Browsing by Subject "3121 General medicine, internal medicine and other clinical medicine"

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  • Böttiger, B. W.; Lockey, A.; Aickin, R.; Castren, M.; de Caen, A.; Escalante, R.; Kern, K. B.; Lim, S. H.; Nadkarni, V.; Neumar, R. W.; Nolan, J. P.; Stanton, D.; Wang, T. -L.; Perkins, G. D. (2018)
    "All citizens of the world can save a life". With these words, the International Liaison Committee on Resuscitation (ILCOR) is launching the first global initiative - World Restart a Heart (WRAH) - to increase public awareness and therefore the rates of bystander cardiopulmonary resuscitation (CPR) for victims of cardiac arrest. In most of the cases, it takes too long for the emergency services to arrive on scene after the victim's collapse. Thus, the most effective way to increase survival and favourable outcome in cardiac arrest by two-to fourfold is early CPR by lay bystanders and by "first responders". Lay bystander resuscitation rates, however, differ significantly across the world, ranging from 5 to 80%. If all countries could have high lay bystander resuscitation rates, this would help to save hundreds of thousands of lives every year. In order to achieve this goal, all seven ILCOR councils have agreed to participate in WRAH 2018. Besides schoolchildren education in CPR ("KIDS SAVE LIVES"), many other initiatives have already been developed in different parts of the world. ILCOR is keen for the WRAH initiative to be as inclusive as possible, and that it should happen every year on 16 October or as close to that day as possible. Besides recommending CPR training for children and adults, it is hoped that a unified global message will enable our policy makers to take action to address the inequalities in patient survival around the world.
  • Cannistraci, Carlo Vittorio; Nieminen, Tuomo; Nishi, Masahiro; Khachigian, Levon M.; Viikilä, Juho; Laine, Mika; Cianflone, Domenico; Maseri, Attilio; Yeo, Khung Keong; Bhindi, Ravinay; Ammirati, Enrico (2018)
    Background-ST-elevation acute myocardial infarction (STEMI) represents one of the leading causes of death. The time of STEMI onset has a circadian rhythm with a peak during diurnal hours, and the occurrence of STEMI follows a seasonal pattern with a salient peak of cases in the winter months and a marked reduction of cases in the summer months. Scholars investigated the reason behind the winter peak, suggesting that environmental and climatic factors concur in STEMI pathogenesis, but no studies have investigated whether the circadian rhythm is modified with the seasonal pattern, in particular during the summer reduction in STEMI occurrence. Methods and Results-Here, we provide a multiethnic and multination epidemiological study (from both hemispheres at different latitudes, n= 2270 cases) that investigates whether the circadian variation of STEMI onset is altered in the summer season. The main finding is that the difference between numbers of diurnal (6:00 to 18:00) and nocturnal (18:00 to 6:00) STEMI is markedly decreased in the summer season, and this is a prodrome of a complex mechanism according to which the circadian rhythm of STEMI time onset seems season dependent. Conclusions-The "summer shift" of STEMI to the nocturnal interval is consistent across different populations, and the sunshine duration (a measure related to cloudiness and solar irradiance) underpins this season-dependent circadian perturbation. Vitamin D, which in our results seems correlated with this summer shift, is also primarily regulated by the sunshine duration, and future studies should investigate their joint role in the mechanisms of STEMI etiogenesis.
