Browsing by Subject "3123 Gynaecology and paediatrics"

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  • Petry, K. Ulrich; Nieminen, Pekka J.; Leeson, Simon C.; Bergeron, Christine O.M.A.; Redman, Charles W.E. (2018)
    A refinement of quality indicators (Qls) is described whereby the quality of care can be measured across colposcopy services in different countries and healthcare settings. A five-round Delphi process was conducted at successive satellite meetings from 2011 to 2015 of leading European colposcopists to refine the most high-scoring Qls relevant to colposcopic practice. A review and refinement of the wording of the standards and their criteria was undertaken by national society representatives. Six quality indicators were identified and refined. "Documentation of whether the squamocolumnar junction (SCJ) has been visible or not" was changed into "for cervical colposcopy transformation zone (TZ) type (1, 2 or 3) should be documented". The standard "percentage of cases having a colposcopic examination prior to treatment for abnormal cytology" was changed to "percentage of cases having a colposcopic examination prior to treatment for abnormal cervical screening test". The standard "percentage of all excisional treatments/conizations containing CIN2+ (cervical intra-epithelial neoplasia grade two or worse)" was changed into "percentage of excisional treatments/conizations having a definitive histology of CIN2+. Definitive histology is highest grade from any diagnostic or therapeutic biopsies". The standard "percentage of excised lesions/conizations with clear margins" was unchanged. The remaining two Qls define the minimum caseloads required for colposcopists. However, "cytology" was replaced by "screening results"to acknowledge the introduction of human papillomavirus testing to European screening programmes. Six Qls were identified to define good practice in colposcopy. (C) 2018 The Authors. Published by Elsevier B.V.
  • Tuomilehto, Noora; Sommarhem, Antti; Nietosvaara, Aarno Y. (2018)
    Background and purpose - The long-term outcome of pin-fixed supracondylar humerus fractures (SCHF) in children is not well known. We assessed the 7- to 12-year outcome in 168 children. Patients and methods - During 2002-2006, 210 domestic children (age 7 (1-14) years) with SCHF (Gartland III 79%, Gartland II 19%, and flexion type 2%) were pin fixed in Helsinki. 36 (17%) patients had a nerve palsy. Radiographic alignment was regarded as satisfactory in 81% of patients (Baumann angle (BA) within 10 of normal range and whose anterior humeral line (AHL) crossed the capitulum). After a mean follow-up of 9 (7-12) years, 168 (80%) patients answered a questionnaire regarding elbow appearance (scale 0-10), function (scale 0-10), and pain (scale 0-10), and symmetry of range of motion (ROM) and carrying angle (CA). 65 (31%) patients also attended a clinical follow-up examination. Results - Mean subjective score for appearance was 8.7 (2-10) and for function 9.0 (2-10) (n = 168). Elbow ROM asymmetry was experienced by 28% and elbow CA asymmetry by 17% of the patients. Elbow pain was reported by 14%, and was more common in children with nerve injuries. Long-term outcome was good or excellent in 60/65 and CA in 56/65 of the follow-up visit patients using Flynn's criteria. BA exceeding normal values by 10 was associated with lower subjective outcome; AHL crossing point with the capitulum was not associated with outcome. Interpretation - Long-term subjective outcome is satisfactory with few exceptions if elbow ROM and CA are restored within 10 degrees of the uninjured elbow. Radiographs at fracture union have little prognostic value. Nerve injuries can cause long-term pain.
