Chronic endogenous fungal endophthalmitis: diagnostic and treatment challenges: A case report

Rationale:Endogenous fungal endophthalmitis (EFE) is a sight-threatening complication of systemic fungemia. As the prevalence rises, treatment remains a challenge especially when there is a failure in first-line treatment or drug-resistant fungus. This case report studies a case of chronic EFE, focusing on the diagnostic procedures, treatment options, monitoring parameters and the treatment outcomePatient concerns:A 64-year-old man with underlying well controlled diabetes mellitus was treated with 2 weeks’ course of intravenous antifungal fluconazole for pyelonephritis as his blood culture grew Candida albicans. Concurrently, he complained of 3 months of bilateral painless progressive blurring of vision. At presentation, his visual acuity (VA) was light perception both eyes. Ocular examination revealed non granulomatous inflammation with dense vitritis of both eyes.Diagnosis:He was diagnosed with EFE but the condition responded poorly with the medications.Interventions:He was treated with intravitreal (IVT) amphotericin B and fluconazole was continued. Vitrectomy was performed and intraoperative findings included bilateral fungal balls in the vitreous and retina with foveal traction in the left eye. Postoperatively, vision acuity was 6/24, N8 right eye and 2/60, N unable for left eye with extensive left macular scar and hole. Vitreous cultures were negative. He received multiple IVT amphotericin B and was started on topical steroid eye drops for persistent panuveitis with systemic fluconazole. Ocular improvement was seen after switching to IVT and topical voriconazole. Despite this, his ocular condition deteriorated and he developed neovascular glaucoma requiring 3 topical antiglaucoma agents. Panretinal photocoagulation was subsequently performed.Outcomes:At 3 months’ follow-up, his vision acuity remained at 6/24 for right eye and 2/60 for the left eye. There was no recurrence of inflammation or infection in both eyes.Lessons:Voriconazole could serve as a promising broad spectrum tri-azole agent in cases of failure in first-line treatment or drug-resistant fungus.     

Shortened Telomere Length in Sputum Cells of Bronchiectasis Patients is Associated with Dysfunctional Inflammatory Pathways

Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta?=????1.167, P_Adj?=?2.75?×?10^?4). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.

     

Engagement of the inhibitory receptor CD158a interrupts TCR signaling,preventing dynamic membrane reorganization in CTL/tumor cell interaction

Renal cell carcinoma (RCC) infiltrating lymphocytes (TILs) express killer cell immunoglobulinlike receptors (KIRs) that inhibit the antitumor CD8(+) T-cell lysis. In the present study, to better examine the functional consequences of KIR engagement on cytotoxic T lymphocyte (CTL)/tumor interaction, we have investigated the influence of KIR CD158a on early steps of T-cell activation. We show that coengagement of T-cell receptor (TCR) and CD158a by tumor cells inhibited tyrosine phosphorylation of early signaling proteins ZAP-70 and LAT, lipid raft coalescence, and TCR/CD3 accumulation at the CTL/tumor cell interface. In addition, the guanine exchange factor Vav was not phosphorylated, and no actin cytoskeleton rearrangement was observed. Our data indicate a role of KIR CD158a in the dynamic events induced by TCR triggering, preventing CTL membrane reorganization, and subsequent completion of CTL activation program. Accordingly, the expression of CD158 by TILs may favor tumor cell escape to the immune response.     

Carcinoma of colon presenting as fever of unknown origin

Fever of unknown origin (FUO) is defined as fever of more than 38.3 degrees C, the cause of which remains elusive after 1 week of intensive investigation. Most cases of FUO are restricted to infections, malignancies, and inflammatory diseases. FUO was previously reported as the presenting symptom of a few solid tumors such as lymphoma, renal cell carcinoma, and hepatocellular carcinoma. Colon carcinoma manifesting as FUO has been rarely reported. We describe three female patients who presented with classical FUO and microcytic anemia. As a control, we retrospectively evaluated 28 matched patients with carcinoma of colon and no fever. The evaluation included review of patient files, clinical and laboratory data, and pathologic specimens. In the three patients (mean age, 58 years) who presented with FUO and had left-sided colon carcinoma and microcytic anemia, pathologic evaluation of the tumor tissues demonstrated a severe organized inflammatory process forming abscesses in the pericolic fat. The 28 control matched patients showed no such histopathologic changes. In patients presenting with FUO, especially those who present with microcytic anemia, even with no bowel disturbances or elevated carcinoembryonic antigen levels, diagnostic workup should include a search for occult colorectal carcinoma. In our three cases, it appears that microabscesses in the pericolic fat are the cause of fever.     

Impact of carboxylation and hydrolysis functionalisations on the anti-oil staining behaviour of textiles grafted with poly(N-isopropylacrylamide) hydrogel

Novel hydrogel-modified textiles have been prepared through photografting poly(N-isopropylacrylamide) (PNIPAAm) onto pristine and functionalised polyethylene terephthalate (PET) surfaces. In this work, two types of functionalisation, carboxylation (CPET) and hydrolysis (HPET), were performed to scrutinise the hydrogel grafting efficiency. Basic characterisation of the pristine, functionalised and grafted textiles was carried out via fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and field emission scanning electron microscopy (FESEM) analyses. Then, the functional characteristics of these samples were determined based on the oil staining performance. Functionalisation of the PET textiles via hydrolysis and carboxylation gives rise to different chemical reactivity and interactions on the PET surface. Impressively, the surface formed via hydrolysis functionalisation of PET was found to be more efficient compared to that formed via carboxylation, and the untreated one. The HPET surface was remarkably more hydrophilised and rougher than both the UPET and CPET surfaces. The accessibility of the –OH groups for hydrogen abstraction from HPET has a great impact on the hydrogel grafting onto the HPET surface. All the grafted textiles (PNIPAAm-g-UPET, PNIPAAm-g-CPET and PNIPAAm-g-HPET) demonstrated anti-oil staining behaviour at 27 °C. In particular, PNIPAAm-g-HPET textiles with a high degree of grafting (DG) exhibited the fastest rate for oil to de-stain from the surface. Moreover, the reversible transition of PNIPAAm hydrogels around the lower critical solution temperature (LCST) ∼ 32 °C from hydrophilic to hydrophobic generates switchable surfaces of the textiles with regard to the oil wettability. Specifically, PNIPAAm-g-HPET textiles also displayed the highest degree of wettability switching as a result of having the highest DG. Taken together, the PNIPAAm hydrogels grafted onto PET textiles were significantly enhanced though hydrolysis functionalisation and possessed excellent switchable surfaces toward oil-staining, having great potential to be used for applications in oil and water separation as well as smart textiles.

Functionalisation, especially via hydrolysis, has created efficient PNIPAAm hydrogels grafted onto PET textiles with superior anti-oil staining performance.