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.

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.

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.

Clinical application of cytokine-induced killer (CIK) cell therapy in colorectal cancer: Current strategies and future challenges.

Colorectal cancer (CRC) remains a significant global health burden and is the second leading cause of cancer-related death. Cytokine induced killer (CIK) cell therapy is an immunotherapy which has the potential to meet this need. Clinical trials of CIK cell therapy for the management of CRC have reported improved clinical outcomes. However, production and delivery protocols varied significantly, and many studies were reported only in Chinese language journals. Here we present the most comprehensive review of the clinical CIK cell therapy trials for CRC management to date. We accessed both English and Chinese language clinical studies, and summarise how CIK cell therapy has been implemented, from manufacturing to patient delivery. We discuss current challenges that impede wider adoption of CIK cell therapy in CRC management.

Surgery's Rosetta Stone: Natural language processing to predict discharge and readmission after general surgery.

BACKGROUND: This study aimed to examine the accuracy with which multiple natural language processing artificial intelligence models could predict discharge and readmissions after general surgery. METHODS: Natural language processing models were derived and validated to predict discharge within the next 48 hours and 7 days and readmission within 30 days (based on daily ward round notes and discharge summaries, respectively) for general surgery inpatients at 2 South Australian hospitals. Natural language processing models included logistic regression, artificial neural networks, and Bidirectional Encoder Representations from Transformers. RESULTS: For discharge prediction analyses, 14,690 admissions were included. For readmission prediction analyses, 12,457 patients were included. For prediction of discharge within 48 hours, derivation and validation data set area under the receiver operator characteristic curves were, respectively: 0.86 and 0.86 for Bidirectional Encoder Representations from Transformers, 0.82 and 0.81 for logistic regression, and 0.82 and 0.81 for artificial neural networks. For prediction of discharge within 7 days, derivation and validation data set area under the receiver operator characteristic curves were, respectively: 0.82 and 0.81 for Bidirectional Encoder Representations from Transformers, 0.75 and 0.72 for logistic regression, and 0.68 and 0.67 for artificial neural networks. For readmission prediction within 30 days, derivation and validation data set area under the receiver operator characteristic curves were, respectively: 0.55 and 0.59 for Bidirectional Encoder Representations from Transformers and 0.77 and 0.62 for logistic regression. CONCLUSION: Modern natural language processing models, particularly Bidirectional Encoder Representations from Transformers, can effectively and accurately identify general surgery patients who will be discharged in the next 48 hours. However, these approaches are less capable of identifying general surgery patients who will be discharged within the next 7 days or who will experience readmission within 30 days of discharge.

Opioid prescribing, pain, and hospital stay of general surgery patients with oxycodone allergies in South Australia.

BACKGROUND: The frequency of oxycodone adverse reactions, subsequent opioid prescription, effect on pain and patient care in general surgery patients are not well known. This study aimed to determine prevalence of documented oxycodone allergy and intolerances (independent variables) in a general surgical cohort, and association with prescribing other analgesics (particularly opioids), subjective pain scores, and length of hospital stay (dependent variables). METHODS: This retrospective cohort study included general surgery patients from two South Australian hospitals between April 2020 and March 2022. Multivariable logistic regression evaluated associations between previous oxycodone allergies and intolerances, prescription records, subjective pain scores, and length of hospital stay. RESULTS: Of 12 846 patients, 216 (1.7%) had oxycodone allergies, and 84 (0.7%) oxycodone intolerances. The 216 oxycodone allergy patients had lower odds of receiving oxycodone (OR 0.17, P < 0.001), higher odds of tramadol (OR 3.01, P < 0.001) and tapentadol (OR 2.87, P = 0.001), but 91 (42.3%) still received oxycodone and 19 (8.8%) morphine. The 84 with oxycodone intolerance patients had lower odds of receiving oxycodone (OR 0.23, P < 0.001), higher odds of fentanyl (OR 3.6, P < 0.001) and tramadol (OR 3.35, P < 0.001), but 42 (50%) still received oxycodone. Patients with oxycodone allergies and intolerances had higher odds of elevated subjective pain (OR 1.60, P = 0.013; OR 2.36, P = 0.002, respectively) and longer length of stay (OR 1.36, P = 0.038; OR 2.24, P = 0.002, respectively) than patients without these. CONCLUSIONS: General surgery patients with oxycodone allergies and intolerances are at greater risk of worse postoperative pain and longer length of stay, compared to patients without. Many still receive oxycodone, and other opioids that could cause cross-reactivity.

