Reduced risk of CIN2+ recurrence in women immunized with a 9-valent HPV vaccine post-excision: Retrospective cohort study.

The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.

High PD-L1 expression on immune cells along with increased density of tumor-infiltrating lymphocytes predicts a favorable survival outcome for patients with loco-regionally advanced head and neck cancer: early results from a prospective study.

Introduction: In the era of personalized medicine and treatment optimization, use of immune biomarkers holds promise for estimating the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive treatment. Methods: To evaluate the prognostic potential of immune biomarkers, we conducted a prospective monocentric cohort study with loco-regionally advanced HNSCC patients indicated for definitive radiotherapy/radiochemotherapy at the Department of Oncology, Ostrava University Hospital, Czech Republic, between June 2020 and August 2023. We focused on the expression of programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) relative to overall survival (OS) and specific survival rates. Associations between biomarkers and survival rates were assessed by crude and adjusted hazard ratios (cHR, aHR, respectively) obtained from Cox proportional hazards regression. Results: Among a total of 55 patients within a median follow-up of 19.7 months, there were 21 (38.2%) all-cause deaths and 15 (27.3%) cancer-related deaths. An overall survival (OS) rate of 61.8% and a disease-specific survival (DSS) rate of 72.7% were recorded. A significant association between survival rates and a ≥10% difference in PD-L1 expression on immune versus tumor cells (high PD-L1IC expression) was documented regardless of the type of analysis (univariate or multivariate). In addition, a stronger association was confirmed for OS and the composite biomarker high PD-L1IC expression along with either median-higher CD8+ TIL count or increased TIL density ≥30%, as indicated by an aHR of 0.08 (95% CI, 0.01 to 0.52) and 0.07 (95% CI, 0.01 to 0.46), respectively. Similar results were demonstrated for other specific survival rates. Discussion: The early outcomes of the present study suggest the utility of a strong prognostic factor involving a composite biomarker high PD-L1IC expression along with increased TIL density in HNSCC patients undergoing definitive radiotherapy and radiochemotherapy. Trial registration: The study is registered with Clinicaltrials.gov. - NCT05941676.

Understanding the time-driven shifts of vaccine effectiveness against any and severe COVID-19 before and after the surge of Omicron variants within 2.5 years of vaccination: A meta-regression.

OBJECTIVES: The COVID-19 pandemic required rapid development of vaccines within a short period of time which did not allow to assess vaccine effectiveness (VE) in the long-term. METHODS: A computerized literature search was undertaken to identify eligible studies, with no language restrictions, published between 1 December 2020 and 30 June 2023. RESULTS: Out of a total of 27,597 publications, 761 studies were included. Early VE of 87.2% decreased to 55.1% after 9 months among populations fully immunized not only with mRNA (proxy mRNA) vaccines, and 66.3% decreased to 23.5% in populations immunized exclusively with non-mRNA vaccines. Protection against severe COVID-19 declined to 80.9% for proxy mRNA vaccines and 67.2% for non-mRNA vaccines. Omicron variants significantly diminished VE. Within 6-8 months of receiving a single booster of an mRNA vaccine, VE declined to 14.0% and 67.7% for any and severe COVID-19, respectively. Multiple mRNA booster doses restored protection that declined to 29.5% and 70.6% for any and severe COVID-19, respectively, within 5-7 months. CONCLUSION: Outcomes of this meta-regression underscore the evolving nature of COVID-19 in response to vaccination, dosing schedules, and emerging variants, and provide crucial insights for public health interventions and vaccination strategies.

Timing of HPV vaccination as adjuvant treatment of CIN2+ recurrence in women undergoing surgical excision: a meta-analysis and meta-regression.

