Persistent Inflammation Associated With HLA-B27 After Pars Plana Vitrectomy With Scleral Buckle Placement.

Purpose: To report 2 cases of persistent inflammation associated with human leukocyte antigen-B27 (HLA-B27) after pars plana vitrectomy (PPV) with scleral buckling. Methods: Two cases were analyzed. Results: A 47-year-old man had pars plana vitrectomy (PPV), scleral buckle (SB) placement, and endolaser for a macula-on rhegmatogenous retinal detachment (RRD). A 61-year-old man also had uneventful PPV, SB placement, and endolaser for a macula-off RRD. Postoperatively, both patients reported eye pain and had persistent intraocular inflammation. Both were found to be HLA-B27 positive despite having no previous signs or symptoms that would warrant HLA-B27 testing. Conclusions: Discovering the source of prolonged postoperative inflammation is critical in initiating the correct treatment and removing suspicion of infection. Although intraocular inflammation associated with HLA-B27 does not often present initially after surgery, HLA-B27 testing should be considered in cases of persistent, unexpected postoperative inflammation.

Hit and Run: Bilateral Massive Intraocular Lymphomatous Infiltration after CAR-T Therapy.

PURPOSE: We report a case of bilateral intraocular infiltration of DLBCL after CAR-T therapy. METHODS: Retrospective case report. RESULTS: A 62-year-old Caucasian male with medical history of high-grade DLBCL presented with papillitis and vitritis upon completion of CAR-T therapy. Thorough infectious and diagnostic work-ups were performed. Diagnostic vitreous tap revealed intraocular lymphoma. The patient received external beam radiotherapy to both orbits with dramatic improvement in disc edema and vitritis. However, subsequent MRI showed development of intracranial metastatic disease, and the patient died within the same month. CONCLUSION: Atypical intraocular metastasis of DLBCL may occur following CAR-T therapy and may indicate secondary changes in immunosurveillance within immune-privileged sites such as the eye.

Extracellular Tau Oligomers Damage the Axon Initial Segment.

BACKGROUND: In Alzheimer's disease (AD) brain, neuronal polarity and synaptic connectivity are compromised. A key structure for regulating polarity and functions of neurons is the axon initial segment (AIS), which segregates somatodendritic from axonal proteins and initiates action potentials. Toxic tau species, including extracellular oligomers (xcTauOs), spread tau pathology from neuron to neuron by a prion-like process, but few other cell biological effects of xcTauOs have been described. OBJECTIVE: Test the hypothesis that AIS structure is sensitive to xcTauOs. METHODS: Cultured wild type (WT) and tau knockout (KO) mouse cortical neurons were exposed to xcTauOs, and quantitative western blotting and immunofluorescence microscopy with anti-TRIM46 monitored effects on the AIS. The same methods were used to compare TRIM46 and two other resident AIS proteins in human hippocampal tissue obtained from AD and age-matched non-AD donors. RESULTS: Without affecting total TRIM46 levels, xcTauOs reduce the concentration of TRIM46 within the AIS and cause AIS shortening in cultured WT, but not TKO neurons. Lentiviral-driven tau expression in tau KO neurons rescues AIS length sensitivity to xcTauOs. In human AD hippocampus, the overall protein levels of multiple resident AIS proteins are unchanged compared to non-AD brain, but TRIM46 concentration within the AIS and AIS length are reduced in neurons containing neurofibrillary tangles. CONCLUSION: xcTauOs cause partial AIS damage in cultured neurons by a mechanism dependent on intracellular tau, thereby raising the possibility that the observed AIS reduction in AD neurons in vivo is caused by xcTauOs working in concert with endogenous neuronal tau.

Association of sarcopenia with survival in advanced NSCLC patients receiving concurrent immunotherapy and chemotherapy.

Background: Frailty, sarcopenia and malnutrition are powerful predictors of clinical outcomes that are not routinely measured in patients with non-small cell lung cancer (NSCLC). The primary aim of this study was to investigate the association of sarcopenia, determined by the psoas muscle index (PMI) with overall survival (OS) in patients with advanced NSCLC treated with concurrent immune checkpoint inhibitor (ICI) and chemotherapy (CTX). Methods: We retrospectively reviewed data from a cohort of patients with locally advanced or metastatic NSCLC who were treated between 2015 and 2021 at the University of Virginia Medical Center. The cross-sectional area of the psoas muscle was assessed on CT or PET/CT imaging prior to treatment initiation. Multivariate analysis was performed using Cox proportional hazards regression models. Results: A total of 92 patients (median age: 64 years, range 36-89 years), 48 (52.2%) men and 44 (47.8%) women, were included in the study. The median follow-up was 29.6 months. The median OS was 17.8 months. Sarcopenia, defined by a PMI below the 25th percentile, was associated with significantly lower OS (9.1 months in sarcopenic patients vs. 22.3 months in non-sarcopenic patients, P = 0.002). Multivariate analysis revealed that sarcopenia (HR 2.12, P = 0.0209), ECOG ≥ 2 (HR 2.88, P = 0.0027), prognostic nutritional index (HR 3.02, P = 0.0034) and the absence of immune related adverse events (HR 2.04, P = 0.0185) were independently associated with inferior OS. Conclusions: Sarcopenia is independently associated with poor OS in patients with advanced NSCLC undergoing concurrent ICI and CTX.