Medical education and physician training in the era of artificial intelligence.

ABSTRACT: With the rise of generative artificial intelligence (AI) and AI-powered chatbots, the landscape of medicine and healthcare is on the brink of significant transformation. This perspective delves into the prospective influence of AI on medical education, residency training and the continuing education of attending physicians or consultants. We begin by highlighting the constraints of the current education model, challenges in limited faculty, uniformity amidst burgeoning medical knowledge and the limitations in 'traditional' linear knowledge acquisition. We introduce 'AI-assisted' and 'AI-integrated' paradigms for medical education and physician training, targeting a more universal, accessible, high-quality and interconnected educational journey. We differentiate between essential knowledge for all physicians, specialised insights for clinician-scientists and mastery-level proficiency for clinician-computer scientists. With the transformative potential of AI in healthcare and service delivery, it is poised to reshape the pedagogy of medical education and residency training.

A functional personalised oncology approach against metastatic colorectal cancer in matched patient derived organoids.

Globally, colorectal cancer (CRC) is the third most frequently occurring cancer. Progression on to an advanced metastatic malignancy (metCRC) is often indicative of poor prognosis, as the 5-year survival rates of patients decline rapidly. Despite the availability of many systemic therapies for the management of metCRC, the long-term efficacies of these regimens are often hindered by the emergence of treatment resistance due to intratumoral and intertumoral heterogeneity. Furthermore, not all systemic therapies have associated biomarkers that can accurately predict patient responses. Hence, a functional personalised oncology (FPO) approach can enable the identification of patient-specific combinatorial vulnerabilities and synergistic combinations as effective treatment strategies. To this end, we established a panel of CRC patient-derived organoids (PDOs) as clinically relevant biological systems, of which three pairs of matched metCRC PDOs were derived from the primary sites (ptCRC) and metastatic lesions (mCRC). Histological and genomic characterisation of these PDOs demonstrated the preservation of histopathological and genetic features found in the parental tumours. Subsequent application of the phenotypic-analytical drug combination interrogation platform, Quadratic Phenotypic Optimisation Platform, in these pairs of PDOs identified patient-specific drug sensitivity profiles to epigenetic-based combination therapies. Most notably, matched PDOs from one patient exhibited differential sensitivity patterns to the rationally designed drug combinations despite being genetically similar. These findings collectively highlight the limitations of current genomic-driven precision medicine in guiding treatment strategies for metCRC patients. Instead, it suggests that epigenomic profiling and application of FPO could complement the identification of novel combinatorial vulnerabilities to target synchronous ptCRC and mCRC.

Case report: From palliative to potentially curative - the advent of immunotherapy providing hope to advanced gallbladder adenocarcinoma.

Introduction: Biliary tract cancers (BTC) are often diagnosed at an advanced stage where prognosis is poor and curative-intent surgery is infeasible. First-line cisplatin-gemcitabine chemotherapy for advanced gallbladder cancer has remained unchanged over more than a decade, but recent developments in immunotherapy such as durvalumab have highlighted promise as a combination treatment regime with current standard chemotherapy. Methods: In this case description, we present a case of locally-advanced gallbladder adenocarcinoma involving the biliary confluence that was initially planned for an extended right hepatectomy after portal vein embolization. Interval imaging revealed peritoneal metastasis, which was confirmed on diagnostic laparoscopy and biopsy. The patient underwent 8 cycles of cisplatin 25 mg/m2 and gemcitabine 1,000 mg/m2 chemotherapy on days 1 and 8 of each 21-day cycle, with durvalumab (Imfinzi®) 1,500 mg immunotherapy on day 1 of every cycle, in accordance with the treatment protocol of the TOPAZ-1 trial. Repeat imaging demonstrated a stable primary lesion with no further evidence of peritoneal disease. The patient subsequently underwent curative-intent conversion surgery with an extended right hepatectomy and Roux-en-Y hepaticojejunostomy, which were completed through a fully minimally-invasive laparoscopic approach. Results: Final pathological TNM classification was ypT1aN0, with near-complete pathological response to pre-surgical therapy, uninvolved margins (R0 resection) and tumour shrinkage from 2.5 centimetres on pre-operative cross-sectional imaging to 0.5 centimetres on final histology. The patient had an uneventful post-operative course, and was fit for discharge by the fourth post-operative day. He remained well after three months of routine post-operative follow-up, with no significant post-operative complications and biochemical or radiological evidence of disease recurrence. Conclusion: Our case description highlights the immense potential of combination durvalumab immunotherapy with cisplatin-gemcitabine chemotherapy in the treatment of advanced gallbladder adenocarcinoma. The patient's locally advanced disease was initially planned for complex open surgery, prior to discovery of peritoneal metastasis rendering it inoperable. This was successfully down-staged with combination therapy to eventual R0 resection via minimally-invasive surgery. In addition, this case description demonstrates the feasibility of a fully laparoscopic approach with postulated benefits of diagnostic re-evaluation of peritoneal disease, reduced wound pain and shorter length of hospital stay.

