Browsing by Subject "NATURAL-HISTORY"

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  • Kuhle, J.; Hardmeier, M.; Disanto, G.; Gugleta, K.; Ecsedi, M.; Lienert, C.; Amato, M. P.; Baum, K.; Buttmann, M.; Bayas, A.; Brassat, D.; Brochet, B.; Confavreux, C.; Edan, G.; Färkkilä, Markus; Fredrikson, S.; Frontoni, M.; D'Hooghe, M.; Hutchinson, M.; De Keyser, J.; Kieseier, B. C.; Kuempfel, T.; Rio, J.; Polman, C.; Roullet, E.; Stolz, C.; Vass, K.; Wandinger, K. P.; Kappos, L.; European Long Term Follow Up Study (2016)
    Objectives: To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). Methods: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. Results: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R-2: 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited (R-2: 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained <5% of the variability. Conclusions: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.
  • Lamichhane, Santosh; Ahonen, Linda; Dyrlund, Thomas Sparholt; Siljander, Heli; Hyöty, Heikki; Ilonen, Jorma; Toppari, Jorma; Veijola, Riitta; Hyötyläinen, Tuulia; Knip, Mikael; Oresic, Matej (2018)
    Early prediction and prevention of type 1 diabetes (T1D) are currently unmet medical needs. Previous metabolomics studies suggest that children who develop T1D are characterised by a distinct metabolic profile already detectable during infancy, prior to the onset of islet autoimmunity. However, the specificity of persistent metabolic disturbances in relation T1D development has not yet been established. Here, we report a longitudinal plasma lipidomics dataset from (1) 40 children who progressed to T1D during follow-up, (2) 40 children who developed single islet autoantibody but did not develop T1D and (3) 40 matched controls (6 time points: 3, 6, 12, 18, 24 and 36 months of age). This dataset may help other researchers in studying age-dependent progression of islet autoimmunity and T1D as well as of the age-dependence of lipidomic profiles in general. Alternatively, this dataset could more broadly used for the development of methods for the analysis of longitudinal multivariate data.
  • Palosuo, Kati; Karisola, Piia; Savinko, Terhi; Fyhrquist, Nanna; Alenius, Harri; Mäkelä, Mika J. (2021)
    BACKGROUND: Egg allergy is the second most common food allergy in children. Persistent food allergy increases the risk of anaphylaxis and reduces the quality of life. OBJECTIVE: To determine the efficacy of oral immunotherapy (OIT) with raw egg white powder and study its effects on humoral responses in children with persistent egg allergy. METHODS: Fifty children aged 6 to 17 years with egg allergy, diagnosed by double-blind, placebo-controlled food challenge, were randomized 3:2 to 8 months of OIT with a maintenance dose of 1 g of egg white protein or 6 months of avoidance after which the avoidance group crossed over to OIT. We examined changes in IgE, IgG4, and IgA concentrations to Gal d 1-4 during OIT compared with avoidance and assessed clinical reactivity at 8 and 18 months. RESULTS: After 8 months, 22 of 50 children (44%) on OIT and 1 of 21 (4.8%) on egg avoidance were desensitized to the target dose, 23 of 50 (46%) were partially desensitized (dose
  • Type 1 Diabet TrialNet Study Grp; Redondo, Maria J.; Geyer, Susan; Steck, Andrea K.; Knip, Mikael (2018)
    OBJECTIVEWe tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals.RESEARCH DESIGN AND METHODSWe studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients' relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2-51.8], 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). Of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. Of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial-Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables.RESULTSHigher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06-1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS >0.295, 95% CI 1.47-3.51; P = 0.0002).CONCLUSIONSThe T1D GRS independently predicts progression to T1D and improves prediction along T1D stages in autoantibody-positive relatives.
