Can side effect expectations be assessed implicitly? A comparison of explicit and implicit expectations of vaccination side effects.

OBJECTIVE: Treatment expectations alter the probability of experiencing unpleasant side effects from an intervention, including vaccinations. To date, expectations have mostly been assessed explicitly bearing the risk of bias. This study aims to compare implicit expectations of side effects from COVID-19 and flu vaccinations and to examine their relationships with vaccine attitudes and intentions. METHODS: N = 248 participants took part in a cross-sectional online survey assessing explicit and implicit expectations, as well as vaccine-related attitudes and personal characteristics. A Single Category Implicit Association Test (SC-IAT) was developed to assess implicit side effect expectations. Explicit side effect expectations were measured with the Treatment Expectation Questionnaire (TEX-Q). RESULTS: Whereas explicit and implicit expectations regarding COVID-19 vaccine were significantly correlated (r = -0.325, p < .001), those correlations could not be found regarding flu vaccine (r = -0.072, p = .32). Explicit measures (COVID-19: ß = -0.576, p < .001; flu: ß = -0.301, p < .001) predicted the intention to receive further vaccinations more than implicit measures (COVID-19: ß = -0.005, p = .93; flu: ß = 0.004, p = .96). Explicit measures (COVID-19: OR = 0.360, p < .001; flu: OR = 0.819, p = .03) predicted vaccination status, while implicit measures did not (COVID- 19: OR = 2.643, p = .35; flu: OR = 0.829, p = .61). CONCLUSION: Expectations to experience side effects from vaccinations can be measured implicitly, in addition to explicit measures. Further investigation needs to determine the relative contribution and additive value of using implicit measures to assess treatment expectations.

Oral-Health-Related Quality of Life in Patients with Medication-Related Osteonecrosis of the Jaw: A Prospective Clinical Study.

Medication-related osteonecrosis of the jaw (MRONJ) represents an adverse side effect of antiresorptive and antiangiogenic medications. It is associated with impaired quality of life, oral health, and oral function and can be classified into various stages. The purpose of this prospective clinical study is to evaluate the impact of stages I and II MRONJ on oral-health-related quality of life (OHRQoL) and related parameters. Patients' OHRQoL, satisfaction with life, oral discomfort, and oral health were assessed using the German version of the Oral Health Impact Profile (OHIP-G49), visual analog scales (VAS), and Satisfaction with Life Scale (SWLS) at baseline (T0), 10 days (T1), and 3 months after treatment (T2) in 36 patients. Data were analyzed using Kolmogorov-Smirnov test, two-way mixed ANOVAs, and follow-up Mann-Whitney U tests. The impact of treatment effects on the original seven OHIP domain structures and the recently introduced four-dimensional OHIP structure were evaluated using linear regression analysis. Thirty-six patients received surgical MRONJ treatment. Before treatment, patients' perceived OHRQoL, oral discomfort, oral health, and satisfaction with life were negatively affected by MRONJ. Surgical treatment significantly improved OHRQoL and related parameters (all p ≤ 0.012). This improvement was greater in patients with higher impairment at T0. OHRQoL and oral restrictions were still impaired after treatment in patients who needed prosthetic treatment. The four-dimensional structure revealed valuable information beyond the standard seven OHIP domains. Increased awareness of MRONJ risks and an interdisciplinary treatment approach for MRONJ patients are needed.

Free Skin Grafting to Reconstruct Donor Sites after Radial Forearm Flap Harvesting: A Prospective Study with Platelet-Rich Fibrin (PRF).

Reconstruction of the donor site after radial forearm flap harvesting is a common procedure in maxillofacial plastic surgery. It is normally carried out with split-thickness or full-thickness free skin grafts. Unfortunately, free skin graft transplantation faces wound healing impairments such as necrosis, (partial) graft loss, or tendon exposure. Several studies have investigated methods to reduce these impairments and demonstrated improvements if the wound bed is optimised, for example, through negative-pressure wound therapy or vacuum-assisted closure. However, these methods are device-dependent, expansive, and time-consuming. Therefore, the application of platelet-rich fibrin (PRF) to the wound bed could be a simple, cost-effective, and device-independent method to optimise wound-bed conditions instead. In this study, PRF membranes were applied between the wound bed and skin graft. Results of this study indicate improvements in the PRF versus non-PRF group (93.44% versus 86.96% graft survival, p = 0.0292). PRF applied to the wound bed increases graft survival and reduces impairments. A possible explanation for this is the release of growth factors, which stimulate angiogenesis and fibroblast migration. Furthermore, the solid PRF membranes act as a mechanical barrier ("lubrication" layer) to protect the skin graft from tendon motion. The results of this study support the application of PRF in donor-site reconstruction with free skin grafts.

Development of an Extracorporeal Perfusion Device for Small Animal Free Flaps.