OBJECTIVE: The main aim was to determine the overall vaccine effectiveness (VE) against recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+) including specific VE associated with timing of human papillomavirus (HPV) vaccination using data from published studies. DESIGN: Meta-analysis and meta-regression. DATA SOURCES: A computerised literature search was undertaken using the MEDLINE, EMBASE, International Pharmaceutical Abstracts, Derwent Drug File, ProQuest Science and Technology, Cochrane and MedRxiv databases. To be eligible, the studies, with no language restrictions, had to be published between 1 January 2001 and 25 May 2023. REVIEW METHODS: Included were studies with an unvaccinated reference group that assessed CIN2+ recurrence irrespective of the HPV genotype in women undergoing conisation provided. The present study was carried out in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines. The risk of study bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to assess the strength of evidence for the primary outcome. Data synthesis was conducted using meta-analysis and meta-regression. RESULTS: Out of a total of 14 322 publications, 20 studies with a total of 21 estimates were included. The overall VE against recurrent CIN2+ irrespective of the HPV genotype achieved 69.5% (95% CI: 54.7% to 79.5%). While the HPV vaccine valency, follow-up duration, type of study including its risk of bias had no effect on VE, the highest VE of 78.1% (95% CI: 68.7% to 84.7%) was reported for women receiving their first dose not earlier than the day of excision. This outcome was supported by additional analyses and a VE prediction interval ranging from 67.1% to 85.4%. CONCLUSIONS: The outcome of this meta-analysis and meta-regression convincingly showed the beneficial effect of post-excisional HPV vaccination against CIN2+ recurrence. Studies published to date have been unable to determine whether or not vaccination, completed or initiated before conisation, would be associated with more favourable results. PROSPERO REGISTRATION NUMBER: CRD42022353530.

BMI-Associated Anti-Apolipoprotein A-1 Positivity in Healthy Adults after mRNA-Vaccination against COVID-19.

Elevated anti-apolipoprotein A-1 (AAA1) antibody levels associated with cardiovascular risk have been observed in previously SARS-CoV-2-infected or COVID-19-vaccinated individuals. Since patient safety is generally a priority in vaccination, we sought to investigate AAA1 antibody levels in healthy adults after mRNA vaccination. We conducted a prospective cohort study in healthy adult volunteers recruited from military workers of the Transport Air Base in Prague who had received two doses of mRNA vaccines. Anti-apolipoprotein A-1 antibody levels were determined using ELISA from serum samples obtained at three and four time points after the first and second vaccine doses, respectively, within almost 17 weeks of follow-up. The transient AAA1 positivity rate achieved 24.1% (95% confidence interval CI: 15.4-34.7%), i.e., 20 out of 83 participants had at least one positive post-vaccination sample, with a repeat positivity confirmed in only 5 of them. This rate was associated with a BMI > 26 kg/m2, as documented by an adjusted odds ratio of 6.79 (95% CI: 1.53-30.01). In addition, the highest positivity rate of 46.7% (21.3-73.4%) was observed in obese subjects with >30 kg/m2. Since the incidence rate of AAA1 positivity remained unchanged after the first and second vaccine doses, any relationship between AAA1 positivity and mRNA vaccination was inconclusive. The present study showed a transient AAA1 positivity rate associated with overweight or obesity without a proven association with mRNA vaccination.

Programmed Cell Death Ligand 1 Expression on Immune Cells and Survival in Patients With Nonmetastatic Head and Neck Cancer: A Systematic Review and Meta-analysis.