  • Harjutsalo, Valma; Maric-Bilkan, Christine; Forsblom, Carol; Groop, Per-Henrik; FinnDiane Study Grp (2016)
    Aims/hypothesis The aim of this study was to evaluate the relationship among age at onset of diabetes, age at onset of menarche and risk of diabetic nephropathy and laser-treated retinopathy in type 1 diabetes. Methods Data related to age at menarche were collected through questionnaires and were available for 1,304 women who participated in the Finnish Diabetic Nephropathy Study (FinnDiane). A possible association between age at menarche and diabetic nephropathy and retinopathy was investigated. Results There was an inverse relationship between the age at onset of diabetes and age at menarche: the younger the age at onset of diabetes, the higher the age at menarche (p <0.0001). A non-linear relationship between the age of menarche and risk of diabetic microvascular complications was found in patients with diabetes onset before menarche, but there was no such association in patients with diabetes onset after menarche. Women with delayed menarche (> mean age+ 2 years) had a 2.30 (95% CI 1.27, 4.17; p <0.006) times higher risk of nephropathy compared with the women who underwent menarche at the mean age +/- 2 years. Delayed menarche also increased the risk of retinopathy (OR 2.34 [95% CI 1.36, 4.01]). After excluding patients with nephropathy, the OR for retinopathy was 2.11 (95% CI 1.15, 3.90). Earlier menarche (<mean age-2 years) did not have any effect on this risk. Conclusions/interpretation Delayed menarche was associated with an increased risk of diabetic nephropathy and retinopathy, whereas early menarche was not. Delayed menarche may be used as a new tool to identify women at risk of diabetic microvascular complications.
  • Honkamäki, Jasmin; Hisinger-Mölkänen, Hanna; Ilmarinen, Pinja; Piirilä, Päivi; Tuomisto, Leena E.; Andersen, Heidi; Huhtala, Heini; Sovijärvi, Anssi; Backman, Helena; Lundbäck, Bo; Rönmark, Eva; Lehtimäki, Lauri; Kankaanranta, Hannu (2019)
    Background: Asthma is currently divided into different phenotypes, with age at onset as a relevant differentiating factor. In addition, asthma with onset in adulthood seems to have a poorer prognosis, but studies investigating age-specific incidence of asthma with a wide age span are scarce. Objective: To evaluate incidence of asthma diagnosis at different ages and differences between child- and adult-diagnosed asthma in a large population-based study, with gender-specific analyzes included. Methods: In 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland. After two reminders, 4173 (52.3%) subjects responded. Incidence rate of asthma was retrospectively estimated based on the reported age of asthma onset. Adult-diagnosed asthma was defined as a physician-diagnosis of asthma made at >= 18 years of age. Results: Among those with physician-diagnosed asthma, altogether, 63.7% of subjects, 58.4% of men and 67.8% of women, reported adult-diagnosed asthma. Incidence of asthma diagnosis was calculated in 10-year age groups and it peaked in young boys (0-9 years) and middle-aged women (40-49 years) and the average incidence rate during the examined period between 1946 and 2015 was 2.2/1000/year. Adult-diagnosed asthma became the dominant phenotype among those with physician-diagnosed asthma by age of 50 years and 38 years in men and women, respectively. Conclusions: Asthma is mainly diagnosed during adulthood and the incidence of asthma diagnosis peaks in middle-aged women. Asthma diagnosed in adulthood should be considered more in clinical practice and management guidelines.
  • Piippo, Sonja; Viljanen, Mirva; Savilahti, Erkki; Kuitunen, Mikael (2020)
    Background The association between atopic sensitisation, atopic eczema (AE) and asthma is known, but distinct roles of allergies on long-term health are unestablished. Objective Evaluation of allergic symptoms and sensitisation in adolescents who in infancy had AE and verified cows' milk allergy (CMA) or AE and a negative CMA challenge, and controls. Methods Children with AE, with and without CMA, from a randomised controlled study in 1999-2001 examining the effect of probiotics on AE severity at older than 12 months of age, attended a follow-up visit at age 16 to 18, with age-matched controls. Data came from a questionnaire (ISAAC questionnaire), analysis of serum antigen-specific immunoglobulin Es (IgEs), and clinical evaluation. Group comparisons were carried out (chi(2)tests and logistic regression). Results Fifty-two patients with AE and CMA (AE/CMA+ group), 52 with AE and suspicion of CMA (AE/CMA- group), and 57 controls attended a study visit. IgE-mediated sensitisation was significantly more prevalent in the AE/CMA+ group vs the controls, for horse, cat, dog, egg white and wheat (P <.024 for all). For birch, timothy and mugwort (P <.008 for all), sensitisation was more prevalent in both the AE/CMA+ group and the AE/CMA- group vs controls. On the basis of questionnaire data the AE/CMA + group reported a significantly higher lifetime prevalence of wheezing (64% vs 35% and 32%;P = .001), noninfectious rhinitis (85% vs 62% and 56%;P = .004), and hay fever (77% vs 52% and 33%;P <.001) vs the AE/CMA- group and the control group, respectively. Conclusion and Clinical Relevance Patients with AE and CMA in infancy, as opposed to patients with AE only, or controls, report more allergic symptoms and exhibit more allergic sensitisation in adolescence. This indicates that CMA in infancy is an independent risk factor of allergic disease in adolescence.