Harnessing the potential of large language models in medical education: promise and pitfalls.

OBJECTIVES: To provide balanced consideration of the opportunities and challenges associated with integrating Large Language Models (LLMs) throughout the medical school continuum. PROCESS: Narrative review of published literature contextualized by current reports of LLM application in medical education. CONCLUSIONS: LLMs like OpenAI's ChatGPT can potentially revolutionize traditional teaching methodologies. LLMs offer several potential advantages to students, including direct access to vast information, facilitation of personalized learning experiences, and enhancement of clinical skills development. For faculty and instructors, LLMs can facilitate innovative approaches to teaching complex medical concepts and fostering student engagement. Notable challenges of LLMs integration include the risk of fostering academic misconduct, inadvertent overreliance on AI, potential dilution of critical thinking skills, concerns regarding the accuracy and reliability of LLM-generated content, and the possible implications on teaching staff.

The incidence of adverse outcome in donors after living donor liver transplantation: A meta-analysis of 60,829 donors.

The scarcity of liver grafts has prompted developments in living donor liver transplantations (LDLT), with previous literature illustrating similar outcomes in recipients compared to deceased donor transplants. However, significant concerns regarding living donor morbidity and mortality have yet to be examined comprehensively. This study aims to provide estimates of the incidence of various outcomes in living liver donors. In this meta-analysis, Medline and Embase were searched from inception to July 2022 for articles assessing the incidence of outcomes in LDLT donors. Complications in the included studies were classified into respective organ systems. Analysis of incidence was conducted using a generalized linear mixed model with Clopper-Pearson intervals. Eighty-seven articles involving 60,829 living liver donors were included. The overall pooled incidence of complications in LDLT donors was 24.7% (CI: 21.6%-28.1%). The incidence of minor complications was 17.3% (CI: 14.7%-20.3%), while the incidence of major complications was lower at 5.5% (CI: 4.5%-6.7%). The overall incidence of donor mortality was 0.06% (CI: 0.0%-0.1%) in 49,027 individuals. Psychological complications (7.6%, CI: 4.9%-11.5%) were the most common among LDLT donors, followed by wound-related (5.2%, CI: 4.4%-6.2%) and respiratory complications (4.9%, CI: 3.8%-6.3%). Conversely, cardiovascular complications had the lowest incidence among the subgroups at 0.8% (CI: 0.4%-1.3%). This study presents the incidence of post-LDLT outcomes in living liver donors, illustrating significant psychological, wound-related, and respiratory complications. While significant advancements in recent decades have contributed towards decreased morbidity in living donors, our findings call for targeted measures and continued efforts to ensure the safety and quality of life of liver donors post-LDLT.

Post Living Donor Liver Transplantation Small-for-size Syndrome: Definitions, Timelines, Biochemical, and Clinical Factors for Diagnosis: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: When a partial liver graft is unable to meet the demands of the recipient, a clinical phenomenon, small-for-size syndrome (SFSS), may ensue. Clear definition, diagnosis, and management are needed to optimize transplant outcomes. METHODS: A Consensus Scientific committee (106 members from 21 countries) performed an extensive literature review on specific aspects of SFSS, recommendations underwent blinded review by an independent panel, and discussion/voting on the recommendations occurred at the Consensus Conference. RESULTS: The ideal graft-to-recipient weight ratio of ≥0.8% (or graft volume standard liver volume ratio of ≥40%) is recommended. It is also recommended to measure portal pressure or portal blood flow during living donor liver transplantation and maintain a postreperfusion portal pressure of <15 mm Hg and/or portal blood flow of <250 mL/min/100 g graft weight to optimize outcomes. The typical time point to diagnose SFSS is the postoperative day 7 to facilitate treatment and intervention. An objective 3-grade stratification of severity for protocolized management of SFSS is proposed. CONCLUSIONS: The proposed grading system based on clinical and biochemical factors will help clinicians in the early identification of patients at risk of developing SFSS and institute timely therapeutic measures. The validity of this newly created grading system should be evaluated in future prospective studies.

