Superior antibody and membrane protein-specific T-cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents.

BACKGROUND: Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents. METHODS: Participants aged 11-17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively. RESULTS: Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2)+CD4+, SNM-specific IL-2+CD8+, S-specific IL-2+CD8+, N-specific IL-2+CD4+, N-specific IL-2+CD8+ and M-specific IL-2+CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+CD4+, interferon-γ+CD8+ and IL-2+CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions. CONCLUSION: This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

Humoral and Cellular Immunogenicity of 3 Doses of BNT162b2 in Children With Kidney Diseases.

Introduction: Patients with severe kidney diseases are at risk of complications from COVID-19; however, little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. Methods: We investigated the immunogenicity and safety of an accelerated 3-dose primary series of COVID-19 vaccination among 59 pediatric patients with chronic kidney disease (CKD) (mean age 12.9 years; 30 male) with or without immunosuppression, dialysis, or kidney transplant. Dosage was 0.1 ml BNT162b2 to those aged 5 to 11 years, and 0.3 ml BNT162b2 to those aged 11 to 18 years. Results: Three doses of either vaccine type elicited significant antibody responses that included spike receptor-binding domain (S-RBD) IgG (90.5%-93.8% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6%-79.3%). There were notable T cell responses. Weaker neutralization responses were observed among those on immunosuppression, especially those receiving higher number of immunosuppressants or on mycophenolate mofetil. Neutralization was reduced against Omicron BA.1 compared to wild type (WT, i.e., ancestral) (post-dose 3 sVNT% level; 82.7% vs. 27.4%; P < 0.0001). However, the T cell response against Omicron BA.1 was preserved, which likely confers protection against severe COVID-19. Infected patients exhibited hybrid immunity after vaccination, as evidenced by the higher Omicron BA.1 neutralization response among these infected patients who received 2 doses compared with those who were uninfected. Generally mild or moderate adverse reactions following vaccines were reported. Conclusion: An accelerated 3-dose primary series with BNT162b2 is immunogenic and safe in young children and adolescents with kidney diseases.

Cardiovascular disease risk models and dementia or cognitive decline: a systematic review.

Background: Health cognitive promotion and protection is a critical topic. With the world's aging population and rising life expectancy, there will be many people living with highly age-related dementia illnesses. Cardiovascular disease (CVD) and dementia share the same risk factors, such as unhealthy lifestyles and metabolic factors. These recognized risks associated with CVD and dementia frequently co-occur. CVD risk models may have a close association with dementia and cognitive decline. So, this systematic review aimed to determine whether CVD risk models were connected with dementia or cognitive decline and compare the predictive ability of various models. Methods: PubMed, Web of Science, PsychINFO, Embase, Cochrane Library, CNKI, Sinomed, and WanFang were searched from 1 January 2014 until 16 February 2023. Only CVD risk models were included. We used the Newcastle-Ottawa scale (NOS) for the quality assessment of included cohort studies and the Agency for Healthcare Research and Quality (AHRQ) for cross-sectional studies. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement's guidelines were followed in this systematic study. Results: In all, 9,718 references were screened, of which 22 articles were included. A total of 15 CVD risk models were summarized. Except for the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) health index, the other 14 CVD risk models were associated with dementia and cognitive decline. In comparison, different CVD risk models and domain-specific cognitive function correlation variation depended on cohort characteristics, risk models, cognitive function tests, and study designs. Moreover, it needed to be clarified when comparing the predicting performance of different CVD risk models. Conclusion: It is significant for public health to improve disease risk prediction and prevention and mitigate the potential adverse effects of the heart on the brain. More cohort studies are warranted to prove the correlation between CVD risk models and cognitive function. Moreover, further studies are encouraged to compare the efficacy of CVD risk models in predicting cognitive disorders.

Tumor vaccine based on extracellular vesicles derived from γδ-T cells exerts dual antitumor activities.

