Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Background Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), 416,746 individuals from 10 countries completed demographic and dietary questionnaires at recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident lung cancer (n = 3731) risk relative to haem iron, non-haem iron, and total dietary iron intake. A corresponding analysis was conducted among a nested subset of 800 lung cancer cases and 1489 matched controls for whom serum cotinine was available. Results Haem iron was associated with lung cancer risk, including after adjustment for details of smoking history (time since quitting, number of cigarettes per day): as a continuous variable (HR per 0.3 mg/1000 kcal 1.03, 95% CI 1.00-1.07), and in the highest versus lowest quintile (HR 1.16, 95% CI 1.02-1.32; trend across quintiles: P = 0.035). In contrast, non-haem iron intake was related inversely with lung cancer risk; however, this association attenuated after adjustment for smoking history. Additional adjustment for serum cotinine did not considerably alter the associations detected in the nested case-control subset. Conclusions Greater haem iron intake may be modestly associated with lung cancer risk.Peer reviewe

Silmänpohjakameran soveltuminen neurologisten päivystyspotilaiden tutkimiseen verrattuna oftalmoskooppiin

Silmänpohjan tutkiminen on tärkeä tutkimus osana usean akuutin neurologisen sairauden diagnostiikkaa. Neurologisille potilaille ei kuitenkaan suositella pupillin laajentamista, mikä vaikeuttaa oftalmoskopointia. Epäonnistuneen oftalmoskopoinnin takia potilaalta voi jäädä huomaamatta aivopaineen kohoamiseen tai muuhun välitöntä hoitoa vaativaan sairauteen viittaava löydös. Pilottitutkimuksessamme selvitimme, onnistuuko kannettava silmänpohjakamera paremmin neurologisten päivystyspotilaitten silmänpohjatutkimuksessa kuin oftalmoskooppi. Aineisto koostui 60 potilaasta, jotka olivat hoidossa Oulun yliopistollisen sairaalan neurologian päivystyksessä 18.8.2016–31.5.2017 välisenä aikana. Sisäänottokriteereinä oli täysi-ikäisyys, vapaaehtoisuus ja työdiagnoosina joko päänsärky, AVH tai sekavuus. Osa potilaista täytti useamman oirekuvan. Potilaista 17 oli miehiä ja 43 naisia. Mediaani-ikä oli 59 vuotta. Päänsärkypotilaita oli 30, AVH potilaita 28 ja sekavia potilaita 7. Potilaiden ko-operaatiota arvioitiin määrittämällä modifioitu Rankin score ja Glasgow coma score (GCS). Potilaille tehtiin non-mydriaattinen silmänpohjatutkimus ensin oftalmoskoopilla, ja sitten SmartScope Pro silmänpohjakameralla. Tutkimuksen onnistuminen kummallakin menetelmällä määriteltiin kolmiluokkaisesti: onnistui, onnistui osittain, epäonnistui. Mahdolliset silmänpohjamuutokset kirjattiin ylös myöhempää silmälääkärin tulkintaan tehtävää vertailua varten. Silmänpohjakamerakuvaus onnistui 56 (93,3 %), onnistui osittain 2 (3,3 %) ja epäonnistui 2 (3,3 %) potilaalla silmänpohjatutkimuksessa. Oftalmoskopointi onnistui 35 (58,3 %), onnistui osittain 14 (23,3 %) ja epäonnistui 11 (18,3 %) potilaalla silmänpohjatutkimuksessa. Eron tilastollinen merkitsevyys on p<0,0005. Viidenkymmenen kahdeksan potilaan kuvista tutkija ja silmälääkäri olivat löytäneet samat löydökset 54 tapauksessa (93 %). Kuudessa tapauksessa (7 %) tutkijalta oli jäänyt ei-kriittinen löydös havaitsematta. Silmänpohjakamera soveltuu neurologiseen silmänpohjatutkimukseen paremmin kuin oftalmoskooppi. Ero on tilastollisesti ja kliinisesti merkittävä. Jatkotutkimuksia tarvitaan

