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.

Evaluation of a culture change program to reduce unprofessional behaviours by hospital co-workers in Australian hospitals.

BACKGROUND: Unprofessional behaviours between healthcare workers are highly prevalent. Evaluations of large-scale culture change programs are rare resulting in limited evidence of intervention effectiveness. We conducted a multi-method evaluation of a professional accountability and culture change program "Ethos" implemented across eight Australian hospitals. The Ethos program incorporates training for staff in speaking-up; an online system for reporting co-worker behaviours; and a tiered accountability pathway, including peer-messengers who deliver feedback to staff for 'reflection' or 'recognition'. Here we report the final evaluation component which aimed to measure changes in the prevalence of unprofessional behaviours before and after Ethos. METHODS: A survey of staff (clinical and non-clinical) experiences of 26 unprofessional behaviours across five hospitals at baseline before (2018) and 2.5-3 years after (2021/2022) Ethos implementation. Five of the 26 behaviours were classified as 'extreme' (e.g., assault) and 21 as incivility/bullying (e.g., being spoken to rudely). Our analysis assessed changes in four dimensions: work-related bullying; person-related bullying; physical bullying and sexual harassment. Change in experience of incivility/bullying was compared using multivariable ordinal logistic regression. Change in extreme behaviours was assessed using multivariable binary logistic regression. All models were adjusted for respondent characteristics. RESULTS: In total, 3975 surveys were completed. Staff reporting frequent incivility/bullying significantly declined from 41.7% (n = 1064; 95% CI 39.7,43.9) at baseline to 35.5% (n = 505; 95% CI 32.8,38.3; χ2(1) = 14.3; P < 0.001) post-Ethos. The odds of experiencing incivility/bullying declined by 24% (adjusted odds ratio [aOR] 0.76; 95% CI 0.66,0.87; P < 0.001) and odds of experiencing extreme behaviours by 32% (aOR 0.68; 95% CI 0.54,0.85; P < 0.001) following Ethos. All four dimensions showed a reduction of 32-41% in prevalence post-Ethos. Non-clinical staff reported the greatest decrease in their experience of unprofessional behaviour (aOR 0.41; 95% CI 0.29, 0.61). Staff attitudes and reported skills to speak-up were significantly more positive at follow-up. Awareness of the program was high (82.1%; 95% CI 80.0, 84.0%); 33% of respondents had sent or received an Ethos message. CONCLUSION: The Ethos program was associated with significant reductions in the prevalence of reported unprofessional behaviours and improved capacity of hospital staff to speak-up. These results add to evidence that staff will actively engage with a system that supports informal feedback to co-workers about their behaviours and is facilitated by trained peer messengers.

Surgical interhospital transfer mortality: national analysis.

BACKGROUND: Interhospital transfers of surgical patients are an independent risk factor for mortality. The Australian and New Zealand Audit of Surgical Mortality (ANZASM) aims to improve surgical care through assessment of all cases of surgical mortality. This study aimed to describe common clinical management issues that contributed to interhospital transfer patient mortality. METHODS: Data for all surgical patient mortality in Australia (except New South Wales) that underwent interhospital transfer between 1 January 2010 and 31 December 2019 were extracted from ANZASM. The surgeons' reports and assessors' evaluations were examined to identify clinical management issues. Thematic analysis was performed to develop pertinent themes and subthemes. RESULTS: Some 8679 patients were identified over the 10-year period. Of these, 2171 (25.0 per cent) had 3259 clinical management issues identified. Prominent themes were operative design (n = 466, 14.3 per cent), decision to operate (n = 425, 13.0 per cent), medical conditions (n = 344, 10.6 per cent), diagnosis (n = 326, 10 per cent), transfer (n = 293, 10.0 per cent), intraoperative issues (n = 278, 8.5 per cent), inadequate assessment (n = 238, 7.3 per cent), communication (n = 224, 6.9 per cent), delay in recognizing complications (n = 180, 5.5 per cent), coagulopathy (n = 151, 4.6 per cent), insufficient monitoring (n = 127, 3.9 per cent), infection (n = 107, 3.3 per cent), and hospital resources (n = 100, 3.1 per cent). Assessors considered 58.4 per cent of clinical management issues (n = 1903) probably or definitely preventable. CONCLUSION: This study identified 13 themes of potentially avoidable management issues present in surgical mortality following interhospital transfers. Quality-improvement initiatives targeting these areas may improve surgical patient outcomes.

