Proceedings of the 28th Annual Congress of the International Liver Transplantation Society.

The 2023 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE) held in Rotterdam, the Netherlands, marked a significant recovery milestone for the liver transplant community after COVID-19. With 1159 participants and a surge in abstract submissions, the event focused on "Liver Disorders and Transplantation: Innovations and Evolving Indications." This conference report provides a comprehensive overview of the key themes discussed during the event, encompassing Hepatology, Anesthesia and Critical Care, Acute Liver Failure, Infectious Disease, Immunosuppression, Pediatric Liver Transplantation, Living Donor Liver Transplantation, Transplant Oncology, Surgical Approaches, and Machine Perfusion. The congress provided a platform for extensive discussions on a wide range of topics, reflecting the continuous advancements and collaborative efforts within the liver transplant community.

Minimizing Metabolic and Cardiac Risk Factors to Maximize Outcomes After Liver Transplantation.

Cardiovascular disease (CVD) is a leading complication after liver transplantation and has a significant impact on patients' outcomes posttransplant. The major risk factors for post-liver transplant CVD are age, preexisting CVD, nonalcoholic fatty liver disease, chronic kidney disease, and metabolic syndrome. This review explores the contemporary strategies and approaches to minimizing cardiometabolic disease burden in liver transplant recipients. We highlight areas for potential intervention to reduce the mortality of patients with metabolic syndrome and CVD after liver transplantation.

Obesity management for the hepatologist-What to do, how to do it and why?

Obesity is highly prevalent in hepatology clinics and has a significant impact on chronic liver disease and patient management. Hepatologists and gastroenterologists need to be actively engaged in the management of obesity. This review provides a detailed approach to this challenging comorbidity.

Primary prevention of hepatic encephalopathy post-TIPS: A systematic review and meta-analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) can be an effective treatment for cirrhotic patients who develop variceal bleeding and ascites. However, TIPS placement is associated with an increased risk of developing hepatic encephalopathy (HE). Recently, there have been efforts to use the typical medical therapies prophylactically in patients undergoing TIPS placement to prevent post-TIPS HE. METHODS: We conducted literature searches in MEDLINE, Embase, CINAHL, Scopus, and Cochrane to examine studies that use prophylactic medical therapy for preventing post-TIPS HE. A narrative synthesis and grading of recommendations assessment assessment were done for all studies. Meta-analysis was performed for eligible studies using the Mantel-Haenszel method random-effects model. Nine hundred twenty-one articles were screened and 5 studies were included in the study after 2 levels of screening. The medications studied were rifaximin, lactulose, lactitol, L-Ornithine-L-aspartate (LOLA), albumin, and combination therapies. RESULTS: Narrative results showed that lactulose, lactitol, LOLA and albumin prophylaxis were not associated with reduction in HE occurrence or mortality. A combination of rifaximin and lactulose was found to be associated with lower occurrence of HE, and the results were not different when LOLA was added. Meta-analysis (n = 3) showed that rifaximin treatment was not associated with changes in HE occurrences. CONCLUSION: In conclusion, a vast majority of medications were not found to be effective post-TIPS HE prophylaxis when used alone. A rifaximin and lactulose combination therapy may be beneficial. Overall, there is significant limitation in the current data and more studies are needed to yield more robust meta-analysis results in the future.

Clinical Indicators for Primary Cranial CT Imaging after Mild Traumatic Brain Injury-A Retrospective Analysis.

