Prognostic Value of BAP1 Protein Expression in Uveal Melanoma.

The prognostic value of the traditional pathologic parameters that form part of the American Joint Committee on Cancer staging system and genetic classifications using monosomy chromosome 3 and structural alterations in chromosome 8 are well established and are part of the diagnostic workup of uveal melanoma (UM). However, it has not been fully clarified whether nuclear protein expression of the tumor suppressor gene BAP1 (nBAP1) by immunohistochemistry alone is as powerful a predictor of overall survival (OS) and/or disease-specific survival (DSS) as chromosome analysis. The protein expression of nBAP1 was evaluated in a retrospective cohort study of 308 consecutive patients treated by primary enucleation between January 1974 and December 2022. We correlated clinical, pathologic, and cytogenetic characteristics to identify the best prognostic indicators for OS and DSS. Loss of nBAP1 was detected in 144/308 (47%) of patients. Loss of nBAP1 expression was significantly associated with poor survival. In patients with disomy chromosome 3, nBAP1 negative is significantly associated with poorer OS but not DSS. We observed that older age (>63 years), presence of metastasis, and nBAP1 negative remained independent prognostic factors in multivariate analysis. nBAP1 protein expression proved to be a more reliable prognostic indicator for OS than the American Joint Committee on Cancer staging, M3 status, or The Cancer Genome Atlas classification in this cohort. This study provides support for accurate prognostication of UM patients in routine histology laboratories by immunohistochemistry for nBAP1 alone.

Computational approaches in rheumatic diseases - Deciphering complex spatio-temporal cell interactions.

Inflammatory arthritis, including rheumatoid (RA), and psoriatic (PsA) arthritis, are clinically and immunologically heterogeneous diseases with no identified cure. Chronic inflammation of the synovial tissue ushers loss of function of the joint that severely impacts the patient's quality of life, eventually leading to disability and life-threatening comorbidities. The pathogenesis of synovial inflammation is the consequence of compounded immune and stromal cell interactions influenced by genetic and environmental factors. Deciphering the complexity of the synovial cellular landscape has accelerated primarily due to the utilisation of bulk and single cell RNA sequencing. Particularly the capacity to generate cell-cell interaction networks could reveal evidence of previously unappreciated processes leading to disease. However, there is currently a lack of universal nomenclature as a result of varied experimental and technological approaches that discombobulates the study of synovial inflammation. While spatial transcriptomic analysis that combines anatomical information with transcriptomic data of synovial tissue biopsies promises to provide more insights into disease pathogenesis, in vitro functional assays with single-cell resolution will be required to validate current bioinformatic applications. In order to provide a comprehensive approach and translate experimental data to clinical practice, a combination of clinical and molecular data with machine learning has the potential to enhance patient stratification and identify individuals at risk of arthritis that would benefit from early therapeutic intervention. This review aims to provide a comprehensive understanding of the effect of computational approaches in deciphering synovial inflammation pathogenesis and discuss the impact that further experimental and novel computational tools may have on therapeutic target identification and drug development.

Assessment of baseline rates of functional and absolute iron deficiency in bariatric surgery candidates: a retrospective study.

BACKGROUND: Preoperative optimization of iron status is a priority in candidates for bariatric surgery. Inflammation is strongly associated with obesity, and as a consequence, functional iron deficiency (ID) is potentially an underreported issue in surgical candidates. OBJECTIVES: In light of updated practice guidelines, to retrospectively review preoperative iron status in an Irish cohort of bariatric surgery candidates, taking account of the relative incidence rate of functional ID. SETTING: A tertiary care obesity service with bariatric surgery referral in Ireland. METHODS: Baseline nutritional biochemistry records were reviewed between February 2017 and February 2020 in a hospital, Dublin, Ireland. Absolute ID was defined as serum ferritin <30 µg/L; functional ID was defined as ferritin, 30 to 100 µg/L, in the presence of C-reactive protein >5 mg/L. Anemia was indexed with reference to hemoglobin and qualified by vitamin B12 and folate status to rule out anemia unrelated to primary ID. RESULTS: The analysis included 120 patients, 68% female, 49.6 ± 9.3 years, and body mass index, 52.0 ± 9.6 kg/m2. The prevalence of absolute and functional ID was 11.7% and 30.8%, respectively (P = .0003). Anemia was associated with absolute ID and functional ID in 14.3% and 10.8% of patients (P = .29). Folate and vitamin B12 deficiency occurred in <5% of patients. CONCLUSION: In patients seeking bariatric surgery for severe obesity, the prevalence of baseline functional ID is substantial and can be associated with anemia. These findings raise queries with regard to how best to optimize preoperative iron status in the context of ongoing inflammation.