Importance: The failure or success of radical treatment in patients with head and neck squamous cell carcinoma (HNSCC) is associated with many known and unknown factors; hence, there is a search for further prognostic markers to help optimize therapeutic strategy and improve treatment outcomes. Objective: To assess the association of programmed cell death ligand 1 (PD-L1) expression on immune or tumor cells, including its composite expression on both cell types, with overall survival (OS) or specific survival. Data Sources: MEDLINE, Embase, PQSciTech, and HCAPlus databases were systematically searched for cohort studies focused on the prognostic role of PD-L1 expression in patients with HNSCC in curative stages of the disease. Search results generated publications from January 1, 2010, to January 6, 2023. Study Selection: Of 3825 publications identified, a total of 17 cohort studies in the English language met inclusion criteria of this systematic review and meta-analysis. Eligible studies reported adjusted hazard ratios (aHRs) with 95% CIs for the association of PD-L1 expression levels with OS and arbitrary specific survival. Data Extraction and Synthesis: Data from studies were extracted independently by 2 researchers strictly adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines and recommendations. The risk of bias was assessed using the Quality in Prognosis Studies tool and Newcastle-Ottawa Scale. Pooled effect estimates were obtained using a random-effect or fixed-effect model based on homogeneity of studies. Main Outcomes and Measures: The primary outcome was to investigate whether there was an association between PD-L1 expression on immune or tumor cells and OS. Results: In 17 cohort studies of the association of PD-L1 expression with survival in 3190 patients with HNSCC, high PD-L1 expression on immune cells was associated with a favorable OS (pooled aHR, 0.39; 95% CI, 0.25-0.59). There was no association between composite PD-L1 expression on immune and tumor cells and OS (pooled aHR, 0.79; 95% CI, 0.55-1.14) or between PD-L1 expressed only on tumor cells and OS (pooled aHR, 1.22; 95% CI, 0.87-1.70). A high level of PD-L1 expression on immune cells was associated with favorable specific survival (pooled aHR, 0.52; 95% CI, 0.38-0.72). There were no interactions between tumor location or type of primary treatment (ie, surgery vs radiotherapy or radiochemotherapy) and the association between PD-L1 expression and OS. Conclusions and Relevance: This study's findings suggest that PD-L1 expression on immune cells may serve as a new prognostic biomarker in patients with HNSCC. However, future studies may be warranted to verify this potential role given the limited number of studies on this topic conducted and published to date.

Risk factors affecting COVID-19 vaccine effectiveness identified from 290 cross-country observational studies until February 2022: a meta-analysis and meta-regression.

BACKGROUND: Observational studies made it possible to assess the impact of risk factors on the long-term effectiveness of mRNA and adenoviral vector (AdV) vaccines against COVID-19. METHODS: A computerized literature search was undertaken using the MEDLINE, EMBASE, and MedRxiv databases to identify eligible studies, with no language restrictions, published up to 28 February 2022. Eligible were observational studies assessing vaccine effectiveness (VE) by disease severity with reference groups of unvaccinated participants or participants immunized with one, two, or three vaccine doses. Our study was carried out in compliance with the PRISMA and MOOSE guidelines. The risk of study bias was identified using the Newcastle-Ottawa Quality Assessment Scale. The GRADE guidelines were applied to assess the strength of evidence for the primary outcome. The synthesis was conducted using a meta-analysis and meta-regression. RESULTS: Out of a total of 14,155 publications, 290 studies were included. Early VE of full vaccination against COVID-19 of any symptomatology and severity decreased from 96% (95% CI, 95-96%) for mRNA and from 86% (95% CI, 83-89%) for AdV vaccines to 67% for both vaccine types in the last 2 months of 2021. A similar 1-year decline from 98 to 86% was found for severe COVID-19 after full immunization with mRNA, but not with AdV vaccines providing persistent 82-87% effectiveness. Variant-reduced VE was only associated with Omicron regardless of disease severity, vaccine type, or vaccination completeness. The level of protection was reduced in participants aged >65 years, with a comorbidity or those in long-term care or residential homes independently of the number of doses received. The booster effect of the third mRNA dose was unclear because incompletely restored effectiveness, regardless of disease severity, declined within a short-term interval of 4 months. CONCLUSIONS: Full vaccination provided an early high, yet waning level of protection against COVID-19 of any severity with a strong impact on the high-risk population. Moreover, the potential risk of new antigenically distinct variants should not be underestimated, and any future immunization strategy should include variant-updated vaccines.

Links between macrophages in perivascular adipose tissue and arterial wall: a role in atherosclerosis initiation?

