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Competing Interests: James J. Augsburger and Cassandra C. Skinner have no conflicts of interest to report. Zelia M. Correa's spouse is a consultant for Castle Biosciences, Inc.

Purpose: The purpose of this study was to determine whether the metastatic rates in patients with gene expression profile (GEP) class 1A versus 1B posterior uveal malignant melanoma supported or contradicted predictions of very low metastatic rate in GEP 1A cases and moderate rate in GEP 1B cases., Patients/methods: 164 patients with a cytopathologically confirmed primary posterior uveal malignant melanoma classified by GEP testing as class 1 (100 GEP 1A, 64 GEP 1B) were evaluated. Kaplan-Meier rates of metastasis were computed and plotted for the GEP class 1 subgroups. Median follow-up of patients who were still alive without metastasis on the date of data analysis was 100.5 months for the GEP 1A patients and 97.2 months for the GEP 1B patients., Results: The actuarial 5-year rate of uveal melanoma metastasis was 10.8% (std. error = 3.2%) in the GEP 1A patients versus 0% in the GEP 1B patients, and the actuarial 10-year rate of metastasis was 12.2% (std. error = 3.5%) in the GEP 1A patients versus 2.1% (std. error 2.1%) in the GEP 1B patients., Conclusion: The results of this retrospective single-center study cast doubt on the validity of the prognostic stratification of GEP class 1 posterior uveal malignant melanomas into very low risk (GEP 1A) versus intermediate risk (GEP 1B) of metastasis subgroups provided by the commercially available GEP test., Competing Interests: Authors James J. Augsburger and Cassandra C. Skinner have no conflicts of interest to declare. Author Zelia M. Correa is a consultant for Castle Biosciences, Inc., which markets the DecisionDx-UM test., (Copyright © 2022 by S. Karger AG, Basel.)

Background: Pharmacy-led medication reconciliation identifies and corrects medication errors that can potentially cause moderate to severe harm. This research sought to identify the impact of pharmacy-led medication reconciliation on patient outcomes and describe the changes in healthcare workers' perceptions of the program., Methods: A pharmacy-led admission medication reconciliation program pilot started in July 2019, and a discharge medication reconciliation proof of concept was tested in September 2020 at a 432-bed hospital. The following periods were compared: August 2018 to February 2019 (pre-program implementation) and August 2019 to February 2020 (post-program implementation). Endpoints included patient outcomes, workforce productivity and interdisciplinary healthcare team satisfaction through program surveys. Patient outcomes were assessed with chisquared tests. Survey responses were assessed using the Likert scale. Descriptive statistics were used for productivity outcomes and the number of discharge medication reconciliations completed., Results: Approximately 18,000 admissions were recorded for each period. The adverse drug event (ADE) rate decreased 49% (p < 0.001), and the complication rate decreased 29.7% (p = 0.001). During post-pilot implementation, 6,530 medication histories were completed, and 70,050 medications were reviewed. Of medication histories completed, 22.6% of patient allergies/adverse drug reactions were updated, 52.3% of medications were clarified, and 54.7% of preferred outpatient pharmacies were updated. Pharmacy services completed medication histories in 38.8% of inpatients. In the proof of concept, 168 discharge medication lists were drafted. Survey results showed statistically significant improvement in healthcare team satisfaction., Conclusion: A pharmacy-led medication reconciliation program involving designated pharmacists and pharmacy technicians has shown to decrease ADEs and complications while improving interdisciplinary healthcare team satisfaction., Competing Interests: Conflicts of Interest The authors declare they have no conflicts of interest., (© 2021 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Purpose: To describe the surgical approach with a screen-based "heads up" digital viewing technology for the successful repair of a retinal detachment in a patient with severe kyphosis., Methods: Case report., Results: An 89-year-old man with vision loss in the left eye from a macula-involving retinal detachment of 4 weeks was scheduled for pars plana vitrectomy and retinal detachment repair. The patient had severe thoracic kyphosis, causing a fixed spinal flexion that presented a significant challenge to traditional intraoperative positioning and management. Surgery was performed using the NGENUITY system for primary surgical viewing, the surgeon operating heads up, and the patient in Trendelenburg position. There were no intraoperative or postoperative complications. Visual acuity improved to 20/80 and the retina remained attached with 11 weeks of follow-up., Conclusion: Heads up digitally assisted viewing technology may be useful or preferred for patients requiring vitreoretinal surgery in the setting of severe musculoskeletal limitations or other positioning challenges.

Purpose: Determine which posterior uveal melanoma (PUM) size classification with three categories has the best prognostic discrimination., Methods: Single-institution study of 424 consecutive patients with PUM. The tumor's largest basal diameter (LBD), smallest basal diameter (SBD), and thickness (TH) were estimated by fundus mapping and ultrasonography. Tumors were assigned to "small," "medium," or "large" size categories defined by 11 different classifications (Linear LBD, Rectangular LBD × TH, Cubic LBD × SBD × TH, Warren Original, Warren Modified, Augsburger, COMS Original, COMS Revised, TNM 2002, and modified TNM 2010 classification [a,b]). Prognostic significance of classifications was evaluated by Kaplan-Meier event curves with computation of log rank test for trend statistic., Results: In six classification systems (Warren Original, Warren Modified, COMS Revised, TNM 2002, TNM 2010a, TNM 2010b) >50% of tumors fell within one subgroup. In the Warren Original classification <5% of tumors fell within one subgroup. Separation of Kaplan-Meier curves among three size categories was judged "excellent" in four classifications (Linear LBD, Cubic Volume, TNM 2010a, and TNM 2010b) and "very poor" in the Warren Original. Linear LBD classification was associated with highest log rank statistic value. TNM 2010a, TNM 2010b, TNM 2002, Augsburger, and Cubic Volume classifications were also determined to be quite good., Conclusions: Linear LBD classification was the best three-size category discriminator among low-, intermediate-, and high-risk subgroups. Considering our findings, it seems possible that the arduous work required to apply complex classifications, especially for three-category systems, for PUM may not be justified in routine clinical practice.

The folate receptor (FR) is overexpressed on the vascular side of cancerous cells including those of the breast, ovaries, testes, and cervix. We hypothesized that a folate-conjugated immunoglobulin (F-IgG) would bind to the FR that is overexpressed on melanoma tumor cells to target these cells for lysis by natural killer (NK) cells. Folate receptor expression was confirmed in the Mel-39 (human melanoma) cell line by flow cytometry and immunoblot analysis using KB (human oral epithelial) and F01 (human melanoma) as a positive and a negative control, respectively. FR-positive and FR-negative cell lines were treated with F-IgG or control immunoglobulin G in the presence or absence of cytokines to determine NK cell ability to lyse FR-positive cell lines. NK cell activation was significantly upregulated and lysis of Mel 39 tumor cells increased following treatment with F-IgG compared with control immunoglobulin G at all effector : target (E : T) ratios (P<0.01). This trend further increased by NK cell stimulation with the activating cytokine interleukin-12. NK cell production of cytokines such as interferon-gamma, macrophage inflammatory protein 1α, and regulated on activation normal T-cell expressed and secreted (RANTES) was also significantly increased in response to costimulation with interleukin-12 stimulation and F-IgG-coated Mel 39 target cells compared with controls (P<0.01). In contrast, F-IgG did not bind to the FR-negative cell line F01 and had no significant effect on NK cell lysis or cytokine production. This research indicates the potential use of F-IgG for its ability to induce an immune response from NK cells against FR-positive melanoma tumor cells, which can be further increased by the addition of cytokines.

Optimally effective antitumor therapies would not only activate immune effector cells but also engage them at the tumor. Folate conjugated to immunoglobulin (F-IgG) could direct innate immune cells with Fc receptors to folate receptor-expressing cancer cells. F-IgG bound to human KB and HeLa cells, as well as murine L1210JF, a folate receptor (FR)-overexpressing cancer cell line, as determined by flow cytometry. Recognition of F-IgG by natural killer (NK) cell Fc receptors led to phosphorylation of the ERK transcription factor and increased NK cell expression of CD69. Lysis of KB tumor cells by NK cells increased by about 5-fold after treatment with F-IgG, an effect synergistically enhanced by treatment with IL2, IL12, IL15, or IL21 (P< 0.001). F-IgG also enhanced the lysis of chronic lymphocytic leukemia cells by autologous NK cells. NK cells significantly increased production of IFNγ, MIP-1α, and RANTES in response to F-IgG-coated KB target cells in the presence of the NK cell-activating cytokine IL12, and these coculture supernatants induced significant T-cell chemotaxis (P< 0.001). F-IgG-coated targets also stimulated FcR-mediated monocyte effector functions. Studies in a murine leukemia model confirmed the intratumoral localization and antitumor activity of F-IgG, as well as enhancement of its effects by IL12 (P =0.05). The antitumor effect of this combination was dependent on NK cells and led to decreased tumor cell proliferation in vivo Thus, F-IgG can induce an immune response against FR-positive tumor cells that is mediated by NK cells and can be augmented by cytokine therapy., (©2016 American Association for Cancer Research.)