γδ-T cells are innate-like T cells with dual antitumor activities. They can directly eradicate tumor cells and function as immunostimulatory cells to promote antitumor immunity. Previous studies have demonstrated that small extracellular vesicles (EVs) derived from γδ-T cells (γδ-T-EVs) inherited the dual antitumor activities from their parental cells. However, it remains unknown whether γδ-T-EVs can be designed as tumors vaccine to improve therapeutic efficacy. Here, we found that γδ-T-EVs had immune adjuvant effects on antigen-presenting cells, as revealed by enhanced expression of antigen-presenting and co-stimulatory molecules, secretion of pro-inflammatory cytokines and antigen-presenting ability of DCs after γδ-T-EVs treatment. The γδ-T-EVs-based vaccine was designed by loading tumor-associated antigens (TAAs) into γδ-T-EVs. Compared with γδ-T-EVs, the γδ-T-EVs-based vaccine effectively promoted more tumor-specific T-cell responses. In addition, the vaccine regimen preserved direct antitumor effects and induced tumor cell apoptosis. Interestingly, the allogeneic γδ-T-EVs-based vaccine showed comparable preventive and therapeutic antitumor effects to their autologous counterparts, indicating a better way of centralization and standardization in clinical practice. Furthermore, the allogeneic γδ-T-EVs-based vaccine displayed advantages over the DC-EVs-based vaccine through their dual antitumor activities. This study provides a proof-of-concept for using the allogeneic γδ-T-EVs-based vaccine in cancer control.

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents.

The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 5 months after 2 doses, S IgG, S IgG Fc receptor-binding, and neutralising antibody responses waned significantly, yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ+ and IL-2+ CD8+ T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ+ and IL-2+ CD4+ and CD8+ T cell responses in adolescents and adults were comparable or non-inferior. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, against Omicron BA.2, as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1, BA.2 and BA.5. Sera from 100 and 96% of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after three doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.

Validity and reliability of the Chinese version of the Normalization MeAsure Development(NoMAD).

BACKGROUND: The Normalization MeAsure Development (NoMAD) is a brief quantitative tool based on the Normalization Process Theory (NPT), which can measure the implementation process of new technologies and complex interventions. The aim of our study was to translate and culturally adapt the NoMAD into Chinese, and to evaluate the psychometric properties of the Chinese version of NoMAD. METHODS: According to the NoMAD translation guideline, we undertook forward translation, backward translation, and compared these translations to get a satisfactory result, then we performed cognitive interviews to achieve cross-culture adaptation. And the psychometric properties of the final version were evaluated among clinical nurses who used the pressure injuries management system via WeChat mini-program at a tertiary hospital in northwestern China. RESULTS: A total of 258 nurses were enrolled in our study, and the response rate was 92.1%. The Cronbach's alpha of four dimensions were as follow: Coherence (0.768), Cognitive Participation (0.904), Collective Action (0.820), and Reflexive Monitoring (0.808). The overall internal consistency was 0.941. The confirmatory factor analysis results showed a good fit for its theoretical structure (CFI = 0.924, TLI = 0.910, RMSEA = 0.0079, SRMSR = 0.046, χ2/df = 2.61). The item-level content validity index ranged from 0.857 to 1, and the scale-level content validity index was 0.95. There were positive correlations between four constructs scores and three general normalization scores. CONCLUSIONS: The Chinese version of NoMAD is a reliable and valid tool to evaluate the implementation process of innovations.

Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in children and adults with inborn errors of immunity.

Our study (NCT04800133) aimed to determine the safety and immunogenicity in patients with IEIs receiving a 3-dose primary series of mRNA vaccine BNT162b2 (age 12+) or inactivated whole-virion vaccine CoronaVac (age 3+) in Hong Kong, including Omicron BA.1 neutralization, in a nonrandomized manner. Intradermal vaccination was also studied. Thirty-nine patients were vaccinated, including 16 with homologous intramuscular 0.3ml BNT162b2 and 17 with homologous intramuscular 0.5ml CoronaVac. Two patients received 3 doses of intradermal 0.5ml CoronaVac, and 4 patients received 2 doses of intramuscular BNT162b2 and the third dose with intradermal BNT162b2. No safety concerns were identified. Inadequate S-RBD IgG and surrogate virus neutralization responses were found after 2 doses in patients with humoral immunodeficiencies and especially so against BA.1. Dose 3 of either vaccine increased S-RBD IgG response. T cell responses against SARS-CoV-2 antigens were detected in vaccinated IEI patients by intracellular cytokine staining on flow cytometry. Intradermal third dose vaccine led to high antibody response in 4 patients. The primary vaccination series of BNT162b2 and CoronaVac in adults and children with IEIs should include 3 doses for optimal immunogenicity.

Exosomes derived from γδ-T cells synergize with radiotherapy and preserve antitumor activities against nasopharyngeal carcinoma in immunosuppressive microenvironment.

