. Demographic data included surgical outcome, waiting time, operation time, and hospital stay.
A total of 51 consecutive patients were included in this study. There were significantly shorter waiting times and operation times in the wide-awake local anesthesia group. The other parameters showed no significant differences. The overall success rate was 76.47 percent, with a mean overall operation time of 207 minutes.
In selected patients, finger replantation can be successfully performed under wide-awake local anesthesia, which has lower anesthesia risk and fewer medical expenses than general anesthesia. The method is feasible for single-digit replantation. Therefore, the finger replantation under wide-awake local anesthesia is a practicable alternative to general anesthesia.
Therapeutic, III.
Severe soft tissue damage with destruction of the dermis requires plastic reconstructive treatment. For multimorbid patients or patients unable to undergo major reconstructive surgery, use of dermal ...substitutes, such as a collagen-elastin matrix (CEM) with a split-thickness skin graft (STSG), instead of local or free flap surgery, may be a valid and easy treatment option. We aimed to investigate and compare the outcomes and rate of successful defect reconstruction using CEM plus STSG, using either a one-step approach (simultaneous CEM and STSG) or a two-step approach (CEM and negative wound pressure therapy (NPWT), with secondary STSG transplantation).
A single-centre, retrospective follow-up study of patients who had received CEM was conducted. Wounds had been treated with an STSG transplantation covering a CEM (MatriDerm, MedSkin Solutions Dr. Suwelack AG, Germany). Previous attempts at wound closure with conventional methods had failed in the selected patient population, which would usually have resulted in flap surgery.
Overall, 46 patients were included (mean age 60.9±20.0 years), with a total of 49 wound sites. We analysed 38 patients with wounds that did not require flap coverage; 18 patients received the one-step approach and 20 patients received the two-step approach. The mean follow-up in these patients was 22±11.5 months, and one patient was lost to follow-up. Overall, 29 (78.4%) wounds remained closed. Wounds which did not successfully heal were related to comorbidities, such as diabetes, alcohol misuse and smoking. Using the one-step approach, long-term defect coverage was achieved in 13 (76.5%) wounds and 16 (80.0%) wounds were closed using the two-step approach. However, there was no statistically significant differences between the one- or two-step approaches regarding the rate of development of a wound healing disorder.
Wound closure was achieved in 38 complex wounds using CEM plus STSG, while 11 wounds needed secondary flap coverage. In the flap-free wounds, there were no statistically significant differences between the one-step versus two-step approach. Using a simple defect reconstruction algorithm, we successfully used CEM plus STSG to treat complex wounds.
The study examines a sample of patients presenting for viscerocranial computer tomography that does not display any apparent signs of asymmetry, assesses the three-dimensional congruency of the ...mandibular ramus, and focuses on differences in age and gender.
This cross-sectional cohort study screened viscerocranial CT data of patients without deformation or developmental anomalies. Segmentations were obtained from the left and right sides and superimposed according to the best-fit alignment. Comparisons were made to evaluate three-dimensional congruency and compared between subgroups according to age and gender.
Two hundred and sixty-eight patients were screened, and one hundred patients met the inclusion criteria. There were no statistical differences between the left and right sides of the mandibular ramus. Also, there were no differences between the subgroups. The overall root mean square was 0.75 ± 0.15 mm, and the mean absolute distance from the mean was 0.54 ± 0.10 mm.
The mean difference was less than one millimetre, far below the two-millimetre distance described in the literature that defines relative symmetry. Our study population displays a high degree of three-dimensional congruency.
Our findings help to understand that there is sufficient three-dimensional congruency of the mandibular ramus, thus contributing to facilitating CAD-CAM-based procedures based on symmetry for this specific anatomic structure.
Background
Bioprinting is one of the most rapidly developing fields in medicine. Plastic and reconstructive surgery will be affected enormously by bioprinting, due to its original purpose of ...restoring injured or lost tissue. This article in particular has the purpose to analyze the current state of bioprinted tissues as well as research engagement for its application in plastic and reconstructive surgery.
Material and methods
A systematic search for the time span between 2000 and 2022 was performed on EMBASE, PubMed, Scopus, and Web of Science databases according to the PRISMA Guidelines. Criteria for the selection of publications were in vitro, animal in vivo, and human in vivo studies where three-dimensional bioprinting of tissue was performed. We extracted data such as (a) author’s country of origin, (b) in vitro study, (c) animal in vivo study, and (d) human in vivo study and categorized the publications by topics such as (1) neural tissue, (2) vascularization, (3) skin, (4) cartilage, (5) bone, and (6) muscle. Additionally, recent discoveries of in vivo animal trials were summarized.
Results
Out of a pool of 1.629 articles, only 29 publications met our criteria. Of these publications, 97% were published by university institutions. Publications from China (28%,
n
=8), the USA (28%,
n
=8), and Germany (10%,
n
=3) led the publication list on 3D bioprinting. Concerning the publications, 45% (
n
=13) were in vitro studies, 52% (
n
=15) in vivo studies on animal models, and 3% (
n
=1) pilot clinical studies on humans as reported by Zhou et al. (
EBioMedicine
28: 287–302, 2018). Regarding the classification of topics, our study revealed that publications were mainly in the field of 3D printing of cartilage (
n
=13, 39%), skin (
n
=7, 21%), bone (
n
=6, 18%), and vascularization (
n
=5, 15%).
Conclusions
To this date, it has not been yet possible to bioprint whole tissue systems. However, the progress in three-dimensional bioprinting is rapid. There are still some challenges, which need to be overcome regarding cell survival before and during the printing process, continuation of architecture of bioprinted multilinear cells, and long-term stabilization and survival of complex tissues.
Level of evidence
: Not ratable.
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