BACKGROUND: Inflammation of adipose tissue in relation to atherosclerosis is currently widely studied in patients with advanced disease. However, data regarding polarization of adipose tissue and arterial wall macrophages and their mutual link in the early stages of atherosclerosis are scarce. The main aim of this cross-sectional study was to characterize macrophage subpopulations in arterial wall and adjacent adipose tissue; and to determine links between different subpopulations in a relatively healthy population living kidney donors. METHODS: The presence of cardiovascular risk factors was established in 68 living kidney donors. Macrophage polarization was analyzed by flow cytometry and confirmed by RT-PCR in samples of visceral adipose tissue, renal artery and adjacent perivascular adipose tissue collected during hand-assisted retroperitoneoscopic nephrectomy. RESULTS: CD14+CD16+CD36high macrophages were found only in adipose tissues and were strongly positively associated with several cardiovascular risk factors. The CD14+CD16+CD36low subpopulation was positively associated with the presence of several cardiovascular risk factors to a lesser extent in all studied tissues. In contrast, the proportion of CD14+CD16-CD36low macrophages was negatively linked to several cardiovascular risk factors and increased in subjects on statin therapy. The proportion of CD14+CD16+CD36low macrophages in perivascular, not visceral adipose tissue was associated with that of both macrophage subtypes in the arterial wall, suggesting a direct link between perivascular adipose tissue and the arterial wall. CONCLUSIONS: We confirmed the association of three macrophage subtypes in adipose tissue and arterial wall to the studied cardiovascular risk factors. Macrophage polarization in perivascular, but not visceral adipose tissue was linked to macrophage polarization in the arterial wall.

SARS-CoV-2 vaccination in the context of original antigenic sin.

Immunological memory is the ability of the adaptive immune system to ensure a persistent protective effect after immunization. However, it can also be a limitation to building a sufficient level of protective antibodies specific to new mutations of the virus. It is imperative to bear this phenomenon (called "original antigenic sin") in mind and make every effort to overcome its inherent pitfalls when updating current and designing new vaccines.

Can Vaccination Trigger Autoimmune Disorders? A Meta-Analysis.

Vaccination as an important tool in the fight against infections has been suggested as a possible trigger of autoimmunity over the last decades. To confirm or refute this assumption, a Meta-analysis of Autoimmune Disorders Association With Immunization (MADAWI) was conducted. Included in the meta-analysis were a total of 144 studies published in 1968-2019 that were available in six databases and identified by an extensive literature search conducted on 30 November 2019. The risk of bias classification of the studies was performed using the Newcastle-Ottawa Quality Assessment Scale. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. While our primary analysis was conducted in terms of measures of association employed in studies with a low risk of bias, the robustness of the MADAWI outcome was tested using measures independent of each study risk of bias. Additionally, subgroup analyses were performed to determine the stability of the outcome. The pooled association of 0.99 (95% confidence interval, 0.97-1.02), based on a total of 364 published estimates, confirmed an equivalent occurrence of autoimmune disorders in vaccinated and unvaccinated persons. The same level of association reported by studies independently of the risk of bias was supported by a sufficient number of studies, and no serious limitation, inconsistency, indirectness, imprecision, and publication bias. A sensitivity analysis did not reveal any discrepancy in the primary result. Current common vaccination is not the cause of any of the examined autoimmune disorders in the medium and long terms.

Statins Directly Influence the Polarization of Adipose Tissue Macrophages: A Role in Chronic Inflammation.

Statins represent one of the most widely used classes of drugs in current medicine. In addition to a substantial decrease in atherogenic low density lipoprotein (LDL) particle concentrations, several large trials have documented their potent anti-inflammatory activity. Based on our preliminary data, we showed that statins are able to decrease the proportion of pro-inflammatory macrophages (CD14+16+CD36high) in visceral adipose tissue in humans. In the present study including 118 healthy individuals (living kidney donors), a very close relationship between the pro-inflammatory macrophage proportion and LDL cholesterol levels was found. This was confirmed after adjustment for the most important risk factors. The effect of statins on the proportion of pro-inflammatory macrophages was also confirmed in an experimental model of the Prague hereditary hypercholesterolemia rat. A direct anti-inflammatory effect of fluvastatin on human macrophage polarization in vitro was documented. Based on modifying the LDL cholesterol concentrations, statins are suggested to decrease the cholesterol inflow through the lipid raft of macrophages in adipose tissue and hypercholesterolemia to enhance the pro-inflammatory macrophage phenotype polarization. On the contrary, due to their opposite effect, statins respond with anti-inflammatory activity, affecting the whole organism.