  • Chin, Mathieu; Leppanen, Mari; Kulmala, Juha-Pekka; Vasankari, Tommi; Parkkari, Jari; Pasanen, Kati (2021)
    Lateral ankle sprains are highly prevalent during sporting activities, as it accounts for approximately 60% of all athletic injuries. There is currently a paucity of research which provides kinetic and kinematic assessments of sprains and giving-way episodes of the ankle joint. The aim of this case study was to examine the kinetics and kinematics of the ankle and knee during a giving-way episode in a female ice hockey player during a 180-degree pivot turn, which was conducted in a 3D motion capture laboratory. Three trials were conducted on this participant (one accident trial, two control trials). Kinetic and kinematic analysis was conducted on the outside leg during a left 180-degree pivot turn (right leg). The plantarflexion angle of the giving-way trial was larger than the control trials from the point of initial contact until the end of the trial. Inversion was also 27-degrees greater 150 ms after initial contact in the giving-way trial and 26-degrees greater compared to control trials 1 and 2. Substantially greater plantarflexion, inversion and internal rotation angles of the ankle were observed during the giving-way trial compared to control trials. The maximum vertical and horizontal ground reaction forces, as well as ankle inversion and internal rotation moments, were lower for the giving-way trial in comparison to the control trials. Further research is needed to understand the influence of plantarflexion angle with a giving-way episode of the ankle. This study provides valuable kinetic and kinematic information regarding a giving-way episode of the ankle. (c) 2021 Elsevier Ltd. All rights reserved.
  • Tammiste, Triin; Kask, Keiu; Padrik, Peeter; Idla, Kulli; Rosenstein, Karin; Jatsenko, Tatjana; Veerus, Piret; Salumets, Andres (2019)
    BackgroundOvarian insufficiency is a major concern for long-term cancer survivors. Although semen freezing is well established to preserve male fertility, the possibilities to secure post-cancer female fertility are mostly limited to oocyte or embryo freezing. These methods require time-consuming ovarian stimulation with or without in vitro fertilization (IVF) that evidently delays cancer therapy. Ovarian tissue cryopreservation and subsequent thawed tissue autotransplantation are considered the most promising alternative strategy for restoring the fertility of oncology patients, which has not yet received the full clinical acceptance. Therefore, all successful cases are needed to prove its reliability and safety.Case presentationHere we report a single case in Estonia, where a 28-year-old woman with malignant breast neoplasm had ovarian cortex cryopreserved before commencing gonadotoxic chemo- and radiotherapy. Two years after cancer therapy, the patient underwent heterotopic ovarian tissue transplantation into the lateral pelvic wall. The folliculogenesis was stimulated in the transplanted tissue by exogenous follicle-stimulating hormone and oocytes were collected under ultrasound guidance for IVF and embryo transfer. The healthy boy was born after full-term gestation in 2014, first in Eastern Europe.ConclusionDespite many countries have reported the first implementation of the ovarian tissue freezing and transplantation protocols, the data is still limited on the effectiveness of heterotopic ovarian transplant techniques. Thus, all case reports of heterotopic ovarian tissue transplantation and long-term follow-ups to describe the children's health are valuable source of clinical experience.
  • GEMO Study Collaborators; EMBRACE Collaborators; kConFab Investigators; HEBON Investigators; ABCTB Investigators; Coignard, Juliette; Lush, Michael; Beesley, Jonathan; Blomqvist, Carl; Kiiski, Johanna I.; Nevanlinna, Heli (2021)
    Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P
  • Saavalainen, Liisu; Lassus, Heini; But, Anna; Tiitinen, Aila; Harkki, Paivi; Gissier, Mika; Pukkala, Eero; Heikinheimo, Oskari (2019)
    Introduction The association between endometriosis and breast cancer is unclear. We assessed the risk of breast cancer in women with surgically verified endometriosis, with special focus on the age at cancer diagnosis, time from endometriosis diagnosis and breast cancer histology. Material and methods All women with first endometriosis-associated diagnoses occurring concomitantly with relevant surgical codes during 1987-2012 were retrieved from the Finnish Hospital Discharge Register in Finland. Breast cancers diagnosed after the endometriosis diagnosis were identified from the Finnish Cancer Registry. The Finnish female population served as the reference. The endometriosis cohort consisted of 49 933 women (23 210 cases of ovarian, 20 187 peritoneal and 2372 deep infiltrating endometriosis). The outcome measure was the standardized incidence ratio (SIR) with 95% confidence interval (95% CI) of breast cancer calculated for the whole cohort and for the subtypes of endometriosis, stratified by the age at breast cancer diagnosis, histology and time from endometriosis diagnosis. Results The overall risk of breast cancer (1555 cases) was similar to the reference population (SIR 0.99; 95% CI 0.94-1.03), did not differ in types of endometriosis, and was similar for ductal and lobular breast cancer. However, the SIR of breast cancer was increased in the age group of 20-29 years (SIR 4.44; 95% CI 2.22-7.94) and in the age group of 30-39 years (SIR 1.28; 95% CI 1.03-1.57). The risk of in situ breast cancer (170 cases) was increased in the entire endometriosis cohort (SIR 1.25; 95% CI 1.07-1.44). Conclusions The overall risk of breast cancer in women with surgically verified endometriosis was similar to that of general population. However, the risk of breast cancer at young age was increased. Young women with surgically verified endometriosis represent highly symptomatic patients with more frequent surgeries and additional therapies that might also contribute to the risk of breast cancer.
