A Comparison of the Use of Two-Dimensional and Three-Dimensional Visualization Systems by Novice and Experienced Microsurgeons in Microsurgical Vessel Anastomosis: An Analysis Using the Chicken Model.

BACKGROUND: Various studies have discussed the benefits of applying three-dimensional (3D) techniques, specifically its advantages with respect to ergonomics, feasibility, and the rate of learning achievable in microsurgery training. However, no study has been conducted that compares the operator experience of using two-dimensional (2D) and 3D systems in microsurgical training. The aim of this study is to compare 2D- and 3D-assisted microsurgical training in novices based on anastomosis of chicken femoral arteries. METHODS: The participants were grouped by previous microsurgical experience. Group A includes novice participants. Group B includes 2D-experienced participants. Group C includes both participants in groups A and B. A questionnaire composed of 10 parameters in the field of image quality, dexterity, ergonomic, and feasibility will be filled out after each participant finished their anastomoses by the 2D and 3D systems. RESULTS: The results demonstrated 3D system was scored better on "field of view" (p = 0.004), "less tremor" (p = 0.005), "neck/upper back comfort" (p = 0.043), "lower back comfort" (p = 0.015), "technical feasibility" (p = 0.020), and "educational feasibility" (p = 0.004) in group A (N = 12). In group B (N = 9), 3D system was scored better on "field of view" (p = 0.041) but worse on "image resolution" (p = 0.031). CONCLUSION: With the 3D visualization system for microsurgical anastomosis of chicken femoral model, there are significant improvements in the field of view, stability, ergonomics, and educational value compared with 2D system among all participants. Accordingly, 3D-assisted microsurgery training can be a novel and potential popular training method.

Impact of an autophagy-inducing peptide on immunogenicity and protection efficacy of an adenovirus-vectored SARS-CoV-2 vaccine.

Because of continual generation of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to design the next generation of vaccines to combat the threat posed by SARS-CoV-2 variants. We developed human adenovirus (HAd) vector-based vaccines (HAd-Spike/C5 and HAd-Spike) that express the whole Spike (S) protein of SARS-CoV-2 with or without autophagy-inducing peptide C5 (AIP-C5), respectively. Mice or golden Syrian hamsters immunized intranasally (i.n.) with HAd-Spike/C5 induced similar levels of S-specific humoral immune responses and significantly higher levels of S-specific cell-mediated immune (CMI) responses compared with HAd-Spike vaccinated groups. These results indicated that inclusion of AIP-C5 induced enhanced S-specific CMI responses and similar levels of virus-neutralizing titers against SARS-CoV-2 variants. To investigate the protection efficacy, golden Syrian hamsters immunized i.n. either with HAd-Spike/C5 or HAd-Spike were challenged with SARS-CoV-2. The lungs and nasal turbinates were collected 3, 5, 7, and 14 days post challenge. Significant reductions in morbidity, virus titers, and lung histopathological scores were observed in immunized groups compared with the mock- or empty vector-inoculated groups. Overall, slightly better protection was seen in the HAd-Spike/C5 group compared with the HAd-Spike group.

Significance of Preexisting Vector Immunity and Activation of Innate Responses for Adenoviral Vector-Based Therapy.

An adenoviral (AdV)-based vector system is a promising platform for vaccine development and gene therapy applications. Administration of an AdV vector elicits robust innate immunity, leading to the development of humoral and cellular immune responses against the vector and the transgene antigen, if applicable. The use of high doses (1011-1013 virus particles) of an AdV vector, especially for gene therapy applications, could lead to vector toxicity due to excessive levels of innate immune responses, vector interactions with blood factors, or high levels of vector transduction in the liver and spleen. Additionally, the high prevalence of AdV infections in humans or the first inoculation with the AdV vector result in the development of vector-specific immune responses, popularly known as preexisting vector immunity. It significantly reduces the vector efficiency following the use of an AdV vector that is prone to preexisting vector immunity. Several approaches have been developed to overcome this problem. The utilization of rare human AdV types or nonhuman AdVs is the primary strategy to evade preexisting vector immunity. The use of heterologous viral vectors, capsid modification, and vector encapsulation are alternative methods to evade vector immunity. The vectors can be optimized for clinical applications with comprehensive knowledge of AdV vector immunity, toxicity, and circumvention strategies.

Progress towards the Development of a Universal Influenza Vaccine.