BACKGROUND: Extracorporeal perfusion (ECP) might prolong the vital storage capabilities of composite free flaps, potentially opening a wide range of clinical applications. Aim of the study was the development a validated low-cost extracorporeal perfusion model for further research in small animal free flaps. METHODS: After establishing optimal perfusion settings, a specially designed extracorporeal perfusion system was evaluated during 8-hour perfusion of rat epigastric flaps followed by microvascular free flap transfer. Controls comprised sham-operation, ischemia and in vivo perfusion. Flaps and perfusate (diluted blood) were closely monitored by blood gas analysis, combined laser Doppler flowmetry and remission spectroscopy and Indocyanine-Green angiography. Evaluations were complemented by assessment of necrotic area and light microscopy at day 7. RESULTS: ECP was established and maintained for 8 hours with constant potassium and pH levels. Subsequent flap transfer was successful. Notably, the rate of necrosis of extracorporeally perfused flaps (27%) was even lower than after in vivo perfusion (49%), although not statistically significant (P = 0,083). After sham-operation, only 6% of the total flap area became necrotic, while 8-hour ischemia led to total flap loss (98%). Angiographic and histological findings confirmed these observations. CONCLUSIONS: Vital storage capabilities of microvascular flaps can be prolonged by temporary ECP. Our study provides important insights on the pathophysiological processes during extracorporeal tissue perfusion and provides a validated small animal perfusion model for further studies.

Structure-related antibacterial activity of a titanium nanostructured surface fabricated by glancing angle sputter deposition.

The aim of this study was to reproduce the physico-mechanical antibacterial effect of the nanocolumnar cicada wing surface for metallic biomaterials by fabrication of titanium (Ti) nanocolumnar surfaces using glancing angle sputter deposition (GLAD). Nanocolumnar Ti thin films were fabricated by GLAD on silicon substrates. S. aureus as well as E. coli were incubated with nanostructured or reference dense Ti thin film test samples for one or three hours at 37 °C. Bacterial adherence, morphology, and viability were analyzed by fluorescence staining and scanning electron microscopy and compared to human mesenchymal stem cells (hMSCs).Bacterial adherence was not significantly different after short (1 h) incubation on the dense or the nanostructured Ti surface. In contrast to S. aureus the viability of E. coli was significantly decreased after 3 h on the nanostructured film compared to the dense film and was accompanied by an irregular morphology and a cell wall deformation. Cell adherence, spreading and viability of hMSCs were not altered on the nanostructured surface. The results show that the selective antibacterial effect of the cicada wing could be transferred to a nanostructured metallic biomaterial by mimicking the natural nanocolumnar topography.

Perforator flaps--how many perforators are necessary to keep a flap alive?

Perforator flaps are becoming increasingly important in reconstructive microsurgery because of their reduced donor-site morbidity. However, one drawback is partial necrosis caused by vasospasm or inconsistency of delicate perforator vessels. In this study we have evaluated the number and capacity of perforator vessels with respect to the size of a flap, and the influence of vascular endothelial growth factor (VEGF) on the capacity of perforators in a standard animal model. We realised an epigastric perforator flap 4cm×7cm in 36 rats. In 3 control groups (n=6 in each), flaps were raised based on 4, 2, or 1 perforator vessel(s), while all other perforators as well as the epigastric vessels were ligated. In three study groups (n=6 in each), set up in the same way as the control groups, we also injected a single dose of VEGF into the wound area. After one week, all areas of necrosis were assessed planimetrically. We also evaluated the wounds by laser Doppler flowmetry preoperatively and after one week, and by histological and immunohistochemical examination. An increased number of perforators, together with VEGF, was associated with a significant reduction in the areas of necrosis. This observation was particularly true in flaps based on only one perforator. The inclusion of additional perforators has a more important role in the success of a flap than theoretical models suggest. Proangiogenetic factors may improve the viability of perforator flaps.

Microvascular training of medical students and surgeons - a comparative prospective study.

Since microsurgical experience remains the most important skill in various surgical fields it should be in general part of the training program, either in medical studies or residency. This study compares the results of microsurgical education after completion of a comprehensive microsurgical course program between students and surgeons. 59 clinical medical students and 19 surgeons participated at a weekly 14-day microsurgical training course. Two examiners assessed the participants independently and blinded. Comparison between the groups demonstrated that the students achieved higher scores with a significant difference in tissue handling (p = 0.04). The surgeons had more days of absence from the course compared with the students. In the practical examination, the students scored a mean 13.71 points compared with 11.73 points for the surgeons (p < 0.0001). In the theoretical part students achieved 15.27 points compared to the mean of 13.50 points of the surgeons (p = 0.009). Prior to participation the students described an ambition to a career in a specialty performing microsurgery in 23 cases, after the microsurgical course following completion 50 participants worked in a surgical field. Microsurgical education can be part of undergraduate medical studies. The microsurgery training course influenced the students' ambition in relation to microsurgery as a future career.