The primary aim was to determine the clinical indicators for primary cranial CT imaging in patients after mild traumatic brain injury (mTBI). The secondary aim was to evaluate the need for post-traumatic short-term hospitalization based on primary clinical and CT findings. This was an observational retrospective single-centre study of all the patients who were admitted with mTBI over a five-year period. Demographic and anamnesis data, the clinical and radiological findings, and the outcome were analyzed. An initial cranial CT (CT0) was performed at admission. Repeat CT scans (CT1) were performed after positive CT0 findings and in cases with in-hospital secondary neurological deterioration. Intracranial hemorrhage (ICH) and the patient's outcome were evaluated using descriptive statistical analysis. A multivariable analysis was performed to find associations between the clinical variables and the pathologic CT findings. A total of 1837 patients (mean age: 70.7 years) with mTBI were included. Acute ICH was detected in 102 patients (5.5%), with a total of 123 intracerebral lesions. In total, 707 (38.4%) patients were admitted for 48 h for in-hospital observation and six patients underwent an immediate neurosurgical intervention. The prevalence of delayed ICH was 0.05%. A Glasgow Coma Scale (GCS) of <15, loss of consciousness, amnesia, seizures, cephalgia, somnolence, dizziness, nausea, and clinical signs of fracture were identified as clinical factors with significantly higher risk of acute ICH. None of the 110 CT1 presented clinical relevance. A GCS of <15, loss of consciousness, amnesia, seizures, cephalgia, somnolence, dizziness, nausea, and clinical signs of cranial fractures should be considered absolute indicators for primary cranial CT imaging. The reported incidence of immediate and delayed traumatic ICH was very low and hospitalization should be decided individually considering both the clinical and CT findings.

Management of older adults after mild head trauma in an oral and maxillofacial surgery clinic.

PURPOSE: The primary aim was to determine the incidence of intracranial hemorrhage (ICH) after mild traumatic brain injury (mTBI) in patients aged ≥ 65 years. The secondary aim was to identify risk factors for intracranial lesions and evaluate the need for in-hospital observation in this age group. METHODS: This observational retrospective single-center study included all patients aged ≥ 65 years who were referred to our clinic for oral and plastic maxillofacial surgery following mTBI over a five-year period. Demographic and anamnesis data, clinical and radiological findings, and treatment were analyzed. Acute and delayed ICH and patient outcomes during hospitalization were evaluated using descriptive statistical analysis. A multivariable analysis was performed to find associations between CT findings and clinical data. RESULTS: A total of 1,062 patients (55.7% male, 44.2% female) with a mean age of 86.3 years were included in the analysis. Ground-level fall was the most frequent cause of trauma (52.3%). Fifty-nine patients (5.5%) developed an acute traumatic ICH, and 73 intracerebral lesions were radiologically observed. No association was detected between ICH rate and antithrombotic medication (p = 0.4353). The delayed ICH rate was 0.09% and the mortality rate was 0.09%. Significant risk factors for increased ICH were a Glasgow Coma Scale score of < 15, loss of consciousness, amnesia, cephalgia, somnolence, dizziness, and nausea according to multivariable analysis. CONCLUSION: Our study showed a low prevalence of acute and delayed ICH in older adults with mTBI. The ICH risk factors identified here should be considered when revising guidelines and developing a valid screening tool. Repeat CT imaging is recommended in patients with secondary neurological deterioration. In-hospital observation should be based on an assessment of frailty and comorbidities and not on CT findings alone.

Non-Coding RNA as Biomarkers for Survival in Colorectal Cancer Patients.

Colorectal cancer (CRC) has a high incidence and fatality rate worldwide. It ranks second concerning death worldwide. Cancer patients are diagnosed with the disease at a later stage due to the absence of early diagnostic methods, which leads to increased death. With the help of recent advancements in the fields of diagnosis and therapy, the development of novel methods using new targets could be helpful for the long-term survival of CRC patients when CRC is detected early. However, the prognosis for the advanced stage of CRC is abysmal. New biomarkers are emerging as promising alternatives since they can be utilized for early detection of CRC, are simple to use, and are non-invasive. Non-coding RNAs (ncRNAs) have been seen to have an aberrant expression in the development of many malignancies, including CRC. In the past two decades, much research has been done on non-coding RNAs, which may be valuable as biomarkers and targets for antitumor therapy. Non-coding RNAs can be employed in detecting and treating CRC. Non-coding RNAs play an essential role in regulating gene expression. This article reviews ncRNAs and their expression levels in CRC patients that might qualify them as potential biomarkers. Various ncRNAs have been associated with CRC, such as microRNAs, long non-coding RNAs, circular RNAs, etc. The expression of these non-coding RNAs may provide insights into the stages of cancer and the prognosis of cancer patients and thus take proper preliminary measures to decrease cancer-related deaths.

