Hepatitis B surface antigen seroprevalence among pre- and post-vaccine cohorts in Cambodia, 2017

Background: Hepatitis B virus (HBV) infection is highly endemic in most low income countries including Cambodia. This nationwide serosurvey was conducted to assess the impact of hepatitis B vaccination and to determine whether Cambodia met the WHO regional 2017 target of hepatitis B surface antigen (HBsAg) seroprevalence less than 1% in five-year-old children.Methods: A cross-sectional multi-stage cluster survey was conducted among children born during 2010–2012 and their mothers in Cambodia. HBsAg prevalence was estimated by rapid point-of-care testing, and demographic data, including vaccination history, was collected. Vaccine coverage in children and the prevalence of HBsAg among children and mothers was calculated taking into account the complex survey design. Factors associated with children’s failure to receive timely (within 24 h) vaccination were analysed by multivariate logistic analysis.Findings: A total of 2,520 children 5–7 years old and 2,028 mothers were recruited. In total, 78.4% of children received hepatitis B vaccination birth-dose (HepB-BD); of these, 58.7% were administered ≤ 24 h. Birth at home or “other” location were independent risk factors for children’s failure to receive timely HepB-BD. Overall HBsAg seroprevalence was 4.39% (95%CI: 3.53%–5.45%) among mothers and 0.56% (95%CI: 0.32%–0.98%) among children. The prevalence among children without hepatitis B vaccination was 4.62% (95%CI: 1.31%–14.97%). Among children with a HBsAg-positive mother, prevalence was 10.11% (95%CI: 5.41%–18.11%).Interpretation: Having achieved the 2017 target of less than 1% HBsAg prevalence among 5 years old children, Cambodia can now focus on eliminating mother-to-child transmission of HBV. Moreover, the high HBsAg prevalence among mothers suggests that routine screening with proper linkage to care and treatment is needed. Strengthening measures to improve vaccination coverage further and eliminate mother-to-child transmission by coordinated programming with other services offering additional HBV interventions will help move towards the global goal of hepatitis B elimination by 2030.Funding: As per sources of funding.     

Antigen specific vaccine hesitancy in pregnancy

BackgroundVaccinations in pregnancy are recommended for the potential benefits of preventing severe pertussis disease in newborns and for preventing the impact of influenza on the pregnant woman, her foetus in utero and, the newborn in the first six months of life. Published data in Australia suggested that coverage rates were sub-optimal so the reasons for this were reviewed.MethodsA cross-sectional survey of 1014 postnatal women, aged 18 years and older, who had given birth in the previous six months was undertaken on the Gold Coast in Queensland, Australia. Participants completed a brief questionnaire on provided smart tablets at public vaccination clinics or with a researcher by phone or via an on-line link.ResultsJust over 85% of survey respondents received a pertussis booster with many of those not receiving vaccine having had it in a recent pregnancy. Only 36.7% of respondents had an influenza vaccine in pregnancy with key barriers being belief in influenza vaccine, seasonality of parturition and a lack of recommendation from the attending obstetric carers.DiscussionWhile maternal pertussis vaccine programs are a success, work needs to be done to improve the public perception of the risk benefit equation surrounding influenza vaccine in general, and particularly its use in pregnancy. Research is required into approaches to altering practitioner attitudes as well as how to alter public perceptions.     

The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population

ImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and ParticipantsThis retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined ‘older patient’ as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0.Main Outcomes and MeasuresStudy outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.ResultsOur study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65–74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64–74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28–43.9, 95% CI) and 17 months (0–36.9, 95% CI) in the age <65 and age 64–74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.Conclusion and RelevanceOur results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.     

Sentinel lymph node localization and staging with a low-dose of superparamagnetic iron oxide (SPIO) enhanced MRI and magnetometer in patients with cutaneous melanoma of the extremity - The MAGMEN feasibility study

BackgroundIn patients with melanoma, sentinel lymph node (SLN) status is pivotal for treatment decisions. Current routine for SLN detection combines Technetium^99m (Tc⁹⁹) lymphoscintigraphy and blue dye (BD). The primary aim of this study was to examine the feasibility of using a low dose of superparamagnetic iron oxide (SPIO) injected intracutaneously to detect and identify the SLN, and the secondary aim was to investigate if a low dose of SPIO would enable a preoperative MRI-evaluation of SLN status.MethodsPatients with melanoma of the extremities were eligible. Before surgery, a baseline MRI of the nodal basin was followed by an injection of a low dose (0.02–0.5 mL) of SPIO and then a second MRI (SPIO-MRI). Tc⁹⁹ and BD was used in parallel and all nodes with a superparamagnetic and/or radioactive signal were harvested and analyzed.ResultsFifteen patients were included and the SLNB procedure was successful in all patients (27 SLNs removed). All superparamagnetic SLNs were visualized by MRI corresponding to the same nodes on scintigraphy. Micrometastatic deposits were identified in four SLNs taken from three patients, and SPIO-MRI correctly predicted two of the metastases. There was an association between MRI artefacts in the lymph node and the dose SPIO given.DiscussionIt is feasible to detect SLN in patients with melanoma using a low dose of SPIO injected intracutaneously compared with the standard dual technique. A low dose of SPIO reduces the lymph node MRI artefacts, opening up for a non-invasive assessment of SLN status in patients with cancer.     

On the Relationship between Dynamic Contrast-Enhanced Ultrasound Parameters and the Underlying Vascular Architecture Extracted from Acoustic Angiography

Dynamic contrast-enhanced ultrasound (DCE-US) has been proposed as a powerful tool for cancer diagnosis by estimation of perfusion and dispersion parameters reflecting angiogenic vascular changes. This work was aimed at identifying which vascular features are reflected by the estimated perfusion and dispersion parameters through comparison with acoustic angiography (AA). AA is a high-resolution technique that allows quantification of vascular morphology. Three-dimensional AA and 2-D DCE-US bolus acquisitions were used to monitor the growth of fibrosarcoma tumors in nine rats. AA-derived vascular properties were analyzed along with DCE-US perfusion and dispersion to investigate the differences between tumor and control and their evolution in time. AA-derived microvascular density and DCE-US perfusion exhibited good agreement, confirmed by their spatial distributions. No vascular feature was correlated with dispersion. Yet, dispersion provided better cancer classification than perfusion. We therefore hypothesize that dispersion characterizes vessels that are smaller than those visible with AA.     

Association of PD-L1 gene rs4143815 C>G polymorphism and human cancer susceptibility: A systematic review and meta-analysis

Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer.     

Tongue cancer treatment and oncological outcomes: The role of glossectomy classification

BackgroundNowadays surgery remains the gold standard of treatment for tongue cancer. Via a more clear and precise terminology, the glossectomy classification by Ansarin et al. facilitates shared communication between surgeons, allowing comparison between published research and improving surgical practice and patient care. To establish the association of glossectomies, according to their classification by Ansarin et al. with overall survival (OS), disease-free survival (DSF), and cause-specific survival (CSS) in tongue cancer, we conducted a systemic retrospective study on 300 consecutive patients affected by primary oral tongue cancer and treated with surgery at the European Institute of Oncology, IRCCS (IEO).MethodsThree hundred patients with tongue squamous cell carcinoma and treated at the Division of Otorhinolaryngology and Head and Neck Surgery of the European Institute of Oncology, IRCCS were cataloged according to the glossectomy classification. OS, DFS, and CSS were compared by surgical treatments.ResultsOS-5yrs was 80% for the type I glossectomy group, 75% for type II, 65% for type III, and 35% for type IV-V. DFS-5yrs was 74%, 60%, 55%, and 27%, respectively for I, II, III, and IV-V glossectomy group; CSS-5yrs was 82%, 80%, 72%, and 48%, respectively for I, II, III, and IV-V glossectomy group (p < 0.01).ConclusionsThis study confirmed that the application of the glossectomy classification was statistically correlated with patients' oncological outcomes.     

The influence of environmental and health indicators on premature mortality: An empirical analysis of the City of Toronto's 140 neighborhoods

The objective of this paper was to assess the link between premature mortality and a combination of neighbourhood contextual (environmental and health) and compositional (socioeconomic and demographic) characteristics. We statistically and spatially examined six environmental variables (ultrafine particles, carcinogenic and non-carcinogenic pollutants, pollution released to air, tree cover, and walkability index), six health service indicators (number health providers, breast, colorectal and cervical cancer screening uptake rates, student nutrition program uptake rates, and healthy food index), and eight socioeconomic indicators (total income, Gini coefficient, two age categories – below and above 40 years, proportion of females to males, visible minorities, Indigenous peoples, education, less than grade 9) among 140 neighbourhoods of the City of Toronto in Ontario (Canada). We applied principal component analysis to identify patterns and to reduce the number of explanatory variables into combined component axes that represent unique variation in these confounded and overlapping factors. We then applied regression analysis to model the relationship between the indices of enviro-health and socioeconomics and their potential relationship with premature mortality. Residual spatial analysis was used to investigate any remaining spatial structure (such as neighbourhoods with higher residual premature mortality rates). Neighbourhood Equity Index was correlated with our enviro-health and socioeconomic indices. Premature mortality within neighbourhoods was predicted by poor cancer screenings, pollution, lack of tree canopy, increased uptake of student nutrition programs and high walkability index. A negative association between premature mortality and pollution was associated low walkability index and presence of visible minorities within neighbourhoods. There was some unexplained residual spatial variation in our model of premature mortality - especially along the shores of Lake Ontario and in neighbourhoods with major highways or road corridors: premature mortality in Toronto neighbourhoods was higher than expected along highway-corridor neighbourhoods and shorelines. Our analysis revealed a significant relationship between neighbourhood contextual features – both environmental and health – and premature mortality, suggesting that these contextual components of neighbourhoods can predict rates of urban premature mortality in Toronto.