  • Aghdassi, Ali A.; Schneider, Alexander; Kahl, Matthias; Schuette, Kerstin; Kuliaviene, Irma; Salacone, Paola; Lutz, Jon; Tukiainen, Eija; Simon, Peter; Schauer, Birgit; Uomo, Generoso; Hauge, Truls; Ceyhan, Gueralp O. (2017)
    Background & objectives: Chronic pancreatitis (CP) and liver cirrhosis (LC) are common gastroentero-logical disorders but their co-incidence is considered to be rare. This study was designed to identify lifestyle factors that are associated with the development of concomitant LC in patients with CP. Methods: In a retrospective case-control study between 2000 and 2005 122 patients with both CP and LC and 223 matched control patients with CP and no known liver disease were identified in 11 European university medical centers. Another 24 patients and 48 CP controls were identified in the period between 2006 and 2012. Results: Alcoholism was most commonly regarded as aetiology for both CP (82.2%; 95% confidence interval (CI): 75.0-88.0%) and LC (79.5%; 95% CI: 72.0-85.7%) as compared to controls with CP only (68.6%; 95% CI: 62.7-74.1%). The preferred type of alcoholic beverage and pattern of alcohol intake were the only significant lifestyle factors in multivariate analysis. Frequency of alcohol intake (p = 0.105) and smoking status (p = 0.099) were not significant in bivariate analysis and dropped out of the multivariate model. Recurrent and chronic pancreatic pain was observed more often in patients with only CP, whereas gallstones were more common in individuals with both chronic disorders. Conclusions: These findings indicate that certain lifestyle factors might be important for the development of concomitant CP and LC. More studies will be needed to identify additional genetic and environmental factors underlying this association. (C) 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.
  • Pohjola, Anni; Lehto, Hanna; Hafez, Ahmad; Oulasvirta, Elias; Koroknay-Pál, Päivi; Laakso, Aki (2018)
    BACKGROUND: Arteriovenous malformations (AVMs) of the posterior fossa are demanding lesions that often present with rupture. Studies including outcome analyses in surgically operated patients with ruptured infratentorial AVMs are scarce. Certain anatomic and demographic features have shown associations with postoperative outcomes. METHODS: Eighty-six patients with infratentorial AVM were collected from our AVM database. Fifty-four patients were admitted from 1990 onward, and their demographic, lesion, and treatment characteristics were analyzed. The cohort was further refined to 38 consecutive patients with surgically treated ruptured infratentorial AVM admitted to our center between 1990 and 2014, and statistical analyses of factors influencing outcomes were conducted. RESULTS: Twenty-seven patients (69%) had a favorable outcome at early follow-up and 24 (67%) had a favorable outcome at final follow-up. Factors associated with poor outcome in early recovery on univariate analyses were deep venous drainage of the lesion (odds ratio (OR 5.3; P = 0.037) and high Hunt & Hess score (P = 0.003). In the multivariate model, independent predictors for poor outcome were deep venous drainage (OR, 14.5; P = 0.010) and older age at admission (OR, 1.06; P = 0.028). The sole independent predictor for poor outcome at last follow-up was deep venous drainage (OR, 5.00; P = 0.046). The total follow-up time was 370 person-years. CONCLUSIONS: AVMs of the posterior fossa usually present with rupture and thus require prompt clinical treatment. The majority of surgically treated patients recover favorably. Our data show that venous drainage patterns have the greatest influence on the patient's postoperative condition. Other influencing factors include the severity of hemorrhage and patient age at admission.