Changing Landscape of Liver Transplantation in the Post-DAA and Contemporary ART Era.

Combination anti-retroviral therapy has drastically improved solid organ transplantation outcomes in persons living with HIV. DAA therapy has led to the successful eradication of HCV. While recent data have suggested improvement in outcomes in HIV/HCV-coinfected liver transplant recipients, temporal trends in patient survival within pre- and post-DAA eras are yet to be elucidated. The UNOS database was utilized to identify deceased donor liver transplant recipients between 1 January 2000 and 30 September 2020 and stratify them by HIV and HCV infection status. A total of 85,730 patients met the inclusion criteria. One-year and five-year patient survival improved (93% and 80%, respectively) for all transplants performed post-2015. For HIV/HCV-coinfected recipients, survival improved significantly from 78% (pre-2015) to 92% (post-2015). Multivariate regression analyses identified advanced recipient age, Black race, diabetes mellitus and decompensated cirrhosis as risk factors associated with higher one-year mortality. Liver transplant outcomes in HIV/HCV-coinfected liver transplant recipients have significantly improved over the last quinquennium in the setting of the highly effective combination of ART and DAA therapy. The presence of HIV, HCV, HIV/HCV-coinfection and active HCV viremia at the time of transplant do not cause higher mortality risk in liver transplant recipients in the current era.

Laboratory Detection and Initial Diagnosis of Monoclonal Gammopathies.

CONTEXT.­: The process for identifying patients with monoclonal gammopathies is complex. Initial detection of a monoclonal immunoglobulin protein (M protein) in the serum or urine often requires compilation of analytical data from several areas of the laboratory. The detection of M proteins depends on adequacy of the sample provided, available clinical information, and the laboratory tests used. OBJECTIVE.­: To develop an evidence-based guideline for the initial laboratory detection of M proteins. DESIGN.­: To develop evidence-based recommendations, the College of American Pathologists convened a panel of experts in the diagnosis and treatment of monoclonal gammopathies and the laboratory procedures used for the initial detection of M proteins. The panel conducted a systematic literature review to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were created based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework. RESULTS.­: Nine guideline statements were established to optimize sample selection and testing for the initial detection and quantitative measurement of M proteins used to diagnose monoclonal gammopathies. CONCLUSIONS.­: This guideline was constructed to harmonize and strengthen the initial detection of an M protein in patients displaying symptoms or laboratory features of a monoclonal gammopathy. It endorses more comprehensive initial testing when there is suspicion of amyloid light chain amyloidosis or neuropathies, such as POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome, associated with an M protein.

Personalizing Diabetes Management in Liver Transplant Recipients: The New Era for Optimizing Risk Management.

Post-transplant diabetes mellitus (PTDM) is a significant contributor to morbidity and mortality in liver transplant recipients (LTRs). With concurrent comorbidities and use of various immunosuppression medications, identifying a safe and personalized regimen for management of PTDM is needed. There are many comorbidities associated with the post-transplant course including chronic kidney disease, cardiovascular disease, allograft steatosis, obesity, and de novo malignancy. Emerging data suggest that available diabetes medications may carry beneficial or, in some cases, harmful effects in the setting of these co-existing conditions. Sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists have shown the most promising beneficial results. Although there is a deficiency of LTR-specific data, they appear to be generally safe. Effects of other medications are varied. Metformin may reduce the risk of malignancy. Pioglitazone may be harmful in patients combatting obesity or heart failure. Insulin may exacerbate obesity and increase the risk of developing malignancy. This review thoroughly discusses the roles of these extra-glycemic effects and safety considerations in LTRs. Through weighing the risks and benefits, we conclude that alternatives to insulin should be strongly considered, when feasible, for personalized long-term management based on risk factors and co-morbidities.

Investigation of Patient-Specific Maxillofacial Implant Prototype Development by Metal Fused Filament Fabrication (MF3) of Ti-6Al-4V.

