Prediction of renal outcome in Henoch-Schonlein nephritis based on biopsy findings

Background In Henoch-Schonlein nephritis (HSN), a risk factor for unfavorable outcome is prolonged proteinuria, but the value of renal biopsies in prognosis assessment is debatable. Methods We evaluated serial renal biopsies from 26 HSN patients. Follow-up biopsy occurred at median 2.1 years after diagnostic biopsy. Patients formed two groups at the follow-up biopsy: patients without proteinuria (group I; n = 11) and with proteinuria (group II; n = 15). Biopsies underwent evaluation according to three classifications: International Study of Kidney Disease in Children (ISKDC), Oxford (MEST-C), and semiquantitative classification (SQC) including an activity and chronicity score. Analysis also included expression of pro-fibrotic (alpha-smooth muscle actin and vimentin) and inflammatory (P-selectin glycoprotein ligand-1) molecules in the diagnostic biopsy specimens. Definition of unfavorable outcome was active renal disease or reduced renal function at last follow-up. Results Between the biopsies, SQC chronicity score increased in 22 (85%) patients, whereas activity score and ISKDC grade decreased in 21 (81%) and 17 (65%), respectively. Of the MEST-C parameters, endocapillary proliferation (from 83 to 13%; p <0.001) and crescents (from 63 to 25%; p = 0.022) showed significant reduction, and segmental glomerulosclerosis (from 38 to 79%; p = 0.006) significant increment. These changes occurred similarly in groups I and II. Expression of the pro-fibrotic and inflammatory molecules showed no clinically significant differences between groups I and II. None in group I and five (33%) patients in group II had unfavorable outcome (p = 0.053). Conclusions Our results suggest that follow-up biopsies provide limited additional information to clinical symptoms in HSN outcome prediction.Peer reviewe

Severe ulcerative proctitis, pyoderma gangrenosum, hidradenitis suppurativa and fever in a patient with a rare variant of the PSTPIP1 gene

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A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn's disease patients in Finland

Background Real-world evidence to support optimal ustekinumab dosing for refractory Crohn's disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland. Methods Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017-2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability. Results Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period. Conclusions Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification.Peer reviewe

Evaluation of the Finnish National Biodiversity Action Plan 1997-2005

The results of the evaluation of the Finnish National Biodiversity Action Plan 1997-2005 indicate clear changes towards better consideration of biodiversity in the routines and policies of many sectors of the administration and economy. There are many indications that actors across society have recognized the need to safeguard biodiversity and have begun to adjust their practices accordingly. Several concrete measures have been undertaken in forests, agricultural habitats and in other habitats significantly affected by human activities. Biodiversity research has expanded significantly and the knowledge of Finland´s biological diversity has increased. In general, the Action Plan has supported public discussion of the need to safeguard biodiversity and this discussion has resulted in more positive attitudes towards nature conservation.So far, however, the implemented measures have not been sufficiently numerous or efficient to stop the depletion of original biological diversity. Many habitats remain far from their original state. More species will become endangered in the immediate future unless more effective and far-reaching measuresare taken. The objective of the EU to halt the decline of biodiversity by 2010 will not be achieved given the current development. Although the deterioration in biodiversity may have slowed down in several cases, many economic activities continue to have a negative impact on biodiversity. The scale of these activities is normally greater than that of the measures taken to manage and restore biodiversity.The evaluation focused on detecting changes in the administration of key sectors, analysing the recent development of biodiversity and observing interlinkages between these two. The analysis of administrative measures was based on interviews and on examining policy documents, reports and other relevant literature. The analysis covered changes in the administration of nature conservation, forestry,  agriculture, land use and regional and development cooperation. The analysis of the development of biodiversity was based on employing 75 pressure, state, impact and response indicators. There were 5 to 15 indicators for each of the nine major habitat types of Finland.Three separate case studies were made to provide further insights into some key issues: 1) A GISanalysis was made of the development of land use patterns in North Karelia and south-west Finland between 1990 and 2000, 2) two scenarios on the development of forest structure in North Karelia until 2050 were developed using a special MELA-model and 3) the cost-effectiveness of the agri-environmental support scheme was examined by comparing different land allocation choices and their effects on biodiversity on an average farm in southern Finland. The evaluation also paid special attention to the role of research in safeguarding biodiversity and reflected Finnish experiences against an international background