  • Deneau, Mark R.; Valentino, Pamela L.; Mack, Cara; Alqoaer, Khaled; Amin, Mansi; Amir, Achiya Z.; Aumar, Madeleine; Auth, Marcus; Broderick, Annemarie; DiGuglielmo, Matthew; Draijer, Laura G.; El-Matary, Wael; Ferrari, Federica; Furuya, Katryn N.; Gottrand, Frederic; Gupta, Nitika; Homan, Matjaz; Jensen, M. K.; Kamath, Binita M.; Kim, Kyung Mo; Kolho, Kaija-Leena; Koot, Bart; Iorio, Raffaele; Martinez, Mercedes; Miloh, Tamir; Mohan, Parvathi; Palle, Sirish; Papadopoulou, Alexandra; Ricciuto, Amanda; Saubermann, Lawrence; Sathya, Pushpa; Shteyer, Eyal; Smolka, Vratislav; Tanaka, Atsushi; Varier, Raghu; Venkat, Veena; Vitola, Bernadette; Woynarowski, Marek; Guthery, Stephen (2020)
    Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. Methods: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. Results: Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. Conclusions: All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.
  • Kurtelius, Arttu; Väntti, Nelli; Jahromi, Behnam Rezai; Tähtinen, Olli; Manninen, Hannu; Koskenvuo, Juha; Tulamo, Riikka; Kotikoski, Satu; Nurmonen, Heidi; Kämäräinen, Olli-Pekka; Huttunen, Terhi; Huttunen, Jukka; Fraunberg, Mikael von Und Zu; Koivisto, Timo; Jääskeläinen, Juha E.; Lindgren, Antti E. (2019)
    Background-Varying degrees of co-occurrence of intracranial aneurysms (IA) and aortic aneurysms (AA) have been reported. We sought to compare the risk for AA in fusiform intracranial aneurysms (fIA) and saccular intracranial aneurysms (sIA) disease and evaluate possible genetic connection between the fIA disease and AAs. Additionally, the characteristics and aneurysms of the fIA and sIA patients were compared. Methods and Results-The Kuopio Intracranial Aneurysm Database includes all 4253 sIA and 125 fIA patients from its Eastern Finnish catchment population, and 13 009 matched population controls and 18 455 first-degree relatives to the IA patients were identified, and the Finnish national registers were used to identify the individuals with AA. A total of 33 fIA patients were studied using an exomic gene panel of 37 genes associated with AAs. Seventeen (14.4%) fIA patients and 48 (1.2%) sIA patients had a diagnosis of AA. Both fIA and sIA patients had AAs significantly more often than their controls (1.2% and 0.5%) or relatives (0.9% and 0.3%). In a competing risks Cox regression model, the presence of fIA was the strongest risk factor for AA (subdistribution hazard ratio 7.6, 95% CI 3.9-14.9, P Conclusions-The prevalence of AAs is increased slightly in sIA patients and significantly in fIA patients. fIA patients are older and have more comorbid diseases than sIA patients but this alone does not explain their clinically significant AA risk.
