The emerging role of generative artificial intelligence in transplant medicine.

Generative artificial intelligence (AI), a subset of machine learning that creates new content based on training data, has witnessed tremendous advances in recent years. Practical applications have been identified in health care in general, and there is significant opportunity in transplant medicine for generative AI to simplify tasks in research, medical education, and clinical practice. In addition, patients stand to benefit from patient education that is more readily provided by generative AI applications. This review aims to catalyze the development and adoption of generative AI in transplantation by introducing basic AI and generative AI concepts to the transplant clinician and summarizing its current and potential applications within the field. We provide an overview of applications to the clinician, researcher, educator, and patient. We also highlight the challenges involved in bringing these applications to the bedside and need for ongoing refinement of generative AI applications to sustainably augment the transplantation field.

Recurrent Primary Sclerosing Cholangitis: Current Understanding, Management, and Future Directions.

Patients with primary sclerosing cholangitis (PSC) constitute 5 to 15% of patients listed for liver transplantation worldwide. Although post-transplant outcomes are favorable, recurrent PSC (rPSC) occurs in an important subset of patients, with higher prevalence rates reported with increasing time from transplant. Given its association with poor graft outcomes and risk of retransplant, effort has been made to understand rPSC, its pathophysiology, and risk factors. This review covers these facets of rPSC and focuses on implicated risk factors including pretransplant recipient characteristics, inflammatory bowel-disease-related factors, and donor-specific and transplant-specific factors. Confirming a diagnosis of rPSC requires thoughtful consideration of alternative etiologies so as to ensure confidence in diagnosis, management, subsequent risk assessment, and counseling for patients. Unfortunately, no cure exists for rPSC; however, future large-scale efforts are underway to better characterize the natural history of rPSC and its associated risk factors with hopes of identifying potential key targets for novel therapies.

Early postoperative acute myocardial infarction in kidney transplant recipients: A nested case-control study.

INTRODUCTION: The epidemiology of early acute myocardial infarctions after kidney transplantation has not been well characterized. This study sought to examine the incidence, risk factors, and clinical outcomes of early acute myocardial infarctions or EAMI in kidney transplant recipients. METHODS: A total of 1976 patients who underwent kidney transplantation at our center from Jan 1, 2000, to Sept 30, 2016, were included. A nested case-control design was used to study EAMI risk factors using a conditional logistic regression model. A Cox proportional hazards model was used to assess the association of EAMI with death-censored graft failure, death with graft function, and total graft failure. RESULTS: Seventy four patients had an EAMI within 3 months post-transplant. Based on univariable analyses, risk factors for EAMI included age and recipient history of diabetes mellitus or coronary artery disease. After adjustment, recipient history of coronary artery disease was the only independent predictor for EAMI (OR 3.76, p < .001). Patients who experienced EAMI were more likely to experience death-censored graft failure, death with graft function, and total graft failure. CONCLUSION: While the incidence of EAMI in kidney transplant recipients is relatively low, these data show that EAMI has profound long-term effects on morbidity and mortality.

Review article: pathophysiology and management of primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC), an immune-mediated disease characterised by destruction of intrahepatic bile ducts, results in progressive damage to the biliary tree, cholestasis and ultimately advanced liver disease. In the last decade, advances in practice have improved clinical care, driven novel therapeutic options and improved risk stratification tools. AIMS: To provide an overview of the disease characteristics of PBC and review a patient-centred management approach for the clinical team caring for those with PBC. METHODS: We reviewed the current literature and guidelines on PBC with a focus on management and therapies. RESULTS: A confident diagnosis of PBC is usually made based on serum liver tests and immune serology. Management of PBC should focus on three main 'process' pillars: (a) treat and risk-stratify through use of biochemical and prognostic criteria; (b) manage concurrent symptoms and other associated diseases; and (c) stage disease, monitor progression and prevent complications. With ongoing complexities in management, including a newly licensed therapy (obeticholic acid) and alternative non-licensed treatments and ongoing clinical trials, discussion with PBC expert centres is encouraged. CONCLUSIONS: PBC is a dynamic disease wherein current treatment goals have become appropriately ambitious. Goals of care should prioritise prevention of end-stage liver disease and amelioration of patient symptom burden for all.

Onychomadesis following hand, foot, and mouth disease in a pregnant woman: A case report.

Hand, foot, and mouth disease is an enteroviral infection characterized by vesicles on the hands, feet, and oral mucosa. Given its rising incidence among adults, it is important to recognize its variable presentations and sequelae. These include onychomadesis, a complication of hand, foot, and mouth disease that is well described in children, with limited reports in adults. We present the unique case of a pregnant woman who developed onychomadesis following hand, foot, and mouth disease, with no adverse pregnancy outcomes. This case illustrates that (1) onychomadesis can occur in pregnant women with hand, foot, and mouth disease; (2) onychomadesis is typically a benign change that can occur following hand, foot, and mouth disease; and (3) onychomadesis is not necessarily associated with more severe disease or adverse pregnancy outcomes.

Sinecatechins ointment for the treatment of warts in children.

