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Background: Cardiac sarcoidosis (CS) predisposes to sudden cardiac death (SCD). Guidelines for implantable cardioverter defibrillators (ICDs) in CS have been issued by the Heart Rhythm Society in 2014 and the American College of Cardiology/American Heart Association/Heart Rhythm Society consortium in 2017. How well they discriminate high from low risk remains unknown. Methods: We analyzed the data of 398 patients with CS detected in Finland from 1988 through 2017. All had clinical cardiac manifestations. Histological diagnosis was myocardial in 193 patients (definite CS) and extracardiac in 205 (probable CS). Patients with and without Class I or IIa ICD indications at presentation were identified, and subsequent occurrences of SCD (fatal or aborted) and sustained ventricular tachycardia were recorded, as were ICD indications emerging first on follow-up. Results: Over a median of 4.8 years, 41 patients (10.3%) had fatal (n=8) or aborted (n=33) SCD, and 98 (24.6%) experienced SCD or sustained ventricular tachycardia as the first event. By the Heart Rhythm Society guideline, Class I or IIa ICD indications were present in 339 patients (85%) and absent in 59 (15%), of whom 264 (78%) and 30 (51%), respectively, received an ICD. Cumulative 5-year incidence of SCD was 10.7% (95% CI, 7.4%–15.4%) in patients with ICD indications versus 4.8% (95% CI, 1.2%–19.1%) in those without (χ 2 =1.834, P =0.176). The corresponding rates of SCD were 13.8% (95% CI, 9.1%–21.0%) versus 6.3% (95% CI, 0.7%–54.0%; χ 2 =0.814, P =0.367) in definite CS and 7.6% (95% CI, 3.8%–15.1%) versus 3.3% (95% CI, 0.5%–22.9%; χ 2 =0.680, P =0.410) in probable CS. In multivariable regression analysis, SCD was predicted by definite histological diagnosis ( P =0.033) but not by Class I or IIa ICD indications ( P =0.210). In patients without ICD indications at presentation, 5-year incidence of SCD, sustained ventricular tachycardia, and emerging Class I or IIa indications was 53% (95% CI, 40%–71%). By the American College of Cardiology/American Heart Association/Heart Rhythm Society guideline, all patients with complete data (n=245) had Class I or IIa indications for ICD implantation. Conclusions: Current ICD guidelines fail to distinguish a truly low-risk group of patients with clinically manifest CS, the 5-year risk of SCD approaching 5% despite absent ICD indications. Further research is needed on prognostic factors, including the role of diagnostic histology. Meanwhile, all patients with CS presenting with clinical cardiac manifestations should be considered for an ICD implantation.

Background and purpose Soong classification is used to estimate volar locking plate prominence and evaluate the risk for flexor tendon ruptures after surgical treatment of distal radius fractures (DRFs). However, the scientific community has questioned the Soong classification due to lacking evidence. Therefore, this study aimed to evaluate the accuracy of Soong grading as a predictor for flexor tendon issues and plate removal. Patients and methods We performed a retrospective single-center review of adult distal radius fracture patients treated with a volar locking plate between 2009 and 2019. In total, 2779 patients were included in the study. The primary outcome was a flexor tendon issue (flexor tendon rupture, tendinitis, or flexor irritation), whereas plate removal was a secondary outcome. Using Soong grade 0 as a reference, we used univariable and multivariable logistic regression to calculate odds ratios (OR) with 95% confidence intervals (CI) for flexor tendon issues and plate removal. Results In total, 756 (27%) patients were graded as Soong 0, 1679 (60%) Soong 1, and 344 (12%) Soong 2, respectively. There were 32 (1.2%) patients with flexor tendon issues, of which 4 were flexor tendon ruptures, 8 tendinitises, and 20 flexor irritations. The adjusted OR for flexor tendon issues was 4.4 (CI 1.1–39.7) for Soong grade 1 and 9.7 (CI 2.2–91.1) for Soong grade 2. The plate was removed from 167 (6.0%) patients. Soong grade 1 had a univariable OR of 1.8 (CI 1.2–2.8) for plate removal, and Soong grade 2 had an OR of 3.5. (CI 2.1–5.8), respectively. Conclusion Flexor tendon ruptures are rare complications after the volar plating of DRFs. A higher Soong grade is a risk factor for flexor tendon issues and plate removal. Trial registration The trial was retrospectively registered.

Background Etanercept (ETN) is widely used tumour necrosis factor (TNF) blocker in the treatment of juvenile idiopathic arthritis (JIA) when traditional synthetic disease modifying antirheumatic drug (sDMARD) therapy is not sufficient. There is limited information about the effects of methotrexate (MTX) on serum ETN concentration in children with JIA. We aimed to investigate whether ETN dose and concomitant MTX would effect ETN serum trough levels in JIA patients, and whether concomitant MTX have an influence on the clinical response in patients with JIA receiving ETN. Methods In this study, we collected the medical record data of 180 JIA patients from eight Finnish pediatric rheumatological centres. All these patients were treated with ETN monotherapy or combination therapy with DMARD. To evaluate the ETN concentrations, blood samples of the patients were collected between injections right before the subsequent drug. Free ETN level was measured from serum. Results Ninety-seven (54%) of the patients used concomitant MTX, and 83 (46%) received either ETN monotherapy or used sDMARDs other than MTX. A significant correlation was noted between ETN dose and drug level [r = 0.45 (95% CI: 0.33–0.56)]. The ETN dose and serum drug level were correlated (p = 0.030) in both subgroups – in MTX group [r = 0.35 (95% CI: 0.14–0.52)] and in non-MTX group [r = 0.54 (95% CI: 0.39–0.67)]. Conclusion In the present study, we found that concomitant MTX had no effect on serum ETN concentration or on clinical response. In addition, a significant correlation was detected between ETN dose and ETN concentration.

Background Incisional hernia is a frequent complication after loop-ileostomy closure, rationalizing hernia prevention. Biological meshes have been widely used in contaminated surgical sites instead of synthetic meshes in fear of mesh related complications. However, previous studies on meshes does not support this practice. The aim of Preloop trial was to study the safety and efficacy of synthetic mesh compared to a biological mesh in incisional hernia prevention after loop-ileostomy closure. Methods The Preloop randomized, feasibility trial was conducted from April 2018 until November 2021 in four hospitals in Finland. The trial enrolled 102 patients with temporary loop-ileostomy after anterior resection for rectal cancer. The study patients were randomized 1:1 to receive either a light-weight synthetic polypropylene mesh (Parietene Macro™, Medtronic) (SM) or a biological mesh (Permacol™, Medtronic) (BM) to the retrorectus space at ileostomy closure. The primary end points were rate of surgical site infections (SSI) at 30-day follow-up and incisional hernia rate during 10 months’ follow-up period. Results Of 102 patients randomized, 97 received the intended allocation. At 30-day follow-up, 94 (97%) patients were evaluated. In the SM group, 1/46 (2%) had SSI. Uneventful recovery was reported in 38/46 (86%) in SM group. In the BM group, 2/48 (4%) had SSI (p > 0.90) and in 43/48 (90%) uneventful recovery was reported. The mesh was removed from one patient in both groups (p > 0.90). Conclusions Both a synthetic mesh and biological mesh were safe in terms of SSI after loop-ileostomy closure. Hernia prevention efficacy will be published after the study patients have completed the 10 months’ follow-up.