  • Honkamäki, Jasmin; Piirilä, Päivi; Hisinger-Mölkänen, Hanna; Tuomisto, Leena E.; Andersen, Heidi; Huhtala, Heini; Sovijärvi, Anssi; Lindqvist, Ari; Backman, Helena; Lundbäck, Bo; Rönmark, Eva; Lehtimäki, Lauri; Pallasaho, Paula; Ilmarinen, Pinja; Kankaanranta, Hannu (2021)
    BACKGROUND: Child-onset asthma is known to remit with high probability, but remission in adult-onset asthma is seem-ingly less frequent. Reports of the association between remission and asthma age of onset up to late adulthood are scarce. OBJECTIVE: To evaluate the association between asthma remission, age at diagnosis and gender, and assess risk factors of nonremission. METHODS: In 2016, a random sample of 16,000 subjects aged 20 to 69 years from Helsinki and Western Finland were sent a FinEsS questionnaire. Physician-diagnosed asthma was catego-rized by age at diagnosis to early-(0-11 years), intermediate-(12-39 years), and late-diagnosed (40-69 years) asthma. Asthma remission was defined by not having had asthma symptoms and not having used asthma medication in the past 12 months. RESULTS: Totally, 8199 (51.5%) responded, and 879 reported physician-diagnosed asthma. Remission was most common in early-diagnosed (30.2%), followed by intermediate-diagnosed (17.9%), and least common in late-diagnosed asthma (5.0%) (P < .001), and the median times from diagnosis were 27, 18.5, and 10 years, respectively. In males, the corresponding remission rates were 36.7%, 20.0%, and 3.4%, and in females, 20.4%, 16.6%, and 5.9% (gender difference P < .001). In multivariable binary logistic regression analysis, signifi-cant risk factors of asthma nonremission were intermediate (odds ratio [OR] = 2.15, 95% confidence interval: 1.373.36) and late diagnosis (OR = 11.06, 4.82-25.37) compared with early diagnosis, chronic obstructive pulmonary disease (COPD) (OR = 5.56, 1.26-24.49), allergic rhinitis (OR = 2.28, 1.50-3.46), and family history of asthma (OR = 1.86, 1.22-2.85). Results were similar after excluding COPD. CONCLUSION: Remission was rare in adults diagnosed with asthma after age 40 years in both genders. Late-diagnosed asthma was the most significant independent risk factor for nonremission. (C) 2020 American Academy of Allergy, Asthma & Immunology
  • Tantiyavarong, Pichaya; Kramer, Anneke; Heaf, James G.; Finne, Patrik; Asberg, Anders; Cases, Aleix; Caskey, Fergus J.; Massy, Ziad A.; Jager, Kitty J.; Noordzij, Marlies (2020)
    Background. Kidney transplantation should improve abnormalities that are common during dialysis treatment, like anaemia and mineral and bone disorder. However, its impact is incompletely understood. We therefore aimed to assess changes in clinical indicators after the transition from chronic dialysis to kidney transplantation. Methods. We used European Renal Association-European Dialysis and Transplant Association Registry data and included adult dialysis patients for whom data on clinical indicators before and after transplantation (2005-15) were available. Linear mixed models were used to quantify the effect of transplantation and of time after transplantation for each indicator. Results. In total, 16 312 patients were included. The mean age at transplantation was 50.1 (standard deviation 14.2) years, 62.9% were male and 70.2% were on haemodialysis before transplantation. Total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglycerides increased right after transplantation but decreased thereafter. All other indicators normalized or approached the target range soon after transplantation and these improvements were sustained for the first 4 years of follow-up. In patients with higher estimated glomerular filtration rate (eGFR) levels (30-60 and >60 mL/min/1.73 m(2)), the improvement of haemoglobin, ferritin, ionized calcium, phosphate, parathyroid hormone, HDL cholesterol, triglycerides, albumin and C-reactive protein levels was more pronounced than in patients with a lower eGFR ( Conclusions. Except for total cholesterol, LDL cholesterol and triglycerides, all clinical indicators improved after transplantation. These improvements were related to eGFR. Nevertheless, values remained out of range in a considerable proportion of patients and anaemia and hyperparathyroidism were still common problems. Further research is needed to understand the complex relationship between eGFR and the different clinical indicators.
