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  • 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.
  • 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 (
  • Roininen, Saara; Laine, Outi; Kauppila, Marjut; Vesanen, Marko; Ramet, Maria; Sinisalo, Marjatta; Jantunen, Esa; Saily, Marjaana; Räty, Riikka; Elonen, Erkki; Wartiovaara-Kautto, Ulla (2017)
    Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually hampers patients' lives and may also endanger efficient leukemia treatment. Although many factors have been suggested to account for an elevated risk of VTs in patients with ALL, there still is a lack of studies focusing on CVTs and especially in the setting of adult ALL patients. We studied in our retrospective population-based cohort the occurrence, characteristics, as well as risk factors for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a national pediatric-inspired treatment protocol ALL2000. In the risk factor analyses for VTs we found a distinction of the characteristics of the patients acquiring CVT from those with other kinds of VTs or without thrombosis. In contrast to previous studies we were also able to compare the effects of asparaginase in relation to CVT occurrence. Notably, more than half of the CVTs were diagnosed prior the administration of asparaginase which accentuates the role of other risk factors on the pathophysiology of CVT compared to truncal or central venous line (CVL) VTs in adult ALL patients.
  • Hitti-Malin, Rebekkah J.; Burmeister, Louise M.; Lingaas, Frode; Kaukonen, Maria; Pettinen, Inka; Lohi, Hannes; Sargan, David; Mellersh, Cathryn S. (2021)
    Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases characterized by photoreceptor cell death in the retina, leading to visual impairment. Despite the identification of multiple PRA-causing variants, extensive heterogeneity of PRA is observed across and within dog breeds, with many still genetically unsolved. This study sought to elucidate the causal variant for a distinct form of PRA in the Shetland sheepdog, using a whole-genome sequencing approach. Filtering variants from a single PRA-affected Shetland sheepdog genome compared to 176 genomes of other breeds identified a single nucleotide variant in exon 11 of the Bardet-Biedl syndrome-2 gene (BBS2) (c.1222G > C; p.Ala408Pro). Genotyping 1386 canids of 155 dog breeds, 15 cross breeds and 8 wolves indicated the c.1222G > C variant was only segregated within Shetland sheepdogs. Out of 505 Shetland sheepdogs, seven were homozygous for the variant. Clinical history and photographs for three homozygotes indicated the presence of a novel phenotype. In addition to PRA, additional clinical features in homozygous dogs support the discovery of a novel syndromic PRA in the breed. The development and utilization of a diagnostic DNA test aim to prevent the mutation from becoming more prevalent in the breed.
  • Ryhänen, Eeva; Leijon, Helena; Metso, Saara; Eloranta, Eija; Korsoff, Pirkko; Ahtiainen, Petteri; Kekäläinen, Päivi; Tamminen, Marjo; Ristamaki, Raija; Knutar, Otto; Loyttyniemi, Eliisa; Niskanen, Leo; Väisänen, Mika; Heiskanen, Ilkka Sten; Välimäki, Matti; Laakso, Markku; Haglund, Caj; Arola, Johanna; Schalin-Jantti, Camilla (2017)
    Background: Parathyroid carcinoma (PC) is rare and diagnostically challenging. Reported outcomes are rather poor and the incidence might be increasing.Material and methods: We performed a nationwide study on all cases (n=32) diagnosed in 2000-2011 in Finland, and compared clinical and histopathological characteristics and outcome to atypical parathyroid (APA; n=28) and parathyroid adenomas (PA; n=72). The incidence in years 1955-1999 was compared to that in 2000-2013.Results: Preoperatively, calcium and parathyroid hormone concentrations were higher in PC compared to APA and PA (1.76, 1.56 and 1.44mmol/l, p
  • Brusa, Roberta; Magri, Francesca; Papadimitriou, Dimitra; Govoni, Alessandra; Del Bo, Roberto; Ciscato, Patrizia; Savarese, Marco; Cinnante, Claudia; Walter, Maggie C.; Abicht, Angela; Bulst, Stefanie; Corti, Stefania; Moggio, Maurizio; Bresolin, Nereo; Nigro, Vincenzo; Comi, Giacomo Pietro (2018)
    Limb girdle muscular dystrophy (LGMD) type 2G is a rare form of muscle disease, described only in a few patients worldwide, caused by mutations in TCAP gene, encoding the protein telethonin. It is characterised by proximal limb muscle weakness associated with distal involvement of lower limbs, starting in the first or second decade of life. We describe the case of a 37-year-old woman of Greek origin, affected by disto-proximal lower limb weakness. No cardiac or respiratory involvement was detected. Muscle biopsy showed myopathic changes with type I fibre hypotrophy, cytoplasmic vacuoles, lipid overload, multiple central nuclei and fibre splittings; ultrastructural examination showed metabolic abnormalities. Next generation sequencing analysis detected a homozygous frameshift mutation in the TCAP gene (c.90_91del), previously described in one Turkish family. Immunostaining and Western blot analysis showed complete absence of telethonin. Interestingly, Single Nucleotide Polymorphism analysis of the 10 Mb genomic region containing the TCAP gene showed a shared homozygous haplotype of both the Greek and the Turkish patients, thus suggesting a possible founder effect of TCAP gene c.90_91del mutation in this part of the Mediterranean area. (C) 2018 Elsevier B.V. All rights reserved.
  • Kaipainen, Aku L.; Pitkänen, Johanna; Haapalinna, Fanni; Jääskeläinen, Olli; Jokinen, Hanna; Melkas, Susanna; Erkinjuntti, Timo; Vanninen, Ritva; Koivisto, Anne M.; Lötjönen, Jyrki; Koikkalainen, Juha; Herukka, Sanna-Kaisa; Julkunen, Valtteri (2021)
    Purpose Automated analysis of neuroimaging data is commonly based on magnetic resonance imaging (MRI), but sometimes the availability is limited or a patient might have contradictions to MRI. Therefore, automated analyses of computed tomography (CT) images would be beneficial. Methods We developed an automated method to evaluate medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), and the severity of white matter lesions (WMLs) from a CT scan and compared the results to those obtained from MRI in a cohort of 214 subjects gathered from Kuopio and Helsinki University Hospital registers from 2005 - 2016. Results The correlation coefficients of computational measures between CT and MRI were 0.9 (MTA), 0.82 (GCA), and 0.86 (Fazekas). CT-based measures were identical to MRI-based measures in 60% (MTA), 62% (GCA) and 60% (Fazekas) of cases when the measures were rounded to the nearest full grade variable. However, the difference in measures was 1 or less in 97-98% of cases. Similar results were obtained for cortical atrophy ratings, especially in the frontal and temporal lobes, when assessing the brain lobes separately. Bland-Altman plots and weighted kappa values demonstrated high agreement regarding measures based on CT and MRI. Conclusions MTA, GCA, and Fazekas grades can also be assessed reliably from a CT scan with our method. Even though the measures obtained with the different imaging modalities were not identical in a relatively extensive cohort, the differences were minor. This expands the possibility of using this automated analysis method when MRI is inaccessible or contraindicated.
  • Rossi, Daniela; Palmio, Johanna; Evila, Anni; Galli, Lucia; Barone, Virginia; Caldwell, Tracy A.; Policke, Rachel A.; Aldkheil, Esraa; Berndsen, Christopher E.; Wright, Nathan T.; Malfatti, Edoardo; Brochier, Guy; Pierantozzi, Enrico; Jordanova, Albena; Guergueltcheva, Velina; Romero, Norma Beatriz; Hackman, Peter; Eymard, Bruno; Udd, Bjarne; Sorrentino, Vincenzo (2017)
    A novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two members of a French family affected by distal myopathy and in one healthy relative. This FLNC c.5161delG mutation is one nucleotide away from a previously reported FLNC mutation (c.5160delC) that was identified in patients and in asymptomatic carriers of three Bulgarian families with distal muscular dystrophy, indicating a low penetrance of the FLNC frameshift mutations. Given these similarities, we believe that the two FLNC mutations alone can be causative of distal myopathy without full penetrance. Moreover, comparative analysis of the clinical manifestations indicates that patients of the French family show an earlier onset and a complete segregation of the disease. As a possible explanation of this, the two French patients also carry a OBSCN c.13330C>T (p.Arg4444Trp) mutation. The p.Arg4444Trp variant is localized within the OBSCN Ig59 domain that, together with Ig58, binds to the ZIg9/ZIg10 domains of titin at Z-disks. Structural and functional studies indicate that this OBSCN p.Arg4444Trp mutation decreases titin binding by similar to 15-fold. On this line, we suggest that the combination of the OBSCN p.Arg4444Trp variant and of the FLNC c.5161delG mutation, can cooperatively affect myofibril stability and increase the penetrance of muscular dystrophy in the French family.
  • Hirschfield, Gideon M.; Beuers, Ulrich; Kupcinskas, Limas; Ott, Peter; Bergquist, Annika; Färkkilä, Martti; Manns, Michael P.; Pares, Albert; Spengler, Ulrich; Stiess, Michael; Greinwald, Roland; Prols, Markus; Wendum, Dominique; Drebber, Uta; Poupon, Raoul (2021)
    Background & Aims: In patients with primary biliary cholangitis (PBC), the efficacy of budesonide, a synthetic corticosteroid displaying high first-pass metabolism, is unresolved. In a placebo-controlled, double-blind trial, we evaluated the added-value of budesonide in those with PBC and ongoing risk of progressive disease despite ursodeoxycholic acid (UDCA) treatment. Methods: We evaluated 62 patients with PBC who had histologically confirmed hepatic inflammatory activity, according to the Ishak score, and an alkaline phosphatase (ALP) >1.5x upper limit of normal (ULN), after at least 6 months of UDCA therapy. Participants were randomly assigned 2:1 to receive budesonide (9 mg/day) or placebo once daily, for 36 months, with UDCA treatment (12-16 mg/kg body weight/day) maintained. Primary efficacy was defined as improvement of liver histology with respect to inflammation and no progression of fibrosis. Secondary outcomes included changes in biochemical markers of liver injury. Results: Recruitment challenges resulted in a study that was underpowered for the primary efficacy analysis. Comparing patients with paired biopsies only (n = 43), the primary histologic endpoint was not met (p>0.05). The proportion of patients with ALP = 15% decrease in ALP and normal bilirubin was higher in the budesonide group than in the placebo group at 12, 24, and 36 months (p Conclusion: Budesonide add-on therapy was not associated with improved liver histology in patients with PBC and insufficient response to UDCA; however, improvements in biochemical markers of disease activity were demonstrated in secondary analyses. Lay summary: Around one-third of patients with primary biliary cholangitis (PBC) needs additional medical therapy alongside ursodeoxycholic acid (UDCA) treatment. In this clinical trial, the addition of the corticosteroid budesonide did not improve liver histology; there were however relevant improvements in liver blood tests. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.
  • Sippola, Suvi; Grönroos, Juha; Sallinen, Ville; Rautio, Tero; Nordström, Pia; Rantanen, Tuomo; Hurme, Saija; Leppäniemi, Ari; Meriläinen, Sanna; Laukkarinen, Johanna; Savolainen, Heini; Virtanen, Johanna; Salminen, Paulina (2018)
    Introduction Recent studies show that antibiotic therapy is safe and feasible for CT-confirmed uncomplicated acute appendicitis. Spontaneous resolution of acute appendicitis has already been observed over a hundred years ago. In CT-confirmed uncomplicated acute diverticulitis (left-sided appendicitis), studies have shown no benefit from antibiotics compared with symptomatic treatment, but this shift from antibiotics to symptomatic treatment has not yet been widely implemented in clinical practice. Recently, symptomatic treatment of uncomplicated acute appendicitis has been demonstrated in a Korean open-label study. However, a double-blinded placebo-controlled study to illustrate the role of antibiotics and spontaneous resolution of uncomplicated acute appendicitis is still lacking. Methods and analysis The APPAC III (APPendicitis ACuta III) trial is a multicentre, double-blind, placebo-controlled, superiority randomised study comparing antibiotic therapy with placebo in the treatment CT scan-confirmed uncomplicated acute appendicitis aiming to evaluate the role of antibiotics in the resolution of uncomplicated acute appendicitis. Adult patients (18-60 years) with CT scan-confirmed uncomplicated acute appendicitis (the absence of appendicolith, abscess, perforation and tumour) will be enrolled in five Finnish university hospitals. Primary endpoint is success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without surgical intervention within 10 days after initiating randomised treatment (treatment efficacy). Secondary endpoints include postintervention complications, recurrent symptoms after treatment up to 1year, late recurrence of acute appendicitis after 1year, duration of hospital stay, sick leave, treatment costs and quality of life. A decrease of 15 percentage points in success rate is considered clinically important difference. The superiority of antibiotic treatment compared with placebo will be analysed using Fisher's one-sided test and CI will be calculated for proportion difference. Ethics and dissemination This protocol has been approved by the Ethics Committee of Turku University Hospital and the Finnish Medicines Agency (FIMEA). The findings will be disseminated in peer-reviewed academic journals. Trial registration number NCT03234296; Pre-results.