BACKGROUND: Radiotherapy is the first-line treatment for patients nasopharyngeal carcinoma (NPC), but its therapeutic efficacy is poor in some patients due to radioresistance. Adoptive T cell-based immunotherapy has also shown promise to control NPC; however, its antitumor efficacy may be attenuated by an immunosuppressive tumor microenvironment. Exosomes derived from γδ-T cells (γδ-T-Exos) have potent antitumor potentials. However, it remains unknown whether γδ-T-Exos have synergistic effect with radiotherapy and preserve their antitumor activities against NPC in an immunosuppressive tumor microenvironment. METHODS: γδ-T-Exos were stained with fluorescent membrane dye, and their interactions with NPC were determined both in vitro and in vivo. NPC cell deaths were detected after treatment with γδ-T-Exos and/or irradiation. Moreover, effects of γδ-T-Exos on radioresistant cancer stem-like cells (CSCs) were determined. The therapeutic efficacy of combination therapy using γδ-T-Exos and irradiation on NPC tumor progression was also monitored in vivo. Finally, the tumor-killing and T cell-promoting activities of γδ-T-Exos were determined under the culture in immunosuppressive NPC supernatant. RESULTS: γδ-T-Exos effectively interacted with NPC tumor cells in vitro and in vivo. γδ-T-Exos not only killed NPC cells in vitro, which was mainly mediated by Fas/Fas ligand (FasL) and death receptor 5 (DR5)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathways, but also controlled NPC tumor growth and prolonged tumor-bearing mice survival in vivo. Furthermore, γδ-T-Exos selectively targeted the radioresistant CD44+/high CSCs and induced profound cell apoptosis. The combination of γδ-T-Exos with radiotherapy overcame the radioresistance of CD44+/high NPC cells and significantly improved its therapeutic efficacy against NPC in vitro and in vivo. In addition, γδ-T-Exos promoted T-cell migration into NPC tumors by upregulating CCR5 on T cells that were chemoattracted by CCR5 ligands in the NPC tumor microenvironment. Although NPC tumor cells secreted abundant tumor growth factor beta to suppress T-cell responses, γδ-T-Exos preserved their direct antitumor activities and overcame the immunosuppressive NPC microenvironment to amplify T-cell antitumor immunity. CONCLUSIONS: γδ-T-Exos synergized with radiotherapy to control NPC by overcoming the radioresistance of NPC CSCs. Moreover, γδ-T-Exos preserved their tumor-killing and T cell-promoting activities in the immunosuppressive NPC microenvironment. This study provides a proof of concept for a novel and potent strategy by combining γδ-T-Exos with radiotherapy in the control of NPC.

The prevalence and incidence of community-acquired pressure injury: A protocol for systematic review and meta-analysis.

BACKGROUND: Pressure injury (PI) is a serious problem in health care settings globally. It leads to tremendous burden both individuals and healthcare systems. Since 2008, hospital-acquired pressure injuries have been a major focus of nursing quality improvement programs within hospitals and are considered never events. However, insufficiency attention has been paid to community-acquired pressure injuries (CAPI) or pressure ulcers that occur at home or in nursing homes. The prevalence or incidence of community-acquired pressure injury has been reported but never been synthesized in a meta-analysis manner. To fill the gaps in the evidence matrix, the aims of this study are to estimate the prevalence of CAPI in the general population and to pool the overall incidence of CAPI in the general population. METHODS: PubMed, Web of Science, EMBASE, CINHAL, the Cochrane Library, Chongqing VIP, and China National Knowledge Infrastructure were electronically searched to identify eligible studies updated to May 2020 to collect studies on the prevalence or incidence of community-acquired pressure injuries. Two reviewers independently will screen the literature, extracted data, and assess the risk of bias of included studies using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. Meta-analyses of pooled weighted estimates will be calculated using random effect models with 95% CIs reported due to high heterogeneity. RESULTS: Of the 5242 studies initially identified, of the 22 studies (total 479,761 participants) 17 reporting prevalence of community-acquired pressure injury and 5 reporting incidence were included. Other results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will summarize the pooled estimate prevalence and incidence of community-acquired pressure injuries and the pooled estimate of frequencies of different anatomic sites. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required, because this study is a meta-analysis based on published studies. INPLASY REGISTRATION NUMBER: INPLASY202080044.

Investigating the physiological responses of patients listening to music in the intensive care unit.