Objectives To explore mortality and causes of death among Norwegian patients with RA, PsA and axial spondyloarthritis (axSpA) compared with the general population by conducting a nationwide registry-based cohort study. Methods Patients with RA, PsA and axSpA were identified from the Norwegian Patient Registry based on ICD-10 codes between 2008 and 2017. Using age as the time variable, all-cause and cause-specific mortality were estimated between 2010 and 2017 with the Kaplan–Meier estimator and the cumulative incidence competing risk method, respectively. Sex-, education level-, health region- and age group-adjusted hazard ratios (HRs) for mortality were estimated using Cox regression models. Results We identified 36 095 RA, 18 700 PsA and 16 524 axSpA patients (70%, 53% and 45% women, respectively). RA and axSpA were associated with increased all-cause mortality (HR 1.45 [95% CI: 1.41, 1.48] and HR 1.38 [95% CI: 1.28, 1.38], respectively). Women but not men with PsA had a slightly increased mortality rate (HR 1.10 [95% CI: 1.00, 1.21] among women and 1.02 [95% CI: 0.93, 1.11] among men). For all patient groups as well as for the general population, the three leading causes of death were cardiovascular diseases, neoplasms and respiratory diseases. RA patients had increased mortality from all of these causes, while axSpA patients had increased mortality from cardiovascular and respiratory diseases. Conclusion Even in the era of modern treatments for IJDs, patients with RA and axSpA still have shortened life expectancy. Our findings warrant further attention to the prevention and management of comorbidities.

Aim: To determine the ability of serum glial fibrillary acidic protein (GFAp) and tau protein to predict neurological outcome after out-of-hospital cardiac arrest (OHCA). Methods: We measured plasma concentrations of GFAp and tau of patients included in the previously published COMACARE trial (NCT02698917) on intensive care unit admission and at 24, 48, and 72 h after OHCA, and compared them to neuron specific enolase (NSE). NSE concentrations were determined already during the original trial. We defined unfavourable outcome as a cerebral performance category (CPC) score of 3-5 six months after OHCA. We determined the prognostic accuracy of GFAp and tau using the receiver operating characteristic curve and area under the curve (AUROC). Results: Overall, 39/112 (35%) patients had unfavourable outcomes. Over time, both markers were evidently higher in the unfavourable outcome group (p < 0.001). At 48 h, the median (interquartile range) GFAp concentration was 1514 (886-4995) in the unfavourable versus 238 (135-463) pg/ ml in the favourable outcome group (p < 0.001). The corresponding tau concentrations were 99.6 (14.5-352) and 3.0 (2.2-4.8) pg/ml (p < 0.001). AUROCs at 48 and 72 h were 0.91 (95% confidence interval 0.85-0.97) and 0.91 (0.85-0.96) for GFAp and 0.93 (0.86-0.99) and 0.95 (0.89-1.00) for tau. Corresponding AUROCs for NSE were 0.86 (0.79-0.94) and 0.90 (0.82-0.97). The difference between the prognostic accuracies of GFAp or tau and NSE were not statistically significant. Conclusions: At 48 and 72 h, serum both GFAp and tau demonstrated excellent accuracy in predicting outcomes after OHCA but were not superior to NSE. Clinical trial registration: NCT02698917 (https://www.clinicaltrials.gov/ct2/show/NCT02698917).

Background Myocardial perfusion SPECT (MPS) images often suffer from artefacts caused by low-count statistics. Poor-quality images can lead to misinterpretations of perfusion defects. Deep learning (DL)-based methods have been proposed to overcome the noise artefacts. The aim of this study was to investigate the differences among several DL denoising models. Methods Convolution neural network (CNN), residual neural network (RES), UNET and conditional generative adversarial neural network (cGAN) were generated and trained using ordered subsets expectation maximization (OSEM) reconstructed MPS studies acquired with full, half, three-eighths and quarter acquisition time. All DL methods were compared against each other and also against images without DL-based denoising. Comparisons were made using half and quarter time acquisition data. The methods were evaluated in terms of noise level (coefficient of variation of counts, CoV), structural similarity index measure (SSIM) in the myocardium of normal patients and receiver operating characteristic (ROC) analysis of realistic artificial perfusion defects inserted into normal MPS scans. Total perfusion deficit scores were used as observer rating for the presence of a perfusion defect. Results All the DL denoising methods tested provided statistically significantly lower noise level than OSEM without DL-based denoising with the same acquisition time. CoV of the myocardium counts with the different DL noising methods was on average 7% (CNN), 8% (RES), 7% (UNET) and 14% (cGAN) lower than with OSEM. All DL methods also outperformed full time OSEM without DL-based denoising in terms of noise level with both half and quarter acquisition time, but this difference was not statistically significant. cGAN had the lowest CoV of the DL methods at all noise levels. Image quality and polar map uniformity of DL-denoised images were also better than reduced acquisition time OSEM’s. SSIM of the reduced acquisition time OSEM was overall higher than with the DL methods. The defect detection performance of full time OSEM measured as area under the ROC curve (AUC) was on average 0.97. Half time OSEM, CNN, RES and UNET provided equal or nearly equal AUC. However, with quarter time data CNN, RES and UNET had an average AUC of 0.93, which was lower than full time OSEM’s AUC, but equal to quarter acquisition time OSEM. cGAN did not achieve the defect detection performance of the other DL methods. Its average AUC with half time data was 0.94 and 0.91 with quarter time data. Conclusions DL-based denoising effectively improved noise level with slightly lower perfusion defect detection performance than full time reconstruction. cGAN achieved the lowest noise level, but at the same time the poorest defect detection performance among the studied DL methods.

Recent longitudinal studies in youth have reported MRI correlates of prospective anxiety symptoms during adolescence, a vulnerable period for the onset of anxiety disorders. However, their predictive value has not been established. Individual prediction through machine-learning algorithms might help bridge the gap to clinical relevance. A voting classifier with Random Forest, Support Vector Machine and Logistic Regression algorithms was used to evaluate the predictive pertinence of gray matter volumes of interest and psychometric scores in the detection of prospective clinical anxiety. Participants with clinical anxiety at age 18–23 (N = 156) were investigated at age 14 along with healthy controls (N = 424). Shapley values were extracted for in-depth interpretation of feature importance. Prospective prediction of pooled anxiety disorders relied mostly on psychometric features and achieved moderate performance (area under the receiver operating curve = 0.68), while generalized anxiety disorder (GAD) prediction achieved similar performance. MRI regional volumes did not improve the prediction performance of prospective pooled anxiety disorders with respect to psychometric features alone, but they improved the prediction performance of GAD, with the caudate and pallidum volumes being among the most contributing features. To conclude, in non-anxious 14 year old adolescents, future clinical anxiety onset 4–8 years later could be individually predicted. Psychometric features such as neuroticism, hopelessness and emotional symptoms were the main contributors to pooled anxiety disorders prediction. Neuroanatomical data, such as caudate and pallidum volume, proved valuable for GAD and should be included in prospective clinical anxiety prediction in adolescents.

Objectives: To investigate tympanostomy tube (TT) treatment in young children, with special interest in bloodless surgical methods (laser and radiofrequency), myringosclerosis formation and tympanometric testing.Methods: This prospective study includes 76 children whose 121 ears with middle ear effusion were treated with tympanostomy tubes. Myringotomy was performed with CO2 laser in 37, radiofrequency in 40 and myringotomy knife in 44 ears. The ears were evaluated with otomicroscopy and tympanometry preoperatively and post-operatively every 3-4 months until spontaneous tube extrusion.Results: All tubes extruded spontaneously (mean 12.8 months, range 3-36 months), with no persistent perfora-tions or cholesteatomas. CO2 laser and radiofrequency inserted tympanostomy tubes extruded faster (mean 11 months) compared to incisional myringotomy (mean 15 months, p = 0.002). Myringosclerosis was noted in 25 (21%) ears after treatment. There was a tendency to less myringosclerosis with bloodless techniques, but the difference was not significant. Flat tympanograms on the day of procedure predicted continuation of ventilation problems also after TT treatment (p = 0.003). Ears with preoperative type B tympanogram had significantly more myringosclerosis 21/75 (28%) compared with type A and C tympanograms 4/41 (10%) (p = 0.032).Conclusions: While all myringotomy methods were effective and safe, the traditional incisional myringotomy with a tympanostomy knife is still a good, feasible and cost-effective myringotomy method. No surgical removal of tympanostomy tubes is needed before 3 years of uncomplicated tympanostomy treatment. Tympanometry turned out to be a useful tool in prediction of post TT treatment ventilation problems of the middle ear.

