The Continuing Problem of Expert Evidence in Medical Litigation - A Surgical Perspective with Reference to Daubert.

The tension that exists between the medical and legal professions regarding expert evidence is longstanding. In this article, we will examine some of the issues regarding expert evidence particularly as it relates to matters involving surgeons. Many of the current aspects of the Australian uniform evidence law in relation to expert testimony were based on the Federal Rules of Evidence promulgated in the United States in 1975. We will discuss some of the problems of expert evidence in surgical matters, particularly in New South Wales, and offer some thoughts on how the so-called Daubert trilogy could form a basis on which to re-examine the concept of an "expert". Our analysis offers suggestions for further improvements to the process of adducing expert evidence in claims involving surgical matters.

Failure to rescue following oesophagectomy in Australia: a multi-site retrospective study using American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: Failure to rescue (FTR), defined as death after a major complication, is increasingly being used as a surrogate for assessing quality of care following major cancer resection. The aim of this paper is to determine the failure to rescue (FTR) rate after oesophagectomy and explore factors that may contribute to FTR within Australia. METHODS: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database from 2015 to 2023 at five Australian hospitals was conducted to identify patients who underwent an oesophagectomy. The primary outcome was FTR rate. Perioperative parameters were examined to evaluate predictive factors for FTR. Secondary outcomes include major complications, overall morbidity, mortality, length of stay and 30-day readmissions. RESULTS: A total of 155 patients were included with a median age of 65.2 years, 74.8% being male. The FTR rate was 6.3%. In total, 50.3% of patients (n = 78) developed at least one postoperative complication with the most common complication being pneumonia (20.6%) followed by prolonged intubation (12.9%) and organ space SSI/anastomotic leak (11.0%). Multivariate logistic regression analysis was performed to determine any factors that were predictive for FTR however none reached statistical significance. CONCLUSION: This study is the first to evaluate the FTR rates following oesophagectomy within Australia, with FTR rates and complication profile comparable to international benchmarks. Integration of multi-institutional national databases such as ACS NSQIP into units is essential to monitor and compare patient outcomes following major cancer surgery, especially in low to moderate volume centres.

Systematic Review of Preoperative Prognostic Biomarkers in Perihilar Cholangiocarcinoma.

Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative mortality and morbidity rates are high, with a low 5-year survival rate. Use of preoperative prognostic biomarkers to predict survival outcomes after surgery for pCCA are not well-established currently. This systematic review aimed to identify and summarise preoperative biomarkers associated with survival in pCCA, thereby potentially improving treatment decision-making. The Embase, Medline, and Cochrane databases were searched, and a systematic review was performed using the PRISMA guidelines. English-language studies examining the association between serum and/or tissue-derived biomarkers in pCCA and overall and/or disease-free survival were included. Our systematic review identified 64 biomarkers across 48 relevant studies. Raised serum CA19-9, bilirubin, CEA, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and tumour MMP9, and low serum albumin were most associated with poorer survival; however, the cutoff values used widely varied. Several promising molecular markers with prognostic significance were also identified, including tumour HMGA2, MUC5AC/6, IDH1, PIWIL2, and DNA index. In conclusion, several biomarkers have been identified in serum and tumour specimens that prognosticate overall and disease-free survival after pCCA resection. These, however, require external validation in large cohort studies and/or in preoperatively obtained specimens, especially tissue biopsy, to recommend their use.

Enhancing the Small-Scale Screenable Biological Space beyond Known Chemogenomics Libraries with Gray Chemical Matter─Compounds with Novel Mechanisms from High-Throughput Screening Profiles.

Phenotypic assays have become an established approach to drug discovery. Greater disease relevance is often achieved through cellular models with increased complexity and more detailed readouts, such as gene expression or advanced imaging. However, the intricate nature and cost of these assays impose limitations on their screening capacity, often restricting screens to well-characterized small compound sets such as chemogenomics libraries. Here, we outline a cheminformatics approach to identify a small set of compounds with likely novel mechanisms of action (MoAs), expanding the MoA search space for throughput limited phenotypic assays. Our approach is based on mining existing large-scale, phenotypic high-throughput screening (HTS) data. It enables the identification of chemotypes that exhibit selectivity across multiple cell-based assays, which are characterized by persistent and broad structure activity relationships (SAR). We validate the effectiveness of our approach in broad cellular profiling assays (Cell Painting, DRUG-seq, and Promotor Signature Profiling) and chemical proteomics experiments. These experiments revealed that the compounds behave similarly to known chemogenetic libraries, but with a notable bias toward novel protein targets. To foster collaboration and advance research in this area, we have curated a public set of such compounds based on the PubChem BioAssay dataset and made it available for use by the scientific community.