The Effectiveness of Post-Vaccination and Post-Infection Protection in the Hospital Staff of Three Prague Hospitals: A Cohort Study of 8-Month Follow-Up from the Start of the COVID-19 Vaccination Campaign (COVANESS).

Continuous assessment of the effectiveness of approved COVID-19 vaccines is crucial to gain an insight into the longer-term impact on health outcomes, and eventually boosting public confidence. For this reason, we conducted a multicenter, retrospective cohort study using data on infection and vaccination rates among employees of three Prague hospitals in the period between 27 December 2020 and 31 August 2021. The post-vaccination and post-infection protectiveness were assessed in a total of 11,443 hospital workers who were followed up for more than 14 days either after their Comirnaty vaccination or study enrolment, depending on their previous SARS-CoV-2 infection. The effectiveness of full vaccination against any SARS-CoV-2 infection achieved 88.3% (83.2-91.8%) over the eight months of follow-up, a figure not much different from the 92.5% (76.5-97.6%) level of protection built by a previous infection. Despite this, the post-vaccination level of protection declined to about 65% between June and August. No case of breakthrough infection was registered among hospital workers having received one or two vaccine doses more than three months after previous infection. The eight-month effectiveness of the Comirnaty vaccine exhibited a declining trend requiring a new booster dose. The need for vaccination in the previously infected employees was not demonstrated conclusively in this study.

Long-term outcomes of thrombectomy for acute ischaemic stroke by occluded artery and stroke aetiology: a PRAGUE-16 substudy.

BACKGROUND: Thrombectomy is an effective treatment for acute ischaemic stroke (AIS). AIMS: The aim of this study was to compare clinical outcomes with intracranial artery occlusion site among AIS patients treated in the setting of a cardiology cath lab. METHODS: This was a single-centre, prospective registry of 214 consecutive patients with AIS enrolled between 2012 and 2018. All thrombectomy procedures were performed in a cardiology cath lab with stent retrievers or aspiration systems. The functional outcome was assessed by the modified Rankin Scale (mRS) after three months. RESULTS: Ninety-three patients (44%) had middle cerebral artery (MCA) occlusion, 28 patients (13%) had proximal internal carotid artery (ICA) occlusion, 27 patients (13%) had tandem (ICA+MCA) occlusion, 39 patients (18%) had terminal ICA (T-type) occlusion, and 26 patients (12%) had vertebrobasilar (VB) stroke. Favourable clinical outcome (mRS ≤2) was reached in 58% of MCA occlusions and in 56% of isolated ICA occlusions, but in only 31% of T-type occlusions and in 27% of VB stroke. Poor clinical outcome in T-type occlusions and VB strokes was influenced by the lower recanalisation success (mTICI 2b-3 flow) rates: 56% (T-type) and 50% (VB) compared to 82% in MCA occlusions, 89% in isolated ICA occlusions and 96% in tandem occlusions. CONCLUSIONS: Catheter-based thrombectomy achieved significantly better clinical results in patients with isolated MCA occlusion, isolated ICA occlusions or tight stenosis and tandem occlusions compared to patients with T-type occlusion and posterior strokes. Visual summary. Endovascular intervention of isolated MCA or ICA occlusions provides greatest clinical benefit, while interventions in posterior circulation have lower chance for clinical success.

Risk of Breast Cancer Revealed by Mammographic Screening in Czech Women Aged 40-45 Years, a Monocentric Cohort Study.