Background In a chronic pain-causing disease such as juvenile idiopathic arthritis, the quality of coping with pain is crucial. Parents have a substantial influence on their children’s pain-coping strategies. This study aimed to develop scales for assessing parents’ strategies for coping with their children’s pain and a shorter improved scale for children usable in clinical practice. Methods The number of items in the Finnish version of the pain-coping questionnaire for children was reduced from 39 to 20. A corresponding reduced scale was created for parental use. We recruited consecutive patients from nine hospitals evenly distributed throughout Finland, aged 8–16 years who visited a paediatric rheumatology outpatient clinic and reported musculoskeletal pain during the past week. The patients and parents rated the child’s pain on a visual analogue scale from 0 to 100 and completed pain-coping questionnaires and depression inventories. The selection process of pain questionnaire items was performed using factor analyses. Results The average (standard deviation) age of the 130 patients was 13.0 (2.3) years; 91 (70%) were girls. Four factors were retained in the new, improved Pain-Coping Scales for children and parents. Both scales had 15 items with 2–5 items/factor. The goodness-of-fit statistics and Cronbach’s alpha reliability coefficients were satisfactory to good in both scaled. The criterion validity was acceptable as the demographic, disease related, and the depression and stress questionnaires correlated with the subscales. Conclusions We created a shorter, feasible pain-coping scale for children and a novel scale for caregivers. In clinical work, the pain coping scales may serve as a visualisation of different types of coping strategies for paediatric patients with pain and their parents and facilitate the identification of families in need of psychological support.

BackgroundContinued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies.MethodsThe EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014–2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined.FindingsAmong 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions.InterpretationResults from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors. Background: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies. Methods: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014–2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined. Findings: Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions. Interpretation: Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors.

Background: Low ferritin without anaemia has been linked to adverse health effects. Objectives: To investigate the prevalence and clinical significance of low ferritin in screen-detected coeliac disease. Methods: Seventy-six screen-detected coeliac disease patients were enrolled in the prospective collection of comprehensive clinical, laboratory and histological data at diagnosis and after 1–2 years on a gluten-free diet (GFD). All variables were compared between patients with different ferritin levels. Results: At coeliac disease diagnosis, six patients had anaemia. Of the 70 nonanaemic patients, ferritin levels were

Aim Inflammatory signals in the sacroiliac (SI) joints and the aorta of patients with axial spondyloarthritis (axSpA) were graded by positron emission tomography/computed tomography (PET/CT) imaging before and after treatment with sulfasalazine (SSZ) or adalimumab (ADA). Methods Patients with axSpA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, were recruited. Disease‐modifying antirheumatic drug‐naïve patients started SSZ for 12 weeks, whereas those with prestudy treatment with or contraindication to SSZ commenced ADA for 16 weeks. In addition, those patients in the SSZ group with insufficient response commenced ADA for 16 weeks. 18F‐fluorodeoxyglucose PET/CT was performed after inclusion and after treatment with SSZ and ADA. Maximum standardized uptake value (SUVmax) was assessed for the aorta and the SI joints, and maximal target‐to‐blood‐pool ratio (TBRmax) only for the aorta. Results Among five SSZ patients, mean ± SD BASDAI was 4.7 ± 1.6 before and 3.5 ± 1.4 after treatment (p = .101). In 13 ADA patients, the BASDAI decreased from 5.4 ± 1.6 to 2.8 ± 2.2 (p, We launched this small open‐label study to test the hypothesis that axial spondyloarthritis (axSpA) induces positron emission tomography (PET)‐detectable inflammation in the sacroiliac (SI) joints and cardiovascular tissues and that the effects of treatment with sulfasalazine and adalimumab (ADA) for axSpA can be visualized and confirmed by PET. Our results imply that sulfasalazine may reduce PET‐computed tomography‐detectable inflammation in the SI joints, with a trend towards a reduction in the aorta. In the ADA group, however, we did not observe any change in the PET signals in the SI joints nor in the aorta.

Purpose Recent studies have suggested that higher postmenopausal follicle stimulating hormone (FSH) may be associated with lower risk of diabetes. However, relatively little is known about postmenopausal FSH levels, including the level of variation between women and whether reproductive factors are associated with this variation. Methods We assessed the relationship of multiple reproductive factors with FSH levels among 588 postmenopausal women in the Kuopio Ischaemic Heart Disease Risk Factor Study. Participants were aged 53 to 73 years and not using hormone therapy at study enrollment (1998–2001) when reproductive factors were assessed and FSH was measured. Results After adjustment for age, menopause timing, sex steroid levels, adiposity and behavioral factors, we observed numbers of pregnancies and age at first birth were each inversely associated with FSH levels. For example, women with ≥ 3 births and an age at first birth ≥ 25 years had mean FSH levels that were 7.8 IU/L lower than those of women with 1–2 births and an age at first birth ≤ 24 years (P = 0.003). Number of miscarriages was inversely associated with FSH levels (-2.7 IU/L per miscarriage; P = 0.02). Women reporting 4 or more years of past hormone therapy use had significantly higher mean FSH levels than women who had never used hormone therapy (P for trend = 0.006). Conclusion Multiple reproductive factors were associated with postmenopausal FSH, independent of estradiol, adiposity and other confounders. These findings warrant replication and further exploration of potential underlying mechanism.

Introduction: The current manuscript presents a protocol for a systematic review and meta-analysis of the evidence regarding the determinants of responsiveness to multidisciplinary management of chronic pain, with pain intensity, pain-related interference, physical functioning and health-related quality of life as the main outcomes, with consideration to multiple secondary outcomes. Methods and analysis: To identify relevant studies, the Ovid MEDLINE, PubMed, Ovid PsycINFO, EBSCO CINAHL and Scopus databases will be searched for all studies exploring factors associated with responsiveness to multidisciplinary pain management from study inception to the present. Cohorts, case-control studies and randomised controlled trials will be included. Independent screening for eligible studies will be completed by a total of four researchers using defined criteria. Data extraction will be executed by two researchers. Study heterogeneity will be estimated using the I2 index. A meta-analysis will be performed using random effects models. Publication bias will be evaluated by means of funnel plots and Egger's test. Ethics and dissemination: The proposed study does not involve collection of primary data. Therefore, no ethical approval is required. The results of the systematic review and meta-analysis will be presented in a peer-reviewed journal and at conferences. Prospero registration number: CRD42021236424.

Key messages Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Abstract Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1–2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.