  • Toijonen, Anna E.; Heinonen, Seppo T.; Gissler, Mika V. M.; Macharey, Georg (2020)
    Purpose To determine if the common risks for breech presentation at term labor are also eligible in preterm labor. Methods A Finnish cross-sectional study included 737,788 singleton births (24-42 gestational weeks) during 2004-2014. A multivariable logistic regression analysis was used to calculate the risks of breech presentation. Results The incidence of breech presentation at delivery decreased from 23.5% in pregnancy weeks 24-27 to 2.5% in term pregnancies. In gestational weeks 24-27, preterm premature rupture of membranes was associated with breech presentation. In 28-31 gestational weeks, breech presentation was associated with maternal pre-eclampsia/hypertension, preterm premature rupture of membranes, and fetal birth weight below the tenth percentile. In gestational weeks 32-36, the risks were advanced maternal age, nulliparity, previous cesarean section, preterm premature rupture of membranes, oligohydramnios, birth weight below the tenth percentile, female sex, and congenital anomaly. In term pregnancies, breech presentation was associated with advanced maternal age, nulliparity, maternal hypothyroidism, pre-gestational diabetes, placenta praevia, premature rupture of membranes, oligohydramnios, congenital anomaly, female sex, and birth weight below the tenth percentile. Conclusion Breech presentation in preterm labor is associated with obstetric risk factors compared to cephalic presentation. These risks decrease linearly with the gestational age. In moderate to late preterm delivery, breech presentation is a high-risk state and some obstetric risk factors are yet visible in early preterm delivery. Breech presentation in extremely preterm deliveries has, with the exception of preterm premature rupture of membranes, similar clinical risk profiles as in cephalic presentation.
  • Rafiq, Sajjad; Khan, Sofia; Tapper, William; Collins, Andrew; Upstill-Goddard, Rosanna; Gerty, Susan; Blomqvist, Carl; Aittomaki, Kristiina; Couch, Fergus J.; Liu, Jianjun; Nevanlinna, Heli; Eccles, Diana (2014)
  • Perälä, Mia-Maria; von Bonsdorff, Mikaela; Männistö, Satu; Salonen, Minna; Simonen, Mika; Kanerva, Noora Karoliina; Pohjolainen, Pertti; Kajantie, Eero Olavi; Rantanen, Taina; Eriksson, Johan Gunnar (2016)
    Epidemiological studies have shown that a number of nutrients are associated with better physical performance. However, little is still known about the role of the whole diet, particularly a healthy Nordic diet, in relation to physical performance. Therefore, we examined whether a healthy Nordic diet was associated with measures of physical performance 10 years later. We studied 1072 participants from the Helsinki Birth Cohort Study. Participants' diet was assessed using a validated 128-item FFQ at the mean age of 61 years, and a priori-defined Nordic diet score (NDS) was calculated. The score included Nordic fruits and berries, vegetables, cereals, PUFA:SFA and trans-fatty acids ratio, low-fat milk, fish, red and processed meat, total fat and alcohol. At the mean age of 71 years, participants' physical performance was measured using the Senior Fitness Test (SFT), and an overall SFT score was calculated. Women in the highest fourth of the NDS had on average 5 points higher SFT score compared with those in the lowest fourth (P-for trend 0.005). No such association was observed in men. Women with the highest score had 17% better result in the 6-min walk test, 16% better arm curl and 20% better chair stand results compared with those with the lowest score (all P values <0.01). In conclusion, a healthy Nordic diet was associated with better overall physical performance among women and might help decrease the risk of disability in old age.