  • Puustinen, Lauri; Hakkarainen, Antti; Kivisaari, Reetta; Boyd, Sonja; Nieminen, Urpo; Färkkilä, Martti; Lundbom, Nina; Arkkila, Perttu (2017)
    Background: Liver biopsy is the gold standard in evaluating inflammation and fibrosis in autoimmune hepatitis.Aims: In search of non-invasive follow-up tools in autoimmune hepatitis, we evaluated (31)phosphorus magnetic resonance spectroscopy (P-31 MRS).Methods: Twelve consecutive AIH patients (mean age 42.8 years, 10 women) underwent liver biopsy, routine laboratory liver function tests, which were compared to findings in P-31 MRS and transient elastography (TE).Results: Phosphoenolpuryvate (PEP) correlated with the grade of inflammation (r=0.746, p=.005) and thromboplastin time (r=0.592, p=.043). It also differentiated patients with active inflammation from patients without (t=3.781, p=.009). There was no correlation between PEP and aminotransferase or immunoglobulin G levels.The phosphoethanolamine (PE)/phosphocholine (PC) ratio, PE/glyserophosphoethanolamine (GPE) ratio and PC/[total phosphomonoester (PME)+phosphodiester (PDE)] ratios correlated with immunoglobulin G (r=0.764, p=.006; r=0.618, p=.043; and r=-0.636, p=.035, respectively).PME/PDE and PE/GPE correlated with fibrosis (r=0.668, p=.018 and r=0.604, p=.037). PE/GPE also differentiated F3 from F0-2 patients (t=3.810, p=.003).Phosphorus metabolites did not correlate with TE results and TE did not correlate with liver histology or laboratory parameters.Conclusions: P-31 MRS seems to detect active inflammation and advanced fibrosis in AIH patients. TE was ineffective in fibrosis quantification.
  • Autio, Juho; Stenbäck, Ville; Gagnon, Dominique D.; Leppäluoto, Juhani; Herzig, Karl-Heinz (2020)
    Regular physical activity (PA) improves cognitive functions, prevents brain atrophy, and delays the onset of cognitive decline, dementia, and Alzheimer's disease. Presently, there are no specific recommendations for PA producing positive effects on brain health and little is known on its mediators. PA affects production and release of several peptides secreted from peripheral and central tissues, targeting receptors located in the central nervous system (CNS). This review will provide a summary of the current knowledge on the association between PA and cognition with a focus on the role of (neuro)peptides. For the review we define peptides as molecules with less than 100 amino acids and exclude myokines. Tachykinins, somatostatin, and opioid peptides were excluded from this review since they were not affected by PA. There is evidence suggesting that PA increases peripheral insulin growth factor 1 (IGF-1) levels and elevated serum IGF-1 levels are associated with improved cognitive performance. It is therefore likely that IGF-1 plays a role in PA induced improvement of cognition. Other neuropeptides such as neuropeptide Y (NPY), ghrelin, galanin, and vasoactive intestinal peptide (VIP) could mediate the beneficial effects of PA on cognition, but the current literature regarding these (neuro)peptides is limited.
  • Peddinti, Gopal; Bergman, Michael; Tuomi, Tiinamaija; Groop, Leif (2019)
    Context: Early prediction of dysglycemia is crucial to prevent progression to type 2 diabetes. The 1-hour postload plasma glucose (PG) is reported to be a better predictor of dysglycemia than fasting plasma glucose (FPG), 2-hour PG, or glycated hemoglobin (HbA1c). Objective: To evaluate the predictive performance of clinical markers, metabolites, HbA1c, and PG and serum insulin (INS) levels during a 75-g oral glucose tolerance test (OGTT). Design and Setting: We measured PG and INS levels at 0, 30, 60, and 120 minutes during an OGTT in 543 participants in the Botnia Prospective Study, 146 of whom progressed to type 2 diabetes within a 10-year follow-up period. Using combinations of variables, we evaluated 1527 predictive models for progression to type 2 diabetes. Results: The 1-hour PG outperformed every individual marker except 30-minute PG or mannose, whose predictive performances were lower but not significantly worse. HbA1c was inferior to 1-hour PG according to DeLong test P value but not false discovery rate. Combining the metabolic markers with PG measurements and HbA1c significantly improved the predictive models, and mannose was found to be a robust metabolic marker. Conclusions: The 1-hour PG, alone or in combination with metabolic markers, is a robust predictor for determining the future risk of type 2 diabetes, outperforms the 2-hour PG, and is cheaper to measure than metabolites. Metabolites add to the predictive value of PG and HbA1c measurements. Shortening the standard 75-g OGTT to 1 hour improves its predictive value and clinical usability.