AIMS: To determine whether definable subtypes exist within a cohort of patients listening to music with regard to their physiological patterns and to compare whether associated factors vary between subjects in groups with different profiles. BACKGROUND: The intensive care unit (ICU) is one of the most stressful environments for patients among various clinical settings in a hospital. ICU patients are not only compromised by illness but also faced with a wide range of stressors. DESIGN: A repeated-measures design was conducted with one music group. METHOD: One hundred and one patients were recruited in three intensive care units in Hong Kong. There were two main outcome variables: demographic characteristics and physiological outcomes. RESULTS: A cluster analysis yielded two clusters. Patients in cluster 1 typically experienced relatively low therapeutic effects from listening to music. There were more males, of a younger age but more educated and employed than patients in cluster 2, and they represented 41.6% of the total respondents. Cluster 2 comprised almost 58.4% of this study sample and they reported high therapeutic effects of music. There were more females in this group as well as more older people and they mainly used a ventilator in the intensive care unit. CONCLUSION: Our study shows that music may have a more positive effect on groups of patients whose profile is similar to that of the patients in cluster 2, than for patients such as those in cluster 1. A clear profile may help health professionals to design appropriate care therapy to target a specific group of patients to improve their physiological outcomes. RELEVANCE TO CLINICAL PRACTICE: The implication of this study is that music therapy should be provided to patients as a relaxation technique if they are willing to accept it, and the selection of music should be based on their preferences. Information should be given to patients so that they can understand how music therapy works and they should be encouraged to focus their attention on listening to the music to maximise its benefits.

Attitudes of midwives towards perinatal bereavement in Hong Kong.

OBJECTIVE: to explore attitudes towards perinatal bereavement care among midwives working in Hong Kong through examination of relationships between attitudes towards bereavement support, need for bereavement education and appropriate hospital policy. DESIGN: a descriptive correlational survey. SETTING: the obstetric and gynaecology units at two hospitals. INSTRUMENT: a structured self-report questionnaire on attitudes towards perinatal bereavement support; required support and education needs for midwives on bereavement care. PARTICIPANTS: 154 out of 202 midwives (76.2% response rate) working at the two units. FINDINGS: two-step cluster analysis yielded two clusters. Cluster 1 consisted of 91 (59.1%) midwives and cluster 2 consisted of 63 (40.9%) midwives. Cluster 2 midwives were younger, had less obstetric and gynaecology experience, junior ranking and less post-qualification education than cluster 1 midwives. Cluster 1 midwives had additional personal grieving experiences and experience of caring for grieving parents. Attitudes towards bereavement care were positively correlated with educational needs (r(s)=0.55, p< 0.001) and hospital policy support (r(s)=0.50, p< 0.001). CONCLUSIONS: Hong Kong midwives require increased bereavement care knowledge and experience, improved communication skills, and greater hospital and team member support. Findings may be used to improve support of midwives, to ensure sensitive bereavement care in perinatal settings and to reflect training needs in the midwifery education curricula. Study findings highlight the universality of grief for a lost baby, irrespective of cultural differences in approaching emotional topics. This study may help midwives internationally to gain a broader perspective in this area.

Music and its effect on the physiological responses and anxiety levels of patients receiving mechanical ventilation: a pilot study.

AIMS AND OBJECTIVES: The aim of this study was to investigate the effects of music on the anxiety of patients on mechanical ventilation, as assessed by objective parameters and a subjective validated anxiety scale. BACKGROUND: Mechanical ventilation, although sometimes lifesaving, is often associated with levels of anxiety requiring sedatives, which has inevitable implications on costs and complications. DESIGN: A randomized controlled trial design. METHODS: A total of 64 subjects was randomly assigned to undergo either 30 minutes of music intervention or a rest period. The subjects were asked to answer the Chinese State Trait Anxiety Inventory scale before and after the study period and physiological indices and resting behaviours were recorded before and after the study period in both groups. The subjects' satisfaction with music was also obtained after music intervention. RESULTS: The findings indicate that patients on mechanical ventilation that listened to a single 30-minute session of music appeared to show greater relaxation as manifested by a decrease in physiological indices and an increase in comfortable resting behaviours. CONCLUSION: Music can provide an effective method of reducing potentially harmful physiological responses arising from anxiety in mechanically ventilated patients. RELEVANCE TO CLINICAL PRACTICE: As indicated by the results of this study, music therapy can act as a simple and safe nursing intervention to allay anxiety and promote patient comfort. Interest and comments on music therapy provided as a relaxation technique should be elicited from both nurses and patients.