  • Rosendahl, Jenni; Fogelholm, Mikael; Pelkonen, Anna; Makela, Mika J.; Makitie, Outi; Erkkola, Maijaliisa (2017)
    Background/Aims: Vitamin D insufficiency is common in children. We aimed to evaluate the main determinants of vitamin D status in Finnish school-aged children, including the history of allergic diseases. Methods: We conducted a cross-sectional study on 171 ten-year-olds where serum 25-hydroxyvitamin D (25[OH] D) levels were measured, and data on food consumption and use of vitamin D supplements were collected. The history of allergic diseases was evaluated with a validated questionnaire. Results: Vitamin D insufficiency (
  • Syrjälä, Essi; Nevalainen, Jaakko; Peltonen, Jaakko; Takkinen, Hanna-Mari; Hakola, Leena; Åkerlund, Mari; Veijola, Riitta; Ilonen, Jorma; Toppari, Jorma; Knip, Mikael; Virtanen, Suvi M. (2019)
    Several dietary factors have been suspected to play a role in the development of advanced islet autoimmunity (IA) and/or type 1 diabetes (T1D), but the evidence is fragmentary. A prospective population-based cohort of 6081 Finnish newborn infants with HLA-DQB1-conferred susceptibility to T1D was followed up to 15 years of age. Diabetes-associated autoantibodies and diet were assessed at 3-to 12-month intervals. We aimed to study the association between consumption of selected foods and the development of advanced IA longitudinally with Cox regression models (CRM), basic joint models (JM) and joint latent class mixed models (JLCMM). The associations of these foods to T1D risk were also studied to investigate consistency between alternative endpoints. The JM showed a marginal association between meat consumption and advanced IA: the hazard ratio adjusted for selected confounding factors was 1.06 (95% CI: 1.00, 1.12). The JLCMM identified two classes in the consumption trajectories of fish and a marginal protective association for high consumers compared to low consumers: the adjusted hazard ratio was 0.68 (0.44, 1.05). Similar findings were obtained for T1D risk with adjusted hazard ratios of 1.13 (1.02, 1.24) for meat and 0.45 (0.23, 0.86) for fish consumption. Estimates from the CRMs were closer to unity and CIs were narrower compared to the JMs. Findings indicate that intake of meat might be directly and fish inversely associated with the development of advanced IA and T1D, and that disease hazards in longitudinal nutritional epidemiology are more appropriately modeled by joint models than with naive approaches.
  • Salminen, Liina; Nadeem, Nimrah; Jain, Shruti; Grènman, Seija; Carpén, Olli; Hietanen, Sakari; Oksa, Sinikka; Lamminmäki, Urpo; Pettersson, Kim; Gidwani, Kamlesh; Huhtinen, Kaisa; Hynninen, Johanna (2020)
    Objective. Cancer antigen 125 (CM 25) is generally considered the gold standard of biomarkers in the diagnosis and monitoring of high grade serous ovarian carcinoma (HGSC). We recently reported, that two CM 25 glycoforms (CA125-STn and CA125-MGL) have a high specificity to HGSC and further hypothesized, that these cancer specific glycoforms are feasible candidates as biomarkers in HGSC treatment and follow up. Methods. Our cohort consisted of 122 patients diagnosed with HGSC. Serum samples were collected longitudinally at the time of diagnosis, during treatment and follow up. Serum levels of CA125, CM 25-STn and CA125MGL were determined and compared or correlated with different end points (tumor load assessed intraoperatively, residual disease, treatment response, progression free survival). Results. Serum CA125-STn levels at diagnosis differentiated patients with low tumor load and high tumor load (p = 0,030), indicating a favorable detection of tumor volume. Similarly, the CA125-STn levels at diagnosis were significantly lower in patients with subsequent complete cytoreduction than in patients with suboptimal cytoreduction (p = 0,025). Conventional CA125 did not differentiate these patients (p = 0,363 and p = 0,154). The CA125-STn nadir value predicted the progression free survival of patients. The detection of disease relapse was improved with CA125-STn, which presented higher fold increase in 80,0% of patients and earlier increase in 37,0% of patients. Conclusions. CA125-STn showed promise as a useful biomarker in the monitoring and follow up of patients with HGSC utilizing a robust and affordable technique. Our findings are topical as a suitable indicator of tumor load facilitates patient selection in an era of new targeted therapies. (C) 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://