OBJECTIVES To assess long-term survival of pulpotomized primary molars and factors related to the survival of the teeth. MATERIALS AND METHODS This retrospective longitudinal study was based on electronic dental health records of children who attended public health service. Eligible children were

Objectives. Several approaches devised for clinical utilization of cell-based therapies for heart failure often suffer from complex and lengthy preparation stages. Epicardial delivery of autologous atrial appendage micrografts (AAMs) with a clinically used extracellular matrix (ECM) patch provides a straightforward therapy alternative. We evaluated the operative feasibility and the effect of micrografts on the patch-induced epicardial foreign body inflammatory response in a porcine model of myocardial infarction. Design. Right atrial appendages were harvested and mechanically processed into AAMs. The left anterior descending coronary artery was ligated to generate acute infarction. Patches of ECM matrix with or without AAMs were transplanted epicardially onto the infarcted area. Four pigs received the ECM and four received the AAMs patch. Cardiac function was studied by echocardiography both preoperatively and at 3-week follow-up. The primary outcome measures were safety and feasibility of the therapy administration, and the secondary outcome was the inflammatory response to ECM. Results. Neither AAMs nor ECM patch-related complications were detected during the follow-up time. AAMs patch preparation was feasible according to time and safety. Inflammation was greatly reduced in AAMs when compared with ECM patches as measured by the amount of infiltrated inflammatory cells and area of inflammation. Immunohistochemistry demonstrated an increased CD3+ cell density in the AAMs patch infiltrate. Conclusions. Epicardial AAMs transplantation demonstrated safety and clinical feasibility. The use of micrografts significantly inhibited ECM-induced foreign body inflammatory reactivity. Transplantation of AAMs shows good clinical applicability as adjuvant therapy to cardiac surgery and can suppress acute inflammatory reactivity.

Aims Female sex has previously been associated with poorer outcomes after myocardial infarction (MI), although evidence is scarce among young patients. We studied sex differences in cardiovascular outcomes after MI in young patients Methods and results Consecutive young (18–54 years) all-comer patients with out-of-hospital MI admitted to 20 Finnish hospitals (n = 8934, 17.3% women) in 2004–2014 were studied by synergizing national registries. Differences between the sexes were balanced by inverse probability weighting. The median follow-up period was 9.1 years (max 14.8 years). Young women with MI had more comorbidities at baseline, were revascularized less frequently, and received fewer evidence-based secondary prevention medications (P2Y12 inhibitors, renin–angiotensin signalling pathway inhibitors, statins, and lower statin dosages) after MI than young men. Long-term mortality or the occurrence of major adverse cardiovascular events (MACE; recurrent MI, stroke, or cardiovascular death) did not differ between the sexes in the unadjusted analysis. However, after baseline feature and treatment-difference adjustment, men had poorer outcomes after MI. Adjusted long-term mortality was 21.3% in men vs. 17.2% in women [hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.10–1.53; P = 0.002]. Cumulative MACE rate was 33.9% in men vs. 27.9% in women during follow-up (HR 1.23; 95% CI 1.09–1.39; P = 0.001). Recurrent MI and cardiovascular death occurrences were more frequent among men. Stroke occurrence did not differ between the sexes. Conclusions Young women were found to receive less active treatment after MI than young men. Nevertheless, male sex was associated with poorer long-term cardiovascular outcomes after MI in young patients after baseline feature adjustment.

PurposeSelf-fixed mesh is an alternative to suture mesh fixation in inguinal hernia repair. The aim of this study was to evaluate postoperative pain after open inguinal hernia surgery using self-fixed meshes.MethodsA randomized clinical trial comparing self-adhesive mesh (Adhesix™) and self-gripping mesh (Progrip™) was conducted from November 2018 through March 2021. Patients included were male, 18–85 years old, and suitable for day case surgery. The primary endpoint was the number of patients needing follow-up visits due to postoperative pain during the first 3 postoperative months. Secondary endpoints included the intensity of pain, the time of return to work and normal daily activities, quality of life measures and postoperative complications.Results270 patients were enrolled, 132 received Adhesix™ mesh (A group) and 138 Progrip™ mesh (P group), 231 (85.6%) completed 1- or 3-month follow-up. The number of patients needing follow-up for postoperative pain was significantly higher in the P group (19 vs. 4,p= 0.001). The P group had higher numeric rating scale of pain while coughing (P 0.50 vs. A 0.20,p= 0.024) and during exercise (P 1.02 vs. A 0.60,p= 0.057) at 3 months postoperatively. The time of return to normal activity was 16.6 days in the A group and 22.9 days in the P group, (p= 0.004). The postoperative day being fit for work was sooner for the A group (14.3 days vs 17.8 days,p= 0.009).ConclusionThis study demonstrated an advantage of self-adhesive mesh over self-gripping mesh with respect to acute postoperative pain and thus faster recovery after surgery.

Purpose: Unstable forearm shaft fractures in children are preferably treated surgically using elastic stable intramedullary nails. The radius is nailed retrograde from the distal metaphysis. There is a risk of surgery-related soft-tissue complications during the operation. Close evaluation of occult surgery-related soft-tissue lesions has not been possible previously, due to the titanium alloy hardware used in the process. The aim of the present study was to evaluate the potential findings in the surrounding soft tissues after intramedullary nailing of the radius, by using magnetic resonance imaging. Methods: The study population comprised 15 pediatric patients with forearm shaft fractures treated by polylactide-co-glycolide biodegradable intramedullary nails and postoperatively evaluated via magnetic resonance imaging. The main outcome was signal abnormality in any tendon at the entry point postoperatively. Secondarily, other changes in the soft tissues related to nailing were determined. Furthermore, the precise location of the entry point and the anatomic characteristics of the soft-tissue tunnel were described. Results: In total, 5 of 15 patients (33.3%) had transient signal pathology in a tendon postoperatively. Edema around the superficial radial nerve was detected in 13 of 15 patients (86.7%). The most common surgical approach was between the extensor pollicis brevis and the extensor carpi radialis longus tendons, which was applied in 10 of 15 patients (66.7%). Conclusions: One in three patients exhibited transient and occult surgery-related intraparenchymal signal pathology in a tendon, after forearm intramedullary nailing. Caution with surgical prepare of the soft-tissue cleavage is recommended. Level of evidence: IV

Non

Introduction: The European Association of Urology committee in 2020 suggested a new classification, intraoperative adverse incident classification (EAUiaiC), to grade intraoperative adverse events (IAE) in urology. Aims: We applied and validated EAUiaiC, for kidney tumor surgery. Patients and methods: A retrospective multicenter study was conducted based on chart review. The study group comprised 749 radical nephrectomies (RN) and 531 partial nephrectomies (PN) performed in 12 hospitals in Finland during 2016–2017. All IAEs were centrally graded for EAUiaiC. The classification was adapted to kidney tumor surgery by the inclusion of global bleeding as a transfusion of ≥3 units of blood (Grade 2) or as ≥5 units (Grade 3), and also by the exclusion of preemptive conversions. Results: A total of 110 IAEs were recorded in 13.8% of patients undergoing RN, and 40 IAEs in 6.4% of patients with PN. Overall, bleeding injuries in major vessels, unspecified origin and parenchymal organs accounted for 29.3, 24.0, and 16.0% of all IEAs, respectively. Bowel (n = 10) and ureter (n = 3) injuries were rare. There was no intraoperative mortality. IAEs were associated with increased tumor size, tumor extent, age, comorbidity scores, surgical approach and indication, postoperative Clavien–Dindo (CD) complications and longer stay in hospital. 48% of conversions were reactive with more CD-complications after reactive than preemptive conversion (43 vs. 25%). Conclusions: The associations between IAEs and preoperative variables and postoperative outcome indicate good construct validity for EAUiaiC. Bleeding is the most important IAE in kidney tumor surgery and the inclusion of transfusions could provide increased objectivity. publishedVersion

Introduction: The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment. Material and methods: This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases. Results: Treatment interruptions were associated with immunisation in patients using infliximab (p

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Background Treating hemorrhaging patients with prehospital blood product transfusions (PHBT) narrows transfusion delays and potentially benefits the patient. We describe our initial experiences of PHBT in a ground-based emergency medical service (EMS), where the transfusion protocol covers both traumatic and nontraumatic hemorrhaging patients. Methods A descriptive retrospective analysis was performed on the records of all the patients receiving red blood cells, freeze-dried plasma, or both during prehospital care from September 2016 to December 2020. The delays of PHBT and the effects on patients’ vital signs were analyzed and reported as the median and interquartile range (IQR) and analyzed using a Wilcoxon Signed rank test. Results 65 patients received prehospital blood product transfusions (PHBT), 29 (45%) were non-traumatic, and 36 (55%) traumatic. The main two reasons for PHBT were blunt trauma (n = 30, 46%) and gastrointestinal hemorrhage (n = 20, 31%). The median time from the emergency call to the start of PHBT was 54 min (IQR 38), and the transfusion began on a median of 61 min (IQR 42) before arrival at the hospital. The median systolic blood pressure improved from a median 76.5 mmHg (IQR 36.5) before transfusion to a median of 116.60 mmHg (IQR 26.5) (p Conclusions Starting PHBT in ground-based EMS is a feasible and viable option. The PHBT began significantly earlier than it would have started on arrival to the hospital, and it seems to be safe and improve patients’ physiology. Study approval D/2603/07.01.04.05/2019.

