Pulled in or pushed out : understanding the complexities of motivation for alternative therapies use in Ghana

The impact of strong cultural beliefs on specific reasons for traditional medicine (TRM) use among individuals and populations has long been advanced in health care and spatio-medical literature. Yet, little has been done in Ghana and the Ashanti Region in particular to bring out the precise “pull” and “push” relative influences on TRM utilization. With a qualitative research approach involving rural and urban character, the study explored health beliefs and motivations for TRM use in Kumasi Metropolis and Sekyere South District, Ghana. The study draws on data from 36 in-depth interviews with adults, selected through theoretical sampling. We used the a posteriori inductive reduction model to derive broad themes and subthemes. The “pull factors”—perceived benefits in TRM use vis-à-vis the “push factors”—perceived poor services of the biomedical treatments contributed to the growing trends in TRM use. The result however indicates that the “pull factors,” viz.—personal health beliefs, desire to take control of one’s health, perceived efficacy, and safety of various modalities of TRM—were stronger in shaping TRM use. Poor access to conventional medicine accounted for the differences in TRM use between rural and urban areas. Understanding the treatment and health-seeking behaviour of a cultural-related group is critical for developing and sustaining traditional therapy in Ghana

Study protocol for VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer, a UK multicentre randomised controlled trial with an internal pilot (the VIOLET study)

INTRODUCTION: Lung cancer is a leading cause of cancer deaths worldwide and surgery remains the main treatment for early stage disease. Prior to the introduction of video-assisted thoracoscopic surgery (VATS), lung resection for cancer was undertaken through an open thoracotomy. To date, the evidence base supporting the different surgical approaches is based on non-randomised studies, small randomised trials and is focused mainly on short-term in-hospital outcomes. METHODS AND ANALYSIS: The VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer study is a UK multicentre parallel group randomised controlled trial (RCT) with blinding of outcome assessors and participants (to hospital discharge) comparing the effectiveness, cost-effectiveness and acceptability of VATS lobectomy versus open lobectomy for treatment of lung cancer. We will test the hypothesis that VATS lobectomy is superior to open lobectomy with respect to self-reported physical function 5 weeks after randomisation (approximately 1 month after surgery). Secondary outcomes include assessment of efficacy (hospital stay, pain, proportion and time to uptake of chemotherapy), measures of safety (adverse health events), oncological outcomes (proportion of patients upstaged to pathologic N2 (pN2) disease and disease-free survival), overall survival and health related quality of life to 1 year. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment. ETHICS AND DISSEMINATION: This trial has been approved by the UK (Dulwich) National Research Ethics Service Committee London. Findings will be written-up as methodology papers for conference presentation, and publication in peer-reviewed journals. Many aspects of the feasibility work will inform surgical RCTs in general and these will be reported at methodology meetings. We will also link with lung cancer clinical studies groups. The patient and public involvement group that works with the Respiratory Biomedical Research Unit at the Brompton Hospital will help identify how we can best publicise the findings

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer

Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population. Moreover, we demonstrate that Vδ1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral Vδ1 T cells possessed stem-like features and were skewed toward cytolysis and helper T cell type 1 function, akin to intratumoral natural killer and CD8+ T cells considered beneficial to the patient. Indeed, ongoing remission post-surgery was significantly associated with the numbers of CD45RA−CD27− effector memory Vδ1 T cells in tumors and, most strikingly, with the numbers of CD103+ tissue-resident Vδ1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating Vδ1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer

Smallholder Farmers’ Livelihood Security Options amidst Climate Variability and Change in Rural Ghana

Farming as a livelihood activity in the Bosomtwe District is threatened by climate change. This paper ascertained the alternative livelihood options of smallholder farmers against climate variability and change in the Bosomtwe District. Using a cross-sectional survey, 152 smallholder farmers were sampled from 12 communities using a multistage sampling procedure. The quantitative data collected were subjected to binary logistic regression analysis, contingency tables, frequencies, and Nagelkerke tests of association, embedded in the statistical package for social sciences (SPSS) v.17. The results indicate that farmers are resorting to alternative livelihood activities that are less capital intensive and require less skill in order to secure income and household food supply. Significant determinants of farmers’ alternative livelihood are age, household size, and household food supply, which were significant at p<.030, p<.019, and p<.012, respectively. At a 95% confidence interval (CI), these variables had lower to upper CIs for each of the EXP (B), respectively, at CI = 1.134–12.524, CI = 1.359–30.224, and CI = 1.781–104.561, respectively. The paper recommends that government institutes policies that will create opportunities and draw on various local/grassroots opportunities and resources to expand farmers’ asset base for sustainable livelihood strategies

Paraplegia following oesophagectomy

We report a rare case of postoperative paraplegia in a patient with carcinoma of the oesophagus following oesophagectomy. Neurological deficit was characterised by loss of sensation from the spinal level T2 down to T6, together with flaccid paraparesis of both lower extremities. This was initially thought to be secondary to an epidural haematoma and a magnetic resonance scan was arranged. This suggested changes consistent with spinal cord infarction from D2 to D6 with no haematoma or abscess. This severe complication was most probably caused by embolisation from an atherosclerotic plaque of the thoracic aorta, as the nature of the surgery requires aortic manipulation. This may have consequently led to occlusion of a significant part of the spinal blood supply. Even though anterior spinal artery syndrome is a well known problem in the operative management of thoracic aortic aneurysms, this complication is extremely rare after oesophagectomy