  • Lonnrot, Maria; Lynch, Kristian; Larsson, Helena Elding; Lernmark, Ake; Rewers, Marian; Hagopian, William; She, Jin-Xiong; Simell, Olli; Ziegler, Anette-G; Akolkar, Beena; Krischer, Jeffrey; Hyoty, Heikki; TEDDY Study Grp; Knip, Mikael (2015)
    Background: Early childhood environmental exposures, possibly infections, may be responsible for triggering islet autoimmunity and progression to type 1 diabetes (T1D). The Environmental Determinants of Diabetes in the Young (TEDDY) follows children with increased HLA-related genetic risk for future T1D. TEDDY asks parents to prospectively record the child's infections using a diary book. The present paper shows how these large amounts of partially structured data were reduced into quantitative data-sets and further categorized into system-specific infectious disease episodes. The numbers and frequencies of acute infections and infectious episodes are shown. Methods: Study subjects (n = 3463) included children who had attended study visits every three months from age 3 months to 4 years, without missing two or more consecutive visits during the follow-up. Parents recorded illnesses prospectively in a TEDDY Book at home. The data were entered into the study database during study visits using ICD-10 codes by a research nurse. TEDDY investigators grouped ICD-10 codes and fever reports into infectious disease entities and further arranged them into four main categories of infectious episodes: respiratory, gastrointestinal, other, and unknown febrile episodes. Incidence rate of infections was modeled as function of gender, HLA-DQ genetic risk group and study center using the Poisson regression. Results: A total of 113,884 ICD-10 code reports for infectious diseases recorded in the database were reduced to 71,578 infectious episodes, including 74.0% respiratory, 13.1% gastrointestinal, 5.7% other infectious episodes and 7.2% febrile episodes. Respiratory and gastrointestinal infectious episodes were more frequent during winter. Infectious episode rates peaked at 6 months and began declining after 18 months of age. The overall infectious episode rate was 5.2 episodes per person-year and varied significantly by country of residence, sex and HLA genotype. Conclusions: The data reduction and categorization process developed by TEDDY enables analysis of single infectious agents as well as larger arrays of infectious agents or clinical disease entities. The preliminary descriptive analyses of the incidence of infections among TEDDY participants younger than 4 years fits well with general knowledge of infectious disease epidemiology. This protocol can be used as a template in forthcoming time-dependent TEDDY analyses and in other epidemiological studies.
  • Saare, Merli; Laisk, Triin; Teder, Hindrek; Paluoja, Priit; Palta, Priit; Koel, Mariann; Kirss, Fred; Karro, Helle; Soritsa, Deniss; Salumets, Andres; Krjutskov, Kaarel; Peters, Maire (2019)
  • Hague, William M.; Callaway, Leonie; Chambers, Jennifer; Chappell, Lucy; Coat, Suzette; de Haan-Jebbink, Jiska; Dekker, Marloes; Dixon, Peter; Dodd, Jodie; Fuller, Maria; Gordijn, Sanne; Graham, Dorothy; Heikinheimo, Oskari; Hennessy, Annemarie; Kaaja, Risto; Khong, Teck Yee; Lampio, Laura; Louise, Jennie; Makris, Angela; Markus, Corey; Marschall, Hanns-Ulrich; Middleton, Philippa; Mol, Ben W.; Morris, Jonathan; Newnham, John P.; Ovadia, Caroline; Peek, Michael; Shand, Antonia; Stark, Michael; Thornton, Jim; Timonen, Susanna; Walker, Susan; Warrilow, David; Williamson, Catherine (2021)
    BackgroundSevere early onset (less than 34weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders.Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach.MethodsWe have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300mg bd) with that of UDCA tablets (up to 2000mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool.DiscussionOur study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial.Trial identifiersAustralian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36.EudraCT number: 2018-004011-44.IRAS: 272398.NHMRC registration: APP1152418 and APP117853.