To evaluate the accuracy of heart rate variability (HRV) parameters obtained with a wrist-worn photoplethysmography (PPG) monitor in patients recovering from minimally invasive colon resection to investigate whether PPG has potential in postoperative patient monitoring. 31 patients were monitored for three days or until discharge or reoperation using a wrist-worn PPG monitor (PulseOn, Finland) with a Holter monitor (Faros 360, Bittium Biosignals, Finland) as a reference measurement device. Beat-to-beat intervals (BBI) and HRV information collected by PPG were compared with RR intervals (RRI) and HRV obtained from the ECG reference after removing artefacts and ectopic beats. The beat-to-beat mean error (ME) and mean absolute error (MAE) of good quality heartbeat intervals obtained by wrist PPG were estimated as − 1.34 ms and 10.4 ms respectively. A significant variation in the accuracy of the HRV parameters was found. In the time domain, SDNN (9.11%), TRI (11.4%) and TINN (11.1%) were estimated with low relative MAE, while RMSSD (34.3%), pNN50 (139%) and NN50 (188%) had higher errors. The logarithmic parameters in the frequency domain (VLF Log, LF Log and HF Log) exhibited the lowest relative error, and for non-linear parameters, SD2 (7.5%), DFA α1 (8.25%) and DFA α2 (4.71%) were calculated much more accurately than SD1 (34.3%). The wrist PPG shows some potential for use in a clinical setting. The accuracy of several HRV parameters analyzed post hoc was found sufficient to be used in further studies concerning postoperative recovery of patients undergoing laparoscopic colon resection, although there were large errors in many common HRV parameters such as RMSSD, pNN50 and NN50, rendering them unusable.ClinicalTrials.gov Identifier: NCT04996511, August 9, 2021, retrospectively registered

Publisher Copyright: © 2022 Heart Rhythm Society Background: Poor R-wave progression (PRWP) is a common clinical finding on the standard 12-lead electrocardiogram (ECG), but its prognostic significance is unclear. Objective: The purpose of this study was to examine the prognosis associated with PRWP in terms of sudden cardiac death (SCD), cardiac death, and all-cause mortality in general population subjects with and without coronary artery disease (CAD). Methods: Data and 12-lead ECGs were collected from a Finnish general population health examination survey conducted during 1978–1980 with follow-up until 2011. The study population consisted of 6854 subjects. Main end points were SCD, cardiac death, and all-cause mortality. PRWP was defined as R-wave amplitude ≤ 0.3 mV in lead V3 and R-wave amplitude in lead V2 ≤ R-wave amplitude in lead V3. Results: PRWP occurred in 213 subjects (3.1%). During the follow-up period of 24.3 ± 10.4 years, 3723 subjects (54.3%) died. PRWP was associated with older age, higher prevalence of heart failure and CAD, and β-blocker medication. In multivariate analyses, PRWP was associated with SCD (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.34–3.39), cardiac death (HR 1.75; 95% CI 1.35–2.15), and all-cause mortality (HR 1.29; 95% CI 1.08–1.54). In the subgroup with CAD, PRWP had a stronger association with cardiac mortality (HR 1.71; 95% CI 1.19–2.46) than in the subgroup without CAD, while the association with SCD was significant only in the subgroup with CAD (HR 2.62; 95% CI 1.38–4.98). Conclusion: PRWP was associated with adverse prognosis in the general population and with SCD in subjects with CAD.

We have followed the clinical course of a 45-year-old man with a severe form of alpha-thalassemia X-linked intellectual disability syndrome for 40 years. The most challenging health issue is the combination of rumination, drooling, and vomiting. The patient achieved present adaptive and motor skills in his teenage years. He is able to move on the floor in a sitting position. He seems happy and has not shown any behavioral or psychiatric symptoms. New signs not described in the literature before are accelerated growth after puberty and atypical sleeping position with upper body resting on legs. Non

Objective Mechanochemical ablation (MOCA) is a nonthermal nontumescent method of treating saphenous vein insufficiency. The feasibility and short-term results of MOCA are good, but its long-term results are unknown. A randomized study was performed to compare MOCA with endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) in the setting of unilateral great saphenous vein (GSV) insufficiency. Methods Venous outpatient clinic patients with varicose veins (CEAP class C2-C4) caused by GSV insufficiency were invited to participate in the study; in total, 132 patients met the inclusion criteria and were willing to participate. Patients were randomized to treatment (2:1:1 for MOCA, EVLA, and RFA, respectively). The state of the GSV with duplex Doppler ultrasound examination and the disease-specific quality of life were assessed at 1 month, 1 year, and 3 years after the treatment. Results Some patients declined to continue in the study after randomization; in total, 117 patients underwent treatment. At 3 years, the occlusion rate was significantly lower with MOCA than with either EVLA or RFA (82% vs 100%; P = .005). Quality of life was similar between the groups. In the MOCA group, GSVs that were larger than 7 mm in diameter preoperatively were more likely to recanalize during the follow-up period. The partial recanalizations of proximal GSV observed at 1 year progressed during the follow-up. Conclusions MOCA is a feasible treatment option in an outpatient setting, but its technical success rates are inferior compared with endovenous thermal ablation. Its use in large-caliber veins should be considered carefully.

Background Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. Methods The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. Results Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0–1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0–1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. Conclusion Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.

Objective To investigate the long-term outcomes of patients with RA after myocardial infarction (MI). Methods All-comer, real-life MI patients with RA (n = 1614, mean age 74 years) were retrospectively compared with propensity score (1:5) matched MI patients without RA (n = 8070) in a multicentre, nationwide, cohort register study in Finland. The impact of RA duration and the usage of corticosteroids and antirheumatic drugs on RA patients’ outcomes were also studied. The median follow-up was 7.3 years. Results RA was associated with an increased 14-year mortality risk after MI compared with patients without RA [80.4% vs 72.3%; hazard ratio (HR) 1.25; CI: 1.16, 1.35; P Conclusion RA is independently associated with poorer prognosis after MI. RA duration and corticosteroid usage and dosage were independent predictors of mortality after MI in RA. Special attention is needed for improvement of outcomes after MI in this vulnerable population.

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.