  • Auvinen, Anssi; Rannikko, Antti; Taari, Kimmo; Kujala, Paula; Mirtti, Tuomas; Kenttämies, Anu; Rinta-Kiikka, Irina; Lehtimäki, Terho; Oksala, Niku; Pettersson, Kim; Tammela, Teuvo L. (2017)
    The current evidence of PSA-based prostate cancer screening shows a reduction in cause-specific mortality, but with substantial overdiagnosis. Recently, new developments in detection of clinically relevant prostate cancer include multiple kallikreins as biomarkers besides PSA, and multiparametric magnetic resonance imaging (mpMRI) for biopsy decision. They offer opportunities for improving the outcomes in screening, particularly reduction in overdiagnosis and higher specificity for potentially lethal cancer. A population-based randomized screening trial will be started, with 67,000 men aged 55-67 years at entry. A quarter of the men will be allocated to the intervention arm, and invited to screening. The control arm will receive no intervention. All men in the screening arm will be offered a serum PSA determination. Those with PSA of 3 ng/ml or higher will have an additional multi-kallikrein panel and those with indications of increased risk of clinically relevant prostate cancer will undergo mpMRI. Men with a malignancy-suspect finding in MRI are referred to targeted biopsies. Screening interval is 6 years for men with baseline PSA <1.5 ng/ml, 4 years with PSA 1.5-3.0 and 2 years if initial PSA > 3. The main outcome of the trial is prostate cancer mortality, with analysis at 10 and 15 years. The statistical power is sufficient for detecting a 28% reduction at 10 years and 22% at 15 years. The proposed study has the potential to provide the evidence to justify screening as a public health policy if mortality benefit can be sustained with substantially reduced overdiagnosis.
  • Johansson, Katarina; Kaprio, Tuomas; Nieminen, Heini; Lehtimäki, Tiina E.; Lantto, Eila; Haglund, Caj; Seppänen, Hanna (2022)
    Background and objective: The growing number of identified intraductal papillary mucinous neoplasm (IPMN) patients places greater pressure on healthcare systems. Only a minority of patients have IPMN-related symptoms. Thus, more precise surveillance is required. Methods: In this retrospective single-center cross-sectional study, patients with an active diagnosis of branch duct IPMN (BD-IPMN) and >6 months of surveillance were classified as follows: presence/absence of worrisome features (WF) or high-risk stigmata (HRS), newly developed WF/HRS, under/over 15 mm cyst, growing/not growing
  • Wallis, Lee A.; Fleming, Julian; Hasselberg, Marie; Laflamme, Lucie; Lundin, Johan (2016)
    Background Each year more than 10 million people worldwide are burned severely enough to require medical attention, with clinical outcomes noticeably worse in resource poor settings. Expert clinical advice on acute injuries can play a determinant role and there is a need for novel approaches that allow for timely access to advice. We developed an interactive mobile phone application that enables transfer of both patient data and pictures of a wound from the point-of-care to a remote burns expert who, in turn, provides advice back. Methods and Results The application is an integrated clinical decision support system that includes a mobile phone application and server software running in a cloud environment. The client application is installed on a smartphone and structured patient data and photographs can be captured in a protocol driven manner. The user can indicate the specific injured body surface(s) through a touchscreen interface and an integrated calculator estimates the total body surface area that the burn injury affects. Predefined standardised care advice including total fluid requirement is provided immediately by the software and the case data are relayed to a cloud server. A text message is automatically sent to a burn expert on call who then can access the cloud server with the smartphone app or a web browser, review the case and pictures, and respond with both structured and personalized advice to the health care professional at the point-of-care. Conclusions In this article, we present the design of the smartphone and the server application alongside the type of structured patient data collected together with the pictures taken at point-of-care. We report on how the application will be introduced at point-of-care and how its clinical impact will be evaluated prior to roll out. Challenges, strengths and limitations of the system are identified that may help materialising or hinder the expected outcome to provide a solution for remote consultation on burns that can be integrated into routine acute clinical care and thereby promote equity in injury emergency care, a growing public health burden.