Early vs late drain removal after pancreatic resection-a systematic review and meta-analysis.

BACKGROUND: Reducing clinically relevant post-operative pancreatic fistula (CR-POPF) incidence after pancreatic resections has been a topic of great academic interest. Optimizing post-operative drain management is a potential strategy in reducing this major complication. METHODS: Studies involving pancreatic resections, including both pancreaticoduodenectomy (PD) and distal pancreatic resections (DP), with intra-operative drain placement were screened. Early drain removal was defined as removal before or on the 3rd post-operative day (POD) while late drain removal was defined as after the 3rd POD. The primary outcome was CR-POPF, International Study Group of Pancreatic Surgery (ISGPS) Grade B and above. Secondary outcomes were all complications, severe complications, post-operative haemorrhage, intra-abdominal infections, delayed gastric emptying, reoperation, length of stay, readmission, and mortality. RESULTS: Nine studies met the inclusion criteria and were included for analysis. The studies had a total of 8574 patients, comprising 1946 in the early removal group and 6628 in the late removal group. Early drain removal was associated with a significantly lower risk of CR-POPF (OR: 0.24, p < 0.01). Significant reduction in risk of post-operative haemorrhage (OR: 0.55, p < 0.01), intra-abdominal infection (OR: 0.35, p < 0.01), re-admission (OR: 0.63, p < 0.01), re-operation (OR: 0.70, p = 0.03), presence of any complications (OR: 0.46, p < 0.01), and reduced length of stay (SMD: -0.75, p < 0.01) in the early removal group was also observed. CONCLUSION: Early drain removal is associated with significant reductions in incidence of CR-POPF and other post-operative complications. Further prospective randomised trials in this area are recommended to validate these findings.

Histone-lysine N-methyltransferase EHMT2 (G9a) inhibition mitigates tumorigenicity in Myc-driven liver cancer.

Hepatocellular carcinoma (HCC) is the third deadliest and sixth most common cancer in the world. Histone-lysine N-methyltransferase EHMT2 (also known as G9a) is a histone methyltransferase frequently overexpressed in many cancer types, including HCC. We showed that Myc-driven liver tumours have a unique H3K9 methylation pattern with corresponding G9a overexpression. This phenomenon of increased G9a was further observed in our c-Myc-positive HCC patient-derived xenografts. More importantly, we showed that HCC patients with higher c-Myc and G9a expression levels portend a poorer survival with lower median survival months. We demonstrated that c-Myc interacts with G9a in HCC and cooperates to regulate c-Myc-dependent gene repression. In addition, G9a stabilises c-Myc to promote cancer development, contributing to the growth and invasive capacity in HCC. Furthermore, combination therapy between G9a and synthetic-lethal target of c-Myc, CDK9, demonstrates strong efficacy in patient-derived avatars of Myc-driven HCC. Our work suggests that targeting G9a could prove to be a potential therapeutic avenue for Myc-driven liver cancer. This will increase our understanding of the underlying epigenetic mechanisms of aggressive tumour initiation and lead to improved therapeutic and diagnostic options for Myc-driven hepatic tumours.

Uses of a dedicated 3D reconstruction software with augmented and mixed reality in planning and performing advanced liver surgery and living donor liver transplantation (with videos).

The development of digital intelligent diagnostic and treatment technology has opened countless new opportunities for liver surgery from the era of digital anatomy to a new era of digital diagnostics, virtual surgery simulation and using the created scenarios in real-time surgery using mixed reality. In this article, we described our experience on developing a dedicated 3 dimensional visualization and reconstruction software for surgeons to be used in advanced liver surgery and living donor liver transplantation. Furthermore, we shared the recent developments in the field by explaining the outreach of the software from virtual reality to augmented reality and mixed reality.

The role of acute in-patient rehabilitation on short-term outcomes after liver transplantation: A systematic review of the literature and expert panel recommendations.

