Ten-year survival trends of neovascular age-related macular degeneration at first presentation

BACKGROUND: To describe 10-year trends in visual outcomes, anatomical outcomes and treatment burden of patients receiving antivascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD). METHODS: Retrospective cohort study of treatment-naïve, first-affected eyes with nAMD started on ranibizumab before January 1, 2009. The primary outcome was time to best-corrected visual acuity (BCVA) falling ≤35 ETDRS letters after initiating anti-VEGF therapy. Secondary outcomes included time to BCVA reaching ≥70 letters, proportion of eyes with BCVA ≥70 and ≤35 letters in 10 years, mean trend of BCVA and central retinal thickness over 10 years, and mean number of injections. RESULTS: For our cohort of 103 patients, Kaplan-Meier analyses demonstrated median time to BCVA reaching ≤35 and ≥70 letters were 37.8 (95% CI 22.2 to 65.1) and 8.3 (95% CI 4.8 to 20.9) months after commencing anti-VEGF therapy, respectively. At the final follow-up, BCVA was ≤35 letters and ≥70 letters in 41.1% and 21%, respectively, in first-affected eyes, while this was the case for 5.4% and 48.2%, respectively, in a patient's better-seeing eye. Mean injection number was 37.0±24.2 per eye and 53.6±30.1 at patient level (63.1% of patients required injections in both eyes). CONCLUSIONS: The chronicity of nAMD disease and its management highlights the importance of long-term visual prognosis. Our analyses suggest that one in five patients will retain good vision (BCVA ≥70 ETDRS letters) in the first-affected eye at 10 years after starting anti-VEGF treatment; yet, one in two patients will have good vision in their better-seeing eye. Moreover, our data suggest that early treatment of nAMD is associated with better visual outcomes

IDH1-mutated Crohn's disease-associated small bowel adenocarcinomas: Distinctive pathological features and association with MGMT methylation and serrated-type dysplasia

Aims: Patients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD-SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1-mutated CrD-SBAs. Methods and results: An international multicentre series of surgically resected CrD-SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6-methylguanine-DNA methyltransferase (MGMT) and long interspersed nuclear element-1 (LINE-1) methylation were compared between IDH1-mutated and IDH1 wild-type CrD-SBAs. Ten (20%) of the 49 CrD-SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild-type cases, IDH1-mutated CrD-SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1-mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non-conventional subtype (two serrated dysplastic lesions and one goblet cell-deficient dysplasia). In particular, non-conventional serrated dysplasia was significantly associated with IDH1-mutated CrD-SBAs (P = 0.029). No significant cancer-specific survival difference between IDH1-mutated CrD-SBA patients and IDH1 wild-type CrD-SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16–1.89; P = 0.313). Conclusions: IDH1-mutated CrD-SBAs, which represent approximately one-fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1-mutated non-conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD-SBAs

Towards sustainable agriculture: fossil-free ammonia

Citation: Pfromm, P. H. (2017). Towards sustainable agriculture: Fossil-free ammonia. Journal of Renewable and Sustainable Energy, 9(3), 034702. https://doi.org/10.1063/1.4985090About 40% of our food would not exist without synthetic ammonia (NH3) for fertilization. Yet, NH3 production is energy intensive. About 2% of the world's commercial energy is consumed as fossil fuels for NH3 synthesis based on the century-old Haber-Bosch (H.-B.) process. The state of the art and the opportunities for reducing the fossil energy footprint of industrial H.-B. NH3 synthesis are discussed. It is shown that even a hypothetical utterly revolutionary H.-B. catalyst could not significantly reduce the energy demand of H.-B. NH3 as this is governed by hydrogen production. Renewable energy-enabled, fossil-free NH3 synthesis is then evaluated based on the exceptional and continuing cost decline of renewable electricity. H.-B. syngas (H2, N2) is assumed to be produced by electrolysis and cryogenic air separation, and then supplied to an existing H.-B. synthesis loop. Fossil-free NH3 could be produced for energy costs of about $232 per tonne NH3 without claiming any economic benefits for the avoidance of about 1.5 tonnes of CO2 released per tonne NH3 compared to the most efficient H.-B. implementations. Research into alternatives to the H.-B. process might be best targeted at emerging markets with currently little NH3 synthesis capacity but significant future population growth such as Africa. Reduced capital intensity, good scale-down economics, tolerance for process upsets and contamination, and intermittent operability are some desirable characteristics of NH3 synthesis in less developed markets, and for stranded resources. Processes that are fundamentally different from H.-B. may come to the fore under these specific boundary conditions