The influence of different VEGF administration protocols on the perfusion of epigastric flaps in rats.

In this study we investigated the impact of the time at which vascular endothelial growth factor (VEGF) was given on the overall survival of flaps and time of the achievement of full perfusion in the rat epigastric flap model. Epigastric flaps were raised in 144 rats. VEGF was given to 108 rats at different time points. Perioperatively blood flow, velocity, haemoglobin (Hb) concentration, and oxygen saturation were measured non-invasively using laser-Doppler spectrophotometry. On postoperative days 3, 5, 7, or 10, the pedicle of the flap was ligated. One week later, the flap was harvested for immunohistochemical assessment of the density of microvessels. Differences significant from those in the control group were found in all specimens 3 and 5 days after the first operation, whereas no differences in the area of necrosis were detected after 7 and 10 days. Preoperative values of measured Hb (p<0.0001, 95% confidence interval (CI) 0.57 to 1.02), flow (p<0.0001, 95% CI -0.32 to -0.13), and velocity (p<0.0001, 95% CI 0.48 to 1.89) predicted necrosis. After ligation of the pedicle, SO2 (p<0.0001, 95% CI -1.12 to -0.83) and flow (p<0.0001, 95% CI -0.38 to -0.26) were prognostic factors. The topical use of VEGF increases overall survival of flaps and decreases the time needed for a free flap to achieve full perfusion. The time of application of VEGF has no part in the postoperative course. The perfusion of vascularised free flaps in their wound beds was achieved between postoperative days 5 and 7 in the control group and postoperative days 3 and 5 after VEGF had been given.

Autonomization of epigastric flaps in rats.

The question of how long a flap depends on its pedicle cannot be answered clearly from the available literature. To address this, we investigated the time to flap autonomization in the wound bed and the length of time to the point when flap necrosis is reduced to a clinically negligible level. The superficial epigastric flap was raised in 24 rats. After 3, 5, 7, or 10 days of wound healing, the pedicle was again exposed, ligated, and divided. Values of blood flow (flow), velocity (velocity), hemoglobin level (Hb), and oxygen saturation (SO(2) ) were noninvasively measured using Laser spectrophotometry. The area of necrosis of the flap was 62.77 ± 1.71% after 3 days, 16.26 ± 0.86% after 5 days, 2.88 ± 0.14% after 7 days, and 1.64 ± 0.16% after 10 days (P < 0.001). Hb, flow, and velocity were found to be significant factors on developing flap necrosis at the preoperative and postoperative time point (P < 0.0001), whereas SO(2) and flow were significant predictors of necrosis at the time of pedicle ligation (P < 0.0001). The percentage changes of SO(2) (P < 0.0001), flow (P < 0.0001), and velocity (P = 0.001) between the different time points were significant predictors of flap necrosis. The time needed for the complete autonomization of vascularized free flaps in their wound beds has been found as completed between the 5th and 7th day postoperatively in this rat model. The area of flap necrosis depends on the present value of SO(2) , Hb, flow, and velocity at different time points, but, more importantly, also on the perioperative change of these parameters.

Intraoral defect coverage with prelaminated epigastric fat flaps with human amniotic membrane in rats.

BACKGROUND: The aim of this study was to investigate whether or not wound healing after the use of microvascular anastomosed fat flaps prelaminated with human amniotic membrane, for intraoral defect coverage, is improved when compared wth wound healing of pure fat flaps. METHODS: Microsurgical transplantation of the superficial epigastric fat flap prelaminated with HAM was evaluated using 47 Sprague-Dawley rats. Standardized oral mucosa defects were created and covered by HAM or polyglactin910/polydioxanon patches only, prelaminated and bare flaps, uncovered or by HAM after flap insertion. After 7, 15, and 35 days, postoperatively, the flaps were reassessed. RESULTS: The mean value of the defect size after 7 days was 47.73 ± 2.63 mm(2) in the control, 48.63 ± 2.23 mm(2) in the bare flaps covered by HAM after insertion, and 36.85 ± 2.79 mm(2) in the prelaminated HAM group. The mean value of the wound closure time in all rats was 13.74 ± 2.05 days (range 11-18). Intraoral defects were covered with mucosa after 15.67 ± 1.66 days in the pure flap group and 11.89 ± 0.78 days in the HAM group (p < 0.0001). CONCLUSIONS: Prelaminated flaps with HAM used in the repair of large mucosa defects complete epithelialization from the surrounding margins faster than bare flaps. Wound healing can be enhanced by using HAM as a prelaminated epithelial structure within microvascular anastomosed flaps.