Prosthesis-Patient Mismatch Increases Early and Late Mortality in Low Risk Aortic Valve Replacement

PPM was highly associated with long-term all-cause mortality. Small Aortic Valve Annulus MDT (SAVA-MDT) exploring options to prevent PPM, including the implantation of newer generation prosthetic valves, aortic root enlargement and TAVI, should be established.

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Global colorectal cancer research, 2007-2021: Outputs and funding

The purpose of this study was to provide an evidence base for colorectal cancer research activity that might influence policy, mainly at the national level. Improvements in healthcare delivery have lengthened life expectancy, but within a situation of increased cancer incidence. The disease burden of CRC has risen significantly, particularly in Africa, Asia and Latin America. Research is key to its control and reduction, but few studies have delineated the volume and funding of global research on CRC. We identified research papers in the Web of Science (WoS) from 2007 to 2021, and determined the contributions of the leading countries, the research domains studied, and their sources of funding. We identified 62 716 papers, representing 5.7% of all cancer papers. This percentage was somewhat disproportionate to the disease burden (7.7% in 2015), especially in Eastern Europe. International collaboration increased over the time period in almost all countries except in China. Genetics, surgery and prognosis were the leading research domains. However, research on palliative care and quality-of-life in CRC was lacking. In Western Europe, the main funding source was the charity sector, particularly in the UK, but in most other countries government played the leading role, especially in China and the USA. There was little support from industry. Several Asian countries provided minimal contestable funding, which may have reduced the impact of their CRC research. Certain countries must perform more CRC research overall, especially in domains such as screening, palliative care and quality-of-life. The private-non-profit sector should be an alternative source of support.     

American Cancer Society nutrition and physical activity guideline for cancer survivors

The overall 5-year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence-based, cancer-specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer-specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta-analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.     

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Dysplastic naevi (DN) are benign lesions with atypical features intermediate between that of common melanocytic naevi (CMN) and malignant melanoma (MM). Debate remains over whether DN represent progressive lesions from CMN. Through gene expression profiling and analysis of molecular gene signatures, our study revealed progressive increases in immune activation and regulation, along with pathways implicated in melanomagenesis, from CMN to DN to MM. Using criteria of 1.5‐fold change and false discovery rate ≤0.05, we found differential expression of 7186 probes (6370 unique genes) with the largest difference detected between DN and MM from the standpoint of genomic melanoma progression. Despite progressive increases in the T‐helper type 1 (Th1)‐inducing gene (IL‐12), RT‐PCR indicated impaired Th1 or cytotoxic T‐cell response (decreased IFN‐γ) in MM. Concordantly, our results indicated progressive increases in molecular markers associated with regulatory T cells, exhausted T cells and tolerogenic dendritic cells, including detection of increased expression of suppressor of cytokine signalling 3 (SOCS3) in dendritic cells associated with MM. All together, our findings suggest that the increased immunosuppressive microenvironment of melanoma may contribute to unhampered proliferation of neoplastic cells. In addition, the detection of increased markers associated with tolerogenic dendritic cells in MM suggests that targeting these suppressive immune cell types may represent an alternative avenue for future immunotherapy.     

Personalizing surgical margins in retroperitoneal sarcomas: an update

Introduction: Tumor biology, as well as completeness of surgical resection, are two important prognostic factors when treating retroperitoneal sarcoma (RPS). A frontline extended surgical approach is associated with improved local control and possibly improved survival. However, this approach has to be tailored to each histological subtype, as the patterns of growth and recurrence risks vary significantly among them.

Areas covered: We provide a review of the literature in RPS, describing the behavior of each of the five main histologic subtypes: well-differentiated liposarcoma (WDLPS), dedifferentiated liposarcoma (DDLPS), leiomyosarcoma (LMS), solitary fibrous tumor (SFT) and malignant peripheral nerve sheath tumor (MPNST). The prognostic factors relevant to oncologic outcomes of RPS, the role of margins and the importance of local control are discussed. Finally, a histologic specific surgical approach to RPS is provided in detail.

Expert opinion: While tumor-related factors are paramount, the only intervenable predictive factor is extent and quality of surgery. The extended surgical approach has been advocated for previously and again we describe it in more detail, tailored specifically to the tumor subtype. The aim of this approach is to maximize the possibility of achieving a complete resection through a standardized approach based on histologic behavior and site of origin.     

The Extension of the Crimes (Mental Impairment and Unfitness to be Tried) Act 1997 to the Children’s Court: Opportunities and Shortfalls

In 2014, the Crimes (Mental Impairment and Unfitness to be Tried) Act 1997 in Victoria was extended to the Children’s Court of Victoria. This article describes the processes that preceded this change and the changes that occurred. The potential opportunities consequent to the changes are described, with their corresponding ethical implications. The decision not to resource some of the changes as recommended by the Victorian Law Reform Commission is described, with reference to the lack of establishment of an adolescent forensic mental health facility. The shortfalls currently occurring and their ethical implications are also discussed. We note the need for data regarding the number of children whose matters are being heard under the Crimes (Mental Impairment and Unfitness to be Tried) Act 1997, and the resourcing implications that flow from this.