Management of long-term complications from immunosuppression.

This review discusses long-term complications from immunosuppressants after liver transplantation and the management of these complications. Common complications of calcineurin inhibitors include nephrotoxicity and metabolic diseases. Nephrotoxicity can be managed by targeting a lower drug level and/or adding an immunosuppressant of a different class. Metabolic disorders can be managed by treating the underlying condition and targeting a lower drug level. Gastrointestinal adverse effects and myelosuppression are common complications of antimetabolites that are initially managed with dose reduction or discontinuation if adverse events persist. Mammalian targets of rapamycin inhibitors are associated with myelosuppression, proteinuria, impaired wound healing, and stomatitis, which may require dose reduction or discontinuation. Induction agents and agents used for steroid-refractory rejection or antibody-mediated rejection are reviewed. Other rare complications of immunosuppressants are discussed as well.

Gaps in Confirmatory Fibrosis Risk Assessment in Primary Care Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: As recommendations for non-invasive fibrosis risk assessment in nonalcoholic fatty liver disease (NAFLD) emerge, it is not known how often they are performed in primary care. AIMS: We investigated the completion of confirmatory fibrosis risk assessment in primary care patients with NAFLD and indeterminate-risk or greater Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Scores (NFS). METHODS: This retrospective cohort study of electronic health record data from a primary care clinic identified patients with diagnoses of NAFLD from 2012 through 2021. Patients with a diagnosis of a severe liver disease outcome during the study period were excluded. The most recent FIB-4 and NFS scores were calculated and categorized by advanced fibrosis risk. Charts were reviewed to identify the outcome of a confirmatory fibrosis risk assessment by liver elastography or liver biopsy for all patients with indeterminate-risk or higher FIB-4 (≥ 1.3) and NFS (≥ - 1.455) scores. RESULTS: The cohort included 604 patients diagnosed with NAFLD. Two-thirds of included patients (399) had a FIB-4 or NFS score greater than low-risk, 19% (113) had a high-risk FIB-4 (≥ 2.67) or NFS (≥ 0.676) score, and 7% (44) had high-risk FIB-4 and NFS values. Of these 399 patients with an indication for a confirmatory fibrosis test, 10% (41) underwent liver elastography (24) or liver biopsy (18) or both (1). CONCLUSIONS: Advanced fibrosis is a key indicator of future poor health outcomes in patients with NAFLD and a critical signal for referral to hepatology. Significant opportunities exist to improve confirmatory fibrosis risk assessment in patients with NAFLD.

Limited-Stage Small Cell Lung Cancer: Is Prophylactic Cranial Irradiation Necessary?

PURPOSE: Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases in patients with limited stage small cell lung cancer (LS-SCLC). However, PCI is associated with neurotoxicity. Previous studies have not consistently used pretreatment magnetic resonance imaging. Modern imaging improvements continue to enhance early metastasis detection, potentially decreasing the utility of PCI. We sought to determine whether PCI was associated with improved outcomes in LS-SCLC patients with modern imaging. METHODS AND MATERIALS: We identified LS-SCLC patients with no intracranial disease who were treated between 2007 and 2018. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated and multivariate Cox proportional hazards models were generated. The cumulative incidence of brain metastases was estimated using competing risks methodology. RESULTS: Ninety-two patients were identified without intracranial disease at initial staging, 39 of whom received PCI. Median follow-up was 56.7 months. The median OS for the cohort was 35.5 months (95% CI, 25.8-49.3), and median PFS was 19.1 months (95% CI, 12.3-30.5). Median OS with PCI versus observation was 37.9 months (95% CI, 31.8-not reached) versus 30.5 months (95% CI, 14.6-56.1; P = .07), whereas median PFS was 26.3 months (95% CI 19.1-not reached) versus 12.3 months (95% CI, 8.5-30.5; P = .02), respectively. Overall, at 2 years, the cumulative incidence of brain metastases was 10% with PCI and 29% without; this increased to 32% and 29% by 4 years (P = .66). In those patients who had negative magnetic resonance imaging of the brain after completing initial treatment, the 1-year cumulative incidence of brain metastasis was not significantly different at 8% versus 11% (P = .46) respectively. Both PCI and treatment response were independent predictors for PFS on multivariate analysis. Stratified by disease response, patients with a complete response did not benefit from PCI (P = .50), whereas those with partial response or stable disease experienced improved PFS (P = .01). CONCLUSIONS: Overall, PCI was associated with improved PFS and reduced early incidence of brain metastases. Patients achieving a complete response to initial therapy did not experience a PFS benefit with PCI. This may indicate that subsets of LS-SCLC patients can potentially be spared from PCI in the era of modern imaging.

Surgical resection and postoperative radiosurgery versus staged radiosurgery for large brain metastases.

PURPOSE: The purpose of this study was to retrospectively evaluate the new treatment paradigm of staged stereotactic radiosurgery (SRS) for the treatment of large brain metastases (BM) compared to the standard of surgical resection followed by SRS. METHODS: We evaluated 78 patients with large BM treated 2012-2017 with surgical resection and postoperative SRS (surgery + SRS) or staged SRS separated by 1 month. Overall survival (OS) was estimated using the Kaplan Meier method and compared across groups using the log-rank test. Cumulative incidence of neurologic death and local and distant brain failure (LF, DBF) were estimated using competing risk methodology. RESULTS: Forty patients were treated with surgery + SRS and 38 patients were treated with staged SRS. Median follow-up was 23.2 months (95% CI 20.5-39.3). Median OS was 13.2 months for staged SRS compared to surgery + SRS 9.7 months (p = 0.53). Cumulative incidence of neurologic death at 1 year was 23% after surgery + SRS, 27% after staged SRS (p = 0.69); cumulative incidence of LF at 1 year was 6% and 8% (p = 0.65) and 1-year DBF was 59% and 21% (p ≤ 0.01). Overall rates of leptomeningeal failure and radiation necrosis were similar between the groups (p = 0.63 and p = 1.0). CONCLUSIONS: Though surgery and postoperative SRS is the standard, staged SRS represents an attractive treatment paradigm for treating large BM without sacrificing LC or survival, and potentially decreases DBF. Prospective studies are needed to validate these findings.