Influenza viruses are responsible for millions of cases globally and significantly threaten public health. Since pandemic and zoonotic influenza viruses have emerged in the last 20 years and some of the viruses have resulted in high mortality in humans, a universal influenza vaccine is needed to provide comprehensive protection against a wide range of influenza viruses. Current seasonal influenza vaccines provide strain-specific protection and are less effective against mismatched strains. The rapid antigenic drift and shift in influenza viruses resulted in time-consuming surveillance and uncertainty in the vaccine protection efficacy. Most recent universal influenza vaccine studies target the conserved antigen domains of the viral surface glycoproteins and internal proteins to provide broader protection. Following the development of advanced vaccine technologies, several innovative strategies and vaccine platforms are being explored to generate robust cross-protective immunity. This review provides the latest progress in the development of universal influenza vaccines.

The Impact of COVID-19 Surges in 2019-2021 on Patient-Reported Outcome Measures After Spine Surgery at an Academic Tertiary Referral Center in Taiwan: A Retrospective Observational Cohort Study.

Aim: Limited data are available on the impact of the coronavirus disease 2019 (COVID-19) pandemic on patient-reported outcome measures (PROMs) in patients who underwent spine surgery. In this study, we aimed to investigate the associations between the COVID-19 outbreak in Taiwan (May 2021) and PROMs in patients who underwent spine surgery. Method: We retrospectively identified patients who underwent spine surgery during identical defined 6-week time-intervals (May 16 to June 30) in 2019, 2020, and 2021. PROMs, including visual analog scale (VAS) score for pain, Oswestry disability index (ODI), and EuroQol-5D (EQ-5D), were investigated before surgical intervention and at a 1-month follow-up. Relevant clinical information was collected from the electronic medical records of patients. Linear regression analysis was used to examine the association between the pandemic in 2021 (vs. 2019/2020) and the PROMs after adjusting for age, sex, and relevant clinical variables. Results: The number of patients who underwent spine surgery at our hospital during the identical defined 6-week time-intervals in 2019, 2020, and 2021 was 77, 70, and 48, respectively. The surgical intervention significantly improved VAS, ODI, and EQ-5D of the patients (1 month after surgery vs. before surgery, all p < 0.001) in all three study periods. However, there was a significant between-group difference in change from baseline in VAS (p = 0.002) and EQ-5D (p = 0.010). The decrease in VAS and increase in EQ-5D after surgery in 2021 were not as much as those in 2019 and 2020. The associations between the pandemic in 2021 (vs. 2019/2020) and changes in VAS (ß coefficient 1.239; 95% confidence interval [CI] 0.355 to 2.124; p = 0.006) and EQ-5D (ß coefficient, -0.095; 95% CI, -0.155 to -0.035; p = 0.002) after spine surgery were independent of relevant clinical factors. Conclusion: There was less improvement in short-term PROMs (VAS and EQ-5D) after spine surgery during the COVID-19 pandemic. Assessment of PROMs in surgical patients during a pandemic may be clinically relevant, and psychological support in this condition might help improve patients' outcomes.

Pre-operative anemia was associated with all-cause mortality in patients with vertebral fracture who underwent percutaneous vertebroplasty.

Purpose: We investigated the association between pre-operative anemia and long-term all-cause mortality in patients with vertebral fracture who underwent a vertebroplasty. Materials and methods: We retrospectively selected patients who were admitted for vertebroplasty for vertebral compression fracture between 2013 and 2020. Patients who had pathologic fractures or had no assessment of bone mineral density were excluded. Relevant information was collected from electronic medical records. Patients' survival status was confirmed at the end of March 2021. Cox-proportional hazard models were conducted to examine the effects of anemia (<12 g/dL vs. ≥12 g/dL) and pre-operative hemoglobin levels (as a continuous variable) on all-cause mortality with multivariate adjustments. Results: A total of 167 patients were analyzed (mean age 75.8 ± 9.3 years, male 25.7%). After a median follow-up duration of 2.1 years, pre-operative anemia (hemoglobin <12 g/dL vs. ≥12 g/dL) was independently associated with a higher risk of all-cause mortality (hazard ratio 2.762, 95% CI 1.184 to 6.442, p = 0.019). An increase in pre-operative hemoglobin was associated with a lower risk of all-cause mortality after multivariate adjustment (hazard ratio 0.775, 95% CI 0.606 to 0.991, p = 0.042). Conclusion: Pre-operative anemia (<12 g/dL) was independently associated with survival outcome among patients with vertebral compression fractures who underwent vertebroplasty. Our findings highlight anemia as a risk factor of long-term mortality in this elderly surgical population.