Additive manufacturing (AM) and related digital technologies have enabled several advanced solutions in medicine and dentistry, in particular, the design and fabrication of patient-specific implants. In this study, the feasibility of metal fused filament fabrication (MF3) to manufacture patient-specific maxillofacial implants is investigated. Here, the design and fabrication of a maxillofacial implant prototype in Ti-6Al-4V using MF3 is reported for the first time. The cone-beam computed tomography (CBCT) image data of the patient's oral anatomy was digitally processed to design a 3D CAD model of the hard tissue and fabricate a physical model by stereolithography (SLA). Using the digital and physical models, bone loss condition was analyzed, and a maxillofacial implant initial design was identified. Three-dimensional (3D) CAD models of the implant prototypes were designed that match the patient's anatomy and dental implant requirement. In this preliminary stage, the CAD models of the prototypes were designed in a simplified form. MF3 printing of the prototypes was simulated to investigate potential deformation and residual stresses. The patient-specific implant prototypes were fabricated by MF3 printing followed by debinding and sintering using a support structure for the first time. MF3 printed green part dimensions fairly matched with simulation prediction. Sintered parts were characterized for surface integrity after cutting the support structures off. An overall 18 ± 2% shrinkage was observed in the sintered parts relative to the green parts. A relative density of 81 ± 4% indicated 19% total porosity including 11% open interconnected porosity in the sintered parts, which would favor bone healing and high osteointegration in the metallic implants. The surface roughness of Ra: 18 ± 5 µm and a Rockwell hardness of 6.5 ± 0.8 HRC were observed. The outcome of the work can be leveraged to further investigate the potential of MF3 to manufacture patient-specific custom implants out of Ti-6Al-4V.

Effect of a Best Practice Alert on Birth-Cohort Screening for Hepatitis C Virus.

INTRODUCTION: We assessed the influence of a best practice alert (BPA) embedded within the electronic medical record on improving hepatitis C virus (HCV) birth-cohort screening by primary care physicians (PCPs). METHODS: Screening by 155 PCPs was monitored during 2 consecutive 9-month periods before and after implementation of the BPA. All tests were reviewed to differentiate true screening from other testing indications. RESULTS: Of 155 PCPs, 131 placed screening orders before and after BPA. Twenty-two PCPs started testing after BPA (P = 0.02). The number of tests placed and screening rates per PCP increased from 16 to 84 and from 3.3% to 13.2%, respectively (P < 0.0001). Before BPA, most PCPs rarely ordered screening HCV tests, whereas a small group of physicians generated most tests, indicative of an underlying power-law distribution. After the BPA, a new group of high-performing PCPs emerged, whose screening patterns were again characterized by a power-law distribution. However, pre-BPA test rates of individual PCPs were not predictive of their post-BPA rates. Overall, the introduction of the BPA narrowed the gap between low- and high-performing testers, indicating that modest increases in testing by a large number of low-performing PCPs could drive substantial improvement in program implementation. DISCUSSION: HCV birth-cohort screening by PCPs was shaped by an underlying power-law distribution. This distribution was preserved after the implementation of a BPA, although pre-BPA test rates were not predictive of post-BPA rates. Increases in test rates by high- and low-performing PCPs both contributed to the overall success of the BPA.

Impact of exposure to patients with COVID-19 on residents and fellows: an international survey of 1420 trainees.

OBJECTIVES: To determine how self-reported level of exposure to patients with novel coronavirus 2019 (COVID-19) affected the perceived safety, training and well-being of residents and fellows. METHODS: We administered an anonymous, voluntary, web-based survey to a convenience sample of trainees worldwide. The survey was distributed by email and social media posts from April 20th to May 11th, 2020. Respondents were asked to estimate the number of patients with COVID-19 they cared for in March and April 2020 (0, 1-30, 31-60, >60). Survey questions addressed (1) safety and access to personal protective equipment (PPE), (2) training and professional development and (3) well-being and burnout. RESULTS: Surveys were completed by 1420 trainees (73% residents, 27% fellows), most commonly from the USA (n=670), China (n=150), Saudi Arabia (n=76) and Taiwan (n=75). Trainees who cared for a greater number of patients with COVID-19 were more likely to report limited access to PPE and COVID-19 testing and more likely to test positive for COVID-19. Compared with trainees who did not take care of patients with COVID-19 , those who took care of 1-30 patients (adjusted OR [AOR] 1.80, 95% CI 1.29 to 2.51), 31-60 patients (AOR 3.30, 95% CI 1.86 to 5.88) and >60 patients (AOR 4.03, 95% CI 2.12 to 7.63) were increasingly more likely to report burnout. Trainees were very concerned about the negative effects on training opportunities and professional development irrespective of the number of patients with COVID-19 they cared for. CONCLUSION: Exposure to patients with COVID-19 is significantly associated with higher burnout rates in physician trainees.