Nature and frequency of respiratory involvement in chronic progressive external ophthalmoplegia

Chronic progressive external ophthalmoplegia (CPEO) is a relatively common mitochondrial disorder. Weakness of the extra-ocular, limb girdle and laryngeal muscles are established clinical features. Respiratory muscle involvement however has never been studied systematically, even though respiratory complications are one of the main causes of death. We therefore determined the prevalence and nature of respiratory muscle involvement in 23 patients with genetically confirmed CPEO. The main finding was decreased respiratory muscle strength, both expiratory (76.8% of predicted, p = 0.002) and inspiratory (79.5% of predicted, p = 0.004). Although the inspiratory vital capacity (92.5% of predicted, p = 0.021) and the forced expiratory volume in 1 s (89.3% of predicted, p = 0.002) were below predicted values, both were still within the normal range in the majority of patients. Expiratory weakness was associated with a decreased vital capacity (ρ = 0.502, p = 0.015) and decreased peak expiratory flow (ρ = 0.422, p = 0.045). Moreover, expiratory muscle strength was lower in patients with limb girdle weakness (62.6 ± 26.1% of predicted vs. 98.9 ± 22.5% in patients with normal limb girdle strength, p = 0.003), but was not associated with other clinical features, subjective respiratory complaints, disease severity or disease duration. Since respiratory involvement in CPEO is associated with severe morbidity and mortality, the present data justify periodic assessment of respiratory functions in all CPEO patients

Mortality and morbidity among people living close to incinerators: a cohort study based on dispersion modeling for exposure assessment

<p>Abstract</p> <p>Background</p> <p>Several studies have been conducted on the possible health effects for people living close to incinerators and well-conducted reviews are available. Nevertheless, several uncertainties limit the overall interpretation of the findings. We evaluated the health effects of emissions from two incinerators in a pilot cohort study.</p> <p>Methods</p> <p>The study area was defined as the 3.5 km radius around two incinerators located near Forlì (Italy). People who were residents in 1/1/1990, or subsequently became residents up to 31/12/2003, were enrolled in a longitudinal study (31,347 individuals). All the addresses were geocoded. Follow-up continued until 31/12/2003 by linking the mortality register, cancer registry and hospital admissions databases. Atmospheric Dispersion Model System (ADMS) software was used for exposure assessment; modelled concentration maps of heavy metals (annual average) were considered the indicators of exposure to atmospheric pollution from the incinerators, while concentration maps of nitrogen dioxide (NO₂) were considered for exposure to other pollution sources. Age and area-based socioeconomic status adjusted rate ratios and 95% Confidence Intervals were estimated with Poisson regression, using the lowest exposure category to heavy metals as reference.</p> <p>Results</p> <p>The mortality and morbidity experience of the whole cohort did not differ from the regional population. In the internal analysis, no association between pollution exposure from the incinerators and all-cause and cause-specific mortality outcomes was observed in men, with the exception of colon cancer. Exposure to the incinerators was associated with cancer mortality among women, in particular for all cancer sites (RR for the highest exposure level = 1.47, 95% CI: 1.09, 1.99), stomach, colon, liver and breast cancer. No clear trend was detected for cancer incidence. No association was found for hospitalizations related to major diseases. NO₂levels, as a proxy from other pollution sources (traffic in particular), did not exert an important confounding role.</p> <p>Conclusions</p> <p>No increased risk of mortality and morbidity was found in the entire area. The internal analysis of the cohort based on dispersion modeling found excesses of mortality for some cancer types in the highest exposure categories, especially in women. The interpretation of the findings is limited given the pilot nature of the study.</p

New entity of adult ultra-short coeliac disease: the first international cohort and case–control study

Background: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. Methods: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. Findings: Patients with USCD (n=137, median age 27 years, IQR 21–43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1–5.9) vs 12.6×ULN (IQR 3.3–18.3), p<0.001). Patients: with USCD had the same number of symptoms overall (median 3 (IQR 2–4) vs 3 (IQR 1–4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006). Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4. At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440–2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2–1.4) vs 0.7 ULN (IQR 0.2–2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. Interpretation: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup