Publications by authors named "Heini Huhtala"

489 Publications

Human induced pluripotent stem cell-based platform for modeling cardiac ischemia.

Sci Rep 2021 Feb 18;11(1):4153. Epub 2021 Feb 18.

Heart Group, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520, Tampere, Finland.

Ischemic heart disease is a major cause of death worldwide, and the only available therapy to salvage the tissue is reperfusion, which can initially cause further damage. Many therapeutics that have been promising in animal models have failed in human trials. Thus, functional human based cardiac ischemia models are required. In this study, a human induced pluripotent stem cell derived-cardiomyocyte (hiPSC-CM)-based platform for modeling ischemia-reperfusion was developed utilizing a system enabling precise control over oxygen concentration and real-time monitoring of the oxygen dynamics as well as iPS-CM functionality. In addition, morphology and expression of hypoxia-related genes and proteins were evaluated as hiPSC-CM response to 8 or 24 h hypoxia and 24 h reoxygenation. During hypoxia, initial decrease in hiPSC-CM beating frequency was observed, after which the CMs adapted to the conditions and the beating frequency gradually increased already before reoxygenation. During reoxygenation, the beating frequency typically first surpassed the baseline before settling down to the values close the baseline. Furthermore, slowing on the field potential propagation throughout the hiPSC-CM sheet as well as increase in depolarization time and decrease in overall field potential duration were observed during hypoxia. These changes were reversed during reoxygenation. Disorganization of sarcomere structures was observed after hypoxia and reoxygenation, supported by decrease in the expression of sarcomeric proteins. Furthermore, increase in the expression of gene encoding glucose transporter 1 was observed. These findings indicate, that despite their immature phenotype, hiPSC-CMs can be utilized in modeling ischemia-reperfusion injury.
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http://dx.doi.org/10.1038/s41598-021-83740-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893031PMC
February 2021

Long-Term Follow-Up After Maxillary Sinus Balloon Sinuplasty and ESS.

Ear Nose Throat J 2021 Feb 19:145561320986030. Epub 2021 Feb 19.

Skin and Allergy Hospital, 159841Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Objectives: The aim of this controlled follow-up study was to compare the need for revision surgery, long-term efficacy, and satisfaction in chronic rhinosinusitis patients who had undergone maxillary sinus operation with either balloon sinuplasty or traditional endoscopic sinus surgery (ESS) technique.

Methods: Thirty-nine ESS patients and 36 balloon patients of our previously described cohort, who had been primarily operated in 2008 to 2010, were contacted by phone. Symptoms, satisfaction, and need for revision surgery were asked. In addition, we collected data of patients who had undergone primary maxillary sinus balloon sinuplasty in the Helsinki University Hospital during the years 2005 to 2019. As a control group, we collected data of patients who had undergone primary maxillary sinus ESS at 3 Finnish University Hospitals, and 1 Central Hospital in years 2005, 2008, and 2011.

Results: Altogether, 77 balloon patients and 82 ESS patients were included. The mean follow-up time was 5.3 years in balloon group and 9.8 years in ESS group. Revision surgery was performed on 17 balloon patients and 6 ESS patients. In the survival analysis, the balloon sinuplasty associated significantly with a higher risk of revision surgery compared to ESS. According to the phone interviews, 82% of ESS patients and 75% of balloon patients were very satisfied with the primary operation.

Conclusion: Although the patient groups expressed equal satisfaction and change in symptoms after the operations, the need for revision surgery was higher after balloon sinuplasty than after ESS. This should be emphasized when counselling patients regarding surgical options.
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http://dx.doi.org/10.1177/0145561320986030DOI Listing
February 2021

Newly graduated nurses' evaluation of the received orientation and their perceptions of the clinical environment: An intervention study.

Scand J Caring Sci 2021 Feb 1. Epub 2021 Feb 1.

Faculty of Social Sciences, Tampere University, Tampere, Finland.

Background: New graduate nurses (NGN) are the future of healthcare organizations where a shortage of nurses will soon be reality. The transition from a student to a registered nurse can be a demanding and challenging time, and in order to retain new graduate nurses, the transition should be as smooth as possible.

Aim: The aim of this study was to examine preceptors' education intervention's impact on NGNs' orientation period and their clinical learning environment from NGNs' point of view.

Material And Methods: This survey was a part of a longitudinal quasi-experimental intervention study. Participating units were randomized into intervention group and control group. The intervention group's preceptors (n=174)were provided a face-to-face education about orientation.

Results: NGNs (n=72) were relatively satisfied with the received orientation. However, intervention group was more discontented with their orientation experiences than the control group. The control group's NGNs had longer orientation periods and more feedback discussions. They were also more satisfied with their preceptor's orientation skills and their working environment was more responsive.

Discussion: Even though the impact of the intervention was inconclusive, this study provided us important information about NGNs' first steps towards the nursing profession by giving us clear improvement targets. We need a culture of feedback, individualized orientation and understanding that orientation should be our common interest. Investing in orientation is investing for the future.

Conclusion: This study indicated that the increase in knowledge did not translate into everyday practice. This finding will hopefully give rise to discussion within organizations on how to utilize employees' gained knowledge more effectively.
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http://dx.doi.org/10.1111/scs.12963DOI Listing
February 2021

Risk factors of readmission after geriatric hospital care: An interRAI-based cohort study in Finland.

Arch Gerontol Geriatr 2021 Jan 20;94:104350. Epub 2021 Jan 20.

Tampere University, Faculty of Medicine and Health Technology, and the Gerontology Research Centre (GEREC), P.O. Box 100, 33014 Tampere University, Finland; Tampere University Hospital, Centre of Geriatrics, Elämänaukio 2, 33520 Tampere, Finland.

Purpose: To identify risk factors for readmission after geriatric hospital care.

Methods: A retrospective cohort study of 1,167 community-dwelling patients aged ≥70 years who were hospitalised in two geriatric hospitals and discharged to their homes over a three-year period. We combined the results of the interRAI-post acute care instrument (interRAI-PAC) with hospital discharge records. Factors associated with readmissions within 90 days following discharge were analysed using logistic regression analysis.

Results: The patients' mean age was 84.5 (SD 6.2) years, and 71% (n = 827) were women. The 90-day readmission rate was 29.5%. The risk factors associated with readmission in the univariate analysis were as follows: age, admission from home vs. acute care hospital, Alzheimer's disease, unsteady gait, fatigue, unstable conditions, Activities of Daily Living Hierarchy Scale (ADLH) score, Cognitive Performance Scale (CPS) score, body mass index (BMI), frailty index, bowel incontinence, hearing difficulties, and poor self-rated health. In the multivariable analysis, age of ≥90 years, ADLH ≥1, unsteady gait, BMI <25 or ≥30 kg/m 2 , and frailty remained as risk factors for readmission. Surgical operation during the treatment period was associated with a lower readmission risk.

