Glaucoma progression in patients receiving intravitreal anti-VEGF treatment for neovascular age-related macular degeneration

Purpose: The purpose of this study was to investigate how often glaucoma and neovascular age-related macular degeneration (nAMD) occur in the same patient and to evaluate whether glaucoma progression is faster in eyes treated with intravitreal anti-VEGF medications for nAMD. Methods: This single-centre retrospective real-world data (RWD) consists of medical records of 6314 glaucoma and 2166 nAMD patients treated in 2008–2017 in Tays Eye Centre, Finland. To study glaucoma progression, changes in visual fields (mean deviation [MD], dB/year), IOP (mmHg/year) and fundus photographs (progression, yes/no) were compared in glaucoma eyes with and without anti-VEGF treatment for nAMD and ≥1 year follow-up. Results: During the 10-year period, 147 patients with glaucoma received intravitreal anti-VEGF treatment for nAMD corresponding to 2% of glaucoma and 7% of nAMD patients. The mean change in MD was −0.70 dB/year (SD 1.8) vs. −0.27 dB/year (SD 1.7) (p = 0.027) in glaucoma eyes with (n = 37) and without (n = 4304) anti-VEGF injections, respectively. In patients with bilateral glaucoma and unilateral nAMD treated with anti-VEGF injections (n = 20), MD declined at −0.62 dB/year (SD 1.9) vs 0.33 dB/year (SD 1.5) (p = 0.654), and glaucoma progression was detected in 14/20 vs 10/20 (p = 0.219) fundus photographs in eyes with anti-VEGF treatment compared with their untreated fellow eyes. Conclusion: nAMD and glaucoma were found co-existing in the same eye at rates that were similar to the age-corrected prevalence of the two diseases in the general population. Our results suggest that intravitreal anti-VEGF treatment for nAMD may accelerate glaucoma progression.publishedVersionPeer reviewe

Migreeniä sairastavien työkyvyn lukutaito - Kehittämisehdotus Suomen Migreeniyhdistykselle

Opinnäytetyön tarkoituksena oli selvittää migreeniä sairastavien oman työkyvyn lukutaitoa ja työkykyä sekä esihenkilön roolia näiden tukemisessa. Tarkoituksena oli myös muotoilla migreeniä sairastavien työkyvyn lukutaitoa valmentavia kysymyksiä esihenkilöiden käyttöön sekä tuottaa Suomen Migreeniyhdistykselle kehittämisehdotus migreeniä sairastavien työkyvyn tuesta. Opinnäytetyön tavoitteena oli edistää migreeniä sairastavien oman työkyvyn lukutaitoa, parantaa migreeniä sairastavien ja esihenkilöiden välistä vuorovaikutusta valmentavien kysymysten avulla sekä vahvistaa migreeniä sairastavien toimijuutta työkykynsä ylläpitämisessä. Opinnäytetyö toteutettiin konstruktiivisena tutkimuksena. Määrällisten ja laadullisten menetelmien yhdistelmänä toteutetun tutkimus- ja kehittämistyön aineiston muodostivat kyselytutkimuksesta (vastauksia 266 kpl), kehittämistiimin työskentelystä sekä valmentavien kysymysten testaamisesta saadut aineistot. Opinnäytetyön tulosten mukaan migreeniä sairastavat osaavat lukea omaa työkykyään melko hyvin. Työkyvyn lukutaidon perustana näyttäytyy toimintakyvyn vaihtelun tunnistaminen. Migreeniä sairastavan työkyvyn edistämisessä merkittävä tekijä on itsensä johtamisen taidot. Esihenkilön rooli migreeniä sairastavien työkyvyn tukemisessa voi olla merkittävä ja ennakoivan työkykyjohtamisen merkitys on suuri. Migreeni on usein työkykyyn voimakkaasti vaikuttava sairaus. Opinnäytetyössä muotoiltiin ja testattiin työkyvyn lukutaitoa valmentavia kysymyksiä, joiden arvioidaan voivan parantaa esihenkilöiden ja migreeniä sairastavien välistä ymmärrystä. Ne ohjaavat migreeniä sairastavaa pohtimaan ja sanoittamaan yksilöllistä oireiluaan sekä konkreettisia ratkaisu- ja tukimahdollisuuksia yhdessä esihenkilön kanssa. Valmentavien kysymysten käyttäminen voi tehdä työkykykeskustelusta arkipäiväisempää, rakentaa luottamusta, lisätä ennakoivaa otetta ja ohjata löytämään työkykyä tukevia ratkaisuja arjessa. Opinnäytetyön kokonaisuuden perusteella muotoiltiin kehittämisehdotus Suomen Migreeniyhdistykselle. Opinnäytetyön perusteella migreeniä sairastavien työkyvyn tukemisessa on keskeistä tuen kokonaisvaltainen ja ennakoiva ote sekä migreeniä sairastavan toimijuuden vahvistaminen. Lisäksi työkyvyn tukijärjestelmät vaativat kehittämistä.The purpose of the thesis was to investigate the working ability literacy and working ability of migraine sufferers and the role of a supervisor in supporting them. The purpose was also to prepare coaching questions for the supervisors to improve the working ability literacy of employees with migraines and to produce a development proposal for the Finnish Migraine Association to support the working ability of migraine sufferers. The aim of the thesis was to promote migraine sufferers' own working ability literacy, to improve the interaction between migraine sufferers and supervisors through coaching questions, and to strengthen the agency of migraine sufferers in maintaining their ability to work. The thesis was implemented as a constructive study. The material for the research and development work was gathered with a combination of quantitative and qualitative methods and included the data obtained from a survey (266 replies), developmental teamwork and testing of the coaching questions. According to the results, migraine sufferers know how to read their ability to work quite well. Recognizing the variation of functional ability appears to be the basis of working ability literacy. Self-management skills are a major factor in promoting their working ability. The supervisor's role in supporting working ability can be significant, and the importance of proactive working ability management is considerable. Migraine is often a disease that strongly affects the ability to work. The coaching questions were designed and tested in this thesis to train the working ability literacy. These questions are estimated to improve the understanding between the supervisor and the migraine sufferer. They guide the migraine sufferer to explain and verbalize their individual symptoms and seek for a concrete solution and possible support together with the supervisor. The coaching questions can make the working ability discussion more informal, build trust, increase a proactive approach, and guide to find solutions that support ability to work in everyday life. Based on the entire thesis, a development proposal for the Finnish Migraine Association was also formulated. Based on the thesis, in supporting the ability to work, a comprehensive and proactive approach and strengthening the agency of the migraine sufferers are essential. In addition, the support systems for working ability require development