  • UroSoMe Collaborators; Leow, Jeffrey J. J.; Tan, Wei Shen; Tan, Wei Phin; Tikkinen, Kari A. O.; Teoh, Jeremy Yuen-Chun (2022)
    PurposeThe COVID-19 pandemic has led to competing strains on hospital resources and healthcare personnel. Patients with newly diagnosed invasive urothelial carcinomas of bladder (UCB) upper tract (UTUC) may experience delays to definitive radical cystectomy (RC) or radical nephro-ureterectomy (RNU) respectively. We evaluate the impact of delaying definitive surgery on survival outcomes for invasive UCB and UTUC.MethodsWe searched for all studies investigating delayed urologic cancer surgery in Medline and Embase up to June 2020. A systematic review and meta-analysis was performed.ResultsWe identified a total of 30 studies with 32,591 patients. Across 13 studies (n = 12,201), a delay from diagnosis of bladder cancer/TURBT to RC was associated with poorer overall survival (HR 1.25, 95% CI: 1.09-1.45, p = 0.002). For patients who underwent neoadjuvant chemotherapy before RC, across the 5 studies (n = 4,316 patients), a delay between neoadjuvant chemotherapy and radical cystectomy was not found to be significantly associated with overall survival (pooled HR 1.37, 95% CI: 0.96-1.94, p = 0.08). For UTUC, 6 studies (n = 4,629) found that delay between diagnosis of UTUC to RNU was associated with poorer overall survival (pooled HR 1.55, 95% CI: 1.19-2.02, p = 0.001) and cancer-specific survival (pooled HR of 2.56, 95% CI: 1.50-4.37, p = 0.001). Limitations included between-study heterogeneity, particularly in the definitions of delay cut-off periods between diagnosis to surgery.ConclusionsA delay from diagnosis of UCB or UTUC to definitive RC or RNU was associated with poorer survival outcomes. This was not the case for patients who received neoadjuvant chemotherapy.
  • Vakkilainen, Svetlana; Mäkitie, Riikka; Klemetti, Paula; Valta, Helena; Taskinen, Mervi; Husebye, Eystein Sverre; Mäkitie, Outi (2018)
    Background: Mutations in RMRP, encoding a non-coding RNA molecule, underlie cartilage-hair hypoplasia (CHH), a syndromic immunodeficiency with multiple pathogenetic mechanisms and variable phenotype. Allergy and asthma have been reported in the CHH population and some patients suffer from autoimmune (AI) diseases. Objective: We explored AI and allergic manifestations in a large cohort of Finnish patients with CHH and correlated clinical features with laboratory parameters and autoantibodies. Methods: We collected clinical and laboratory data from patient interviews and hospital records. Serum samples were tested for a range of autoantibodies including celiac, anti-cytokine, and anti-21-hydroxylase antibodies. Nasal cytology samples were analyzed with microscopy. Results: The study cohort included 104 patients with genetically confirmed CHH; their median age was 39.2 years (range 0.6-73.6). Clinical autoimmunity was common (11/104, 10.6%) and included conditions previously undescribed in subjects with CHH (narcolepsy, psoriasis, idiopathic thrombocytopenic purpura, and multifocal motor axonal neuropathy). Patients with autoimmunity more often had recurrent pneumonia, sepsis, high immunoglobulin (Ig) E and/or undetectable IgA levels. The mortality rates were higher in subjects with AI diseases (X-(2)(2) = 14.056, p = 0.0002). Several patients demonstrated serum autoantibody positivity without compatible symptoms. We confirmed the high prevalence of asthma (23%) and allergic rhinoconjunctivitis (39%). Gastrointestinal complaints, mostly persistent diarrhea, were also frequently reported (32/104, 31%). Despite the history of allergic rhinitis, no eosinophils were observed in nasal cytology in five tested patients. Conclusions: AI diseases are common in Finnish patients with CHH and are associated with higher mortality, recurrent pneumonia, sepsis, high IgE and/or undetectable IgA levels. Serum positivity for some autoantibodies was not associated with clinical autoimmunity. The high prevalence of persistent diarrhea, asthma, and symptoms of inflammation of nasal mucosa may indicate common pathways of immune dysregulation.