Conclusions And Implications: InterRAI-PAC performed upon admission to geriatric hospitals revealed patient-related risk factors for readmission. Based on the identified risk factors, we recommend that the patient's functional ability, activities of daily living (ADL) needs, and individual factors underlying ADL disability, as well as nutritional and mobility problems should be carefully addressed and managed during hospitalization to diminish the risk for readmission.
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http://dx.doi.org/10.1016/j.archger.2021.104350DOI Listing
January 2021

Long-term outcome of patients with acute ulcerative colitis after first course of intravenous corticosteroids.

Scand J Gastroenterol 2021 Jan 26:1-8. Epub 2021 Jan 26.

Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.

Background And Aims: Every fifth patient with ulcerative colitis (UC) experiences severe acute flare at some point in the course of the disease. Corticosteroids (Cs) remain the treatment of choice in acute flare. Data on the efficacy of first intravenous Cs in the long-term prognosis of UC are scarce and were investigated here.

Materials And Methods: All episodes of patients with acute UC admitted to Tampere University Hospital and treated with intravenous Cs between January 2007 and January 2016 were identified from patient records and reviewed. The risks for colectomy and for continuous use of Cs were evaluated. Predictive factors were analysed.

Results: The study comprised 217 patients of whom 184 (85%) responded to intravenous Cs at index flare. Of the 33 non-responders, 31 (94%) were treated with intravenous cyclosporine A and 28 responded. Five (2.3%) patients needed emergency colectomy. Twenty-six (12%) patients underwent colectomy within 1 year of index flare. Overall colectomy rate was 56 (26%) during follow-up (median 7.5 years, range 0.1-10.5). Six months after index flare 66 (30%) patients were still on steroids. In this series 149 (69%) required further Cstherapy and 104 (48%) needed rehospitalization for new flare at some point during follow-up. Overall 155 patients were treated with thiopurines, of whom 72% within the first year after admission. A total of 36 patients had infliximab as a first-line biological treatment, nine needed second-line therapy with adalimumab or vedolizumab after infliximab failed.

Conclusion: Although intravenous Cs were efficient in inducing clinical response in patients with severe acute UC, only one fifth maintained remission in the long term. Two-thirds of patients required further Cs and the overall colectomy rate remained at 26%. High relapse rate indicates the need for closer monitoring of these patients. Enhancement of maintenance therapy should be considered at early stage after acute flare.
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http://dx.doi.org/10.1080/00365521.2020.1867892DOI Listing
January 2021

Independent and cumulative coeliac disease-susceptibility loci are associated with distinct disease phenotypes.

J Hum Genet 2021 Jan 15. Epub 2021 Jan 15.

Coeliac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

The phenotype of coeliac disease varies considerably for incompletely understood reasons. We investigated whether established coeliac disease susceptibility variants (SNPs) are individually or cumulatively associated with distinct phenotypes. We also tested whether a polygenic risk score (PRS) based on genome-wide associated (GWA) data could explain the phenotypic variation. The phenotypic association of 39 non-HLA coeliac disease SNPs was tested in 625 thoroughly phenotyped coeliac disease patients and 1817 controls. To assess their cumulative effects a weighted genetic risk score (wGRS39) was built, and stratified by tertiles. In our PRS model in cases, we took the summary statistics from the largest GWA study in coeliac disease and tested their association at eight P value thresholds (P) with phenotypes. Altogether ten SNPs were associated with distinct phenotypes after correction for multiple testing (P ≤ 0.05). The TLR7/TLR8 locus was associated with disease onset before and the SH2B3/ATXN2, ITGA4/UBE2E3 and IL2/IL21 loci after 7 years of age. The latter three loci were associated with a more severe small bowel mucosal damage and SH2B3/ATXN2 with type 1 diabetes. Patients at the highest wGRS39 tertiles had OR > 1.62 for having coeliac disease-related symptoms during childhood, a more severe small bowel mucosal damage, malabsorption and anaemia. PRS was associated only with dermatitis herpetiformis (P = 0.2, P = 0.02). Independent coeliac disease-susceptibility loci are associated with distinct phenotypes, suggesting that genetic factors play a role in determining the disease presentation. Moreover, the increased number of coeliac disease susceptibility SNPs might predispose to a more severe disease course.
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http://dx.doi.org/10.1038/s10038-020-00888-5DOI Listing
January 2021

The role of Pap smear in the diagnostics of endocervical adenocarcinoma.

APMIS 2021 Jan 14. Epub 2021 Jan 14.

Pathology, Fimlab Laboratories, Tampere, Finland.

In the high-income countries, the amount of cervical adenocarcinomas is on the rise. The pap smear sampling has a low sensitivity and a low specificity for endocervical malignancies, and there are only a few cytomorphological features, that are specifically associated with glandular atypia. In this study, 298 pap smears of 60 patients with endocervical adenocarcinoma or adenocarcinoma in situ (AIS) and 30 patients with high-grade intraepithelial lesion (HSIL) in histology were reviewed. The pap smear type (screening/clinical), the HPV status and the time from sampling to the histological confirmation of diagnosis were recorded for each case. Despite that no cytomorphological features could be associated with adenocarcinoma statistically, 70% of the pap smears were initially correctly diagnosed as an endocervical glandular lesion. Palisading cell borders, nuclear pleomorphism and the lack of single atypical cells present simultaneously were found to be associated with adenocarcinoma and AIS with the corresponding ORs of 5.89 (95% CI 1.96-17.70), 3.71 (95% CI 1.14-12.02) and 10.76 (95% CI 1.20-59.50). This combination of features was seen in smears taken up to 5 years before the histological diagnosis. Of all our screening samples, 10.9% were HPV-positive. There were no HPV-negative samples among patients with adenocarcinoma.
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http://dx.doi.org/10.1111/apm.13115DOI Listing
January 2021

Asthma Remission by Age at Diagnosis and Gender in a Population-Based Study.

J Allergy Clin Immunol Pract 2020 Dec 15. Epub 2020 Dec 15.

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden. Electronic address:

Background: Child-onset asthma is known to remit with high probability, but remission in adult-onset asthma is seemingly less frequent. Reports of the association between remission and asthma age of onset up to late adulthood are scarce.

Objective: To evaluate the association between asthma remission, age at diagnosis and gender, and assess risk factors of nonremission.