Comparison of optic disc evaluation methods in neurology emergency patients

Abstract Background: The optic disc examination is critical for the diagnostics of several acute neurological disorders. However, dilation of the pupil is not recommended for neurological patients, which complicates ophthalmoscopy. Aims of the study: Present pilot study compared a portable fundus camera to an ophthalmoscope in fundus examinations of neurological emergency patients. To our knowledge, this is the first comparative study of the subject. The fundus photographs were later reviewed with an ophthalmologist. Methods: The study included 60 adults, volunteer neurological emergency patients with either headache, cerebrovascular disorder, or acute confusional state (delirium). Patients’ non‐mydriatic fundus examination was conducted with an ophthalmoscope and a Smartscope Pro fundus camera. Results: Fundus photography succeeded in 56 (93%), partially succeeded in 2 (3%), and failed in 2 (3%) cases compared with ophthalmoscopy that succeeded in 35 (58%), partially succeeded in 14 (23%), and failed in 11 (18%) cases (P &lt; 0.0005). The researcher and the ophthalmologist agreed in the findings in 54 out of 58 cases (93%). In six cases (7%), the researcher had failed to detect a non‐critical ophthalmic finding. Conclusions: The neurological fundus examination by fundus camera seems to be superior to regular ophthalmoscopy in defining the critical optic disc findings in emergency patients

Rheumatoid Factor Isotypes in Relation to Antibodies Against Citrullinated Peptides and Anti-Carbamylated Antibodies in Individuals Before the Onset of Rheumatoid Arthritis

Background: The presence of rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and antibodies against citrullinated protein and peptides (ACPA) precedes the onset of symptoms of rheumatoid arthritis (RA) by several years. Relationships between the development of these antibodies are not obvious.  Methods: Three isotypes [immunoglobulin A (IgA), IgG and IgM) of RF were analysed in 321 pre-symptomatic individuals who provided 598 samples collected a median of 6.2 (interquartile range 7.2) years before the onset of symptoms, and in 492 population control subjects. All samples were donated to the Biobank of Northern Sweden. RF isotypes were analysed using the EliA system (Phadia GmbH, Freiburg, Germany) with 96 % specificity according to receiver operating characteristic curves. Ten ACPA specificities were analysed using the ImmunoCAP ISAC system, and anti-CCP2 and anti-CarP antibodies were evaluated using enzyme-linked immunosorbent assays.  Results: The frequencies of RF isotypes in pre-symptomatic individuals were significantly increased compared with control subjects (p &lt; 0.0001). In samples collected &gt;= 15 years before the onset of symptoms, the IgA-RF isotype was significantly more prevalent than the most frequent ACPAs. Combinations of IgM- and IgA-RF isotypes with ACPA specificities [a-enolase (CEP-1/Eno(5-21))], fibrinogen (Fib)beta(36-52), Fiba(580-600), filaggrin (CCP-1/Fil(307-324)) and anti-CCP2 antibodies were associated with a significantly shorter time to onset of symptoms (p &lt; 0.001-0.05). Using conditional inference tree analysis, anti-CCP2 in combination with anti-filaggrin antibodies gave the highest probability, 97.5 %, for disease development.  Conclusions: RF isotypes predicted the development of RA, particularly in combination with ACPA, anti-CCP2 or anti-CarP antibodies. The highest probability for disease development was the presence of anti-CCP2 and anti-filaggrin antibodies.Originally included in thesis in manuscript form, with the title "Rheumatoid Factor Isotypes in Relation to Antibodies Against Citrullinated Peptides and Anti-Carbamylated Antibodies in Individuals Before the Onset of Rheumatoid Arthritis"</p

First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 x 10(-8); odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10-5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 x 10(-10); OR = 1.47; 95% CI, 1.38-1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 x 10(-16); OR = 1.75; 95% CI, 1.64-1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% +/- 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes