Harnois, Denise

Abstract Objective To examine the impact of immunosuppressive regimens on chronic rhinosinusitis (CRS) development in kidney and liver transplant recipients. Study Design Retrospective cohort study. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Patients who underwent kidney or liver transplantation between November 1, 2021, and November 1, 2022, were included. Patients with documented sinonasal complaints before transplantation were excluded. Diagnoses were based on ICD‐10 codes assigned by board‐certified otolaryngologists, with follow‐up extending through November 2024. Demographic data, relevant comorbidities, CRS diagnoses, and immunosuppressive regimens were collected. Results In total, 1459 transplant recipients (986 kidney, 473 liver) with a mean age of 55.1 years and M:F ratio of 1.5:1 were included. Kidney recipients who received anti‐thymocyte globulin (ATG, Thymoglobulin®) for immunosuppressive induction had a greater risk of CRS compared to those who did not (odds ratio [OR] = 3.0, 95% CI [1.3, 6.9], P = .005). Among liver recipients, patients on cyclosporine, mycophenolate mofetil (MMF), and corticosteroids had a greater risk of CRS compared to those on tacrolimus‐based regimens (OR = 6.0, 95% CI [1.5, 24.1], P = .027). Cyclosporine use was also associated with an increased rate of endoscopic sinus surgery (ESS) compared to tacrolimus (4.2% vs 0.3%, P = .015). Conclusion Tacrolimus‐based regimens are associated with significantly decreased rates of CRS compared to cyclosporine, suggesting that immunosuppressive choice is a modifiable risk factor for sinonasal morbidity in this population.

Abstract Objective To estimate the incidence of de novo chronic rhinosinusitis and identify associated risk factors in kidney and liver transplant recipients without pre‐existing sinonasal complaints. Study design Retrospective cohort study. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Records of all patients who underwent kidney or liver transplantation between November 1, 2021, and November 1, 2022 were reviewed. Patients with documented sinonasal complaints prior to transplantation were excluded. Diagnoses were based on ICD‐10 codes assigned by board‐certified otolaryngologists, with follow‐up extending through November 2024. Demographic and clinical variables were collected, and multivariable logistic regression was used to identify predictors of de novo chronic rhinosinusitis. Results Among 1459 transplant recipients (mean age 55.1 years, 59.8% male), the cumulative 2‐year incidence of de novo chronic rhinosinusitis was 2.4% (24/986) in kidney and 2.3% (11/473) in liver transplant recipients ( P = .89). The overall incidence rate was 12.0 cases per 1000 person‐years, exceeding general population estimates. Transplant rejection (OR 3.2, 95% CI 2.5‐3.9, P < .001) and additional organ transplantation (OR 5.0, 95% CI 3.4‐6.5, P = .041) were independently associated with chronic rhinosinusitis development. Conclusion Kidney and liver transplant recipients experience a higher incidence of de novo chronic rhinosinusitis compared to the general population. Transplant rejection and additional organ transplantation significantly increase this risk. Early recognition and management of chronic rhinosinusitis in this population may support improved postoperative outcomes.

Background and Aims Altered bile acid (BA) homeostasis is an intrinsic facet of cholestatic liver diseases, but clinical usefulness of plasma BA assessment in primary sclerosing cholangitis (PSC) remains understudied. We performed BA profiling in a large retrospective cohort of patients with PSC and matched healthy controls, hypothesizing that plasma BA profiles vary among patients and have clinical utility. Approach and Results Plasma BA profiling was performed in the Clinical Biochemical Genetics Laboratory at Mayo Clinic using a mass spectrometry based assay. Cox proportional hazard (univariate) and gradient boosting machines (multivariable) models were used to evaluate whether BA variables predict 5‐year risk of hepatic decompensation (HD; defined as ascites, variceal hemorrhage, or encephalopathy). There were 400 patients with PSC and 302 controls in the derivation cohort (Mayo Clinic) and 108 patients with PSC in the validation cohort (Norwegian PSC Research Center). Patients with PSC had increased BA levels, conjugated fraction, and primary‐to‐secondary BA ratios relative to controls. Ursodeoxycholic acid (UDCA) increased total plasma BA level while lowering cholic acid and chenodeoxycholic acid concentrations. Patients without inflammatory bowel disease (IBD) had primary‐to‐secondary BA ratios between those of controls and patients with ulcerative colitis. HD risk was associated with increased concentration and conjugated fraction of many BA, whereas higher G:T conjugation ratios were protective. The machine‐learning model, PSC‐BA profile score (concordance statistic [C‐statistic], 0.95), predicted HD better than individual measures, including alkaline phosphatase, and performed well in validation (C‐statistic, 0.86). Conclusions Patients with PSC demonstrated alterations of plasma BA consistent with known mechanisms of cholestasis, UDCA treatment, and IBD. Notably, BA profiles predicted future HD, establishing the clinical potential of BA profiling, which may be suited for use in clinical trials.

AbstractAblation is now recommended by international guidelines for the definitive treatment of hepatocellular carcinoma (HCC). Extensive clinical studies have demonstrated outcomes comparable to surgical resection with shorter hospital stays, decreased costs, and improved quality of life. Successful ablation requires complete treatment of both tumor and margin while preserving critical adjacent structures. HCC exhibits highly variable presentations in both anatomic involvement and biology which have significant implications on choice of ablative therapy. There are now abundant ablation modalities and adjunctive techniques which can be used to individualize ablation and maximize curative results. This article provides a patient-centered summary of approaches to HCC ablation in the context of patient performance, hepatic reserve, tumor phenotype and biology, intra- and extrahepatic anatomy, and ablation technology.

Cystic fibrosis (CF) is an autosomal recessive disease characterized by mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator protein (CFTR). CFTR gene mutations manifest as epithelial cell dysfunction in the airways, biliary tract, pancreas, gut, sweat glands, paranasal sinuses, and genitourinary tract. The clinical manifestations of this dysfunction include respiratory tract infections, bronchiectasis, pancreatic insufficiency, malabsorption, intestinal obstruction, liver disease, and male infertility. The liver disease manifestations of CF can include biliary disease, multilobular cirrhosis, and portal hypertension with and without cirrhosis. Pulmonary disease is the main cause for morbidity and mortality in individuals with CF, and according to the International Society for Heart and Lung Transplantation, CF is the third most common indication for lung transplantation in adults, accounting for 16% of procedures performed. The survival after lung transplantation in individuals with CF continues to improve and is now the highest among end‐stage lung diseases requiring transplant. The survival rate at 10 years is close to 50%. Given the potential presence of liver disease in CF patients undergoing an evaluation for lung transplantation and in lung transplant recipients, it is important to understand the manifestations of liver disease in CF patients and the recommended workup and follow‐up. This review aims to discuss the current literature and provide guidance in the management of these patients.