The aim of the present study was to evaluate breast cancer risk in women aged 40-45 years not included in the routine mammographic screening programme in the Czech Republic and to assess the suitability of the screening interval. Our cohort study was conducted using registry data of one mammography centre (Bulovka Hospital in Prague) between 1 January 2008 and 31 December 2017. The risk of breast cancer was evaluated using a positive predictive finding (PPF) corresponding to the Breast Imaging-Reporting and Data System (BI-RADS) scores of 4 and 5. The annual PPF incidence rate achieved 2.25 per 1000 women aged 40-45 years and was not significantly different from that (3.31) of women of 45-50 years of age as demonstrated by an adjusted hazard ratio of 0.75 (95% confidence interval: 0.42-1.33). It was found that a screening interval longer than 3 years increased the chance of PPF occurrence 1.7 times independently of the women's age, signalling a risk of failure of early detection of breast cancer. The same PPF incidence rates both in women aged 40-45 years and in older ones indicates that even younger women should be eligible for enrolment in the routine mammographic screening programme in the Czech Republic.

A Serosurvey Identifying Vulnerability to Measles in Health Care Workers. A Hospital-Based Prospective Seroprevalence Study.

The aim of this serological survey was to assess the persistence of measles antibodies among health care workers (HCWs) at risk of incidental measles. A prospective study of measles-specific antibodies in serum samples obtained from a total of 2782 participants aged 19-89 years was conducted between May 2018 and December 2019. The seropositivity rate of 93.7% (95% CI: 92.4-94.9%) in fully vaccinated participants aged 19-48 years was significantly lower than that of 98.0% (95% CI: 96.5-99.0%) in participants naturally immunised before 54 years. A cohort of those born in 1971-1975, vaccinated predominantly with one dose, showed lower seropositivity persistence (86.6%) than those fully vaccinated with two doses or naturally immunised. Otherwise, seropositivity was not markedly influenced by sex, age, smoking status, overweight, obesity or concomitant disease. The presence of sufficient antibody levels in a high proportion of HCWs irrespective of the way they acquired immunity is a favourable finding for managing incidental measles; hence, in the presence of a risk of a measles outbreak, it would be possible to perform targeted vaccination of only at-risk HCWs with a history of incomplete vaccination or missing information about the way in which immunity is acquired.

Is an Increased Risk of Developing Guillain-Barré Syndrome Associated with Seasonal Influenza Vaccination? A Systematic Review and Meta-Analysis.

While the weight of epidemiological evidence does not support a causal link with influenza vaccination evaluated over the last 30 years, Guillain-Barré syndrome (GBS) has been considered a vaccine-associated adverse event of interest since 1976. To investigate the existence of GBS risk after vaccination against seasonal influenza, a systematic review and meta-analysis have been conducted based on 22 eligible epidemiological studies from 1981 to 2019 reporting 26 effect sizes (ESs) in different influenza seasons. The primary result of our meta-analysis pointed to no risk of vaccine-associated GBS, as documented by a pooled ES of 1.15 (95% CI: 0.97-1.35). Conversely, an obvious high risk of GBS was observed in patients with previous influenza-like illness (ILI), as demonstrated by a pooled ES of 9.6 (95% CI: 4.0-23.0) resulting from a supplementary analysis. While the meta-analysis did not confirm the putative risk of vaccine-associated GBS suggested by many epidemiological studies, vaccination against seasonal influenza reduced the risk of developing ILI-associated GBS by about 88%. However, to obtain strong evidence, more epidemiological studies are warranted to establish a possible coincidence between vaccination and ILI prior to GBS onset.

Factors Influencing Persistence of Diphtheria Immunity and Immune Response to a Booster Dose in Healthy Slovak Adults.

We assessed the long-term persistence of humoral immunity against diphtheria in adults with childhood vaccination and the immunogenicity of a booster dose considering demographic, behavioural and vaccinating factors. We conducted a trial in 200 healthy Slovak adults aged 24-65 years, immunised against diphtheria in childhood and against tetanus at regular 10-15 year intervals, and receiving a dose of a tetanus-diphtheria toxoid vaccine. The response was determined by ELISA antibody concentrations of paired sera before and at 4 weeks post-vaccination. A seroprotection rate of 21% (95% confidence interval, CI 15.6-27.3%) was found in adults up to 59 years since the last vaccination with seroprotective levels of antibodies against diphtheria ≥0.1 IU/mL and a geometric mean concentration of 0.05 IU/mL. Conversely, seropositive levels ≥0.01 IU/mL were observed in 98% of adults (95% CI 95-99.5%). Booster-induced seroprotection was achieved in 78% of adults (95% CI 71.6-83.5%) clearly depending on pre-booster antibody levels correlating with age and time since the last vaccination. Moreover, only 54.2% of smokers and 53.3% of patients on statins exhibited seroprotection. Booster vaccination against diphtheria was unable to confer seroprotection in all recipients of only childhood vaccination.

