Generation and assessment of cytokine-induced killer cells for the treatment of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Cytokine-induced killer (CIK) cells are an adoptive immunotherapy reported to have strong anti-tumour activity across a range of cancers. They are a heterogeneous mix of lymphoid cells generated by culturing human peripheral blood mononuclear cells with cytokines and monoclonal antibodies in vitro. In this study, we investigated the yield and function of CIK cells generated from patients with CRC liver metastases. We first showed that CIK cells generated in serum free medium X-VIVO 15 were comparable to those from RPMI medium with 10% FBS in terms of the number and percentages of the main subsets of cells in the CIK culture, and the intracellular levels of granzyme B and perforin, and the pro-inflammatory cytokines IL-2, IFN-γ and TNF-α. The CIK cells were cytotoxic to CRC cell lines grown in 2D cultures or as spheroids, and against autologous patient-derived tumour organoids. Donor attributes such as age, sex, or prior chemotherapy exposure had no significant impact on CIK cell numbers or function. These results suggest that functional CIK cells can be generated from patients with CRC liver metastatic disease, and support further investigations into the therapeutic application of autologous CIK cells in the management of patients with CRC liver metastases.

Impact of surgical specialization on emergency upper gastrointestinal surgery outcomes: A systematic review and meta-analysis.

BACKGROUND: Emergency presentations make up a large proportion of a general surgeon's workload. Patients who have emergency surgery carry a higher rate of mortality and complications. We aim to review the impact of surgical subspecialization on patients following upper gastrointestinal (UGI) emergency surgery. METHODS: A systematic search of Ovid Embase, Ovid MEDLINE, and Cochrane databases using a predefined search strategy was completed reviewing studies published from 1st of January 1990 to August 27, 2023. The study was prospectively registered with PROSPERO (CRD42022359326). Studies were reviewed for the following outcomes: 30-day mortality, in-hospital mortality, conversion to open, length of stay, return to theater, and readmission. RESULTS: Of 5181 studies, 24 articles were selected for full text review. Of these, seven were eligible and included in this study. There was a statistically significant improvement in 30-day mortality favoring UGI specialists (OR 0.71 [95% CI 0.55-0.92 and p = 0.009]) and in-hospital mortality (OR 0.29 [95% CI 0.14-0.60 and p = 0009]). There was a high degree of study heterogeneity in 30-day mortality; however, a low degree of heterogeneity within in-hospital mortality. There was no statistical significance when considering conversion to open and insufficient data to allow meta-analysis for return to theater or readmission rates. CONCLUSION: In emergency UGI surgery, there was improved 30-day and in-hospital mortality for UGI specialists. Therefore, surgeons should consider early involvement of a subspecialist team to improve patient outcomes.

Effect of lixisenatide on liquid gastric emptying in type 2 diabetes - Implications for the use of GLP-1 receptor agonists before procedures.

Gastric emptying of a glucose drink was measured in people with type 2 diabetes given lixisenatide (20 µg/day or placebo) for 8 weeks. Intragastric retention at 240 min (2 (0-11)% vs 48 (3-97)%; P < 0.0001) was much greater with lixisenatide than placebo. Accordingly, lixisenatide may delay liquid gastric emptying markedly.

Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.

Achieving equity: patient demographics and outcomes after surgical and non-surgical procedures in South Australia, 2022.

BACKGROUND: Although modern Australian healthcare systems provide patient-centred care, the ability to predict and prevent suboptimal post-procedural outcomes based on patient demographics at admission may improve health equity. This study aimed to identify patient demographic characteristics that might predict disparities in mortality, readmission, and discharge outcomes after either an operative or non-operative procedural hospital admission. METHODS: This retrospective cohort study included all surgical and non-surgical procedural admissions at three of the four major metropolitan public hospitals in South Australia in 2022. Multivariable logistic regression, with backwards selection, evaluated association between patient demographic characteristics and outcomes up to 90 days post-procedurally. RESULTS: 40 882 admissions were included. Increased likelihood of all-cause, post-procedure mortality in-hospital, at 30 days, and 90 days, were significantly associated with increased age (P < 0.001), increased comorbidity burden (P < 0.001), an emergency admission (P < 0.001), and male sex (P = 0.046, P = 0.03, P < 0.001, respectively). Identification as ATSI (P < 0.001) and being born in Australia (P = 0.03, P = 0.001, respectively) were associated with an increased likelihood of 30-day hospital readmission and decreased likelihood of discharge directly home, as was increased comorbidity burden (P < 0.001) and emergency admission (P < 0.001). Being married (P < 0.001) and male sex (P = 0.003) were predictive of an increased likelihood of discharging directly home; in contrast to increased age (P < 0.001) which was predictive of decreased likelihood of this occurring. CONCLUSIONS: This study characterized several associations between patient demographic factors present on admission and outcomes after surgical and non-surgical procedures, that can be integrated within patient flow pathways through the Australian healthcare system to improve healthcare equity.