Expression of CEA, CA19-9, CA125, and EpCAM in pseudomyxoma peritonei

Pseudomyxoma peritonei is a fatal clinical syndrome with mucinous tumor cells disseminated into peritoneal cavity and secreting abundant mucinous ascites. The serum tumor markers CEA, CA19-9, and CA125 are used to monitor pseudomyxoma peritonei remission, but their expression at tissue level has not been well characterized. Herein, we analyzed expression of these proteins and the adenocarcinoma marker EpCAM in 92 appendix-derived pseudomyxoma peritonei tumors by immunohistochemistry. All tumors were found to ubiquitously express CEA and EpCAM. In the majority of the tumors (94.6%), CEA showed polarized immunostaining, but in 5 aggressive high-grade tumors containing numerous signet ring cells, a nonpolarized staining was detected. We found preoperative CEA serum values to correlate with peritoneal cancer index. However, the serum values of the advanced cases with nonpolarized staining pattern were normal, and the patients died within 5 years after diagnosis. Thus, serum CEA measurements did not reflect aggressiveness of these tumors. CA19-9 showed strong immunopositivity in most of the tumors (91.3%), and mutated enzyme FUT3 was demonstrated from the cases showing negative or weak staining. CA125 Was infrequently expressed by tumor cells (focal staining in 6.5% of the cases), but in most of the cages (79.3%), adjacent nonneoplastic mesothelial cells showed immunopositivity. As a conclusion, CEA and EpCAM are invariably expressed by pseudomyxoma peritonei tumor cells and could be exploited to targeted therapies against this malignancy. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Outbreak of multiple strains of non-O157 Shiga toxin-producing and enteropathogenic Escherichia coli associated with rocket salad, Finland, autumn 2016

In August 2016, an outbreak of Shiga toxin-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) with 237 cases occurred in the Helsinki metropolitan area, Finland. Gastroenteritis cases were reported at 11 events served by one catering company. Microbiological and epidemiological investigations suggested rocket salad as the cause of the outbreak. STEC ONT:H-11 and EPEC O-111:H8 strains isolated from food samples containing rocket were identical to the patient isolates. In this outbreak, the reported symptoms were milder than considered before for STEC infection, and the guidelines for STEC control measures need to be updated based on the severity of the illness. Based on our experience in this outbreak, national surveillance criteria for STEC have been updated to meet the practice in reporting laboratories covering both PCR-positive and culture-confirmed findings. We suggest that EPEC could be added to the national surveillance since diagnostics for EPEC are routinely done in clinical laboratories.Peer reviewe

Glycomic Profiling Highlights Increased Fucosylation in Pseudomyxoma Peritonei

Peer reviewe

Challenges in using soil carbon modelling in LCA of agricultural products—the devil is in the detail

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Generation of Functional Blood Vessels from a Single c-kit+ Adult Vascular Endothelial Stem Cell