Cardiovascular disease predictors and adipose tissue macrophage polarization: Is there a link?

Background The risk of cardiovascular disease is closely connected to adipose tissue inflammation. The links between cardiovascular risk predictors and pro and anti-inflammatory macrophages in human adipose tissue were analysed to gain an insight into the pathophysiology of cardiovascular disease. Design Subcutaneous and visceral adipose tissues were obtained from 79 subjects, 52 living kidney donors (during nephrectomy) and 27 patients with peripheral artery disease (during arterial tree reconstruction). Methods Macrophage subsets were isolated from adipose tissues and analysed by flow cytometry using CD14, CD16, CD36 and CD163 monoclonal antibodies. The mutually adjusted differences of phagocytic pro-inflammatory (CD14 + CD16 + CD36high), anti-inflammatory (CD14 + CD16-CD163+) and transitional subsets of macrophages were analysed in relation to cardiovascular predictors (sex, age, body mass index, smoking, hypercholesterolaemia, hypertension and statin treatment). Results Age, male sex and hypercholesterolaemia were closely positively associated with the phagocytic pro-inflammatory macrophage subset in visceral adipose tissues. Interestingly, the proportion of phagocytic pro-inflammatory macrophages was relevantly decreased by statin therapy. A strong positive association of body mass index to the phagocytic pro-inflammatory subset was found in subcutaneous adipose tissues only. A minor transitional subpopulation, CD14 + CD16 + CD36lowCD163+, increased with age in both adipose tissues. This transitional subpopulation was also negatively associated with obesity and hypercholesterolaemia in visceral adipose tissues. Conclusion An effect of cardiovascular risk predictors on adipose tissue macrophage subpopulations was revealed. Interestingly, while age, male sex and hypercholesterolaemia were connected with the pro-inflammatory macrophage subpopulation in visceral adipose tissues, body mass index had a prominent effect in subcutaneous adipose tissues only. A decreasing effect of statins on these pro-inflammatory macrophages was documented.

Epidemiology of Invasive Pneumococcal Disease in Czech Children under 5 Years of Age after Routine Immunisation.

BACKGROUND: The introduction of the surveillance of invasive pneumococcal diseases (IPD) in 2007 has helped to monitor changes in serotype occurrence in the Czech population and assess the impact of routine immunisation against IPD on the child population under 5 years of age. METHODS: Observational study of childhood IPD in the Czech Republic based on the state public health surveillance data comparing pre-immunisation (2007-2008) and post-immunisation (2012-2013) periods. RESULTS: In the child population there was an overall decline in IPD occurrence of 46.6% (95% CI 63.4-21.9) observed during the post-immunisation period. There was even greater decrease of 71.6% (95% CI 50.4-83.8) in vaccinated children. In the post-immunisation period, Prevenar 13 (PCV13) and Synflorix (PCV10) contributed to a vaccine-type IPD reduction of 95.4% (95% CI 67.0-99.4) and 76.9% (95% CI 36.0-91.7), respectively, compared to unimmunised children. The occurrence of 10 serotypes contained in both commercial vaccines also decreased in unvaccinated children by 61.4% (95% CI 14.5-82.6). However, a rise in the risk of non-vaccine and unspecified serotype acquisition by up to 153% was revealed in unimmunised children when comparing post-immunisation and pre-immunisation periods. CONCLUSIONS: The findings suggest a shift in IPD caused either by vaccine or non-vaccine serotypes between immunised and unimmunised populations of children, which could result in increased incidence of IPD caused by non-vaccine serotypes. Therefore, routine immunisation using only one vaccine with broader serotype coverage together with a higher vaccination rate could raise hopes of further decrease in IPD in the child population.