Retinal Metastases as the Initial Presentation of Advanced Lung Adenocarcinoma.

Introduction: Most lung cancers are diagnosed at an advanced stage. Common metastatic sites include the brain, bone, liver and adrenal glands. Ocular metastases, however, are extremely rare. We present a case of advanced lung adenocarcinoma presenting exclusively with photopsias attributable to retinal metastases. Case description: We describe a woman in her fifties, a lifetime non-smoker with an unremarkable medical and family history, who presented to the emergency department with photopsias for a week. Ophthalmology evaluation revealed decreased visual acuity bilaterally, and a fundus examination disclosed lesions suggestive of bilateral retinal metastases. A comprehensive evaluation diagnosed a stage IVb lung adenocarcinoma with exon 19 mutation on epidermal growth factor receptor gene. Subsequently, she developed complaints of headaches and dizziness. She received frontline osimertinib 80 mg daily, preceded by upfront whole-brain radiation therapy with partial orbital inclusion for symptomatic ocular and brain metastases. After ten radiation therapy sessions, her complaints were resolved and an ophthalmology revaluation revealed improvement in visual acuity and resolution of photopsia complaints. The patient is currently on osimertinib and preserves an ECOG score of 0. Conclusion: Retinal metastases usually indicate advanced disease, so presenting with isolated ocular symptoms is exceedingly rare. Especially in cases of uncommon metastases, a multidisciplinary approach is fundamental for a prompt diagnosis and timely treatment, impacting prognosis and quality of life. LEARNING POINTS: Ocular metastases in lung cancer are usually a sign of advanced disease.Advanced lung adenocarcinoma presenting solely with retinal metastases is extremely rare.A multidisciplinary team is essential for the diagnosis and treatment of lung cancer with uncommon metastases.

Lessons from Four Decades of Systemic Amyloidosis with Renal Involvement.

BACKGROUND: Apart from ATTR amyloidosis, the epidemiology and outcomes of the most common subtypes of systemic amyloidosis in Portugal remain primarily unknown. METHODS: This retrospective cohort study evaluated patients with renal biopsy-proven amyloidosis, diagnosed from January 1978 to December 2019. Follow-up started at kidney disease presentation and ended at death or August 2020. Clinical presentation, survival, and prognostic factors were analysed. RESULTS: Of 123 patients with amyloid nephropathy, 111 had definite amyloid typing and were analysed. AA amyloidosis was the most frequent type (56.1%) and was related mainly to chronic infection (47.8%) and chronic inflammatory arthritis (29.0%). AL amyloidosis was present in 25.2% of patients and hereditary forms in 6.5% (4.1% AFibE526V, 2.4% ATTRV30M). During follow-up, 73.9% of AA and 54.8% of AL patients progressed to end-stage renal disease, and 79.7% of AA and 77.4% of AL died; median overall survival was 66.0 (95% CI, 33.0-99.0) and 18.0 (95% CI, 9.3-26.7) months (p = 0.025), respectively. There were no significant differences in renal outcome and survival on dialysis between these two types. In multivariate analysis, cardiac involvement at presentation (HR 6.26 [95% CI, 2.89-13.56]) and estimated glomerular filtration rate <30 mL/min/1.73 m2 (HR 2.05 [95% CI, 1.06-3.99]) independently influenced AA and AL amyloidosis survival. Cardiac involvement at presentation was an independent predictor of death (HR 9.65 [95% CI, 2.91-31.95]) and early mortality in AL amyloidosis. CONCLUSIONS: In Portugal, AA amyloidosis and related chronic infections are still relevant. Regarding AL amyloidosis, the low incidence and advanced disease at presentation result from missed and erroneous diagnoses, leading to delayed referrals and poor outcomes in these patients.

Lysozyme Photochemistry as a Function of Temperature. The Protective Effect of Nanoparticles on Lysozyme Photostability.

The presence of aromatic residues and their close spatial proximity to disulphide bridges makes hen egg white lysozyme labile to UV excitation. UVB induced photo-oxidation of tryptophan and tyrosine residues leads to photochemical products, such as, kynurenine, N-formylkynurenine and dityrosine and to the disruption of disulphide bridges in proteins. We here report that lysozyme UV induced photochemistry is modulated by temperature, excitation power, illumination time, excitation wavelength and by the presence of plasmonic quencher surfaces, such as gold, and by the presence of natural fluorescence quenchers, such as hyaluronic acid and oleic acid. We show evidence that the photo-oxidation effects triggered by 295 nm at 20°C are reversible and non-reversible at 10°C, 25°C and 30°C. This paper provides evidence that the 295 nm damage threshold of lysozyme lies between 0.1 µW and 0.3 µW. Protein conformational changes induced by temperature and UV light have been detected upon monitoring changes in the fluorescence emission spectra of lysozyme tryptophan residues and SYPRO® Orange. Lysozyme has been conjugated onto gold nanoparticles, coated with hyaluronic acid and oleic acid (HAOA). Steady state and time resolved fluorescence studies of free and conjugated lysozyme onto HAOA gold nanoparticles reveals that the presence of the polymer decreased the rate of the observed photochemical reactions and induced a preference for short fluorescence decay lifetimes. Size and surface charge of the HAOA gold nanoparticles have been determined by dynamic light scattering and zeta potential measurements. TEM analysis of the particles confirms the presence of a gold core surrounded by a HAOA matrix. We conclude that HAOA gold nanoparticles may efficiently protect lysozyme from the photochemical effects of UVB light and this nanocarrier could be potentially applied to other proteins with clinical relevance. In addition, this study confirms that the temperature plays a critical role in the photochemical pathways a protein enters upon UV excitation.