<div><p>In adults, the growth of blood vessels, a process known as angiogenesis, is essential for organ growth and repair. In many disorders including cancer, angiogenesis becomes excessive. The cellular origin of new vascular endothelial cells (ECs) during blood vessel growth in angiogenic situations has remained unknown. Here, we provide evidence for adult vascular endothelial stem cells (VESCs) that reside in the blood vessel wall endothelium. VESCs constitute a small subpopulation within CD117+ (c-kit+) ECs capable of undergoing clonal expansion while other ECs have a very limited proliferative capacity. Isolated VESCs can produce tens of millions of endothelial daughter cells in vitro. A single transplanted c-kit-expressing VESC by the phenotype lin−CD31+CD105+Sca1+CD117+ can generate in vivo functional blood vessels that connect to host circulation. VESCs also have long-term self-renewal capacity, a defining functional property of adult stem cells. To provide functional verification on the role of c-kit in VESCs, we show that a genetic deficit in endothelial c-kit expression markedly decreases total colony-forming VESCs. In vivo, c-kit expression deficit resulted in impaired EC proliferation and angiogenesis and retardation of tumor growth. Isolated VESCs could be used in cell-based therapies for cardiovascular repair to restore tissue vascularization after ischemic events. VESCs also provide a novel cellular target to block pathological angiogenesis and cancer growth.</p> </div

Isolated adult lin−CD31+CD105+ ECs encompass rare endothelial CFCs.

<p>(A) Quantification of colony-forming ability of lin−CD31+CD105+ cells isolated from the mouse lungs. Freshly isolated cells from ten mice were assayed in duplicate. An EC colony in the semi-solid matrix is also shown. The colonies grow beneath the methylcellulose matrix adhered to the bottom of the culture dish. Scale bar, 150 µm. (B) Freshly isolated GFP-tagged ECs were seeded on standard 2-D EC cultures one CFU per culture dish together with 20 CFUs of wt ECs and grown until the monolayer was confluent. GFP+ cells form a single circular EC batch within the confluent wt EC monolayer, demonstrating the clonal growth pattern of the ECs responsible for creating the confluent monolayer. DAPI and bright field images show also the wt ECs in the confluent monolayer. Scale bar, 200 µm. (C) Colonies formed from isolated lin−CD31+CD105+ mouse lung ECs in low-cell density adherent semi-solid methylcellulose matrix were stained for various cell-surface markers. The colonies express EC markers CD31, CD105, VE-cadherin, and vWF while the cells are negative for the pan-hematopoietic marker CD45. The nuclei are stained with DAPI (blue) to recognize individual cells. MS-1 murine EC line was used as a control. Rabbit anti-β-gal antibodies and rat anti-mouse CD45 antibodies provide the isotype controls for rabbit and rat antibodies, respectively. Scale bars, 50 µm.</p

A genetic deficit in endothelial c-kit expression decreases colony-forming VESCs and results in impaired EC proliferation and angiogenesis, and retardation of tumor growth in vivo.

<p>(A) Equivalent lin−CD31+CD105+ EC populations were detected in mutant C57BL/6J mice with a genetic c-kit expression deficit (C57BL/6J-Kit^W-sh mice) and in the wt C57BL/6J controls. However, the Kit^W-sh mutant mice have very low numbers of CD117+ ECs (here 1% of total lin−CD31+CD105+ ECs). Typical results from FACS analysis of lung ECs are shown. Histograms indicate the percentage of CD117+ cells, control IgG labeling and gatings are also shown. (B) lin−CD31+CD105+ ECs from kit deficient Kit^W-sh mutant mice contain abnormally low levels of endothelial CFCs in comparison to wt mice (<i>p</i><0.0001, the Mann-Whitney test). The horizontal lines indicate 10th, 25th, 50th (median), 75th, and 90th percentiles. The results of 12 independent experiments, each performed in duplicate, are shown. The Mann-Whitney test was used to compare the groups. (C) When syngeneic B16 melanoma tumors were implanted to kit deficient Kit^W-sh mutant mice, a highly significant impairment of tumor angiogenesis was observed (<i>p</i> = 0.0006; <i>n</i> = 7 for each group). vWF/DAPI stains are also shown. The tumor vasculature in kit deficient Kit^W-sh mutant mice contained a significantly diminished number of proliferating ECs (<i>p</i> = 0.01; <i>n</i> = 7 for each group). The percentiles of mean percentages of proliferating (ki-67+) ECs are shown. ki-67/CD31/DAPI stains are also shown. The Mann-Whitney test was used to compare the groups. Scale bars, 100 µm. (D) A highly significant retardation of tumor growth was observed in the kit deficient Kit^W-sh mice. *<i>p</i><0.01; **<i>p</i><0.001; ***<i>p</i><0.0001; <i>n</i> = 17 for each group.</p