  • Eskelund, Christian W.; Kolstad, Arne; Jerkeman, Mats; Räty, Riikka; Laurell, Anna; Eloranta, Sandra; Smedby, Karin E.; Husby, Simon; Pedersen, Lone B.; Andersen, Niels S.; Eriksson, Mikael; Kimby, Eva; Bentzen, Hans; Kuittinen, Outi; Lauritzsen, Grete F.; Nilsson-Ehle, Herman; Ralfkiaer, Elisabeth; Ehinger, Mats; Sundstrom, Christer; Delabie, Jan; Karjalainen-Lindsberg, Marja-Liisa; Workman, Christopher T.; Garde, Christian; Elonen, Erkki; Brown, Peter; Gronbaek, Kirsten; Geisler, Christian H. (2016)
    In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
  • Catapano, Alberico L.; Graham, Ian; De Backer, Guy; Wiklund, Olov; Chapman, M. John; Drexel, Heinz; Hoes, Arno W.; Jennings, Catriona S.; Landmesser, Ulf; Pedersen, Terje R.; Reiner, Zeljko; Riccardi, Gabriele; Taskinen, Marja-Riita; Tokgozoglu, Lale; Verschuren, W. M. Monique; Vlachopoulos, Charalambos; Wood, David A.; Luis Zamorano, Jose (2016)
  • Aboyans, Victor; Ricco, J. B.; Bartelink, Marie-Louise E. L.; Björck, Martin; Brodmann, Marianne; Cohnert, Tina; Collet, Jean-Philippe; Czerny, Martin; De Carlo, Marco; Debus, Sebastian; Espinola-Klein, Christine; Kahan, Thomas; Kownator, Serge; Mazzolai, Lucia; Naylor, A. Ross; Roffi, Marco; Röther, Joachim; Sprynger, Muriel; Tendera, Michal; Tepe, Gunnar; Venermo, Maarit; Vlachopoulos, Charalambos; Desormais, Ileana; ESC Scientific Document Group (2018)
  • Olasveengen, Theresa M.; de Caen, Allan R.; Mancini, Mary E.; Maconochie, Ian K.; Aickin, Richard; Atkins, Dianne L.; Berg, Robert A.; Bingham, Robert M.; Brooks, Steven C.; Castren, Maaret; Chung, Sung Phil; Considine, Julie; Couto, Thomaz Bittencourt; Escalante, Raffo; Gazmuri, Raul J.; Guerguerian, Anne-Marie; Hatanaka, Tetsuo; Koster, Rudolph W.; Kudenchuk, Peter J.; Lang, Eddy; Lim, Swee Han; Lofgren, Bo; Meaney, Peter A.; Montgomery, William H.; Morley, Peter T.; Morrison, Laurie J.; Nation, Kevin J.; Ng, Kee-Chong; Nadkarni, Vinay M.; Nishiyama, Chika; Nuthall, Gabrielle; Ong, Gene Yong-Kwang; Perkins, Gavin D.; Reis, Amelia G.; Ristagno, Giuseppe; Sakamoto, Tetsuya; Sayre, Michael R.; Schexnayder, Stephen M.; Sierra, Alfredo F.; Singletary, Eunice M.; Shimizu, Naoki; Smyth, Michael A.; Stanton, David; Tijssen, Janice A.; Travers, Andrew; Vaillancourt, Christian; Van de Voorde, Patrick; Hazinski, Mary Fran; Nolan, Jerry P.; ILCOR Collaborators (2017)
    The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations summary articles that will include the cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation in the previous year. The review this year includes 5 basic life support and 1 paediatric Consensuses on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Each of these includes a summary of the science and its quality based on Grading of Recommendations, Assessment, Development, and Evaluation criteria and treatment recommendations. Insights into the deliberations of the International Liaison Committee on Resuscitation task force members are provided in Values and Preferences sections. Finally, the task force members have pri-oritised and listed the top 3 knowledge gaps for each population, intervention, comparator, and outcome question. (C) 2017 European Resuscitation Council and American Heart Association, Inc. Published by Elsevier B.V. All rights reserved.
  • ARIA Working Grp; Bousquet, J; Pfaar, O; Togias, A; Haahtela, T; Toppila-Salmi, S (2019)
    Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients.