BACKGROUND: The indication and surgical complexity of orthotopic liver transplantation underscore the need for strategies to optimize the recovery for transplant recipients. We conducted a systematic review aimed at identifying, evaluating, and synthesizing the evidence examining the effect of in-patient rehabilitation for liver transplant recipients and provide related practice recommendations. METHODS: Health research databases were systematically reviewed for studies that included adults who received liver transplantation and participated in acute, post-transplant rehabilitation. Postoperative morbidity, mortality, length of hospital stay, length of intensive care unit stay, and other markers of surgical recovery were extracted. Practice recommendations are provided by an international panel using GRADE. RESULTS: Twelve studies were included in the review (including 3901 participants). Rehabilitation interventions varied widely in design and composition; however, details regarding intervention delivery were poorly described in general. The quality of evidence was rated as very low largely owing to "very serious" imprecision, poor reporting, and limited data from comparative studies. Overall, the studies suggest that in-patient rehabilitation for recipients of liver transplantation is safe, tolerable, and feasible, and may benefit functional outcomes. CONCLUSION: Two practice recommendations related to in-patient rehabilitation following LT were yielded from this review: (1) it is safe, tolerable, and feasible; and (2) it improves postoperative functional outcomes. Each of the recommendations are weak and supported by low quality of evidence. No recommendation could be made related to benefits or harms for clinical, physiological, and other outcomes. Adequately powered and high quality randomized controlled trials are urgently needed in this area.

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma: the PLANET study.

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

A meta-analysis on the incidence of donor-related depression after liver transplant.

Living donor liver transplantation (LDLT) is increasing, yet gaps exist in the understanding of psychological wellbeing of donors after liver transplant. This meta-analysis seeks to evaluate the incidence and risk factors for donor-related depression after liver transplantation. A search was conducted on Medline and Embase database. Articles assessing incidence of depression in LDLT donors were included. Incidence was pooled after Freeman-Turkey double-arcsine transformation. For risk factors, dichotomous variables were analyzed with generalized linear model, while a conventional meta regression with logit transformation was conducted for continuous variables. Of 1069 abstracts, 40 articles underwent full-text review. Seventeen articles were included. The pooled incidence of depression among 1888 LT donors was 7.66% (CI: 4.47-12.80%). Depression rates were significantly higher in Asian compared to Western studies (RR: 1.73, CI: 1.19-2.52, P = 0.0039). Female gender (P < 0.001), Caucasian ethnicity (P = 0.047), employment status (P < 0.001) and lower education levels (P = 0.044) were significantly associated with depression. Donor relationship with recipients was not a significant risk factor. LDLT remains a core aspect of the treatment of end-stage liver disease. However, the high depression rates after LT suggest that there remains room for improvement in the care of donors' mental health post-transplant.

Multimodal prehabilitation before major abdominal surgery: A retrospective study.

INTRODUCTION: Prehabilitation may benefit older patients undergoing major surgeries. Currently, its efficacy has not been conclusively proven. This is a retrospective review of a multimodal prehabilitation programme. METHODS: Patients aged 65 years and above undergoing major abdominal surgery between May 2015 and December 2019 in the National University Hospital were included in our institutional programme that incorporated aspects of multimodal prehabilitation and Enhanced Recovery After Surgery concepts as 1 holistic perioperative pathway to deal with issues specific to older patients. Physical therapy, nutritional advice and psychosocial support were provided as part of prehabilitation. RESULTS: There were 335 patients in the prehabilitation cohort and 256 patients whose records were reviewed as control. No difference in postoperative length of stay (P=0.150) or major complications (P=0.690) were noted. Patients in the prehabilitation group were observed to ambulate a longer distance and participate more actively with their physiotherapists from postoperative day 1 until 4. In the subgroup of patients with cancer, more patients had undergone neoadjuvant therapy in the prehabilitation group compared to the control group (21.7% versus 12.6%, P=0.009). Prehabilitation patients were more likely to proceed to adjuvant chemotherapy (prehabilitation 87.2% vs control 65.6%, P<0.001) if it had been recommended. CONCLUSION: The current study found no differences in traditional surgical outcome measures with and without prehabilitation. An increase in patient mobility in the immediate postoperative period was noted with prehabilitation, as well as an association between prehabilitation and increased adherence to postoperative adjuvant therapy. Larger prospective studies will be needed to validate the findings of this retrospective review.

Factors Attracting or Deterring Female Medical Students in Asia From Pursuing a Surgical Career, and the Impact of Surgical Clerkship, Mentorship, and Role Models: A Multicultural Asian Perspective From a National Prospective Cohort Study.

