Non-attendance at diabetic retinal screening in Te Tai Tokerau, Northland, Aotearoa New Zealand.

AIMS: To explore socio-demographic characteristics of non-attenders at diabetic retinal screening. METHODS: A retrospective, register-based cross-sectional analysis of 10,275 participants invited to diabetic retinal screening in Te Tai Tokerau (Northland) between May 2011 and June 2020 was performed. Multivariable logistic regression analysis was used to assess the association of age, sex, type of diabetes, ethnicity and socio-economic deprivation with non-attendance at diabetic retinal screening. RESULTS: Median age was 66 years and 54.3% of participants were male. The non-attendance rate was 26.4%, with 46.6% of individuals having at least one non-attendance. Younger age was associated with higher odds of non-attendance (OR 1.84 95% CI 1.41-2.40, <0.001 for odds of non-attendance in those aged under 35 years compared with age over 75 years). Maori (OR 2.69, 95% CI 2.44-2.96, p<0.001) and Pacific peoples (OR 1.71, 95% CI 1.25-2.36, p=0.001) had higher odds of non-attendance compared with NZ Europeans. People living in areas of high socio-economic deprivation had higher odds of non-attendance (OR 1.56, 95% CI 1.33-1.82, p<0.001), as did type 1 diabetics (OR 1.31, p5% CI 1.08-1.59, p=0.006). CONCLUSION: Younger age, socio-economic deprivation, type 1 diabetes and Maori and Pacific ethnicity are risk factors for nonattendance at diabetic retinal screening.

Medication use and dry eye symptoms: A large, hypothesis-free, population-based study in the Netherlands.

PURPOSE: To date, population-based studies reporting associations between dry eye disease and medications were hypothesis-driven, did not take into account underlying comorbidities, and did not investigate individual drugs. The purpose of this study was to clarify the association of dry eye symptoms with medication classes and individual drugs, using a hypothesis-free approach. METHODS: 79,606 participants (age 20-97 years, 59.2% female) from the population-based Lifelines cohort in the Netherlands were cross-sectionally assessed for dry eye symptoms using the Womens' Health Study dry eye questionnaire. All medications used were coded with the ATC classification system. Logistic regression was used to assess the risk of the 59 most-used therapeutic/pharmacological subgroups and the 99 most-used individual drugs (all n > 200) on dry eye symptoms, correcting for age, sex, body mass index, and 48 comorbidities associated with dry eye. RESULTS: Thirty-eight (64%) medication subgroups and fifty-two (53%) individual drugs were associated with dry eye symptoms (P < 0.05), after correction for age and sex only. A multivariable model correcting for comorbidities revealed highly significant associations between dry eye symptoms and drugs for peptic ulcer (particularly proton pump inhibitors (PPIs)), antiglaucoma and anticholinergic medications. CONCLUSIONS: This study underlines that medication use is highly informative of risk of dry eye symptoms. Correction for underlying comorbidities is critical to avoid confounding effects. This study confirms suggested associations between medications and dry eye symptoms at a population level and shows several new associations. The novel link between PPIs and dry eye symptoms deserves particular attention given how commonly they are prescribed.

Novel endoscopic management of buried bumper syndrome in percutaneous endoscopic gastrostomy: The Olympus HookKnife.

Buried bumper syndrome (BBS) is an uncommon but serious complication of percutaneous endoscopic ga-strostomy. It involves the internal fixation device, or "bumper", migrating into the gastric wall and subsequent mucosal overgrowth. We described a case series of four patients with BBS treated with a novel endoscopic technique using a HookKnife between June 2016 and February 2017. The HookKnife is a rotating L-shaped cutting wire designed for hooking tissue and pulling it away from the gastric wall towards the lumen. The technique was successful in all four cases with no complications. Each patient was discharged on the day of treatment. The HookKnife is a manoeuvrable, safe and effective device for endoscopic removal of buried bumpers and could avoid surgery in a high risk group of patients. To our knowledge this technique has not been described previously. We suggest that this technique should be added to the treatment algorithms for managing BBS.

CYLD deletion triggers nuclear factor-κB-signaling and increases cell death resistance in murine hepatocytes.

AIM: To analyze the role of CYLD for receptor-mediated cell death of murine hepatocytes in acute liver injury models. METHODS: Hepatocyte cell death in CYLD knockout mice (CYLD(-/-) ) was analyzed by application of liver injury models for CD95- (Jo2) and tumor necrosis factor (TNF)-α- [D-GalN/lipopolysaccharide (LPS)] induced apoptosis. Liver injury was assessed by measurement of serum transaminases and histological analysis. Apoptosis induction was quantified by cleaved PARP staining and Western blotting of activated caspases. Nuclear factor (NF)-κB, ERK, Akt and jun amino-terminal kinases signaling were assessed. Primary Hepatocytes were isolated by two step-collagenase perfusion and treated with recombinant TNF-α and with the CD95-ligand Jo2. Cell viability was analyzed by MTT-assay. RESULTS: Livers of CYLD(-/-) mice showed increased anti-apoptotic NF-κB signaling. In both applied liver injury models CYLD(-/-) mice showed a significantly reduced apoptosis sensitivity. After D-GalN/LPS treatment CYLD(-/-) mice exhibited significantly lower levels of alanine aminotransferase (ALT) (295 U/L vs 859 U/L, P < 0.05) and aspartate aminotransferase (AST) (560 U/L vs 1025 U/L, P < 0.01). After Jo injection CYLD(-/-) mice showed 2-fold lower ALT (50 U/L vs 110 U/L, P < 0.01) and lower AST (250 U/L vs 435 U/L, P < 0.01) serum-levels compared to WT mice. In addition, isolated CYLD(-/-) primary murine hepatocytes (PMH) were less sensitive towards death receptor-mediated apoptosis and showed increased levels of Bcl-2, XIAP, cIAP1/2, survivin and c-FLIP expression upon TNF- and CD95-receptor triggering, respectively. Inhibition of NF-κB activation by the inhibitor of NF-κB phosphorylation inhibitor BAY 11-7085 inhibited the expression of anti-apoptotic proteins and re-sensitized CYLD(-/-) PMH towards TNF- and CD95-receptor mediated cell death. CONCLUSION: CYLD is a central regulator of apoptotic cell death in murine hepatocytes by controlling NF-κB dependent anti-apoptotic signaling.