  • Task Force Members; ESC Comm Practice Guidelines CPG; ESC Natl Cardiac Societies; Mach, Francois; Baigent, Colin; Taskinen, Marja-Riitta (2019)
  • Vuori, Matti A.; Harald, Kennet; Jula, Antti; Valsta, Liisa; Laatikainen, Tiina; Salomaa, Veikko; Tuomilehto, Jaakko; Jousilahti, Pekka; Niiranen, Teemu J. (2020)
    Aims: The objective was to evaluate whether sodium intake, assessed with the gold standard 24-h urinary collections, was related to long-term incidence of death, cardiovascular disease (CVD) and diabetes mellitus (DM). Methods:A cohort of 4630 individuals aged 25-64 years collected 24-h urine samples in 1979-2002 and were followed up to 14 years for the incidence of any CVD, coronary heart disease (CHD), stroke, heart failure (HF) and DM event, and death. Cox proportional hazards models were used to estimate the association between the baseline salt intake and incident events and adjusted for baseline age, body mass index, serum cholesterol, prevalent DM, and stratified by sex and cohort baseline year. Results: During the follow-up, we observed 423 deaths, 424 CVD events (288 CHD events, 142 strokes, 139 HF events) and 161 DM events. Compared with the highest quartile of salt intake, persons in the lowest quartile had a lower incidence of CVD (hazard ratio [HR] 0.70; 95% confidence interval [CI], 0.51-0.95,p = .02), CHD (HR 0.63 [95% CI 0.42-0.94],p = .02) and DM (HR 0.52 [95% CI 0.31-0.87],p = .01). The results were non-significant for mortality, HF, and stroke. Conclusion: High sodium intake is associated with an increased incidence of CVD and DM.
  • Padmapriya, Natarajan; Chen, Bozhi; Goh, Claire Marie Jie Lin; Shek, Lynette Pei Chi; Chong, Yap Seng; Tan, Kok Hian; Chan, Shiao-Yng; Yap, Fabian; Godfrey, Keith M.; Lee, Yung Seng; Eriksson, Johan G.; Bernard, Jonathan Y.; Müller-Riemenschneider, Falk (2021)
    Background: Time spent in movement behaviours, including physical activity (PA), sedentary behaviour (SB) and sleep, across the 24-h day may have distinct health consequences. We aimed to describe 24-h movement behaviour (24 h-MB) profiles in children and how profile membership changed from age 5.5 to 8 years. Methods: Children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort were asked to wear an accelerometer (ActiGraph-GT3X+) on their wrist for seven consecutive days at ages 5.5 and 8 years to measure 24 h-MB patterns. Time spent in night sleep, inactivity (proxy for SB), light PA, moderate PA (MPA), and vigorous PA (VPA) per day were calculated using the R-package GGIR 2.0. Using latent profile analyses (n = 442) we identified 24 h-MB profiles, which were given animal names to convey key characteristics. Latent transition analyses were used to describe the profile membership transition from ages 5.5 to 8 years. Associations with sex and ethnicity were examined. Results: We identified four profiles, "Rabbits" (very high-MPA/VPA, low-inactivity and average-night-sleep), "Chimpanzees" (high-MPA, low-inactivity and average-night-sleep), "Pandas" (low-PA, high-inactivity and high-night-sleep) and "Owls" (low-PA, high-inactivity and low-night-sleep), among children at both time points. At ages 5.5 and 8 years, the majority of children were classified into profiles of "Chimpanzees" (51 and 39%, respectively) and "Pandas" (24 and 37%). Half of the sample (49%), particularly "Rabbits", remained in the same profile at ages 5.5 and 8 years: among children who changed profile the predominant transitions occurred from "Chimpanzees" (27%) and "Owls" (56%) profiles to "Pandas". Sex, but not ethnicity, was associated with profile membership: compared to girls, boys were more likely to be in the "Rabbits" profile (adjusted OR [95% CI]: 3.6 [1.4, 9.7] and 4.5 [1.8, 10.9] at ages 5.5 and 8 years, respectively) and less likely to be in the "Pandas" profile (0.5 [0.3, 0.9] and 0.4 [0.2, 0.6]) at both ages. Conclusions: With increasing age about half the children stayed in the same of four 24 h-MB profiles, while the predominant transition for the remaining children was towards lower PA, higher inactivity and longer sleep duration. These findings can aid development and implementation of public health strategies to promote better health.