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.

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.

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).

Improving Surgical Excellence: Can Coaching Surgeons Improve Patient Engagement?

INTRODUCTION: Non-technical skills complement technical skills in surgeons to provide best possible care for patients. The former is essential to promote patient engagement. Coaching has been introduced to surgeons as a method to improve non-technical skills. We aimed to investigate the impact of coaching for surgeons on patient engagement in the outpatient consultation setting. METHODS: This was a single-centre cohort study conducted in South Australia. Consultant surgeons, suitable coaches, and patients were recruited. Coaches underwent further training by a human factors psychologist on being an effective coach. Outpatient consultations were recorded in an audio-visual format and analysed by investigators. Patient talking time, mutual eye gaze between surgeon and patient, and number of questions asked by the patient were measured as outcomes for patient engagement. RESULTS: 182 patients, 12 surgeons, and 4 coaches participated in the study. Each surgeon underwent 3 coaching sessions, 5 to 6 weeks apart. There were 62 pre-coaching patient consultations, 63 patient consultations after one coaching session, and 57 patient consultations after two coaching sessions. The mean talking time of the patient increased significantly after a single coaching session (P < 0.05) without making significant difference to the total consultation time (p = 0.76). Coaching sessions did not have a significant effect on mutual eye gaze or mean number of questions asked by the patient. CONCLUSION: Coaching of non-technical skills for surgeons appears to objectively improve patient engagement during the outpatient consultation. This would suggest that tailored coaching programs should be developed and delivered to surgeons to improve care delivery.

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.

Depression after stoma surgery: a systematic review and meta-analysis.

BACKGROUND: Depression is the leading cause of global disability and can develop following the change in body image and functional capacity associated with stoma surgery. However, reported prevalence across the literature is unknown. Accordingly, we performed a systematic review and meta-analysis aiming to characterise depressive symptoms after stoma surgery and potential predictive factors. METHODS: PubMed/MEDLINE, Embase, CINAHL and Cochrane Library were searched from respective database inception to 6 March 2023 for studies reporting rates of depressive symptoms after stoma surgery. Risk of bias was assessed using the Downs and Black checklist for non-randomised studies of interventions (NRSIs), and Cochrane RoB2 tool for randomised controlled trials (RCTs). Meta-analysis incorporated meta-regressions and a random-effects model. REGISTRATION: PROSPERO, CRD42021262345. RESULTS: From 5,742 records, 68 studies were included. According to Downs and Black checklist, the 65 NRSIs were of low to moderate methodological quality. According to Cochrane RoB2, the three RCTs ranged from low risk of bias to some concerns of bias. Thirty-eight studies reported rates of depressive symptoms after stoma surgery as a proportion of the respective study populations, and from these, the median rate across all timepoints was 42.9% 42.9% (IQR: 24.2-58.9%). Pooled scores for respective validated depression measures (Hospital Anxiety and Depression Score (HADS), Beck Depression Inventory (BDI), and Patient Health Questionnaire-9 (PHQ-9)) across studies reporting those scores were below clinical thresholds for major depressive disorder according to severity criteria of the respective scores. In the three studies that used the HADS to compare non-stoma versus stoma surgical populations, depressive symptoms were 58% less frequent in non-stoma populations. Region (Asia-Pacific; Europe; Middle East/Africa; North America) was significantly associated with postoperative depressive symptoms (p = 0.002), whereas age (p = 0.592) and sex (p = 0.069) were not. CONCLUSIONS: Depressive symptoms occur in almost half of stoma surgery patients, which is higher than the general population, and many inflammatory bowel disease and colorectal cancer populations outlined in the literature. However, validated measures suggest this is mostly at a level of clinical severity below major depressive disorder. Stoma patient outcomes and postoperative psychosocial adjustment may be enhanced by increased psychological evaluation and care in the perioperative period.