Metsät ilmastosopimuksessa ja Kioton pöytäkirjassa

Ilmakehän kasvihuonekaasupitoisuus kasvaa. Merkittävin ihmisen toiminnasta aiheutuva kasvihuonekaasu on hiilidioksidi. Muita merkittäviä kasvihuonekaasuja ovat metaani ja dityppioksidi. Metsällä on merkittävä rooli hiilidioksidin sitojana ja hiilen varastona. Kasvillisuuteen sitoutunut hiilivarasto on likimain yhtä suuri kuin ilmakehän hiilimäärä. Maapallon metsien yhteyttämistoiminta sitoo ilmakehästä vuosittain suuren määrän hiiltä ja osa tästä varastoituu puuaineeksi ja siten kasvattaa puuston hiilivarastoa. Nielulla tarkoitetaan juuri tätä prosessia, jossa kasvihuonekaasu sitoutuu ja varastoituu kasvillisuuteen tai maaperään. Ilmakehän hiilidioksidipitoisuuden kehitykseen voidaan metsäsektorin toimenpitein vaikuttaa periaatteessa kolmella eri tavalla: (i) suojelemalla ja lisäämällä olemassa olevia hiilivarastoja ja nieluja, (ii) perustamalla uusia hiilivarastoja ja nieluja sekä (iii) korvaamalla fossiilista energiaa, raaka-aineita ja tuotteita uusiutuvalla biomassalla. Vuonna 1992 Rio de Janeirossa, YK:n ympäristö- ja kehityskonferenssissa allekirjoitettiin ilmastosopimus, jonka tavoitteena on vakiinnuttaa ilmakehän kasvihuonekaasupitoisuus turvalliselle tasolle. Kioton pöytäkirjassa vuonna 1997 määriteltiin teollisuus- ja siirtymätalousmaille päästövähennys- ja rajoittamisvelvoitteet ensimmäiselle sitoumuskaudelle 2008-2012. EU:n sisäisen, vuonna 1998 sovitun, taakanjaon mukaan Suomen tulee rajoittaa päästönsä vuoden 1990 tasolle. Kioton pöytäkirjaan on sisällytetty nielut rajoitetussa määrin. Pöytäkirjan mukainen nielu lasketaan metsien hiilivaraston muutoksena. Kioton pöytäkirjan artikloissa 3.3 (metsitys ja metsien hävittäminen), 3.4 (erikseen sovittavat metsiä koskevat lisätoimet) sekä myös artiklassa 3.7 rajataan tarkastelutapaa ja viitataan nielulaskentaan, mutta nieluihin liittyvistä määritelmistä ja laskentatavoista ei ole vielä sovittu kansainvälisesti. Nielut liittyvät myös Kioton pöytäkirjan joustomekanismeihin. Kioton pöytäkirjassa on sovittu tietyistä periaatteista, kuten että hyvitettävän nielun tulee olla ihmistoiminnasta aiheutunutta ja että sen tulee olla todennettavissa. Tulevien päätösten tueksi Hallitustenvälinen ilmastopaneli (IPCC) valmistelee maankäyttöä, maankäytön muutosta ja metsätaloutta koskevan erikoisraportin. Lisäksi valtioiden tulee toimittaa maakohtaisia tietoja tulevien päätösten tueksi. Työryhmä katsoo, että ilmastonmuutoksen hillitsemiseksi ensisijainen tehtävä on fossiilisten polttoaineiden käytöstä aiheutuvien päästöjen vähentäminen. Nielujen ylläpitäminen ja vahvistaminen sekä uudistuvien luonnonvarojen käytön kehittäminen ovat päästöjen vähentämisen tukena. Maa- ja metsätalousministeriön vuonna 1998 asettaman työryhmän tavoitteena on ollut tarkastella ilmastosopimuksen ja Kioton pöytäkirjan vaikutuksia metsä- ja maatalouden näkökulmasta. Raportissa esitetään arvioita nielujen erilaisista vaikutuksista maallemme sekä tarkastellaan erilliskysymyksiä kuten inventointi- ja raportointikäytäntöjen kehittämistä, metsätuotteiden hiilisisällön huomioonottamista, bioenergian käytön lisäämistä ja liittymäkohtia maatalouteen. Työryhmän esittämät johtopäätökset ja ehdotukset tukevat ilmastosopimuksen toimeenpanon ja jatkoneuvotteluiden metsiä sivuavien kantojen valmistelua sekä kansallisella että kansainvälisellä tasolla

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn's disease patients in Finland

Background Real-world evidence to support optimal ustekinumab dosing for refractory Crohn's disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland.Methods Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017-2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability.Results  Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period.Conclusions Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification.</div

Ustekinumab for Crohn's disease: a nationwide real-life cohort study from Finland (FINUSTE)

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn's Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD. Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48 CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey-Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn's disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up. Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p = .0001) and SES-CD from 12 to 3 (p = .009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up. Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed

Ustekinumab for Crohn’s disease: a nationwide real-life cohort study from Finland (FINUSTE)

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn?s Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD.Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48?CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey?Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn?s disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up.Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p?=?.0001) and SES-CD from 12 to 3 (p?=?.009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up.Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed.Peer reviewe

Emissions from a modern log wood masonry heater and wood pellet boiler : Composition and biological impact on air-liquid interface exposed human lung cancer cells

The consumption of wood fuel is markedly increasing in developing and industrialized countries. Known side effects of wood smoke inhalation manifest in proinflammatory signaling, oxidative stress, DNA damage and hence increased cancer risk. In this study, the composition and acute biological impact of emissions of state-of-the-art wood combustion compliances: masonry heater (MH) and pellet boiler (PB) were investigated. Therefore A549 cells were exposed to emission aerosols in an automated air-liquid interface exposure station followed by cytotoxicity, transcriptome and proteome analyses. In parallel, aerosols were subjected to a chemical and physical haracterization. Compared to PB, the MH combustion at the same dilution ratio resulted in a 3-fold higher particle mass concentration (PM2.5) and deposited dose (PB: 27 $\pm$ 2 ng/cm2, MH; 73 $\pm$ 12 ng/cm2). Additionally, the MH aerosol displayed a substantially larger concentration of aldehydes, polycyclic aromatic hydrocarbons (PAH) or oxidized PAH. Gene ontology analysis of transcriptome of A549 cells exposed to MH emissions revealed the activation of proinflammatory response and key signaling cascades MAP kinase and JAK-STAT. Furthermore, CYP1A1, an essential enzyme in PAH metabolism, was induced. PB combustion aerosol activated the proinflammatory marker IL6 and different transport processes. The proteomics data uncovered induction of DNA damage-associated proteins in response to PB and DNA doublestrand break processing proteins in response to MH emissions. Taking together, the MH produces emissions with a higher particle dose and more toxic compounds while causing only mild biological responses. This finding points to a significant mitigating effect of antioxidative compounds in MH wood smoke