  • Erhola, Marina; Vasankari, Tuula; Jormanainen, Vesa; Toppila-Salmi, Sanna; Herrala, Jaakko; Haahtela, Tari (2019)
  • Tuohinen, Suvi Sirkku; Skyttä, Tanja; Huhtala, Heini; Poutanen, Tuija; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka (2021)
    BACKGROUND Radiation therapy (RT) results in myocardial changes consisting of diffuse fibrosis, which may result in changes in diastolic function. OBJECTIVES The aim of this study was to explore RT-associated changes in left ventricular (LV) diastolic function. METHODS Sixty chemotherapy-naive patients with left-sided, early-stage breast cancer were studied with speckle tracking echocardiography at 3 time points: prior to, immediately after, and 3 years after RT. Global and regional early diastolic strain rate (SRe) were quantified, as were parameters of systolic function. RESULTS Regional changes in SRe, particularly the apical and anteroseptat segments, were observed over time and were more evident than global changes. The apical SRe declined from a median of 1.24 (interquartile range: 1.01 to 1.39) s(-1) at baseline to 1.02 (interquartile range: 0.79 to 1.15) s(-1) at 3 years of follow-up (p < 0.001). This decline was associated with the left ventricular maximal radiation dose (beta = 0.36, p = 0.007). The global SRe was CONCLUSIONS RT resulted in changes in the SRe in the apical and anteroseptat segments over 3 years of follow-up. Changes in SRe apical segments were present even in patients with preserved systolic function and were independently associated with RT dose and cardiovascular comorbidities. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
  • Rusanen, Juuso; Kareinen, Lauri; Levanov, Lev; Mero, Sointu Maarit; Pakkanen, Sari Hannele; Kantele, Anu; Amanat, Fatima; Krammer, Florian; Hedman, Klaus; Vapalahti, Olli; Hepojoki, Jussi (2021)
    Accurate and rapid diagnostic tools are needed for management of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Antibody tests enable detection of individuals past the initial phase of infection and help examine vaccine responses. The major targets of human antibody response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the spike glycoprotein (SP) and nucleocapsid protein (NP). We have developed a rapid homogenous approach for antibody detection termed LFRET (protein L-based time-resolved Forster resonance energy transfer immunoassay). In LFRET, fluorophore-labeled protein L and antigen are brought to close proximity by antigen-specific patient immunoglobulins of any isotype, resulting in TR-FRET signal. We set up LFRET assays for antibodies against SP and NP and evaluated their diagnostic performance using a panel of 77 serum/plasma samples from 44 individuals with COVID-19 and 52 negative controls. Moreover, using a previously described SP and a novel NP construct, we set up enzyme linked immunosorbent assays (ELISAs) for antibodies against SARS-CoV-2 SP and NP. We then compared the LFRET assays with these ELISAs and with a SARS-CoV-2 microneutralization test (MNT). We found the LFRET assays to parallel ELISAs in sensitivity (90-95% vs. 90-100%) and specificity (100% vs. 94-100%). In identifying individuals with or without a detectable neutralizing antibody response, LFRET outperformed ELISA in specificity (91-96% vs. 82-87%), while demonstrating an equal sensitivity (98%). In conclusion, this study demonstrates the applicability of LFRET, a 10-min "mix and read" assay, to detection of SARS-CoV-2 antibodies.