BACKGROUND: Female surgeons are highly underrepresented in Asian countries, where prescriptive gender norms are widespread and more deeply embedded in societies. MATERIALS AND METHODS: A nationwide structured questionnaire was completed by 1741 Singaporean third- and fifth-year medical students after the completion of an 8-week general surgery rotation, during 2015-2017. Results were analyzed using mixed-effects hierarchical models which took into account clustering of survey responses under the teaching hospitals which students were posted to and medical students' year of study. RESULTS: Female medical students had a poorer perception of general surgery than male students (3.22 ± 0.91 versus 3.41 ± 0.89; P < 0.0001) before the clerkship. However, the clerkship improved female students' opinion to a greater extent than male students (+0.84 ± 1.06 versus +0.59 ± 1.03; P < 0.0001), resulting in female and male students having comparable attitudes toward surgery after the clerkship (4.06 ± 0.79 versus 4.00 ± 0.87; P = 0.2435). A total of 40.4% of female students responded that they were inspired to pursue a surgical career after the clerkship, and we identified 13 pedagogical traits of faculty and resident mentors which were associated with female students' career aspirations. Female students were more likely to consider intellectual challenges arising from cases (ratio: 1.045 [95% confidence interval 1.004-1.088, P = 0.0292]) and the presence of role models (ratio: 1.068 [95% confidence interval: 1.020-1.118, P = 0.0048]) as "pull" factors compared with their male contemporaries, but were deterred from a surgical career to a greater extent by eight "push" factors. CONCLUSIONS: A surgical clerkship itself could be regarded as an effective intervention for improving female medical students' enthusiasm for surgery, which may help to address the "pipeline problem" of few female students applying for surgical training after medical school. A greater emphasis on "pull factors" and pedagogical qualities of mentors could be used to improve the clerkship experience, to attract more female students to surgery.

Push and pull factors, and the role of residents in nurturing medical students' interest in surgery as a career option in a multicultural Asian context: Results of a prospective national cohort study.

BACKGROUND: Studies in Caucasian populations suggest that interest among medical students in pursuing a surgical career is dwindling. We sought to investigate these trends and to evaluate the impact of resident teaching in a multiethnic Asian population. STUDY DESIGN: Between 2015 and 2017, 1780 Singaporean third- and fifth-year medical students completed a structured anonymized questionnaire following the completion of an 8-week general surgery rotation. Medical students' impressions of their faculty and resident mentors were analyzed using hierarchical multilevel mixed-effects models. RESULTS: Respondents' opinions of general surgery improved from 3.31 ± 0.91 points to 4.03 ± 0.83 points on a 5-point Likert scale (P < 0.0001). Medical students were more likely to regard their interaction with residents as a "pull" factor compared to their interaction with faculty members (74.7% vs 65.6%; P < 0.0001). Our analyses revealed 9 statistically-significant "pull" factors and 5 "push" factors which attract or deter Asian medical students from a career in surgery. Comparing the pedagogical qualities of resident and faculty mentors, we found that residents surpassed faculty mentors in 9 domains, had comparable appraisal scores on 3 domains, and fared worse than faculty on 8 domains. Importantly, residents fared better at promoting interest in a surgical career (P = 0.0006) and influencing the career aspirations of medical students (P < 0.0001) compared with faculty members. CONCLUSIONS: To our knowledge, this is the largest study from a Southeast Asian country providing representative sample numbers. With this knowledge of pull and push factors, the surgical clerkship can be improved by emphasizing pull factors and preparing students to cope with the push factors. Finally, our findings suggest that roping in residents as mentors to medical students may improve the pipeline of students interested in pursuing surgery after medical school.

An international multicenter study of protocols for liver transplantation during a pandemic: A case for quadripartite equipoise.

BACKGROUND & AIMS: The outbreak of COVID-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. METHODS: We performed an international multicenter study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the quadripartite equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. RESULTS: Seventeen large- and medium-sized liver transplant centers from 12 countries across 4 continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a "sickest-first" approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - recipient outcome, donor/graft safety, waiting list mortality and healthcare resources - for 7 countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. CONCLUSIONS: This four-dimensional model of quadripartite equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems. LAY SUMMARY: There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources during the COVID-19 pandemic. We describe a four-dimensional model of quadripartite equipoise that models these ethical tensions and can guide the regulation of transplant activity in response to the increasing burden on healthcare systems.