Background Knowledge of arrhythmias in patients with end-stage renal disease (ESRD) is mainly based on ambulatory electrocardiography (ECG) studies and observations during haemodialysis (HD). We used insertable cardiac monitors (ICMs) to define the prevalence of arrhythmias, focusing on bradyarrhythmias, in ESRD patients treated with several dialysis modes including home therapies. Moreover, we assessed whether these arrhythmias were detected in baseline or ambulatory ECG recordings. Methods Seventy-one patients with a subcutaneous ICM were followed for up to 3 years. Asystole (≥4.0 s) and bradycardia (heart rate Results At recruitment, 44 patients were treated in in-centre HD, 12 in home HD and 15 in peritoneal dialysis. During a median follow-up of 34.4 months, 18 (25.4%) patients had either an asystolic or a bradycardic episode. The median length of each patient’s longest asystole was 6.6 s and that of a bradycardia 13.5 s. Ventricular tachyarrhythmias were detected in 16 (23%) patients, and AF in 34 (51%) patients. In-centre HD and Type II diabetes were significantly more frequent among those with bradyarrhythmias, whereas no bradyarrhythmias were found in home HD. No bradyarrhythmias were evident in baseline or ambulatory ECG recordings. Conclusions Remarkably many patients with ESRD had bradycardia or asystolic episodes, but these arrhythmias were not detected by baseline or ambulatory ECG.

Background Parastomal hernia repair is a complex surgical procedure with high recurrence and complication rates. This retrospective nationwide cohort study presents the results of different parastomal hernia repair techniques in Finland. Methods All patients who underwent a primary end ostomy parastomal hernia repair in the nine participating hospitals during 2007–2017 were included in the study. The primary outcome measure was recurrence rate. Secondary outcomes were complications and re-operation rate. Results In total, 235 primary elective parastomal hernia repairs were performed in five university hospitals and four central hospitals in Finland during 2007–2017. The major techniques used were the Sugarbaker (38.8%), keyhole (16.3%), and sandwich techniques (15.4%). In addition, a specific intra-abdominal keyhole technique with a funnel-shaped mesh was utilized in 8.3% of the techniques; other parastomal hernia repair techniques were used in 21.3% of the cases. The median follow-up time was 39.0 months (0–146, SD 35.3). The recurrence rates after the keyhole, Sugarbaker, sandwich, specific funnel-shaped mesh, and other techniques were 35.9%, 21.5%, 13.5%, 15%, and 35.3%, respectively. The overall re-operation rate was 20.4%, while complications occurred in 26.3% of patients. Conclusion The recurrence rate after parastomal hernia repair is unacceptable in this nationwide cohort study. As PSH repair volumes are low, further multinational, randomized controlled trials and hernia registry data are needed to improve the results.

Background Nonsteroidal anti‐inflammatory drug (NSAID) exacerbated respiratory disease (N‐ERD) is a triad with asthma, chronic rhinosinusitis with nasal polyps, and NSAID intolerance. Uncontrolled N‐ERD forms a major public health problem due to frequent and difficult‐to‐treat exacerbations and/or requiring putatively frequent endoscopic sinus surgeries (ESS). Our aim was to study factors affecting control of N‐ERD. Methods Retrospective patient record data (patient characteristics, prior sinus surgeries, follow‐up data in 2020) from 167 N‐ERD patients undergoing consultation at three tertiary hospitals from 2001 to 2017 was used. Outcome measurements reflecting uncontrolled N‐ERD were revision ESS, corticosteroids/biological therapy, and antibiotic courses during 2016–2020. Associations were analyzed by using nonparametric tests, Cox's proportional hazard, and binary logistic regression models. Results Nasal polyp eosinophilia increased the risk of revision surgery during the follow‐up (adjusted hazard ratio [aHR] 3.21, confidence interval 1.23–8.38). Also baseline oral corticosteroids (OCS; HR, 1.73, 1.04–2.89) and baseline surgery without total ethmoidectomy increased the risk of revision ESS (HR, 2.17, 1.07–4.42) in unadjusted models. In addition, both baseline OCS (adjusted odds ratio [aOR] 2.78, 1.23–6.26) and a history of ≥4 previous ESS (aOR, 2.15, 0.98–4.70) were associated with the use of OCS/biological therapy during the follow‐up, but not with high number of antibiotics. Conclusions Nasal polyp eosinophilia, baseline OCS, and a history of recurrent ESS predict uncontrolled N‐ERD. These factors might be clinically useful in risk‐estimation of uncontrolled disease and for organizing follow‐ups. Prospective cohort studies with larger sample size are needed to further study the factors affecting the upper airway control of N‐ERD., The patient record data of 167 patients with NSAID‐exacerbated respiratory disease was analyzed to study factors affecting the disease control. Nasal polyp eosinophilia increased the risk of revision surgery, and baseline oral corticosteroids and a history of four or more endoscopic sinus surgeries were associated with poor disease control during the follow‐up.

Miika Värri,1 Leo Niskanen,2 Tomi-Pekka Tuomainen,3 Risto Honkanen,1,4 Heikki Kröger,1,5 Marjo T Tuppurainen1,6 1Kuopio Musculoskeletal Research Unit (KMRU), Surgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; 2Department of Endocrinology and Metabolism, Abdominal Centre, Helsinki University Hospital, Universities of Helsinki and Eastern Finland, Helsinki, Finland; 3Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 4Lapland Hospital District, Rovaniemi, Finland; 5Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, Finland; 6Department of Obstetrics and Gynaecology, Kuopio University Hospital, Kuopio, FinlandCorrespondence: Miika VärriKuopio Musculoskeletal Research Unit (KMRU), Surgery, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, FinlandTel +358503655083Fax +358 17 172 611Email mvarri@uef.fiPurpose: Atherosclerosis (AS) and osteoporosis (OP) are common causes of morbidity and mortality in postmenopausal women and are connected via an unknown mechanistic link. Metabolite profiling of blood samples may allow the identification of new biomarkers and pathways for this enigmatic association.Patients and Methods: We studied the difference in 148 metabolite levels from serum samples in postmenopausal women with AS and OP compared with those in healthy participants in this cross-sectional study. Quantitative AS was assessed by carotid artery intima-media thickness (cIMT) and carotid artery calcifications (CACs) by ultrasound, as well as OP by femoral neck (FN) bone mineral density (BMD) and 148 metabolic measures with high-throughput proton (1H) nuclear magnetic resonance (NMR) in serum samples from 280 postmenopausal (PM) women. Subjects were a randomly selected subsample from the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The final study population included the following groups: OP with CAC (n=16, group I), non-OP with no CAC (n=59, group II), high cIMT tertile with OP (n=11, group III) and low cIMT tertile without OP (n=48, group IV).Results: There were differences in several metabolite levels between groups I and II. The acetate level was lower in group I compared to that in group II (group I mean ± SD: 0.033 ± 0.0070; group II: 0.041 ± 0.014, CI95%: 0.018‒0.15, p=0.014). The result was similar with diacylglycerol (p=0.002), leucine (p=0.031), valine (p=0.022) and several very low-density lipoprotein (VLDL) metabolite levels, which were lower in group I compared to those in group II. However, no associations were found in adjusted analyses with total body (TB) fat mass (FM), age and statin use (p> 0.05).Conclusion: Our novel study found differences in the metabolite profiling of altered amino acid and lipoprotein metabolism in participants with OP and AS compared with those in healthy women. The causative mechanisms remain unknown and further studies are needed.Keywords: metabolomics, carotid artery calcification, postmenopausal women, osteoporosis, carotid intima-media thickness, acetate

IntroductionOral infectious diseases are common chronic oral diseases characterized by a chronic inflammatory condition. We investigated chronic oral diseases as potential risk factors for systemic chronic diseases, diabetes mellitus, connective tissue diseases, seropositive rheumatoid arthritis, ulcerative colitis, and Crohn's disease, as well as severe psychotic and other severe mental disorders.MethodsThe cohort comprised 68,273 patients aged ≥ 29 years with at least one dental visit to the Helsinki City Health Services between 2001 and 2002. The cohort was linked to the data on death (Statistics Finland), cancer (Finnish Cancer Registry), and drug reimbursement (Finnish Social Insurance Institution) and followed until death or the end of 2013. The outcomes of interest were the incidences of chronic diseases measured starting with special refund medication, which means Social Insurance Institution partly or fully reimburses medication costs. Outcomes of interest were diabetes mellitus, connective tissue diseases, seropositive rheumatoid arthritis, ulcerative colitis and Crohn's disease, and severe mental disorders.ResultsThe mean follow-up time was 9.8 years. About 25% of the study population had periodontitis, 17% caries, over 70% apical periodontitis, and 9% ConclusionOur epidemiological 10 years follow-up study suggests that the association exists between chronic oral diseases and diabetes, warranting close collaboration among patient's healthcare professionals.