Methods: In 2016, a random sample of 16,000 subjects aged 20 to 69 years from Helsinki and Western Finland were sent a FinEsS questionnaire. Physician-diagnosed asthma was categorized by age at diagnosis to early- (0-11 years), intermediate- (12-39 years), and late-diagnosed (40-69 years) asthma. Asthma remission was defined by not having had asthma symptoms and not having used asthma medication in the past 12 months.

Results: Totally, 8199 (51.5%) responded, and 879 reported physician-diagnosed asthma. Remission was most common in early-diagnosed (30.2%), followed by intermediate-diagnosed (17.9%), and least common in late-diagnosed asthma (5.0%) (P < .001), and the median times from diagnosis were 27, 18.5, and 10 years, respectively. In males, the corresponding remission rates were 36.7%, 20.0%, and 3.4%, and in females, 20.4%, 16.6%, and 5.9% (gender difference P < .001). In multivariable binary logistic regression analysis, significant risk factors of asthma nonremission were intermediate (odds ratio [OR] = 2.15, 95% confidence interval: 1.37-3.36) and late diagnosis (OR = 11.06, 4.82-25.37) compared with early diagnosis, chronic obstructive pulmonary disease (COPD) (OR = 5.56, 1.26-24.49), allergic rhinitis (OR = 2.28, 1.50-3.46), and family history of asthma (OR = 1.86, 1.22-2.85). Results were similar after excluding COPD.

Conclusion: Remission was rare in adults diagnosed with asthma after age 40 years in both genders. Late-diagnosed asthma was the most significant independent risk factor for nonremission.
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http://dx.doi.org/10.1016/j.jaip.2020.12.015DOI Listing
December 2020

Influence of HLA-DQ2.5 Dose on Clinical Picture of Unrelated Celiac Disease Patients.

Nutrients 2020 Dec 9;12(12). Epub 2020 Dec 9.

Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.

The clinical phenotype of celiac disease varies considerably among patients and the dosage of HLA-DQ2.5 alleles has been suggested to be a contributing factor. We investigated whether HLA-DQ2.5 allele dosage is associated with distinct clinical parameters at the time of diagnosis and with patients' response to a gluten-free diet. The final cohort included 605 carefully phenotyped non-related Finnish celiac disease patients grouped as having 0, 1 or 2 copies of HLA-DQ2.5. Clinical data at the time of diagnosis and during gluten-free diet were collected systematically from medical records and supplementary interviews. An increasing HLA-DQ2.5 dose effect was detected for celiac disease antibody positivity at diagnosis ( = 0.021) and for the presence of any first-degree relatives with celiac disease ( = 0.011 and = 0.031, respectively). Instead, DQ2.5-negative patients were suffering most often from classical symptoms at diagnosis ( = 0.007 between HLA groups). In addition, during follow-up they were most often symptomatic despite a gluten-free diet ( = 0.002 between groups). Our results thus suggest that increasing HLA-DQ2.5 dose only has a minor effect on the clinical picture of celiac disease. However, HLA-DQ2.5-negative patients should not be overlooked in clinical practice and particular attention should be paid to this patient group during gluten-free diet.
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http://dx.doi.org/10.3390/nu12123775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764246PMC
December 2020

New technology may help perioperative glucose management but not without a dedicated team?

Acta Anaesthesiol Scand 2020 Dec 14. Epub 2020 Dec 14.

Department of Medicine, Turku University Hospital, Turku, Finland.

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http://dx.doi.org/10.1111/aas.13762DOI Listing
December 2020

Prognostic value of the 2010 consensus definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

J Neurol Sci 2021 01 7;420:117261. Epub 2020 Dec 7.

Tampere University Hospital, Department of Intensive Care, Tampere, Finland; Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland.

Background And Purpose: Delayed cerebral ischemia (DCI) complicates the recovery of approximately 30% of patients with aneurysmal subarachnoid hemorrhage (aSAH). The definition of DCI widely varies, even though a consensus definition has been recommended since 2010. This study aimed to evaluate the prognostic value of the 2010 consensus definition of DCI in a cohort of patients with aSAH.

Methods: We conducted a single-center, retrospective, observational study that included consecutive adult patients with aSAH who were admitted to the intensive care unit from January 2010 to December 2014. DCI was evaluated 48 h to 14 days after onset of aSAH symptoms using the 2010 consensus criteria and outcome was assessed by the Glasgow Outcome Scale (GOS) at discharge from hospital.

Results: A total of 340 patients were analyzed and the incidence of DCI was 37.1%. The median time from primary hemorrhage to the occurrence of DCI was 97 h. Neurological deterioration was observed in most (89.7%) of the patients who fulfilled the DCI criteria. The occurrence of DCI was strongly associated with an unfavorable outcome (GOS 1-3) at hospital discharge (OR 2.65, 95% CI 1.69-4.22, p < 0.001).

Conclusions: The incidence of DCI after aSAH is high and its occurrence is strongly associated with an unfavorable neurological outcome. This finding adds to the previous literature, which has shown that DCI appears to be a major contributor affecting the functional ability of survivors of aSAH. To further advance reliable knowledge of DCI, future studies should adhere to the consensus definition of DCI.
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http://dx.doi.org/10.1016/j.jns.2020.117261DOI Listing
January 2021

Toll-like receptor 10 rs10004195 variation may be protective against Bacillus Calmette-Guérin osteitis after newborn vaccination.

Acta Paediatr 2020 Dec 14. Epub 2020 Dec 14.

Institute of Biomedicine, University of Turku, Turku, Finland.

Aim: Toll-like receptor 1 (TLR1), TLR2, TLR6 and TLR10 form the TLR2 subfamily. In our previous controlled studies in 132 subjects with osteitis after newborn Bacillus Calmette-Guérin (BCG) vaccination, TLR1, TLR2 and TLR6 variations were associated with the risk of BCG osteitis. Now, we evaluated the role of ten single nucleotide polymorphisms (SNP) of the TLR10 gene in this cohort.

Methods: Five synonymous TLR10 SNPs (rs10004195, rs10856837, rs10856838, rs1109695 and rs11466652), and five missense TLR10 SNPs (rs11096955, rs11096957, rs11466649, rs11466653 and rs11466658) were determined by polymerase chain reaction (PCR)-based sequencing in 132 former BCG osteitis patients.

Results: TLR10 rs10004195 polymorphism was associated with the risk of BCG osteitis, compared to Finnish population controls. The variant genotype (AT/AA) was present in 13.6% of cases versus 26.2% of controls (p = 0.024). Correspondingly, the minor allele frequency (MAF) was lower (0.075) in cases than in controls (0.152; p = 0.009). There were no significant differences in the genotypes of the other nine studied TLR10 SNPs or in the corresponding MAFs between cases and controls.

Conclusion: Among ten studied TLR10 gene polymorphisms, the variation only in the TLR10 rs10004195 was associated with the BCG osteitis risk after newborn BCG vaccination.
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http://dx.doi.org/10.1111/apa.15720DOI Listing
December 2020

Prevalence of Inflammatory Bowel Disease and Celiac Disease in Patients with IgA Nephropathy over Time.

Nephron 2021 3;145(1):78-84. Epub 2020 Dec 3.

Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.

Introduction: IgA nephropathy (IgAN) has been connected with increased intestinal permeability and subclinical intestinal mucosal inflammation as well as with inflammatory bowel disease (IBD) and celiac disease - nevertheless, the results are controversial. The prevalence of bowel diseases has increased over time in Western populations. Whether similar trend is seen among IgAN patients remains obscure. Our aim was to study the prevalence of IBD and celiac disease in IgAN patients over time.

Methods: The study cohort consisted of altogether 629 patients with newly diagnosed IgAN during years 1976-2012. Data on diagnosis of IBD and celiac disease were retrospectively collected from medical records. Further, to detect unrecognized celiac disease, IgA-class tissue transglutaminase antibodies (tTGA) were measured from serum samples taken at the time of kidney biopsy during years 1980-2012 (defined as screen-detected celiac disease autoimmunity).

Results: The prevalence of IBD among IgAN patients increased over time from 0 to 4.4%, while the prevalence of clinically diagnosed celiac disease decreased from 2.6 to 0.6%. Moreover, the number of screen-detected tTGA-positive cases decreased from the 1980s to the 21st century (2.8-0.7%).

Conclusion: The prevalence of IBD increased over time in IgAN patients, which exceeds the prevalence of 0.6% in Finnish general population. In parallel, the prevalence of celiac disease and screen-detected celiac disease autoimmunity decreased over time. The coexistence of IBD and IgAN is not negligible. Whether this finding is caused by the increase in the prevalence of IBD in the population or shared pathophysiology between IgAN and IBD remains a matter of further studies.
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http://dx.doi.org/10.1159/000511555DOI Listing
December 2020

Aldosterone-to-renin ratio is related to arterial stiffness when the screening criteria of primary aldosteronism are not met.

Sci Rep 2020 11 13;10(1):19804. Epub 2020 Nov 13.

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Aldosterone-to-renin ratio (ARR) is a screening tool for primary aldosteronism (PA), but the significance of ARR when the PA criteria are not met remains largely unknown. In this cross-sectional study we investigated the association of ARR with haemodynamic variables in 545 normotensive and never-medicated hypertensive subjects (267 men, 278 women, age range 19-72 years) without suspicion of PA. Supine haemodynamic data was recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis. In sex-adjusted quartiles of ARR, determined as serum aldosterone to plasma renin activity ratio, the mean values were 282, 504, 744 and 1467 pmol/µg of angiotensin I/h, respectively. The only difference in haemodynamic variables between the ARR quartiles was higher pulse wave velocity (PWV) in the highest quartile versus other quartiles (p = 0.004), while no differences in blood pressure (BP), heart rate, wave reflections, cardiac output or systemic vascular resistance were observed between the quartiles. In linear regression analysis with stepwise elimination, ARR was an independent explanatory factor for PWV (β = 0.146, p < 0.001, R of the model 0.634). In conclusion, ARR was directly and independently associated with large arterial stiffness in individuals without clinical suspicion of PA. Therefore, ARR could serve as a clinical marker of cardiovascular risk.Trial registration: ClinicalTrails.gov: NCT01742702.
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http://dx.doi.org/10.1038/s41598-020-76718-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666146PMC
November 2020

Ultrasound-guided quadratus lumborum block for postoperative analgesia: A systematic review and meta-analysis.

Eur J Anaesthesiol 2021 Feb;38(2):115-129

From the Department of Anaesthesia (AK, EJ, HK, MLK), Faculty of Medicine and Health Technology (AK, EJ, HK, MLK) and Faculty of Social Sciences, Tampere University, Tampere, Finland (HH).

Background: Ultrasound-guided quadratus lumborum block (QLB) is a truncal block with several technique variations. It has been reported as providing effective analgesia for postoperative pain.

Objectives: The aim of this review was to evaluate the efficacy and safety of QLB for postoperative analgesia. The primary outcome was cumulative opioid consumption at 24 h postoperatively. The main secondary outcomes were the time to the first rescue opioid analgesic, pain scores at 24 h postoperatively and the incidence of postoperative nausea and vomiting (PONV).

Design: This was a systematic review and meta-analyses of observational studies and randomised controlled trials (RCTs). PRISMA-P guidelines were followed, and the review was registered in PROSPERO. GRADE was used to assess the quality of evidence.

Data Sources: The search was performed from several databases (Ovid MEDLINE, PubMed, Scopus, Web of Science, CINAHL and the Cochrane CENTRAL) from inception up to June 2019.

Eligibility Criteria: RCTs and prospective observational studies that investigated the postoperative analgesic properties of US-guided single shot QLB in adult patients undergoing abdominal or hip surgery were included. QLB was compared with other analgesics.

Results: Twenty-seven studies constituting 1557 patients were reviewed. Twelve studies with 803 patients were included in the meta-analysis on the primary outcome. Overall opioid consumption at 24 h postoperatively was reduced [mean difference, -11.15 (95% CI, -15.33 to -6.97) mg, I2 = 99%, moderate certainty in GRADE] and the time to the first opioid analgesic was longer in patients with QLB: 7 studies with 499 patients, mean difference, 189.32 (95% CI, 114.4 to 264.23) min, I2 = 98%. There were no differences in pain grades. The incidence of PONV was lower in patients with QLB [11 studies with 744 patients, OR 0.40 (95% CI, 0.27 to 0.58), I2 = 7%]. Reported complications and adverse effects of QLB were minimal.

Conclusion: QLB reduced postoperative opioid consumption, prolonged the time to the first rescue opioid analgesic and diminished the incidence of PONV. QLB appears to be an applicable option for postoperative analgesia after abdominal and hip surgery.

Registration Number: PROSPERO, https://www.crd.york.ac.uk/prospero/, CRD42016039921.
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http://dx.doi.org/10.1097/EJA.0000000000001368DOI Listing
February 2021

History of cancer and survival after coronary artery bypass grafting: Experiences from the SWEDEHEART registry.

J Thorac Cardiovasc Surg 2020 Sep 17. Epub 2020 Sep 17.

Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.

Objective: To explore the currently unknown association between history of cancer at the time of coronary artery bypass grafting (CABG) and long-term survival.