  • van Beekhuizen, Heleen J.; Stefanovic, Vedran; Schwickert, Alexander; Henrich, Wolfgang; Fox, Karin A.; MHallem Gziri, Mina; Sentilhes, Loic; Gronbeck, Lene; Chantraine, Frederic; Morel, Oliver; Bertholdt, Charline; Braun, Thorsten; Rijken, Marcus J.; Duvekot, Johannes J.; International Society for Placenta accreta spectrum (IS-PAS) (2021)
  • Sofou, Kalliopi; De Coo, Irenaeus F. M.; Isohanni, Pirjo; Ostergaard, Elsebet; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; De Angst, Isabell B.; Lonnqvist, Tuula; Pihko, Helena; Mankinen, Katariina; Bindoff, Laurence A.; Tulinius, Mar; Darin, Niklas (2014)
  • Escala-Garcia, M.; Abraham, J.; Andrulis, I.L.; Anton-Culver, H.; Arndt, V.; Ashworth, A.; Auer, P.L.; Auvinen, P.; Beckmann, M.W.; Beesley, J.; Behrens, S.; Benitez, J.; Bermisheva, M.; Blomqvist, C.; Blot, W.; Bogdanova, N.V.; Bojesen, S.E.; Bolla, M.K.; Børresen-Dale, A.-L.; Brauch, H.; Brenner, H.; Brucker, S.Y.; Burwinkel, B.; Caldas, C.; Canzian, F.; Chang-Claude, J.; Chanock, S.J.; Chin, S.-F.; Clarke, C.L.; Couch, F.J.; Cox, A.; Cross, S.S.; Czene, K.; Daly, M.B.; Dennis, J.; Devilee, P.; Dunn, J.A.; Dunning, A.M.; Dwek, M.; Earl, H.M.; Eccles, D.M.; Eliassen, A.H.; Ellberg, C.; Evans, D.G.; Fasching, P.A.; Figueroa, J.; Flyger, H.; Gago-Dominguez, M.; Gapstur, S.M.; García-Closas, M.; García-Sáenz, J.A.; Gaudet, M.M.; George, A.; Giles, G.G.; Goldgar, D.E.; González-Neira, A.; Grip, M.; Guénel, P.; Guo, Q.; Haiman, C.A.; Håkansson, N.; Hamann, U.; Harrington, P.A.; Hiller, L.; Hooning, M.J.; Hopper, J.L.; Howell, A.; Huang, C.-S.; Huang, G.; Hunter, D.J.; Jakubowska, A.; John, E.M.; Kaaks, R.; Kapoor, P.M.; Keeman, R.; Kitahara, C.M.; Koppert, L.B.; Kraft, P.; Kristensen, V.N.; Lambrechts, D.; Le Marchand, L.; Lejbkowicz, F.; Lindblom, A.; Lubiński, J.; Mannermaa, A.; Manoochehri, M.; Manoukian, S.; Margolin, S.; Martinez, M.E.; Maurer, T.; Mavroudis, D.; Meindl, A.; Milne, R.L.; Mulligan, A.M.; Neuhausen, S.L.; Nevanlinna, H.; Newman, W.G.; Olshan, A.F.; Olson, J.E.; Olsson, H.; Orr, N.; Peterlongo, P.; Petridis, C.; Prentice, R.L.; Presneau, N.; Punie, K.; Ramachandran, D.; Rennert, G.; Romero, A.; Sachchithananthan, M.; Saloustros, E.; Sawyer, E.J.; Schmutzler, R.K.; Schwentner, L.; Scott, C.; Simard, J.; Sohn, C.; Southey, M.C.; Swerdlow, A.J.; Tamimi, R.M.; Tapper, W.J.; Teixeira, M.R.; Terry, M.B.; Thorne, H.; Tollenaar, R.A.E.M.; Tomlinson, I.; Troester, M.A.; Truong, T.; Turnbull, C.; Vachon, C.M.; van der Kolk, L.E.; Wang, Q.; Winqvist, R.; Wolk, A.; Yang, X.R.; Ziogas, A.; Pharoah, P.D.P.; Hall, P.; Wessels, L.F.A.; Chenevix-Trench, G.; Bader, G.D.; Dörk, T.; Easton, D.F.; Canisius, S.; Schmidt, M.K. (2020)
    Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
  • Jääskeläinen, Tiina; Kärkkäinen, Olli; Jokkala, Jenna; Klåvus, Anton; Heinonen, Seppo; Auriola, Seppo; Lehtonen, Marko; FINNPEC Core Invest Grp; Hanhineva, Kati; Laivuori, Hannele (2021)