Background In the current century, sleep apnoea has become a significant public health problem due to the obesity epidemic. To increase awareness, improve diagnostics, and improve treatment, Finland implemented a national sleep apnoea programme from 2002 to 2010. Here, we present changes in the societal burden caused by sleep apnoea from 1996 to 2018. Methods National register data were collected from the Care Register for Health Care, Statistics Finland, the Social Insurance Institution of Finland, and the Finnish Centre for Pensions. Disease prevalence, use of healthcare and social services, and societal costs were estimated. Findings The number of sleep apnoea patients increased in secondary care from 8 600 in 1996 to 61 000 in 2018. There was a continuous increase in outpatient visits in secondary care from 9 700 in 1996 to 122 000 in 2018 (1 160%) and in primary care from 10 000 in 2015 to 29 000 in 2018 (190%). Accordingly, the cumulative annual number of days off work for sleep apnoea increased from 1 100 to 46 000. However, disability pensions for sleep apnoea decreased from 820 to 550 (33%) during the observation period. Societal costs per patient decreased over 50% during the observation period ((sic) 2 800 to (sic)1 200). Interpretation The number of sleep apnoea patients in Finland increased remarkably during the observation period. To control this burden, diagnostic methods and treatment were revised and follow up was reorganised. Consequently, there was a significant decrease in societal costs per patient. The decrease in disability pensions suggests earlier diagnosis and improved treatment. The national sleep apnoea programme was one of the initiators for these improved outcomes. Funding The Finnish Institute for Health and Welfare and the Hospital District of Helsinki and Uusimaa (HUH), Helsinki, Finland. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Objective The aim of this study was to compare reprojected bone SPECT/CT (RBS) against planar bone scintigraphy (BS) in the detection of bone metastases in breast and prostate cancer patients. Methods Twenty-six breast and 105 prostate cancer patients with high risk for bone metastases underwent Tc-99m-HMDP BS and whole-body SPECT/CT, 1.5-T whole-body diffusion-weighted MRI and F-18-NaF or F-18-PSMA-1007 PET/CT within two prospective clinical trials (NCT01339780 and NCT03537391). Consensus reading of all imaging modalities and follow-up data were used to define the reference standard diagnosis. The SPECT/CT data were reprojected into anterior and posterior views to produce RBS images. Both BS and RBS images were independently double read by two pairs of experienced nuclear medicine physicians. The findings were validated against the reference standard diagnosis and compared between BS and RBS on the patient, region and lesion levels. Results All metastatic patients detected by BS were also detected by RBS. In addition, three metastatic patients were missed by BS but detected by RBS. The average patient-level sensitivity of two readers for metastases was 75% for BS and 87% for RBS, and the corresponding specificity was 79% for BS and 39% for RBS. The average region-level sensitivity of two readers was 64% for BS and 69% for RBS, and the corresponding specificity was 96% for BS and 87% for RBS. Conclusion Whole-body bone SPECT/CT can be reprojected into more familiar anterior and posterior planar images with excellent sensitivity for bone metastases, making additional acquisition of planar BS unnecessary.

Concerns over future healthcare capacity along with continuing demands for sustainability call for novel solutions to improve citizens’ health and wellbeing through effective prevention and improved diagnosis and treatment. Part of the solution to tackle the challenge could be making the most of the exploitation of genomic data in personalized risk assessment, creating new opportunities for data-driven precision prevention and public health. Presently, the utilization of genomic data in the Finnish healthcare system is limited to a few medical specialty areas. To successfully extend the use of genomic information in everyday healthcare, evidence-based and feasible strategies are needed. The national actions that Finland is taking towards this goal are 1) providing scientific evidence for the utility of genomic information for healthcare purposes; 2) evaluating the potential health-economic impact of implementing precision healthcare in Finland; 3) developing a relevant legal framework and infrastructures for the utilization of genomic information; 4) building a national multidisciplinary expert network bringing together relevant professionals and initiatives to achieve consensus among the different stakeholders on specific issues vital for translating genomic data into precision healthcare; 5) building competence and genomic literacy skills among various target groups; and 6) public engagement (informing and educating the public). Taken together, these actions will enable building a roadmap towards the expedient application of genomic data in Finnish healthcare and promoting the health of our citizens.

Background Older patients are at high risk of experiencing delayed functional recovery after surgical treatment. This study aimed to identify factors that predict changes in the level of support for activities of daily living and mobility 1 year after colonic cancer surgery. Methods This was a multicentre, observational study conforming to STROBE guidelines. The prospective data included pre-and postoperative mobility and need for support in daily activities, co-morbidities, onco-geriatric screening tool (G8), clinical frailty scale (CFS), operative data, and postoperative surgical outcomes. Results A total of 167 patients aged 80 years or more with colonic cancer were recruited. After surgery, 30 per cent and 22 per cent of all patients had increased need for support and decreased motility. Multivariableanalysis with all patients demonstrated that preoperative support in daily activities outside the home (OR 3.23, 95 per cent c.i. 1.06 to 9.80, P = 0.039) was associated with an increased support at follow-up. A history of cognitive impairment (3.15, 1.06 to 9.34, P = 0.038) haemoglobin less than 120 g/l (7.48, 1.97 to 28.4, P = 0.003) and discharge to other medical facilities (4.72, 1.39 to 16.0, P = 0.013) were independently associated with declined mobility. With functionally independent patients, haemoglobin less than 120 g/l (8.31, 1.76 to 39.2, P = 0.008) and discharge to other medical facilities (4.38, 1.20 to 16.0, P = 0.026) were associated with declined mobility. Conclusion Increased need for support before surgery, cognitive impairment, preoperative anaemia, and discharge to other medical facilities predicts an increased need for support or declined mobility 1 year after colonic cancer surgery. Preoperative assessment and optimization should focus on anaemia correction, nutritional status, and mobility with detailed rehabilitation plan.

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 Results: In all, 377 patients with BD-IPMN were followed for a median of 5.4 years, 28% with WF at diagnosis, and 14% who developed WF/HRS during surveillance. Half had a Conclusions: No carcinomas or HGDs appeared with normal CA 19-9 levels. Patients with

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) deficiency due to the homozygous PCK1 variant has recently been associated with childhood-onset hypoglycemia with a recognizable pattern of abnormal urine organic acids. In this study 21 children and three adult patients with genetically confirmed PEPCK-C deficiency were diagnosed during the years 2016-2019 and the available biochemical and clinical data were collected. All patients were ethnic Finns. Most patients (22 out of 24) had a previously published homozygous PCK1 variant c.925G>A. Two patients had a novel compound heterozygous PCK1 variant c.925G>A and c.716C>T. The laboratory results showed abnormal urine organic acid profile with increased tricarboxylic acid cycle intermediates and inadequate ketone body production during hypoglycemia. The hypoglycemic episodes manifested predominantly in the morning. Infections, fasting or poor food intake, heavy exercise, alcohol consumption and breastfeeding were identified as triggering factors. Five patients presented with neonatal hypoglycemia. Hypoglycemic seizures occurred in half of the patients (12 out of 24). The first hypoglycemic episode often occurred at the age of 1-2 years, but it sometimes presented at a later age, and could re-occur during school-age or adulthood. This study adds to the laboratory data on PEPCK-C deficiency, confirming the recognizable urine organic acid pattern and identifying deficient ketogenesis as a novel laboratory finding. The phenotype is expanded suggesting that the risk of hypoglycemia may continue into adulthood if predisposing factors are present. This article is protected by copyright. All rights reserved.

Background Minimally invasive ventral mesh rectopexy (VMR) is a widely used surgical treatment for posterior pelvic organ prolapse; however, evidence of the utility of revisional surgery is lacking. Our aim was to assess the technical details, safety and outcomes of redo minimally invasive VMR for patients with external rectal prolapse (ERP) recurrence or relapsed symptoms of internal rectal prolapse (IRP). Methods This is a retrospective cohort study of patients with recurrent ERP or symptomatic IRP who underwent redo minimally invasive VMR between 2011 and 2016. The study was conducted at three hospitals in Finland. Data collected retrospectively included patient demographics, in addition to perioperative and short-term postoperative findings. At follow-up, all living patients were sent a questionnaire concerning postoperative disease-related symptoms and quality of life. Results A total of 43 redo minimally invasive VMR were performed during the study period. The indication for reoperation was recurrent ERP in 22 patients and relapsed symptoms of IRP in 21 patients. In most operations (62.8%), the previously used mesh was left in situ and a new one was placed. Ten (23.3%) patients experienced complications, including 2 (4.7%) mesh-related complications. The recurrence rate was 4.5% for ERP. Three patients out of 43 were reoperated on for various reasons. One patient required postoperative laparoscopic hematoma evacuation. Patients operated on for recurrent ERP seemed to benefit more from the reoperation. Conclusions Minimally invasive redo VMR appears to be a safe and effective procedure for treating posterior pelvic floor dysfunction with acceptable recurrence and reoperation rates.

Objective: Long-term evidence on ustekinumab treatment response and persistence in patients with Crohn’s disease in a real-world setting is scarce. We performed a retrospective nationwide chart review study of long-term clinical outcomes in Crohn’s disease patients treated with ustekinumab. Methods: The study was conducted in 17 Finnish hospitals and included adult Crohn’s disease patients who received an initial intravenous dose of ustekinumab during 2017–2018. Disease activity data were collected at baseline, 16 weeks, and 1 year from health records. Results: The study included 155 patients. The disease was stricturing or penetrating in 69 and 59% had prior Crohn’s disease-related surgeries, and 97% had a treatment history of at least one biologic agent. Of 93 patients with ≥1 year of follow-up, 77 (83%) were still on ustekinumab at 1 year. In patients with data available, from baseline to the 1-year follow-up the simple endoscopic score for Crohn’s disease (SES-CD) decreased from 10 to 3 (P = 0.033), C-reactive protein from 7 to 5 mg/L, (P

OBJECTIVES We sought to study the indications, long-term occurrence, and predictors of permanent pacemaker implantation (PPI) after isolated surgical aortic valve replacement with bioprostheses. METHODS The CAREAVR study included 704 patients (385 females, 54.7%) without a preoperative PPI (mean ± standard deviation age 75 ± 7 years) undergoing isolated surgical aortic valve replacement at 4 Finnish hospitals between 2002 and 2014. Data were extracted from electronic patient records. RESULTS The follow-up was median 4.7 years (range 1 day to 12.3 years). Altogether 56 patients received PPI postoperatively, with the median 507 days from the operation (range 6 days to 10.0 years). The PPI indications were atrioventricular block (31 patients, 55%) and sick sinus syndrome (21 patients, 37.5%). For 4 patients, the PPI indication remained unknown. A competing risks regression analysis (Fine–Gray method), adjusted with age, sex, diabetes, coronary artery disease, preoperative atrial fibrillation (AF), left ventricular ejection fraction, New York Heart Association class, AF at discharge and urgency of operation, was used to assess risk factors for PPI. Only AF at discharge (subdistribution hazard ratio 4.34, 95% confidence interval 2.34–8.03) was a predictor for a PPI. CONCLUSIONS Though atrioventricular block is the major indication for PPI after surgical aortic valve replacement, >30% of PPIs are implanted due to sick sinus syndrome during both short-term follow-up and long-term follow-up. Postoperative AF versus sinus rhythm conveys >4-fold risk of PPI. Clinical trial registration clinicaltrials.gov Identifier: NCT02626871

Background In the photodynamic therapy (PDT) of non‐aggressive basal cell carcinomas (BCCs), 5‐aminolevulinic acid nanoemulsion (BF‐200ALA) has shown non‐inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL‐PDT in the treatment of BCCs. Objectives To compare the histological clearance, tolerability (pain and post‐treatment reaction), and cosmetic outcome of MAL, BF‐200 ALA, and low‐concentration HAL in the PDT of non‐aggressive BCCs. Methods Ninety‐eight histologically verified non‐aggressive BCCs met the inclusion criteria, and 54 patients with 95 lesions completed the study. The lesions were randomized to receive LED‐PDT in two repeated treatments with MAL, BF‐200 ALA, or HAL. Efficacy was assessed both clinically and confirmed histologically at three months by blinded observers. Furthermore, cosmetic outcome, pain, post‐treatment reactions fluorescence, and photobleaching were evaluated. Results According to intention‐to‐treat analyses, the histologically confirmed lesion clearance was 93.8% (95% confidence interval [CI] = 79.9–98.3) for MAL, 90.9% (95% CI = 76.4–96.9) for BF‐200 ALA, and 87.9% (95% CI = 72.7–95.2) for HAL, with no differences between the arms (p=0.84). There were no differences between the arms as regards pain, post‐treatment reactions, or cosmetic outcome. Conclusions PDT with low‐concentration HAL and BF‐200 ALA have a similar efficacy, tolerability, and cosmetic outcome compared to MAL. HAL is an interesting new option in dermatological PDT, since good efficacy is achieved with a low concentration. peerReviewed

Background: Fragmented QRS (fQRS) on 12-lead electrocardiogram(ECG) is associated with scarred myocardium and adverse outcome. However, the data on gender differences in terms of its prevalence and prognostic value is sparse. The aim of this study was to evaluate whether gender differences in fQRS exist among subjects drawn from populations with different risk profiles. Methods: We analyzed fQRS from 12-lead ECG in 953 autopsy-confirmed victims of sudden cardiac death (SCD) (78% men; 67.0 +/- 11.4 yrs), 1900 coronary artery disease (CAD) patients with angiographically confirmed stenosis of >= 50% (70% men; 66.6 +/- 9.0 yrs, 43% with previous myocardial infarction [MI]), and in 10,904 adults drawn from the Finnish adult general population (52% men; 44.0 +/- 8.5 yrs). Results: Prevalence of fQRS was associated with older age, male sex and the history and severity of prior cardiac disease of subjects. Among the general population fQRS was more commonly found among men in comparison to women (20.5% vs. 14.8%, p

Background: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. The aim of our longitudinal study was to describe ageing‐related cognitive changes in men with FXS. Method: A neuropsychologist determined the raw scores (RSs) of 19 men with FXS twice with the Leiter International Performance Scale at an average interval of 22 years. The ages of the participants at baseline ranged from 16 to 50 (mean 27) years. Results: At follow‐up, the RSs improved in two men, remained the same in two men and declined in 15 men. Overall, the RS of the study group deteriorated by an average 4 points in RSs (p < 0.001). Conclusion: Cognitive ageing in men with FXS started earlier than that in men in the general population; in many cases, cognitive ageing in men with FXS began before middle age, usually without any medical or other underlying cause.