  • Umeizudike, Kehinde Adesola; Lähteenmäki, Hanna; Räisänen, Ismo T.; Taylor, John J.; Preshaw, Philip M.; Bissett, Susan M.; Tervahartiala, Taina; O Nwhator, Solomon; Pärnänen, Pirjo; Sorsa, Timo (2022)
    Objective: The aim of this study was to determine the diagnostic utility of an MMP-8 biosensor assay in differentiating periodontal health from gingivitis and periodontitis and compare it with an established time-resolved immunofluorescence assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). Background: Currently available antibody-based assays display a wide variability in their ability to accurately measure matrix metalloproteinase-8 (MMP-8) levels in saliva. Methods: Salivary MMP-8 levels were analyzed in 189 systemically healthy participants using an antibody-based biosensor prototype that operates using a surface acoustic wave technology and compared with IFMA and ELISA antibody assays. Participants were categorized into 3 groups: periodontal health (59), gingivitis (63), and periodontitis (67). A sub-population of participants (n = 20) with periodontitis received periodontal treatment and were monitored for 6 months. Results: All the assays demonstrated significantly higher salivary MMP-8 concentrations in participants with periodontitis versus gingivitis, periodontitis versus health, and gingivitis versus health (all p <.05). The biosensor data demonstrated significant correlations with IFMA (r =.354, p <.001) and ELISA (r =.681, p <.001). Significant reductions in salivary MMP-8 concentrations were detected by the biosensor (p =.030) and IFMA (p =.002) in participants with periodontitis 6 months after non-surgical periodontal treatment. IFMA had the best sensitivity (89.2%) for detecting periodontitis and gingivitis versus health and 96.6% for detecting periodontitis versus health and gingivitis. The biosensor had an AUC value of 0.81 and diagnostic accuracy of 74.2% for differentiating periodontitis and gingivitis from health; an AUC value of 0.86 and diagnostic accuracy of 82.8% for periodontitis versus health and gingivitis. Conclusions: The biosensor, IFMA, and ELISA assays differentiated between periodontal health, gingivitis, and periodontitis based on salivary MMP-8 levels. Only the biosensor and, particularly, IFMA identified an effect of periodontal treatment in the participants with periodontitis. Our findings support the potential utility of salivary oral fluid aMMP-8-based point-of-care technology in the future of periodontal diagnostics.
  • Wuokko-Landen, Annina; Blomgren, Karin; Välimaa, Hannamari (2019)
    Background: Odontogenic sinusitis (OS) is a common but underdiagnosed form of acute rhinosinusitis (ARS). OS carries no specific characteristics, but unilateral symptoms and certain microbiological as well as radiological findings indicate odontogenic origin. Aims/objectives: We studied the proportion of OS in ARS patients, the presence and associations of unilateral symptoms, and possible OS microbial and radiological findings. In addition, we investigated how this condition is recognised among ear, nose and throat specialists and radiologists. Materials and methods: All 676 ARS patients treated in the Department of Otorhinolaryngology at Helsinki University Hospital in 2013 were retrospectively enrolled. The data were collected from patients' hospital medical records, the laboratory database and radiological reports. Results: Odontogenic origin of ARS was suspected in 59 (15.3%) patients. Altogether (29.9%) 115 patients complained of unilateral symptoms and these were found to associate with probable oral microbial findings (p <.001). These findings covered 20.2% of isolates. Teeth were mentioned in 89.6% of the radiological reports.