    IntroductionMaternal metabolism changes substantially during pregnancy. However, few studies have used metabolomics technologies to characterize changes across gestation.Objectives and methodsWe applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of serum differs throughout the pregnancy between pre-eclamptic and healthy women in the FINNPEC (Finnish Genetics of Preeclampsia Consortium) Study. Serum samples were available from early and late pregnancy.ResultsProgression of pregnancy had large-scale effects to the serum metabolite profile. Altogether 50 identified metabolites increased and 49 metabolites decreased when samples of early pregnancy were compared to samples of late pregnancy. The metabolic signatures of pregnancy were largely shared in pre-eclamptic and healthy women, only urea, monoacylglyceride 18:1 and glycerophosphocholine were identified to be increased in the pre-eclamptic women when compared to healthy controls.ConclusionsOur study highlights the need of large-scale longitudinal metabolomic studies in non-complicated pregnancies before more detailed understanding of metabolism in adverse outcomes could be provided. Our findings are one of the first steps for a broader metabolic understanding of the physiological changes caused by pregnancy per se.
  • Bjornland, Kristin; Pakarinen, Mikko P.; Stenstrom, Pernilla; Stensrud, Kjetil J.; Neuvonen, Malla; Granström, Anna L.; Graneli, Christina; Pripp, Are H.; Arnbjörnsson, Einar; Emblem, Ragnhild; Wester, Tomas; Rintala, Risto J.; Nordic Pediat Surgery Study Consor (2017)
    Objective: Transanal endorectal pull-through (ERPT) is the most popular technique to treat Hirschsprung disease (HD). Still, there is limited knowledge on long-term bowel function. This cross-sectional, multicenter study assessed long-term bowel function in a large HD population and examined predictors of poor outcome. Methods: Patients older than four years or their parents filled out a validated questionnaire on bowel function. Clinical details were recorded retrospectively from medical records. Results: 73/200 (37%) patients reported absolutely no impaired bowel function, meaning no constipation, fecal accidents, stoma, appendicostomy or need for enemas. Seven (4%) had a stoma, and 33 (17%) used antegrade or rectal colonic enemas. Most disarrangements of fecal control and constipation were significantly less common in older age group, but abnormal defecation frequency and social problems remained unchanged. Syndromic patients (n = 31) experienced frequent fecal accidents (46%) more often than nonsyndromic (14%, P <0.001). Having a syndrome (adjusted OR 5.6, 95% CI 2.1-15, P = 0.001) or a complete transanal ERPT (adjusted OR 2.4, 95% CI 1.1-5.7, P = 0.038) was significantly associated with poor outcome defined as having a stoma, an appendicostomy, daily fecal accidents or need of regular rectal wash outs. Conclusion: A significant number of HD patients experience bowel problems many years after definite surgery. Fecal control was significantly better in older than younger HD patients, but some continued to have considerable bowel problems also as adults. A total transanal ERPT was associated with poorer outcome. Long-term follow-up of HD patients is warranted. (C) 2017 Elsevier Inc. All rights reserved.