Unmasking an unusual presentation of Hodgkin's lymphoma masquerading as ocular inflammation: a case report.

BACKGROUND: Hodgkin's lymphoma (HL) is an extremely rare cause of ocular inflammation that is usually not considered in the typical workup of uveitis and other eye diseases. A few cases of ocular inflammation were reported previously showcasing HL with absence of typical symptoms of HL at presentation. Acknowledging the potential ocular inflammation associated with HL can prompt ophthalmologists to broaden their diagnostic approach and collaborate with internal medicine departments to investigate this rare yet significant etiology. CASE PRESENTATION: A 17-year-old Caucasian woman presenting unilateral panuveitis was later diagnosed with HL. The ocular findings were non-necrotizing scleritis, anterior uveitis, vitritis, white/yellowish chorioretinal lesions, papillitis and vasculitis. A left supra-clavicular lymph node biopsy confirmed the diagnosis of nodular sclerosing Hodgkin's lymphoma stage IIB. Other causes of uveitis were excluded. Chemotherapy led to remission of the disease and the ocular lesions became quiescent with persistent pigmented chorioretinal scars. CONCLUSIONS: Hodgkin's lymphoma should be considered in the differential diagnosis of diseases that can occasionally be revealed by unilateral ocular inflammation. A comprehensive, multidisciplinary approach is key to properly assessing such cases.

High salt diet alleviates disease severity in native experimental autoimmune uveitis.

Background: Recent studies reported a link between high salt diet (HSD) and clinical exacerbation in mouse models of autoimmune diseases, mainly through the induction of pathogenic Th17 cells and/or HSD-induced dysbiosis. However, the topic remains controversial and not fully understood. Purpose: In this study, we investigated the effects of HSD on the development of experimental autoimmune uveitis (EAU) in C57BL/6J mice. Methods and results: Unexpectedly, our data showed a significant attenuating effect of HSD on disease severity of native EAU, induced by direct immunization with IRBP peptide. That said, HSD had no effect on EAU disease severity induced by adoptive transfer of semi-purified auto-reactive IRBP-specific T lymphocytes. Accordingly, HSD did not affect IRBP-specific systemic afferent immune response as attested by no HSD-linked changes in T lymphocytes proliferation, cytokine production and Treg proportion. Gut microbiota analysis from cecal samples in naïve and EAU mice demonstrated that HSD affected differentially α-diversity between groups, whereas ß-diversity was significantly modified in all groups. Unknown Tannerellaceae was the only taxon associated to HSD exposure in all treatment groups. Interestingly, a significantly higher abundance of unknown Gastranaerophilales, with potential anti-inflammatory properties, appeared in HSD-fed native EAU mice, only. Discussion: In conclusion, our study suggests a possible impact of HSD on gut microbiota composition and consequently on development and clinical severity of EAU. Further studies are required to investigate the potential beneficial role of Gastranaerophilales in EAU.

HEART Failure? Episodes of Missed Major Cardiac Events When Applying the HEART Pathway to an Observation Unit Population.

OBJECTIVE: The HEART Pathway risk prediction tool (HEART score plus serial troponin measures at 0 and 3 hours post-presentation) is used to identify low-risk patients with chest pain who may qualify for safe, early discharge. We calculated the percentage of patients in our observation unit that qualified as low risk using HEART Pathway, as well as their associated outcomes. METHODS: We retrospectively reviewed charts on 966 consecutive patients admitted to our observation unit for chest pain (January 2015 to February 2016); HEART Pathway scores were retrospectively calculated and serial cardiac troponin values logged. The primary outcome was 42-day major adverse cardiac events (MACE), including acute myocardial infarction, urgent revascularization, and all-cause death. RESULTS: The patients' mean age was 59, 42% were male, 46% white, and 68 (7.7%) had MACE. HEART Pathway defined 384 patients as low risk (39.8%) and eligible for early discharge. Applying HEART Pathway would have missed 1.2% of patients with MACE; however, all adverse cardiac events occurred in patients with a HEART Pathway score of 3 (4 of 193, 2.1%) and none in those with a HEART Pathway score ≤2 (0 of 134). CONCLUSIONS: While the HEART Pathway identifies a pooled population at low risk for MACE, risk is not homogenous within this population. Patients with a score of 3 may have higher risk of 42-day MACE that may be unacceptable to some providers, while scores ≤2 saw no events. Caution is advised for those with HEART Pathway score of 3 until more data is available to accurately estimate risk.

Wnt/ß-Catenin Signaling Regulates the Expression of the Ammonium Permease Gene RHBG in Human Cancer Cells.

Ammonium is a metabolic waste product mainly detoxified by the liver. Hepatic dysfunction can lead to cytotoxic accumulation of circulating ammonium and to subsequent encephalopathy. Transmembrane ammonium transport is a widely spread process ensured by the highly conserved proteins of the Mep-Amt-Rh superfamily, including the mammalian Rhesus (Rh) factors. The regulatory mechanisms involved in the control of RH genes expression remain poorly studied. Here we addressed the expression regulation of one of these factors, RHBG. We identify HepG2 hepatocellular carcinoma cells and SW480 colon adenocarcinoma cells as expressing RHBG and show that its expression relies on ß-catenin signaling. siRNA-mediated ß-catenin knockdown resulted in significant reduction of RHBG mRNA in both cell lines. Pharmaceutical inhibition of the TCF4/ß-catenin interaction or knockdown of the transcription factor TCF4 also downregulated RHBG expression. We identify a minimal RHBG regulatory sequence displaying a promoter activity and show that ß-catenin and TCF4 bind to this fragment in vivo. We finally characterize the role of potential TCF4 binding sites in RHBG regulation. Taken together, our results indicate RHBG expression as a direct target of ß-catenin regulation, a pathway frequently deregulated in many cancers and associated with tumorigenesis.