Methods: All patients (n = 82,137) undergoing isolated first-time CABG in Sweden during 1997-2015 were included in this retrospective population-based cohort study. Individual patient data from the SWEDEHEART registry and 4 other mandatory nationwide health care registries were merged. Multivariable Cox proportional hazards regression and competing risk models adjusted for age and gender were used to assess associations between history of cancer, and long-term all-cause, cardiovascular and cancer mortality. Median follow-up was 9.0 years (interquartile range, 4.8-13.1).

Results: Altogether, 6819 (8.3%) of the patients had a history of cancer. The annual prevalence increased from 3.8% in 1997 to 14.8% in 2015. Patients with a history of cancer were older (72 vs 66 years; P < .001) and had more comorbidities. Long-term all-cause mortality was significantly greater in patients with a history of cancer (45.7% vs 22.9% at 10 years; adjusted hazard ratio, 1.33; 95% confidence interval [CI], 1.28-1.38, P < .001). According to the competing risk models, history of cancer was associated with an increased risk for cancer death (subdistribution hazard ratio, 2.45; 95% CI, 2.28-2.63, P < .001) but not cardiovascular death (subdistribution hazard ratio, 0.88; 95% CI, 0.83-0.94, P < .001).

Conclusions: The proportion of patients undergoing CABG with a history of cancer has increased over time. History of cancer at the time of surgery is associated with increased cancer deaths over time but not cardiovascular deaths. The same cardiovascular prognosis after CABG can be expected regardless of cancer history.
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http://dx.doi.org/10.1016/j.jtcvs.2020.09.043DOI Listing
September 2020

Type 1 tyrosinemia in Finland: a nationwide study.

Orphanet J Rare Dis 2020 10 12;15(1):281. Epub 2020 Oct 12.

Center for Child Health Research, Tampere University, Tampere, Finland.

Background: Introduction of nitisinone and newborn screening (NBS) have transformed the treatment of type 1 tyrosinemia, but the effects of these changes on the long-term outcomes remain obscure. Also, the predictors for later complications, the significance of drug levels and the normalization of laboratory and imaging findings are poorly known. We investigated these issues in a nationwide study.

Results: Type 1 tyrosinemia was diagnosed in 22 children in 1978-2019 in Finland. Incidence was 1/90,102, with a significant enrichment in South Ostrobothnia (1/9990). Median age at diagnosis was 5 (range 0.5-36) months, 55% were girls and 13 had homozygotic Trp262X mutation. Four patients were detected through screening and 18 clinically, their main findings being liver failure (50% vs. 100%, respectively, p = 0.026), ascites (0% vs. 53%, p = 0.104), renal tubulopathy (0% vs. 65%, p = 0.035), rickets (25% vs. 65%, p = 0.272), growth failure (0% vs. 66%, p = 0.029), thrombocytopenia (25% vs. 88%, p = 0.028) and anaemia (0% vs. 47%, p = 0.131). One patient was treated with diet, seven with transplantation and 14 with nitisinone. Three late-diagnosed (6-33 months) nitisinone treated patients needed transplantation later. Kidney dysfunction (86% vs. 7%, p = 0.001), hypertension (57% vs. 7%, p = 0.025) and osteopenia/osteoporosis (71% vs. 14%, p = 0.017) were more frequent in transplanted than nitisinone-treated patients. Blood/serum alpha-fetoprotein decreased rapidly on nitisinone in all but one patient, who later developed intrahepatic hepatocellular carcinoma. Liver values normalized in 31 months and other laboratory values except thrombocytopenia within 18 months. Imaging findings normalized in 3-56 months excluding five patients with liver or splenic abnormalities. Low mean nitisinone concentration was associated with higher risk of severe complications (r = 0.758, p = 0.003) despite undetectable urine succinylacetone.

Conclusions: Prognosis of type 1 tyrosinemia has improved in the era of nitisinone, and NBS seems to provide further benefits. Nevertheless, the long-term risk for complications remains, particularly in the case of late diagnosis and/or insufficient nitisinone levels.
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http://dx.doi.org/10.1186/s13023-020-01547-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549233PMC
October 2020

Impact of mode of delivery on perinatal outcome in moderately and late preterm twin birth.

Int J Gynaecol Obstet 2020 Oct 11. Epub 2020 Oct 11.

Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland.

Objective: To examine the impact of the mode of delivery on neonatal and maternal outcomes in moderately and late preterm twin birth.

Methods: This single-center cohort study included 275 live diamniotic moderately and late preterm twin deliveries at 32 -36  weeks of gestation. These twin deliveries were divided into two groups according to the planned mode of delivery: trial of labor (TOL) (N=199, 72.4%) and planned cesarean section (CS) (N=76, 27.6%). The primary outcome was neonatal morbidity. Maternal outcome and the effects of gestational age and chorionicity on neonatal outcome were also studied.

Results: Of the women in the TOL group, 170 (85.4%) delivered vaginally. Both for the first and second twin, and for dichorionic or monochorionic deliveries, there were no differences between the TOL and CS groups in composite neonatal morbidity or in other neonatal outcomes. No significant differences were found between the TOL and CS groups when the moderately and late preterm gestational age cohorts were studied separately. Mothers in the planned CS group more often had puerperal infection and surgical complications in comparison with mothers in the TOL group.

Conclusion: Among 275 moderately and late preterm twin deliveries, planned mode of delivery did not affect neonatal outcome.
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http://dx.doi.org/10.1002/ijgo.13418DOI Listing
October 2020

Relation of intraventricular conduction delay to risk of new-onset heart failure and structural heart disease in the general population.

Int J Cardiol Heart Vasc 2020 Dec 25;31:100639. Epub 2020 Sep 25.

Faculty of Medicine and Health Technology, Tampere University, and Finnish Cardiovascular Research Center, Tampere, Finland.

Background: Intraventricular conduction delays (IVCDs) are hallmarks of heart failure (HF) and structural heart disease (SHD) but their prognostic value for HF and SHD is unclear.

Methods: Relation of eight IVCDs and the incidence of first-time HF or SHD was studied in a nationally representative random sample of 6080 Finnish subjects aged ≥ 30 years (mean age 52.1, SD 14.5 years) who participated in the health examination including 12-lead ECG.

Results: During 16.5 years' follow up, half of the subjects with left bundle branch block (LBBB) and one third of the subjects with non-specific IVCD developed HF. After controlling for known clinical risk factors the hazard ratio (HR) for new-onset HF for LBBB was 3.29 (95% confidence interval 1.93-5.63, P < 0.001) and 3.53 for non-specific IVCD (1.65-7.55, P = 0.001). In corresponding analysis, LBBB predicted SHD with HR 2.60 (1.21-5.62, P = 0.015). Excluding subjects with history of heart disease, including coronary heart disease, did not have impact on results. Right bundle branch block and other IVCDs displayed no relation to endpoints.