  • Dohner, Hartmut; Symeonidis, Argiris; Deeren, Dries; Demeter, Judit; Sanz, Miguel A.; Anagnostopoulos, Achilles; Esteve, Jordi; Fiedler, Walter; Porkka, Kimmo; Kim, Hee-Je; Lee, Je-Hwan; Usuki, Kensuke; D'Ardia, Stefano; Won Jung, Chul; Salamero, Olga; Horst, Heinz-August; Recher, Christian; Rousselot, Philippe; Sandhu, Irwindeep; Theunissen, Koen; Thol, Felicitas; Dohner, Konstanze; Teleanu, Veronica; DeAngelo, Daniel J.; Naoe, Tomoki; Sekeres, Mikkael A.; Belsack, Valerie; Ge, Miaomiao; Taube, Tillmann; Ottmann, Oliver G. (2021)
    In this phase 3 trial, older patients with acute myeloid leukemia ineligible for intensive chemotherapy were randomized 2:1 to receive the polo-like kinase inhibitor, volasertib (V; 350 mg intravenous on days 1 and 15 in 4-wk cycles), combined with low-dose cytarabine (LDAC; 20 mg subcutaneous, twice daily, days 1-10; n = 444), or LDAC plus placebo (P; n = 222). Primary endpoint was objective response rate (ORR); key secondary endpoint was overall survival (OS). Primary ORR analysis at recruitment completion included patients randomized >= 5 months beforehand; ORR was 25.2% for V+LDAC and 16.8% for P+LDAC (n = 371; odds ratio 1.66 [95% confidence interval (CI), 0.95-2.89]; P = 0.071). At final analysis (>= 574 OS events), median OS was 5.6 months for V+LDAC and 6.5 months for P+LDAC (n = 666; hazard ratio 0.97 [95% CI, 0.8-1.2]; P = 0.757). The most common adverse events (AEs) were infections/infestations (grouped term; V+LDAC, 81.3%; P+LDAC, 63.5%) and febrile neutropenia (V+LDAC, 60.4%; P+LDAC, 29.3%). Fatal AEs occurred in 31.2% with V+LDAC versus 18.0% with P+LDAC, most commonly infections/infestations (V+LDAC, 17.1%; P+LDAC, 6.3%). Lack of OS benefit with V+LDAC versus P+LDAC may reflect increased early mortality with V+LDAC from myelosuppression and infections.
  • Hagström, Hannes; Adams, Leon A.; Allen, Alina M.; Byrne, C.D.; Chang, Y.; Grønbæk, H.; Ismail, M.; Jepsen, P.; Kanwal, F.; Kramer, J.; Lazarus, J.V.; Long, M.T.; Loomba, R.; Newsome, P.N.; Rowe, I.A.; Ryu, S.; Schattenberg, J.M.; Serper, M.; Sheron, N.; Simon, T.G.; Tapper, E.B.; Wild, S.; Wong, V.W.-S.; Yilmaz, Y.; Zelber-Sagi, S.; Åberg, Fredrik (2021)
    Background and Aims Electronic health record (EHR)-based research allows the capture of large amounts of data, which is necessary in NAFLD, where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Diseases (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues. Approach and Results Researchers with an interest in EHR-based NAFLD research were invited to collectively define which administrative codes are most appropriate for documenting exposures and outcomes. We used a modified Delphi approach to reach consensus on several commonly encountered methodological challenges in the field. After two rounds of revision, a high level of agreement (>67%) was reached on all items considered. Full consensus was achieved on a comprehensive list of administrative codes to be considered for inclusion and exclusion criteria in defining exposures and outcomes in EHR-based NAFLD research. We also provide suggestions on how to approach commonly encountered methodological issues and identify areas for future research. Conclusions This expert panel consensus statement can help harmonize and improve generalizability of EHR-based NAFLD research.
  • Viukari, Marianna; Kokko, Eeva; Pörsti, Ilkka; Leijon, Helena; Vesterinen, Tiina; Hinkka, Tero; Soinio, Minna; Schalin-Jäntti, Camilla; Matikainen, Niina; Nevalainen, Pasi (2022)
    Objective We examined if measurement of adrenal androgens adds to subtype diagnostics of primary aldosteronism (PA) under cosyntropin-stimulated adrenal venous sampling (AVS). Design A prospective pre-specified secondary endpoint analysis of 49 patients with confirmed PA, of whom 29 underwent unilateral adrenalectomy with long-term follow-up. Methods Concentrations of androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were measured during AVS in addition to aldosterone and cortisol. Subjects with lateralisation index (LI) of >= 4 were treated with unilateral adrenalectomy, and the immunohistochemical subtype was determined with CYP11B2 and CYP11B1 stains. The performance of adrenal androgens was evaluated by receiver operating characteristics (ROC) curve analyses in adrenalectomy and medical therapy groups. Results During AVS, the correlations between cortisol and androstenedione, DHEA and DHEAS for LI and selectivity index (SI) were highly significant. The right and left side SIs for androstenedione and DHEA were higher (p < .001) than for cortisol. In ROC analysis, the optimal LI cut-off values for androstenedione, DHEA and DHEAS were 4.2, 4.5 and 4.6, respectively. The performance of these LIs for adrenal androgens did not differ from that of cortisol. Conclusions Under cosyntropin-stimulated AVS, the measurement of androstenedione and DHEA did not improve the cannulation selectivity. The performance of cortisol and adrenal androgens are confirmatory but not superior to cortisol-based results in lateralisation diagnostics of PA.