Evolving challenges of leadership in surgery to improve inclusivity, representation, and well-being.

BACKGROUND: Leadership is a complex and demanding process crucial to maintaining quality in surgical systems of care. Once an autocratic practice, modern-day surgical leaders must demonstrate inclusivity, flexibility, emotional competence, team-building, and a multidisciplinary approach. The complex healthcare environment challenges those in leadership positions. The aim of this narrative review was to consolidate the major challenges facing surgeons today and to suggest evidence-based strategies to support surgical leaders. METHODS: Google Scholar, PubMed, MEDLINE, and Ovid databases were searched to review literature on the challenges faced by surgical leaders. The commonly identified areas that compromise inclusivity and productive leadership practices were consolidated into 10 main subheadings. Further research was conducted using the aforementioned databases to outline the importance of addressing such challenges, and to consolidate evidence-based strategies to resolve them. RESULTS: The importance of increasing representation of marginalized groups in leadership positions, including women, ethnic groups, the queer community, and ageing professionals, has been identified by surgical colleges in many countries. Leaders must create a collegial environment with proactive, honest communication and robust reporting pathways for victims of workplace harassment. The retention of diverse, empowering, and educating leaders relies on equitable opportunities, salaries, recognition, and support. Thus, it is important to implement formal training and mentorship, burnout prevention, conflict management, and well-being advocacy. CONCLUSION: There are two aspects to addressing challenges facing surgical leadership; improving advocacy by and for leaders. Systems must be designed to support surgical leaders through formal education and training, meaningful mentorship programmes, and well-being advocacy, thus enabling them to proactively and productively advocate and care for their patients, colleagues, and professional communities.

Sociocultural and Demographic Factors Predict Readmissions for General Surgery Patients.

INTRODUCTION: Readmission is a poor outcome for both patients and healthcare systems. The association of certain sociocultural and demographic characteristics with likelihood of readmission is uncertain in general surgical patients. METHOD: A multi-centre retrospective cohort study of consecutive unique individuals who survived to discharge during general surgical admissions was conducted. Sociocultural and demographic variables were evaluated alongside clinical parameters (considered both as raw values and their proportion of change in the 1-2 days prior to admission) for their association with 7 and 30 days readmission using logistic regression. RESULTS: There were 12,701 individuals included, with 304 (2.4%) individuals readmitted within 7 days, and 921 (7.3%) readmitted within 30 days. When incorporating absolute values of clinical parameters in the model, age was the only variable significantly associated with 7-day readmission, and primary language and presence of religion were the only variables significantly associated with 30-day readmission. When incorporating change in clinical parameters between the 1-2 days prior to discharge, primary language and religion were predictive of 30-day readmission. When controlling for changes in clinical parameters, only higher comorbidity burden (represented by higher Charlson comorbidity index score) was associated with increased likelihood of 30-day readmission. CONCLUSIONS: Sociocultural and demographic patient factors such as primary language, presence of religion, age, and comorbidity burden predict the likelihood of 7 and 30-day hospital readmission after general surgery. These findings support early implementation a postoperative care model that integrates all biopsychosocial domains across multiple disciplines of healthcare.

Colorectal adenomatous and serrated polyps in rural South Australia: who, why, what and where?

BACKGROUNDS: The adenoma-carcinoma and serrated pathways offer a window of opportunity for the removal of pre-malignant polyps and prevention of colorectal cancer (CRC) through the use of colonoscopy. The aim of this study was to investigate variation in polyp incidence in different age groups, gender and indications for undertaking colonoscopy. We also address histological types of polyps found and where in the bowel they are located. METHODS: This study is based on the colonoscopy data collected prospectively over a one-year period in multiple South Australian rural centres, 24 general surgeons contributed to this study. All histopathology results were subsequently entered into the dataset. RESULTS: A total of 3497 colonoscopies were performed, with a total of 2221 adenomatous and serrated polyps removed. Both serrated and adenomatous polyps were more common in the distal colon. Patients of male gender, aged 70 years and over and with an indication of polyp surveillance had higher adenoma and serrated polyp detection rates (ADR and SPDR). Patients aged 40-49 years old who underwent colonoscopy for positive faecal occult blood had an ADR and SPDR of 25.0% and 6.3%, respectively. CONCLUSIONS: This study has shown variation in ADR and SPDR depending on age, gender and indication for colonoscopy. This variation will help further develop key performance indicators in colonoscopy. The high ADR and SPDR in patients aged 40-49 years old whom underwent colonoscopy for positive faecal occult blood may support lowering the age of commencement of CRC screening in Australia.