Conclusion: LBBB and non-specific IVCD were associated with more than three-fold risk of new-onset HF. Furthermore, LBBB was associated with novel SHD. Their presence should alert clinician even in subjects free from any known heart disease.
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http://dx.doi.org/10.1016/j.ijcha.2020.100639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522339PMC
December 2020

The expression and prognostic relevance of programmed cell death protein 1 in tongue squamous cell carcinoma.

APMIS 2020 Dec 19;128(12):626-636. Epub 2020 Oct 19.

Haartman Institute, University of Helsinki, Helsinki, Finland.

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor which plays an important role in a patient's immune responses to microbial and cancer antigens. It is expressed in tumor-infiltrating lymphocytes (TILs) with many different malignancies. The aim of the study was to evaluate PD-1 expression and its prognostic value in tongue cancer. The data of tongue squamous cell carcinoma (TSCC) patients (N = 81) treated in Tampere University Hospital between 1999 and 2013 were used. Control data consisted of patients with non-malignant tongue mucous membrane lesions (N = 48). The formalin-fixed paraffin-embedded samples were stained immunohistochemically and scanned via digital microscope. The staining of PD-1 was examined semi-quantitatively. The density and intensity of PD-1 + cells were significantly higher in TSCC than in control samples. The expression of PD-1 correlated with better survival. The expression of PD-1 could be a potential prognostic marker in TSCC. Further research using larger sample size is needed.
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http://dx.doi.org/10.1111/apm.13084DOI Listing
December 2020

The prognostic significance of T-wave inversion according to ECG lead group during long-term follow-up in the general population.

Ann Noninvasive Electrocardiol 2021 01 25;26(1):e12799. Epub 2020 Sep 25.

Faculty of Medicine and Health Technology, Tampere University, and Finnish Cardiovascular Research Center, Tampere, Finland.

Background: Inverted T waves in the electrocardiogram (ECG) have been associated with coronary heart disease (CHD) and mortality. The pathophysiology and prognostic significance of T-wave inversion may differ between different anatomical lead groups, but scientific data related to this issue is scarce.

Methods: A representative sample of Finnish subjects (n = 6,354) aged over 30 years underwent a health examination including a 12-lead ECG in the Health 2000 survey. ECGs with T-wave inversions were divided into three anatomical lead groups (anterior, lateral, and inferior) and were compared to ECGs with no pathological T-wave inversions in multivariable-adjusted Fine-Gray and Cox regression hazard models using CHD and mortality as endpoints.

Results: The follow-up for both CHD and mortality lasted approximately fifteen years (median value with interquartile ranges between 14.9 and 15.3). In multivariate-adjusted models, anterior and lateral (but not inferior) T-wave inversions associated with increased risk of CHD (HR: 2.37 [95% confidence interval 1.20-4.68] and 1.65 [1.27-2.15], respectively). In multivariable analyses, only lateral T-wave inversions associated with increased risk of mortality in the entire study population (HR 1.51 [1.26-1.81]) as well as among individuals with no CHD at baseline (HR 1.59 [1.29-1.96]).

Conclusions: The prognostic information of inverted T waves differs between anatomical lead groups. T-wave inversion in the anterior and lateral lead groups is independently associated with the risk of CHD, and lateral T-wave inversion is also associated with increased risk of mortality. Inverted T wave in the inferior lead group proved to be a benign phenomenon.
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http://dx.doi.org/10.1111/anec.12799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816818PMC
January 2021

Thermal suit connected to a forced-air warming unit for preventing intraoperative hypothermia: A randomised controlled trial.

Acta Anaesthesiol Scand 2021 02 7;65(2):176-181. Epub 2020 Oct 7.

Department of Anaesthesia, Tampere University Hospital, Tampere, Finland.

Background: Inadvertent intraoperative hypothermia is a common occurrence in surgical patients. A thermal suit is an option for passive insulation. However, active warming is known to be more effective. Therefore, we hypothesised that a forced-air warming (FAW) unit connected to the thermal suit is superior to a commercial FAW blanket and a warming mattress in breast cancer surgery.

Methods: Forty patients were randomised to this prospective, clinical trial to wear either the thermal suit or conventional hospital clothes under general anaesthesia. The Thermal suit group had a FAW unit set to 38°C and connected to the legs of the suit. The Hospital clothes group had a lower body blanket set to 38°C and a warming mattress set to 37°C. Core temperature was measured with zero-heat-flux sensor. The primary outcome was core temperature on admission to the recovery room.

Results: There was no difference in mean core temperatures at anaesthetic induction (P = .4) or on admission to the recovery room (P = .07). One patient in the Thermal suit group (5%) vs six patients in the Hospital clothes group (32%) suffered from intraoperative hypothermia (P = .04, 95% CI 1.9%-49%). Mean skin temperatures (MSTs) were higher in the Thermal suit group during anaesthesia. No burns or skin irritations were reported. Two patients in the Thermal suit group sweated.

Conclusions: A thermal suit connected to a FAW unit was not superior to a commercial FAW blanket, although the incidence of intraoperative hypothermia was lower in patients treated with a thermal suit.
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http://dx.doi.org/10.1111/aas.13714DOI Listing
February 2021

Long-term health-related quality of life in persons diagnosed with an insulinoma in Finland 1980-2010.

Clin Endocrinol (Oxf) 2021 Feb 26;94(2):250-257. Epub 2020 Nov 26.

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Objective: Insulinomas are rare pancreatic neoplasms, which can usually be cured by surgery. As the diagnostic delay is often long and the prolonged hyperinsulinemia may have long-term effects on health and the quality of life, we studied the long-term health-related quality of life (HRQoL) in insulinoma patients.

Design, Patients And Measurements: The HRQoL of adults diagnosed with an insulinoma in Finland in 1980-2010 was studied with the 15D instrument, and the results were compared to those of an age- and gender-matched sample of the general population. The minimum clinically important difference in the total 15D score has been defined as ±0.015. The clinical characteristics, details of insulinoma diagnosis and treatment, and the current health status of the subjects were examined to specify the possible determinants of long-term HRQoL.

Results: Thirty-eight insulinoma patients participated in the HRQoL survey (response rate 75%). All had undergone surgery with a curative aim, a median of 13 (min 7, max 34) years before the survey. The insulinoma patients had a clinically importantly and statistically significantly better mean 15D score compared with the controls (0.930 ± 0.072 vs 0.903 ± 0.039, P = .046) and were significantly better off regarding mobility, usual activities and eating. Among the insulinoma patients, younger age at the time of survey, higher level of education and smaller number of chronic diseases were associated with better overall HRQoL.