BACKGROUND: Sinecatechins ointment, a green tea derivative, is a novel agent approved for the treatment of anogenital warts in immunocompetent adults and has been reported to be effective in treating extragenital warts as well. Data are lacking in children. We sought to determine the efficacy and tolerability of sinecatechins ointment for treating warts in children. METHODS: A retrospective cohort study was conducted of children with anogenital and/or extragenital warts treated with sinecatechins ointment for at least 1 month. The primary outcome was frequency of complete response (total resolution of warts at follow-up). Secondary outcomes included frequency of partial response (reduction in number and/or size of warts) and adverse events. There was no control group for comparison. RESULTS: Of 24 patients who met the inclusion criteria, 14 (58.3%) had anogenital warts, 7 (29.2%) had extragenital warts, and 3 (12.5%) had both anogenital and extragenital warts. Mean age at treatment initiation was 8.0 years (SD = 3.9). Median duration of warts at treatment initiation was 1.2 years (range 0.09-12.62). Sixteen patients (66.7%) experienced a reduction in the number and/or size of the warts. Four patients (16.7%) had complete resolution. Median treatment duration was 4.5 months (range 0.6-21.8) overall. Median time to complete resolution was 2.9 months (range 1.3-7.7). Fifty-four percent of patients used sinecatechins ointment as prescribed. Adverse events were limited to mild local irritation (7 patients; 29.2%). CONCLUSION: Sinecatechins ointment is a promising therapy for warts in children, and its use should be evaluated in prospective controlled clinical trials.

Magnetic Resonance Elastography to Assess Fibrosis in Kidney Allografts.

BACKGROUND AND OBJECTIVES: Fibrosis is a major cause of kidney allograft injury. Currently, the only means of assessing allograft fibrosis is by biopsy, an invasive procedure that samples <1% of the kidney. We examined whether magnetic resonance elastography, an imaging-based measure of organ stiffness, could noninvasively estimate allograft fibrosis and predict progression of allograft dysfunction. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Kidney allograft recipients >1 year post-transplant undergoing an allograft biopsy first underwent free-breathing, flow-compensated magnetic resonance elastography on a 3.0-T magnetic resonance imaging scanner. Each patient had serial eGFR measurements after the elastography scan for a follow-up period of up to 1 year. The mean stiffness value of the kidney allograft was compared with both the histopathologic Banff fibrosis score and the rate of eGFR change during the follow-up period. RESULTS: Sixteen patients who underwent magnetic resonance elastography and biopsy were studied (mean age: 54±9 years old). Whole-kidney mean stiffness ranged between 3.5 and 7.3 kPa. Whole-kidney stiffness correlated with biopsy-derived Banff fibrosis score (Spearman rho =0.67; P<0.01). Stiffness was heterogeneously distributed within each kidney, providing a possible explanation for the lack of a stronger stiffness-fibrosis correlation. We also found negative correlations between whole-kidney stiffness and both baseline eGFR (Spearman rho =-0.65; P<0.01) and eGFR change over time (Spearman rho =-0.70; P<0.01). Irrespective of the baseline eGFR, increased kidney stiffness was associated with a greater eGFR decline (regression r2=0.48; P=0.03). CONCLUSIONS: Given the limitations of allograft biopsy, our pilot study suggests the potential for magnetic resonance elastography as a novel noninvasive measure of whole-allograft fibrosis burden that may predict future changes in kidney function. Future studies exploring the utility and accuracy of magnetic resonance elastography are needed.

A Case of Topical Ruxolitinib Treatment Failure in Alopecia Areata.

Alopecia areata (AA) is an autoimmune-mediated, nonscarring form of hair loss. Despite its prevalence, current management options are limited, especially when the disease has progressed to alopecia totalis (AT) or alopecia universalis (AU). Recent evidence that janus kinase (JAK) signaling contributes to AA pathogenesis prompted the investigation of JAK inhibitors such as tofacitinib and ruxolitinib as possible oral treatments. However, the potential for significant adverse effects with systemic JAK inhibition makes local administration a more attractive option. Yet, a paucity of data exists on topical JAK inhibition in AA. A success of topical ruxolitinib (0.6% cream) use in a young patient with AU has been reported to date. Here we report the treatment of a 66-year-old with AA with the same formulation of topical ruxolitinib, where it failed to induce hair growth. Our report demonstrates the importance of examining the factors contributing to variation in treatment response in a clinical trial of topical JAK inhibitors in AA. It is likely that both intrinsic factors specific to individual patients and extrinsic factors relating to treatment regimen are involved. Furthermore, characterisation of the specific JAKs overexpressed in AA may better target medication. Finally, this report highlights the need to compare the outcomes of topical vs oral ruxolitinib administration in patients with severe AA, AT, and AU and may support the possibility that extensive disease is more adequately treated with oral administration of ruxolitinib.

Could MRI Be Used To Image Kidney Fibrosis? A Review of Recent Advances and Remaining Barriers.

A key contributor to the progression of nearly all forms of CKD is fibrosis, a largely irreversible process that drives further kidney injury. Despite its importance, clinicians currently have no means of noninvasively assessing renal scar, and thus have historically relied on percutaneous renal biopsy to assess fibrotic burden. Although helpful in the initial diagnostic assessment, renal biopsy remains an imperfect test for fibrosis measurement, limited not only by its invasiveness, but also, because of the small amounts of tissue analyzed, its susceptibility to sampling bias. These concerns have limited not only the prognostic utility of biopsy analysis and its ability to guide therapeutic decisions, but also the clinical translation of experimental antifibrotic agents. Recent advances in imaging technology have raised the exciting possibility of magnetic resonance imaging (MRI)-based renal scar analysis, by capitalizing on the differing physical features of fibrotic and nonfibrotic tissue. In this review, we describe two key fibrosis-induced pathologic changes (capillary loss and kidney stiffening) that can be imaged by MRI techniques, and the potential for these new MRI-based technologies to noninvasively image renal scar.