Improving communication and patient information recall via a question prompt list: randomized clinical trial.

BACKGROUND: Patient-surgeon communication is an important component of the success of a consultation and is known to impact patient outcomes. The aim of this study was to investigate whether a document called a question prompt list, containing suggested questions that a patient may like to ask their doctor, improved communication. METHODS: A prospective RCT was conducted from October 2021 to October 2022 at The Queen Elizabeth Hospital, Adelaide, Australia. Patients 16 years or older, seeing a general surgeon for a pre-surgical consultation, not requiring a translator, were randomized to receive a question prompt list (intervention) or standard care without a question prompt list (control). The primary outcomes were number of questions asked, talk time, and mutual eye gaze. Secondary outcomes were patient recall of information, anxiety, and consultation duration. Randomization was achieved using a computer program, with allocation concealment by opaque sequentially numbered envelopes. Patients were blinded to study group; surgeons were aware of study group, but blinded to outcomes. RESULTS: Patients (59) were randomly allocated to receive the question prompt list (31) or to the control group (28). A patient from the intervention group withdrew before consultation, resulting in 58 patients being included in the analysis. In the question prompt list consultations, 24 per cent more questions were asked (incidence rate ratio = 1.25, 95 per cent c.i. 1.10 to 1.42; P = 0.001). The intervention group recalled 9 per cent more items than the control group (incidence rate ratio = 1.09, 95 per cent c.i. 1.02 to 1.17; P = 0.012). The control group were 26 per cent less likely to correctly recall information about surgical treatment (OR = 0.26, 95 per cent c.i. 0.10 to 0.68; P = 0.006). No statistically significant differences between study arms for talk time, mutual eye gaze, anxiety, or consultation duration were demonstrated. CONCLUSION: The question prompt list was associated with increased question asking and greater patient recall of medical information. It did not increase patient anxiety or consultation duration. REGISTRATION NUMBER: ACTRN12623000089639 (http://www.ANZCTR.org.au).

Staging of colorectal cancer using lipid biomarkers and machine learning.

INTRODUCTION: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Alteration in lipid metabolism and chemokine expression are considered hallmark characteristics of malignant progression and metastasis of CRC. Validated diagnostic and prognostic biomarkers are urgently needed to define molecular heterogeneous CRC clinical stages and subtypes, as liver dominant metastasis has poor survival outcomes. OBJECTIVES: The aim of this study was to integrate lipid changes, concentrations of chemokines, such as platelet factor 4 and interleukin 8, and gene marker status measured in plasma samples, with clinical features from patients at different CRC stages or who had progressed to stage-IV colorectal liver metastasis (CLM). METHODS: High-resolution liquid chromatography-mass spectrometry (HR-LC-MS) was used to determine the levels of candidate lipid biomarkers in each CRC patient's preoperative plasma samples and combined with chemokine, gene and clinical data. Machine learning models were then trained using known clinical outcomes to select biomarker combinations that best classify CRC stage and group. RESULTS: Bayesian neural net and multilinear regression-machine learning identified candidate biomarkers that classify CRC (stages I-III), CLM patients and control subjects (cancer-free or patients with polyps/diverticulitis), showing that integrating specific lipid signatures and chemokines (platelet factor-4 and interluken-8; IL-8) can improve prognostic accuracy. Gene marker status could contribute to disease prediction, but requires ubiquitous testing in clinical cohorts. CONCLUSION: Our findings demonstrate that correlating multiple disease related features with lipid changes could improve CRC prognosis. The identified signatures could be used as reference biomarkers to predict CRC prognosis and classify stages, and monitor therapeutic intervention.

Vital signs and medical emergency response (MER) activation predict in-hospital mortality in general surgery patients: a study of 15 969 admissions.