Conclusions: In the long term, the overall HRQoL of insulinoma patients is slightly better than that of the general population.
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http://dx.doi.org/10.1111/cen.14336DOI Listing
February 2021

Long-term outcome of pre-specified ECG patterns in acute coronary syndrome.

J Electrocardiol 2020 Sep - Oct;62:178-183. Epub 2020 Aug 8.

Faculty of Medicine and Health Technology, Tampere University, Finland; Heart Center, Department of Cardiology, Tampere University Hospital, Finland.

Background: Long-term outcome of real-life acute coronary syndrome (ACS) patients with selected ECG patterns is not well known.

Purpose: To survey the 10-year outcome of pre-specified ECG patterns in ACS patients admitted to a university hospital.

Methods: A total of 1184 consecutive acute coronary syndrome patients in 2002-2003 were included and followed up for 10 years. The patients were classified into nine pre-specified ECG categories: 1) ST elevation; 2) pathological Q waves without ST elevation; 3) left bundle branch block (LBBB); 4) right bundle branch block (RBBB) 5) left ventricular hypertrophy (LVH) without ST elevation except in leads aVR and/or V; 6) global ischemia ECG (ST depression ≥0.5 mm in 6 leads, maximally in leads V with inverted T waves and ST elevation ≥0.5 mm in lead aVR); 7) other ST depression and/or T wave inversion; 8) other findings and 9) normal ECG.

Results: Any abnormality in the ECG, especially Q waves, LBBB, LVH and global ischemia, had negative effect on outcome. In age- and gender adjusted Cox regression analysis, pathological Q waves (HR 2.28, 95%CI 1.20-4.32, p = .012), LBBB (HR 3.25, 95%CI 1.65-6.40, p = .001), LVH (HR 2.53, 95%CI 1.29-4.97, p = .007), global ischemia (HR 2.22, 95%CI 1.14-4.31, p = .019) and the combined group of other findings (HR 3.01, 95%CI 1.56-6.09, p = .001) were independently associated with worse outcome.

Conclusions: During long-term follow-up of ACS patients, LBBB, ECG-LVH, global ischemia, and Q waves were associated with worse outcome than a normal ECG, RBBB, ST elevation or ST depression with or without associated T-wave inversion. LBBB was associated with the highest mortality rates.
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http://dx.doi.org/10.1016/j.jelectrocard.2020.08.001DOI Listing
August 2020

Interleukin 17F gene variations showed no association with BCG osteitis risk after newborn vaccination.

Acta Paediatr 2021 02 2;110(2):618-623. Epub 2020 Oct 2.

Institute of Biomedicine, University of Turku, Turku, Finland.

Aim: Interleukin-17 (IL-17) family cytokines promote the host defence against mycobacterial infections. We have previously shown an association between IL17A variations and Bacillus Calmette-Guérin (BCG) osteitis. This paper evaluates the association of three IL17F polymorphisms with BCG osteitis after newborn vaccination.

Methods: IL17F rs763780, rs11465553 and rs7741835 single nucleotide polymorphisms (SNPs) were studied in 132 adults, who presented with BCG osteitis in infancy. The genotypes and minor allele frequencies (MAFs) were compared between cases and Finnish population-based controls (N = 99) from the 1000 Genomes Project, and MAFs were compared between cases and allele data of Finnish subjects from the large Genome Aggregation Database.

Results: There were no significant differences between former BCG osteitis patients and population-based controls in the IL17F rs763780 (wild 84.4% vs 84.8%), rs11465553 (86.4% vs 91.9%) or rs7741835 (65.7% vs 67.7%) genotypes. Homozygous variant genotypes were only present in 1.5%, 0.8% and 3.8% of cases, respectively. Likewise, MAFs of the three IL17F SNPs did not substantially differ from those of 11 252, 11 939 and 1371 Finnish subjects, respectively, from the available Genome Aggregation Database.

Conclusion: IL17F rs763780, rs11465553 and rs7741835 variations showed no association with the risk of BCG osteitis after newborn vaccination.
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http://dx.doi.org/10.1111/apa.15574DOI Listing
February 2021

Routine Bedside Use of Obstetric Early Warning System in the Postnatal Ward to Identify Maternal Morbidity Among High-Risk Women.

J Patient Saf 2020 Sep 8. Epub 2020 Sep 8.

Department of Obstetrics and Gynecology, Tampere University Hospital.

Objective: Several authorities have recommended the use of an obstetric early warning system (OEWS) to prevent severe morbidity and mortality. Data on the accuracy of OEWS in different clinical settings and maternal populations are still scarce. Our aim was to validate OEWS to detect maternal morbidity among high-risk women in the postnatal ward.

Methods: An OEWS was assigned to women with a body mass index >35 kg/m, postpartum hemorrhage (PPH) >1500 mL, preeclampsia, concern over the maternal condition, chorioamnionitis, or type 1 diabetes. Morbidity was defined as worsening preeclampsia, action on hemorrhage, thromboembolia, diabetic ketoacidosis, puerperal infections, transfer to the intensive care unit, cardiopulmonary dysfunction, or death during the stay in the postnatal ward. The use of OEWS was implemented on November 1, 2016, and the study period ended on April 30, 2018.

Results: The study group included 827 women. The incidence of maternal morbidity was 29%. Women with PPH (odds ratio [OR], 6.4 [95% confidence interval, 3.5-11.6]) and preeclampsia (OR, 5.7 [3.5-9.6]) had the highest risk for morbidity. The sensitivity of OEWS for any morbidity was 42% (35%-48%), the specificity was 83% (80%-86%), the positive predictive value was 50% (44%-56%), and the negative predictive value was 78% (76%-80%). Systolic (OR, 6.8 [4.0-11.5]) and diastolic (OR, 3.3 [1.8-6.0]) blood pressure as well as pulse (OR, 2.1 [1.1-4.2]) predicted morbidity the most.

Conclusions: In high-risk women, OEWS revealed one-half of the morbidity. Women with PPH and preeclampsia benefited most from it. Abnormal blood pressure and pulse had the strongest associations with morbidity.
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http://dx.doi.org/10.1097/PTS.0000000000000766DOI Listing
September 2020

Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities.

Nutrients 2020 Sep 8;12(9). Epub 2020 Sep 8.

Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.