Overview of Morin and Its Complementary Role as an Adjuvant for Anticancer Agents.

The Global cancer incidence and mortality data released by the World Health Organization proposes that out of 18.1 million new cancer cases diagnosed, 9.8 million deaths occurred globally in 2018. Cancer is one of the major health burdens among non-communicable diseases globally responsible for impeding life expectancy in the present century. Disrupting hallmarks of cancer (such as prolonged inflammation, increased growth signal, tissue invasion and metastasis, unlimited proliferation and evasion of apoptosis) with dietary agents is of considerable focus for cancer prevention and therapy. In the last decade, a significant contribution has been provided in finding many plant-derived natural agents that can be identified as promising molecular cancer therapeutics. Our focus in this review is on one such natural dietary agent, Morin (3,5,7,2',4'-pentahydroxyflavone): a bioflavonoid. Morin exerts strong pharmacological properties against a multitude of cancer (liver cancer, cervical cancer, melanoma, breast cancer, prostate, and colon cancer). Recent progress has also been made in examining the potential of morin as a natural dietary agent for fostering the pharmacological effects of other well-known anticancer agents. This review provides an overview of morin and its derivatives in combination with anticancer agents for cancer prevention and therapy.

An audit of inpatient stool ova and parasite (O&P) testing in a multi-hospital health system.

BACKGROUND & OBJECTIVES: Stool ova and parasite (O&P) examinations are routinely ordered initial tests in patients admitted to the hospital with acute diarrhea, despite low test positivity rates. We examined the diagnostic yield of inpatient stool O&P exams and identified risk factors associated with positive tests. METHODS: A retrospective, case-control analysis of inpatients admitted with diarrhea, who underwent O&P examination, was conducted. Clinical and demographic variables of cases were compared with age-and gender-matched controls via uni- and multivariate conditional logistic regression analyses. RESULTS: The yield of inpatient O&P exams was 2.15% (37/1723). Blastocystisspp. represented the most common parasites. All patients with positive tests, excluding Blastocystisspp., had at least one of the following risk factors: smoking, prior parasitic disease, HIV-positive status, travel to an endemic area, and institutionalization. CONCLUSIONS: Superfluous inpatient stool O&P exams confer a financial and labor burden to hospital systems. Stool O&P exams should be restricted to individuals admitted to the hospital for <3 days, having diarrhea >7 days and possessing at least one of the following risk factors: smoking, prior parasitic disease, HIV-positive status, travel to an endemic area, and institutionalization. Such selective testing can confer a 51% reduction in testing, costs, and labor.

Alcohol Withdrawal Mimicking Neuroleptic Malignant Syndrome.

Long-standing, heavy alcohol use can lead to alcohol dependence, which predisposes to alcohol withdrawal if alcohol consumption is suddenly decreased or stopped. Alcohol withdrawal syndrome is characterized by a hyperadrenergic response, with symptoms ranging from mild tremulousness to delirium tremens. We report a 55-year-old male presenting with hyperthermia, tachycardia, tachypnea, altered consciousness, tremors, rigidity, diaphoresis, elevated creatinine kinase, and myoglobinuria. The diagnosis of alcohol withdrawal was made due to a history of alcohol use disorder with the last drink two days ago and no history of any medication or drug intake prior to admission. He was treated with benzodiazepines with an improvement in his condition.