  • Pollanen, Petra M.; Lempainen, Johanna; Laine, Antti-Pekka; Toppari, Jorma; Veijola, Riitta; Vahasalo, Paula; Ilonen, Jorma; Siljander, Heli; Knip, Mikael (2017)
    Aims/hypothesis In this study, we aimed to characterise rapid progressors to type 1 diabetes among children recruited from the general population, on the basis of HLA-conferred disease susceptibility. Methods We monitored 7410 HLA-predisposed children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study for the development of beta cell autoimmunity and type 1 diabetes from birth over a median follow-up time of 16.2 years (range 0.9-21.1 years). Islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD (GADA) and islet antigen 2 (IA-2A) were assessed as markers of beta cell autoimmunity. Rapid progression was defined as progression to clinical type 1 diabetes within 1.5 years of autoantibody seroconversion. We analysed the association between rapid progression and demographic and autoantibody characteristics as well as genetic markers, including 25 non-HLA SNPs predisposing to type 1 diabetes. Results Altogether, 1550 children (21%) tested positive for at least one diabetes-associated autoantibody in at least two samples, and 248 (16%) of seroconverters progressed to type 1 diabetes by the end of 2015. The median time from seroconversion to diagnosis was 0.51 years in rapid progressors (n = 42, 17%) and 5.4 years in slower progressors. Rapid progression was observed both among young (<5 years) and early pubertal children (> 7 years), resulting in a double-peak distribution of seroconversion age. Compared with slower progressors, rapid progressors had a higher frequency of positivity for multiple (>= 2) autoantibodies and had higher titres of ICA, IAA and IA-2A at seroconversion, and there was a higher prevalence of the secretor genotype in the FUT2 gene among those carrying the high-risk HLA genotype. Compared with autoantibody-positive non-progressors, rapid progressors were younger, were more likely to carry the high-risk HLA genotype and a predisposing SNP in the PTPN22 gene, had higher frequency of ICA, IAA, GADA and IA-2A positivity and multipositivity, and had higher titres of all four autoantibodies at seroconversion. Conclusions/interpretation At seroconversion, individuals with rapid progression to type 1 diabetes were characterised by a younger age, higher autoantibody titres, positivity for multiple autoantibodies and higher prevalence of a FUT2 SNP. The double-peak profile for seroconversion age among the rapid progressors demonstrates for the first time that rapid progression may take place not only in young children but also in children in early puberty. Rapid progressors might benefit from careful clinical follow-up and early preventive measures.
  • Seppänen, H.; Puolakkainen, P. (2020)
    Background: Acute pancreatitis is a common disease, the incidence of which is 75-100/100,000/year in Finland. The worldwide incidence of acute pancreatitis is increasing. The identified mildcases usually show rapid recovery with conservative treatment allowing early discharge. Severe cases need early intensive care to reduce the risk of serious complications such as multi-organ failure. The revised Atlanta classification of acute pancreatitis was introduced in 2012-2013. A recurrent acute pancreatitis is defined as two or more well-documented separate attacks of acute pancreatitis with complete resolution in between. Alcoholic pancreatitis is the most common recurrent acute pancreatitis type. Methods: In this review current severity classifications and literature on the prevention of recurrent acute pancreatitis are analyzed. Results: The severity of the disease is classified as mild, moderately severe, and severe acute pancreatitis. Novel entities include acute peripancreatic fluid collections in mild acute pancreatitis and acute necrotic collections in necrotizing acute pancreatitis lesser than 4 weeks after the onset and pancreatic pseudocyst in mild acute pancreatitis and walled-off necrosis in necrotizing acute pancreatitis more than 4 weeks after the onset of the disease. After the first attack of alcohol-induced acute pancreatitis, 46% of the patients develop at least one recurrence within 10- to 20-year follow-up. With repeated intervention against alcohol consumption, it is possible to reduce the recurrences. Removing the gall bladder after biliary pancreatitis is the key preventing recurrences. In mild cases, even during the index admission; in severe cases, it is recommended to wait until the inflammatory changes have resolved. Of total, 59% of the idiopathic pancreatitis had sludge of stones in the gall bladder. In other etiologies, addressing the etiological factor may prevent recurrent acute pancreatitis. Conclusions: This review describes current use of novel severity classifications and also different possibilities to prevent recurrent acute pancreatitis with different etiologies including idiopathic.