Weight loss with subcutaneous semaglutide versus other glucagon-like peptide 1 receptor agonists in type 2 diabetes: a systematic review.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduce elevated blood glucose levels and induce weight loss. Multiple GLP-1 RAs and one combined GLP-1/glucose-dependent insulinotropic polypeptide agonist are currently available. This review was conducted with the aim of summarising direct comparisons between subcutaneous semaglutide and other GLP-1 RAs in individuals with type 2 diabetes (T2D), particularly with respect to efficacy for inducing weight loss and improving other markers of metabolic health. This systematic review of PubMed and Embase from inception to early 2022 was registered on PROSPERO and was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Of the 740 records identified in the search, five studies fulfilled the inclusion criteria. Comparators included liraglutide, exenatide, dulaglutide and tirzepatide. In the identified studies, multiple dosing regimens were utilised for semaglutide. Randomised trials support the superior efficacy of semaglutide over other GLP-1 RAs with respect to weight loss in T2D, but tirzepatide is more effective than semaglutide.

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.

Trends in utilisation of ultrasound by older Australians (2010-2019).

BACKGROUND: Older people have increasingly complex healthcare needs, often requiring appropriate access to diagnostic imaging, an essential component of their health and disease management planning. Ultrasound is a safe imaging tool used to diagnose several conditions commonly experienced by older people such as deep vein thrombosis. PURPOSE: To evaluate the utilisation of major ultrasound services by Australians ≥ 65 years old between 2009- and 2019. METHODS: This population-based and yearly cross-sectional study of ultrasound utilisation per 1,000 Australians ≥ 65 years old was conducted using publicly available data sources. Overall, examination site and age- and sex-specific incidence rate (IR) of ultrasound per 1,000 people, adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using negative binomial regression models. RESULTS: Over the study period, the crude utilisation of ultrasound increased by 83% in older Australians. Most ultrasound examinations were conducted on extremities (39%) and the chest (21%), with 25% of all ultrasounds investigating the vascular system. More men than women use ultrasounds of the chest (184/1,000 vs 268/1,000 people), particularly echocardiograms (177/1,000 vs 261/1,000 people), and abdomen (88/1,000 vs 92/1,000 people), especially in those ≥ 85 years old. Hip and pelvic ultrasound were used more by women than men (212/1,000 vs 182/1,000 people). There were increases in vascular abdominal (IRR:1.07, 95%CI:1.06-1.08) and extremeties (IRR:1.06, 95%CI:1.05-1.07) ultrasounds over the study period, particularly in ≥ 75 years old men. CONCLUSIONS: Ultrasound is a common and increasingly used diagnostic tool for conditions commonly experienced by older Australians.

HTA capacity building in Asia: towards one goal.

OBJECTIVES: The aim of the 2022 Health Technology Assessment International (HTAi) Asia Policy Forum (APF) was to discuss experiences and challenges around health technology assessment (HTA) capacity building for both HTA agencies and companies in the Asia region and to identify possible solutions as part of a capacity building roadmap. METHODS: Discussions during the 2022 APF, informed by a pre-meeting survey of HTA agencies and industry attendees from the region, form the basis of this paper. RESULTS: HTA is an essential element of priority-setting in healthcare; however, the scarcity of skilled technical HTA practitioners is a rate-limiting step in the conduct of HTA. The lack of investment in HTA and the political will to mandate the use of HTA in decision-making may be due to a lack of understanding of the value of the HTA process, and how HTA is interpreted and used in the healthcare decision-making process. CONCLUSIONS: Increased demand for HTA is created when the value of HTA is recognized. HTA capacity-building challenges may be mitigated by educating stakeholders, particularly policymakers, on the value of, and the need to invest in, HTA as a transparent process to ensure equitable access to health care for all. Investigating a means of funding and implementing an HTA intern program between agencies, in partnership with industry, to facilitate a supportive environment to foster HTA skills and knowledge, build capacity or strengthen existing capacity should be a priority.

Best practice considerations on the assessment of robotic assisted surgical systems: results from an international consensus expert panel.

BACKGROUND: Health technology assessments (HTAs) of robotic assisted surgery (RAS) face several challenges in assessing the value of robotic surgical platforms. As a result of using different assessment methods, previous HTAs have reached different conclusions when evaluating RAS. While the number of available systems and surgical procedures is rapidly growing, existing frameworks for assessing MedTech provide a starting point, but specific considerations are needed for HTAs of RAS to ensure consistent results. This work aimed to discuss different approaches and produce guidance on evaluating RAS. METHODS: A consensus conference research methodology was adopted. A panel of 14 experts was assembled with international experience and representing relevant stakeholders: clinicians, health economists, HTA practitioners, policy makers, and industry. A review of previous HTAs was performed and seven key themes were extracted from the literature for consideration. Over five meetings, the panel discussed the key themes and formulated consensus statements. RESULTS: A total of ninety-eight previous HTAs were identified from twenty-five total countries. The seven key themes were evidence inclusion and exclusion, patient- and clinician-reported outcomes, the learning curve, allocation of costs, appropriate time horizons, economic analysis methods, and robotic ecosystem/wider benefits. CONCLUSIONS: Robotic surgical platforms are tools, not therapies. Their value varies according to context and should be considered across therapeutic areas and stakeholders. The principles set out in this paper should help HTA bodies at all levels to evaluate RAS. This work may serve as a case study for rapidly developing areas in MedTech that require particular consideration for HTAs.

Perhexiline: Old Drug, New Tricks? A Summary of Its Anti-Cancer Effects.

Cancer metabolic plasticity, including changes in fatty acid metabolism utilisation, is now widely appreciated as a key driver for cancer cell growth, survival and malignancy. Hence, cancer metabolic pathways have been the focus of much recent drug development. Perhexiline is a prophylactic antianginal drug known to act by inhibiting carnitine palmitoyltransferase 1 (CPT1) and 2 (CPT2), mitochondrial enzymes critical for fatty acid metabolism. In this review, we discuss the growing evidence that perhexiline has potent anti-cancer properties when tested as a monotherapy or in combination with traditional chemotherapeutics. We review the CPT1/2 dependent and independent mechanisms of its anti-cancer activities. Finally, we speculate on the clinical feasibility and utility of repurposing perhexiline as an anti-cancer agent, its limitations including known side effects and its potential added benefit of limiting cardiotoxicity induced by other chemotherapeutics.

Incidence of occult appendiceal neoplasm in patients over 40 years with acute appendicitis: A single-institution review.

OBJECTIVE: To investigate the incidence of occult appendiceal neoplasm in patients aged 40 years and over who underwent appendicectomy for appendicitis. METHODS: The clinical coding electronic database was used to identify patients aged 40 years and over who were diagnosed with appendicitis from September 2010 to September 2022. Patients were included if they were managed operatively. DESIGN: Retrospective cohort study. SETTING: Modified Monash category 3 (large rural town). PARTICIPANTS: Patients aged 40 years and over undergoing appendicectomy for appendicitis. MAIN OUTCOME MEASURES: Incidence of appendiceal neoplasm within appendicectomy specimen. RESULTS: A total of 279 patients aged 40 years and over underwent appendicectomy, with a median age of 53 years (range 40-95). Nineteen patients (7%) were found to have a primary neoplastic lesion within the appendix: seven neuroendocrine neoplasms (37%), six sessile serrated lesions (32%), two colonic-type adenocarcinoma (11%), two goblet cell adenocarcinoma (11%) and two appendiceal mucinous neoplasms (11%). Additionally, one patient had a metastatic adenocarcinoma of pancreaticobiliary aetiology. CONCLUSIONS: Occult appendiceal neoplasm was higher than reported in the literature in our cohort. This would support appendicectomy as the treatment of choice for patients aged 40 years and over with acute appendicitis and caution against nonoperative management in this demographic.

Can Checklists Solve Our Ward Round Woes? A Systematic Review.

BACKGROUND: Accurate and thorough surgical ward round documentation is crucial for maintaining quality clinical care. Accordingly, checklists have been proposed to improve ward round documentation. This systematic review aimed to evaluate the literature investigating the use of checklists to improve surgical ward round documentation. METHODS: MEDLINE, EMBASE, and PsycINFO were searched on August 16, 2021. Study selection, data extraction, and risk of bias assessment were performed in duplicate. We included English studies that investigated the use of checklists during ward rounds in various surgical subspecialties compared to routine care, where the rates of documentation were reported as outcomes. We excluded studies that used checklists in outpatient, non-surgical, or pediatric settings. Due to heterogeneity of outcome measures, meta-analysis was precluded. This study was registered with PROSPERO (ID: CRD42021273735) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020) reporting guidelines. RESULTS: A total of 206 studies were identified, only 9 were suitable for inclusion. All included studies were single-center observational studies, spanning across seven surgical specialties. Rates of documentation on 4-23 parameters were reported. Documentation for all measured outcomes improved in 8/9 studies; however, statistical analyses were not included. There was a high risk of bias due to the nature of observational studies. CONCLUSION: Ward round checklists can serve as a useful tool to improve inpatient care and safety. Currently, there is no high-level evidence showing the effectiveness of checklists on ward round documentation. The synthesis of results indicates that further high-quality research is imperative.

Emergency Neurosurgery Performed by General Surgeons: A Systematic Review.

BACKGROUND: In under-resourced settings, general surgeons may be called upon to perform emergency operations within other specialties. Accordingly, we aimed to characterise patient outcomes after emergency neurosurgery performed by a general surgeon or general surgery trainee. METHODS: PubMed, Embase and the Cochrane Library were searched to 30 May 2021 for observational studies reporting outcomes after emergency neurosurgery performed by a general surgeon. Study screening, data extraction, and risk of bias using the Downs and Black checklist were performed in duplicate. Data on setting, operation undertaken, mortality rates and complications were extracted. Meta-analysis was planned but not possible due to heterogeneity. This study is registered with PROSPERO, CRD42021258097. RESULTS: From 632 records, 14 retrospective observational studies were included, covering a total sample of 1,988 operations. Four studies were from Australia, and the remaining 10 were, respectively, from 10 other countries. Most common operations performed were decompressive surgery with burr holes or craniectomy for head trauma and insertion of intracranial pressure monitors. Rural hospitals were the most common settings. Mortality rates for procedures performed by general surgeons at latest follow-up were heterogenous, ranging from 5% for evacuation of chronic subdural haematoma in Kenya to 81% in head injured patients in a Hong Kong study. CONCLUSIONS: This is the first systematic review that synthesises the literature to characterise patient outcomes after neurosurgical operations performed by a general surgeon. Findings from this study may benefit global surgery performed in rural, remote, military or humanitarian settings.

Devices measuring transepidermal water loss: A systematic review of measurement properties.

OBJECTIVE: The objective of this review is to examine the reliability and measurement error of devices that measure transepidermal water loss (TEWL). INTRODUCTION: TEWL is a physiological property of skin which increases when the epidermis is damaged. It is, therefore, a commonly utilised measure of skin barrier integrity. Devices measuring TEWL are available as open, semi-open or closed chamber. Studies of reliability examine the consistency of measurement, and/or responsiveness whereas measurement error scores in absolute terms the amount of error due to sources of variation. INCLUSION CRITERIA: Studies examining the reliability and/or measurement error of TEWL measurement devices were included. Studies that only report on measurement of TEWL outcomes without examination of reliability and/or measurement error were excluded. METHODS: The search strategy aimed to locate published and unpublished studies. Databases searched included PubMed, Embase, CINAHL and Web of Science, utilising identified keywords and limited to studies in English. Grey literature sources were searched to identify any unpublished documents. Study selection using the inclusion criteria was then assessed by two reviewers for methodological quality utilising the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias tool to assess the reliability and measurement error of outcome measurement instruments. RESULTS: A total of 22 devices were examined in the 38 included studies. The quality of study design was on average rated as 'Adequate' however reliability and measurement error statistical methods were on average rated as 'Doubtful'. DISCUSSION AND CONCLUSION: TEWL measurement devices were found to demonstrate good reliability and frequently correlated with other devices. However, measurement error was highly variable but improves under in vitro conditions. Future research should consider risk of bias factors when designing studies.