BACKGROUND: The applicability of the vital signs prompting medical emergency response (MER) activation has not previously been examined specifically in a large general surgical cohort. This study aimed to characterize the distribution, and predictive performance, of four vital signs selected based on Australian guidelines (oxygen saturation, respiratory rate, systolic blood pressure and heart rate); with those of the MER activation criteria. METHODS: A retrospective cohort study was conducted including patients admitted under general surgical services of two hospitals in South Australia over 2 years. Likelihood ratios for patients meeting MER activation criteria, or a vital sign in the most extreme 1% for general surgery inpatients (<0.5th percentile or > 99.5th percentile), were calculated to predict in-hospital mortality. RESULTS: 15 969 inpatient admissions were included comprising 2 254 617 total vital sign observations. The 0.5th and 99.5th centile for heart rate was 48 and 133, systolic blood pressure 85 and 184, respiratory rate 10 and 31, and oxygen saturations 89% and 100%, respectively. MER activation criteria with the highest positive likelihood ratio for in-hospital mortality were heart rate ≤ 39 (37.65, 95% CI 27.71-49.51), respiratory rate ≥ 31 (15.79, 95% CI 12.82-19.07), and respiratory rate ≤ 7 (10.53, 95% CI 6.79-14.84). These MER activation criteria likelihood ratios were similar to those derived when applying a threshold of the most extreme 1% of vital signs. CONCLUSIONS: This study demonstrated that vital signs within Australian guidelines, and escalation to MER activation, appropriately predict in-hospital mortality in a large cohort of patients admitted to general surgical services in South Australia.

Economic and cost considerations of delivering and using mobile X-ray services in residential aged care facilities: A qualitative study.

OBJECTIVE: To describe the economic and cost considerations of mobile X-ray services (MXS) in residential aged care facilities (RACFs), according to stakeholders (involved in residents' healthcare), residents living in RACFs and informal carers (ICs) of residents. METHODS: Semistructured interviews were conducted with 20 residents and 27 ICs recruited from six RACFs across metropolitan Adelaide (South Australia, Australia), and 22 stakeholders, on their perspectives of using MXS in RACFs. Data relating to economic and cost considerations were extracted and analysed using thematic analysis. RESULTS: Residents' mean age was 85 years, 60% were women and 40% had experienced an MXS in the last 12 months. Most ICs were daughters (70%) and wives (11%) and 30% had a family member who had experienced an MXS in the last 12 months. Stakeholders included RACF staff, GPs, a hospital avoidance program clinician, paramedics, emergency department clinicians, MXS radiographers and manager, and a radiologist. Four themes were presented: (1) business considerations, where private providers found it necessary to charge residents a co-payment to deliver MXS; (2) cost and payment process as a potential barrier to using MXS, with varied willingness and ability to pay for an MXS co-payment, and equity concerns; (3) overcoming cost and payment barriers, with staff and consumers sometimes using strategies to overcome cost barriers; and (4) perceived cost benefits of MXS to the healthcare system, residents and ICs. CONCLUSIONS: Mobile X-ray services providers charge residents an upfront co-payment for business viability, which can be a barrier to some residents wishing to access MXS.

Mobile X-ray services in nursing homes as an enabler to healthcare-in-place for residents: informal carers' views.

BACKGROUND: Informal carers (ICs) of residents living in nursing homes (NH) have a key role in the care of residents, including making decisions about and providing care. As radiology has a role in decision making about care, it is important to understand IC's perspectives about resident's use of mobile X-ray services (MXS). The aim was to explore the perspectives of ICs of residents living in nursing homes about the use of MXS. METHODS: From November 2020 to February 2021, twenty ICs of residents living in four nursing homes in different areas of one Australian city participated. Their perspectives of MXS, including benefits and barriers, were explored in semi-structured interviews. Data were analysed using thematic analysis. RESULTS: ICs were resident's children (80%) and spouses (20%). One resident had received a MXS. Four themes were developed: (1) a priority for resident well-being, where ICs were positive about using MXS, because residents could receive healthcare without transfer; (2) MXS could reduce carer burden; (3) economic considerations, where MXS could reduce health system burden but the MXS call-out fee could result in health inequities; and (4) pathways to translation, including the need to improve consumer awareness of MXS, ensure effective processes to using MXS,, consider nursing home staff levels to manage MXS and ICs expectations about quality and availability of MXS. CONCLUSIONS: ICs consider MXS can benefit resident well-being by potentially reducing transfers to hospital or radiology facilities and advocated equitable access. ICs cautioned that the quality and safety of healthcare delivered in nursing homes should equal what they would receive in hospitals.