Association of Body Mass Index with Long-Term All-Cause Mortality in Patients Who Had Undergone a Vertebroplasty for a Vertebral Compression Fracture.

We aimed to investigate the association between preoperative body mass index (BMI) and postoperative long-term mortality in patients who underwent a vertebroplasty. We retrospectively enrolled patients with a vertebral compression fracture who underwent a vertebroplasty between May 2013 and June 2020 in a medical center in Taiwan. The survival status of the study sample was confirmed by the end of March 2021. Cox-proportional hazard models were conducted to examine the effects of being overweight/obese (≥25 kg/m2 vs. <25 kg/m2) and BMI (as a continuous variable) on all-cause mortality after adjusting for age, sex, history of smoking, diabetes, hypertension, chronic kidney disease, and osteoporosis. A total of 164 patients were analyzed (mean age 75.8 ± 9.3 years, male 25.6%, mean BMI 24.0 ± 4.1 kg/m2) after a median follow-up of 785 days. Compared with a BMI < 25 kg/m2, a BMI ≥ 25 kg/m2 was associated with a significantly lower risk of all-cause mortality (HR 0.297, 95% CI 0.101 to 0.878, p = 0.028). These findings were consistent when BMI was examined as a continuous variable (HR 0.874, 95% CI 0.773 to 0.988, p = 0.031). A low BMI (<22 kg/m2) should be considered as a risk factor for postoperative long-term mortality in this ageing population.

C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis.

CCL17, a chemotactic cytokine produced by macrophages, is known to promote inflammatory and fibrotic effects in multiple organs, but its role in mediating renal fibrosis is unclear. In our study cohort of 234 chronic kidney disease (CKD) patients and 65 healthy controls, human cytokine array analysis revealed elevated CCL17 expression in CKD that correlated negatively with renal function. The area under the receiver operating characteristic curve of CCL17 to predict the development of CKD stages 3b-5 was 0.644 (p < 0.001), with the optimal cut-off value of 415.3 ng/mL. In vitro over-expression of CCL17 in HK2 cells had no effect on cell viability, but increased cell motility and the expression of α-SMA, vimentin and collagen I, as shown by western blot analysis. In a unilateral ureteral obstruction (UUO) mouse model, we observed significantly increased interstitial fibrosis and renal tubule dilatation by Masson's Trichrome and H&E staining, and markedly increased expression of CCL17, vimentin, collagen I, and α-SMA by IHC stain, qRTPCR, and western blotting. CCL17 induced renal fibrosis by promoting the epithelial-mesenchymal transition, resulting in ECM accumulation. CCL17 may be a useful biomarker for predicting the development of advanced CKD.

The Impacts of Reassortant Avian Influenza H5N2 Virus NS1 Proteins on Viral Compatibility and Regulation of Immune Responses.

Avian influenza virus (AIV) can cause severe diseases in poultry worldwide. H6N1 AIV was the dominant enzootic subtype in 1985 in the chicken farms of Taiwan until the initial outbreak of a low pathogenic avian influenza (LPAI) H5N2 virus in 2003; thereafter, this and other LPAIs have been sporadically detected. In 2015, the outbreak of three novel H5Nx viruses of highly pathogenic avian influenza (HPAI) emerged and devastated Taiwanese chicken and waterfowl industries. The mechanism of variation in pathogenicity among these viruses is unclear; but, in light of the many biological functions of viral non-structural protein 1 (NS1), including interferon (IFN) antagonist and host range determinant, we hypothesized that NS genetic diversity contributes to AIV pathogenesis. To determine the impact of NS1 variants on viral infection dynamics, we established a reverse genetics system with the genetic backbone of the enzootic Taiwanese H6N1 for generation of reassortant AIVs carrying exogenous NS segments of three different Taiwanese H5N2 strains. We observed distinct cellular distributions of NS1 among the reassortant viruses. Moreover, exchange of the NS segment significantly influenced growth kinetics and induction of cytokines [IFN-α, IFN-ß, and tumor necrosis factor alpha (TNF-α)] in an NS1- and host-specific manner. The impact of NS1 variants on viral replication appears related to their synergic effects on viral RNA-dependent RNA polymerase activity and IFN response. With these approaches, we revealed that NS1 is a key factor responsible for the diverse characteristics of AIVs in Taiwan.