  • Tainio, Karoliina; Athanasiou, Antonios; Tikkinen, Kari A. O.; Aaltonen, Riikka; Cardenas Hernandes, Jovita; Glazer-Livson, Sivan; Jakobsson, Maija; Joronen, Kirsi; Kiviharju, Mari; Louvanto, Karolina; Oksjoki, Sanna; Tähtinen, Riikka; Virtanen, Seppo; Nieminen, Pekka; Kyrgiou, Maria; Kalliala, Ilkka (2018)
    OBJECTIVE To estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as compliance with follow-up protocols. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1 January 1973 to 20 August 2016. ELIGIBILITY CRITERIA Studies reporting on outcomes of histologically confirmed CIN2 in non-pregnant women, managed conservatively for three or more months. DATA SYNTHESIS Two reviewers extracted data and assessed risk of bias. Random effects model was used to calculate pooled proportions for each outcome, and heterogeneity was assessed using I-2 statistics. MAIN OUTCOME MEASURES Rates of regression, persistence, or progression of CIN2 and default rates at different follow-up time points (3, 6, 12, 24, 36, and 60 months). RESULTS 36 studies that included 3160 women were identified (seven randomised trials, 16 prospective cohorts, and 13 retrospective cohorts; 50% of the studies were at low risk of bias). At 24 months, the pooled rates were 50% (11 studies, 819/1470 women, 95% confidence interval 43% to 57%; I-2= 77%) for regression, 32% (eight studies, 334/1257 women, 23% to 42%; I-2= 82%) for persistence, and 18% (nine studies, 282/1445 women, 11% to 27%; I-2= 90%) for progression. In a subgroup analysis including 1069 women aged less than 30 years, the rates were 60% (four studies, 638/1069 women, 57% to 63%; I-2= 0%), 23% (two studies, 226/938 women, 20% to 26%; I-2= 97%), and 11% (three studies, 163/1033 women, 5% to 19%; I-2= 67%), respectively. The rate of non-compliance (at six to 24 months of follow-up) in prospective studies was around 10%. CONCLUSIONS Most CIN2 lesions, particularly in young women (<30 years), regress spontaneously. Active surveillance, rather than immediate intervention, is therefore justified, especially among young women who are likely to adhere to monitoring.
  • Mammola, Stefano; Lunghi, Enrico; Bilandžija, Helena; Cardoso, Pedro; Grimm, Volker; Schmidt, Susanne I.; Hesselberg, Thomas; Martinez, Alejandro (2021)
    Caves and other subterranean habitats fulfill the requirements of experimental model systems to address general questions in ecology and evolution. Yet, the harsh working conditions of these environments and the uniqueness of the subterranean organisms have challenged most attempts to pursuit standardized research. Two main obstacles have synergistically hampered previous attempts. First, there is a habitat impediment related to the objective difficulties of exploring subterranean habitats and our inability to access the network of fissures that represents the elective habitat for the so-called "cave species." Second, there is a biological impediment illustrated by the rarity of most subterranean species and their low physiological tolerance, often limiting sample size and complicating laboratory experiments. We explore the advantages and disadvantages of four general experimental setups (in situ, quasi in situ, ex situ, and in silico) in the light of habitat and biological impediments. We also discuss the potential of indirect approaches to research. Furthermore, using bibliometric data, we provide a quantitative overview of the model organisms that scientists have exploited in the study of subterranean life. Our over-arching goal is to promote caves as model systems where one can perform standardized scientific research. This is important not only to achieve an in-depth understanding of the functioning of subterranean ecosystems but also to fully exploit their long-discussed potential in addressing general scientific questions with implications beyond the boundaries of this discipline.
  • Huhtakangas, Justiina; Lehecka, Martin; Lehto, Hanna; Jahromi, Behnam Rezai; Niemela, Mika; Kivisaari, Riku (2017)
    Posterior communicating artery (PcomA) aneurysms are frequently encountered, but there are few publications on their morphology. A growing number of aneurysms are incidental findings, which makes evaluation of rupture risk important. Our goal was to identify morphological features and anatomical variants associated with PComA aneurysms and to assess parameters related to rupture. We studied CT angiographies of 391 consecutive patients treated between 2000 and 2014 at a single institution. We determined clinically important morphological parameters and performed univariate and multivariate analysis. There were a total of 413 PComA aneurysms: 258 (62%) were ruptured and 155 (38%) unruptured. Ruptured PComA aneurysms had the potential to cause severe bleeding with IVH and/or temporal ICH (n = 170, 66% of ruptured). The main types of PComA origin were classified as follows: (1) separate (32%), (2) side by side (21%) and (3) a joint neck with the aneurysm (6%). After the multivariate logistic regression, the morphological parameters related to PComA aneurysm rupture were an irregular aneurysm dome, neck diameter, and aspect ratio > 1.5. The most marked morphological features of the PComA aneurysms were: saccular nature (99%), infero-posterior dome orientation (42%), infrequency of large or giant aneurysms (4%), narrow neck compared to the aneurysm size, PComA originating directly from the aneurysm neck or the dome (28%), and fetal or dominant PComA on the side of the aneurysm (35%). There were location-related parameters that were more strongly associated with PComA aneurysm rupture than aneurysm size: an irregular aneurysm dome, larger diameter of the aneurysm neck and aspect ratio > 1.5.