  • Uusi-Rasi, Kirsti; Patil, Radhika; Karinkanta, Saija; Kannus, Pekka; Tokola, Kari; Lamberg-Allardt, Christel; Sievanen, Harri (2017)
    Background: Both exercise and vitamin D are recommended means to prevent falls among older adults, but their combined effects on fallinduced injuries are scarcely studied. Methods: A 2-year follow-up of a previous 2-year randomized controlled trial with vitamin D and exercise (Ex) of 409 older home-dwelling women using a factorial 2 x 2 design (D(-)Ex(-), D(+)Ex(-), D(-)Ex(+), D(+)Ex(+)). Besides monthly fall diaries, femoral neck bone mineral density (fn-BMD), and physical functioning were assessed at 1 and 2 years after the intervention. Results: After the intervention, S-25OHD concentrations declined to baseline levels in both supplement groups. The groups did not differ for change in fn-BMD or physical functioning, except for leg extensor muscle strength, which remained about 10% greater in the exercise groups compared with the reference group (D(-)Ex(-)). There were no between-group differences in the rate of all falls, but medically attended injurious falls reduced in D+ Ex-and D(-)Ex(+) groups compared with D(-)Ex(-). However, all former treatment groups had less medically attended injured fallers, HRs (95% CI) being 0.62 (0.39-1.00) for D+ Ex-, 0.46 (0.28-0.76) for D(-)Ex(+), and 0.55 (0.34-0.88) for D(+)Ex(+), compared with D(-)Ex(-). Conclusions: Exercise-induced benefits in physical functioning partly remained 2 years after cessation of supervised training. Although there was no difference in the rate of all falls, former exercise groups continued to have lower rate of medically attended injured fallers compared with referents even 2 years after the intervention. Vitamin D without exercise was associated with less injurious falls with no difference in physical functioning.
  • Vakkilainen, Svetlana; Taskinen, Mervi; Klemetti, Paula; Pukkala, Eero; Mäkitie, Outi (2019)
    Cartilage-hair hypoplasia (CHH) is a skeletal dysplasia with combined immunodeficiency, variable clinical course and increased risk of malignancy. Management of CHH is complicated by a paucity of long-term follow-up data, as well as knowledge on prognostic factors. We assessed clinical course and risk factors for mortality in a prospective cohort study of 80 patients with CHH recruited in 1985-1991 and followed up until 2016. For all patients we collected additional health information from health records and from the national Medical Databases and Cause-of-death Registry. The primary outcome was immunodeficiency-related death, including death from infections, lung disease and malignancy. Standardized mortality ratios (SMRs) were calculated using national mortality rates as reference. Half of the patients (57%, n = 46) manifested no symptoms of immunodeficiency during follow-up while 19% (n = 15) and 24% (n = 19) demonstrated symptoms of humoral or combined immunodeficiency, including six cases of adult-onset immunodeficiency. In a significant proportion of patients (17/79, 22%), clinical features of immunodeficiency progressed over time. Of the 15 patients with non-skin cancer, eight had no preceding clinical symptoms of immunodeficiency. Altogether 20 patients had deceased (SMR = 7.0, 95% CI = 4.3-11); most commonly from malignancy (n = 7, SMR = 10, 95% CI = 4.1-21) and lung disease (n = 4, SMR = 46, 95% CI = 9.5-130). Mortality associated with birth length below-4 standard deviation (compared to normal, SMR/SMR ratio = 5.4, 95% CI = 1.5-20), symptoms of combined immunodeficiency (compared to asymptomatic, SMR/SMR ratio= 3.9, 95% CI = 1.3-11), Hirschsprung disease (odds ratio (OR) 7.2, 95% CI = 1.04-55), pneumonia in the first year of life or recurrently in adulthood (OR = 7.6/19, 95% CI = 1.3-43/2.6-140) and autoimmunity in adulthood (OR = 39, 95% CI = 3.5-430). In conclusion, patients with CHH may develop adult-onset immunodeficiency or malignancy without preceding clinical symptoms of immune defect, warranting careful follow-up. Variable disease course and risk factors for mortality should be acknowledged.
  • Haahtela, Tari (2019)
    Biodiversity hypothesis states that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution is profoundly changing our environment and lifestyle. Adaptive immunoregulatory circuits and dynamic homeostasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. Loss of immunoprotective factors, derived from nature, is a new kind of health risk poorly acknowledged until recently. The paradigm change has been implemented in the Finnish allergy programme (2008-2018), which emphasized tolerance instead of avoidance. The first results are promising, as allergy burden has started to reduce. The rapidly urbanizing world is facing serious biodiversity loss with global warming, which are interconnected. Biodiversity hypothesis of health and disease has societal impact, for example, on city planning, food and energy production and nature conservation. It has also a message for individuals for health and well-being: take nature close, to touch, eat, breathe, experience and enjoy. Biodiverse natural environments are dependent on planetary health, which should be a priority also among health professionals.