Non-biopsy diagnosis of celiac disease is possible in children with anti-transglutaminase 2 antibodies (TGA) > 10× the upper limit of normal (ULN) and positive anti-endomysial antibodies (EMA). Similar criteria have been suggested for adults, but evidence with different TGA assays is scarce. We compared the performance of four TGA tests in the diagnosis of celiac disease in cohorts with diverse pre-test probabilities. Serum samples from 836 adults with either clinical suspicion or family risk of celiac disease were tested with four commercial TGA assays, EmA and celiac disease-associated genetics. The diagnosis was set based on duodenal lesion or, in some cases, using special methods. 137 (57%) patients with clinical suspicion and 85 (14%) of those with family risk had celiac disease. Positive predictive value (PPV) for 10×ULN was 100% in each TGA test. The first non-diagnostic investigations were encountered with ULN 1.0×-5.1× in the clinical cohort and 1.3×-4.9× in the family cohort, respectively. Using the assays' own cut-offs (1×ULN) the PPVs ranged 84-100%. Serology-based diagnosis of celiac disease was accurate in adults using different commercial kits and pre-test probabilities using 10×ULN. The results also suggest that the ULN threshold for biopsy-omitting approach could be lower.
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http://dx.doi.org/10.3390/nu12092736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551634PMC
September 2020

Clinical characteristics and long-term health in celiac disease patients diagnosed in early childhood: Large cohort study.

Dig Liver Dis 2020 11 6;52(11):1315-1322. Epub 2020 Sep 6.

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Center for Child Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, Tampere, Finland; The University Consortium of Seinäjoki, and Department of Pediatrics, Seinäjoki Central Hospital, Seinäjoki, Finland.

Background: Early detection of celiac disease could theoretically prevent most of the disease-associated complications, but long-term effects of this approach are unclear.

Aims: To investigate features at diagnosis and adulthood health in celiac disease patients diagnosed in early childhood in 1965-2014.

Methods: Medical data on 978 pediatric patients were collected and study questionnaires sent to 559 adult patients who were diagnosed in childhood. Results were compared between patients diagnosed in early (≤3.0 years) and later (3.1-17.9 years) childhood.

Results: Early diagnosed patients (n=131) had more often total villous atrophy (37% vs 25%, p=0.001), gastrointestinal presentation (61% vs 47%, p<0.001), growth disturbances (70% vs 32%, p=0.001) and severe symptoms (30% vs 9%, p<0.001) and were less often screen-detected (10% vs 27%, p<0.001) at diagnosis than those diagnosed later (n=847). Among 239 adult responders, early diagnosed patients (n=36) had fewer comorbidities (33% vs 53%, p=0.034) but considered their health less often good/excellent (69% vs 84%, p=0.029). The groups were comparable in current age, dietary adherence, symptoms and health-related quality of life.

Conclusion: Despite more severe initial presentation, the long-term health in early diagnosed patients was mostly comparable or even better to those diagnosed later in childhood. Poorer self-perceived health suggests a need for support during the transition to adulthood care.
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http://dx.doi.org/10.1016/j.dld.2020.08.010DOI Listing
November 2020

Continuous intravenous infusion of enoxaparin controls thrombin formation more than standard subcutaneous administration in critically ill patients. A sub-study of the ENOKSI thromboprophylaxis RCT.

Acta Anaesthesiol Scand 2021 01 16;65(1):109-115. Epub 2020 Sep 16.

Department of Intensive Care Medicine, Tampere University Hospital, PO Box 2000, Tampere, 33521, Finland.

Introduction: Standard subcutaneous low-molecular-weight heparin (LMWH) thromboprophylaxis yields low anti-factor Xa activity in patients in the intensive care unit (ICU). The aim of the study was to assess coagulation status in ICU patients randomized to receive enoxaparin thromboprophylaxis either as a standard subcutaneous bolus (SCB) or continuous intravenous infusion (CII) for 3 consecutive days after the initiation of LMWH thromboprophylaxis.

Materials And Methods: Thirty-eight patients were studied by conventional coagulation variables: prothrombin fragment F 1+2 (F 1+2) representing FXa inhibition and antithrombin (AT). Additionally, 18 patients were analyzed by the thrombin generation assay-calibrated automated thrombogram (TGA-CAT). Blood samples were collected before the initiation of the LMWH thromboprophylaxis (ie, baseline), at 51 h, and at 72 h.

Results: At beginning, no differences in coagulation biomarkers were observed. The levels of F 1+2 were significantly lower at 51 and 72 h in the CII group than in the SCB group. AT levels increased during the follow-up in the CII group, unlike in the SCB group. TGA-CAT was poor in some patients overall. In a subset of patients at 51 h lag time (4.3 vs 7.5 min, respectively, P < 0.05) and time to peak (7.7 vs 14.3 min, respectively, P < 0.05) were prolonged in the SCB group. At 72 h, however, peak thrombin was lower in the CII than in the SCB group: 271 vs 356 nM, respectively (P < 0.05).

Conclusions: Enoxaparin thromboprophylaxis administered by CII inhibited more prominently FXa and preserved better the AT level, compared with standard subcutaneous care.
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http://dx.doi.org/10.1111/aas.13697DOI Listing
January 2021

Long-term outcome of intraventricular conduction delays in the general population.

Ann Noninvasive Electrocardiol 2021 01 17;26(1):e12788. Epub 2020 Aug 17.

Faculty of Medicine and Health Technology, Tampere University, and Finnish Cardiovascular Research Center, Tampere, Finland.

Background: Previous population studies have presented conflicting results regarding the prognostic impact of intraventricular conduction delays (IVCD).

Methods: We studied long-term prognostic impact and the association with comorbidities of eight IVCDs in a random sample of 6,299 Finnish subjects (2,857 men and 3,442 women, mean age 52.8, SD 14.9 years) aged 30 or over who participated in the health examination including 12-lead ECG. For left bundle branch block (LBBB) and non-specific IVCD (NSIVCD), two different definitions were used.

Results: During 16.5 years' follow-up, 1,309 of the 6,299 subjects (20.8%) died and of these 655 (10.4%) were cardiovascular (CV) deaths. After controlling for known clinical risk factors, the hazard ratio for CV death, compared with individuals without IVCD, was 1.55 for the Minnesota definition of LBBB (95% confidence interval 1.04-2.31, p = .032) and 1.27 (95% confidence interval 0.80-2.02, p = .308) for the Strauss' definition of LBBB. Subjects with NSIVCD were associated with twofold to threefold increase in CV mortality depending on the definition. While right bundle branch block, left anterior fascicular block and incomplete bundle branch blocks were associated with seemingly higher mortality, this was no longer the case after adjustment for age and sex. The presence of R-R' pattern was not associated with any adverse outcome.

Conclusions: In a population study with long-term follow-up, NSIVCD and Minnesota definition of LBBB were independently associated with CV mortality. Other IVCDs had no significant impact on prognosis. The prognostic impact of LBBB and NSIVCD was affected by the definition of the conduction disorder.
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http://dx.doi.org/10.1111/anec.12788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816813PMC
January 2021