  • Unruptured Aneurysms SAH CDE; Hackenberg, Katharina A. M.; Algra, Ale; Salman, Rustam Al-Shahi; Frosen, Juhana; Hasan, David; Juvela, Seppo; Langer, David; Meyers, Philip; Morita, Akio (2019)
    IntroductionVariability in usage and definition of data characteristics in previous cohort studies on unruptured intracranial aneurysms (UIA) complicated pooling and proper interpretation of these data. The aim of the National Institute of Health/National Institute of Neurological Disorders and Stroke UIA and Subarachnoid Hemorrhage (SAH) Common Data Elements (CDE) Project was to provide a common structure for data collection in future research on UIA and SAH.MethodsThis paper describes the development and summarization of the recommendations of the working groups (WGs) on UIAs, which consisted of an international and multidisciplinary panel of cerebrovascular specialists on research and treatment of UIAs. Consensus recommendations were developed by review of previously published CDEs for other neurological diseases and the literature on UIAs. Recommendations for CDEs were classified by priority into Core,' SupplementalHighly Recommended,' Supplemental,' and Exploratory.'ResultsNinety-one CDEs were compiled; 69 were newly created and 22 were existing CDEs. The CDEs were assigned to eight subcategories and were classified as Core (8), SupplementalHighly Recommended (23), Supplemental (25), and Exploratory (35) elements. Additionally, the WG developed and agreed on a classification for aneurysm morphology.ConclusionThe proposed CDEs have been distilled from a broad pool of characteristics, measures, or outcomes. The usage of these CDEs will facilitate pooling of data from cohort studies or clinical trials on patients with UIAs.
  • Lammi, Anne; Arikoski, Pekka; Hakulinen, Arja; Schwab, Ursula; Uusitupa, Matti; Heinonen, Seppo; Savilahti, Erkki; Kinnunen, Tuure; Ilonen, Jorma (2016)
    Objective. The development of gliadin-specific antibody and T-cell responses were longitudinally monitored in young children with genetic risk for celiac disease (CD). Material and methods. 291 newborn children positive for HLA-DQB1*02 and -DQA1*05 alleles were followed until 3-4 years of age by screening for tissue transglutaminase autoantibodies (tTGA) by using a commercial ELISA-based kit and antibodies to deamidated gliadin peptide (anti-DGP) by an immunofluorometric assay. Eighty-five of the children were also followed for peripheral blood gliadin-specific CD4(+) T-cell responses by using a carboxyfluorescein diacetate succinimidyl ester-based in vitro proliferation assay. Results. The cumulative incidence of tTGA seropositivity during the follow-up was 6.5%. CD was diagnosed in nine of the tTGA-positive children (3.1%) by duodenal biopsy at a median 3.5 years of age. All of the children with confirmed CD were both IgA and IgG anti-DGP positive at the time of tTGA seroconversion and in over half of the cases IgG anti-DGP positivity even preceded tTGA seroconversion. Peripheral blood T-cell responses to deamidated and native gliadin were detected in 40.5% and 22.2% of the children at the age of 9 months and these frequencies decreased during the follow-up to the levels of 22.2% and 8.9%, respectively. Conclusions. Anti-DGP antibodies may precede tTGA seroconversion and thus frequent monitoring of both tTGA and anti-DGP antibodies may allow earlier detection of CD in genetically susceptible children. Peripheral blood gliadin-specific T-cell responses are relatively common in HLA-DQ2-positive children and are not directly associated with the development of CD.