Transcriptomic analysis of intestine following administration of a transglutaminase 2 inhibitor to prevent gluten-induced intestinal damage in celiac disease.

Transglutaminase 2 (TG2) plays a pivotal role in the pathogenesis of celiac disease (CeD) by deamidating dietary gluten peptides, which facilitates antigenic presentation and a strong anti-gluten T cell response. Here, we elucidate the molecular mechanisms underlying the efficacy of the TG2 inhibitor ZED1227 by performing transcriptional analysis of duodenal biopsies from individuals with CeD on a long-term gluten-free diet before and after a 6-week gluten challenge combined with 100 mg per day ZED1227 or placebo. At the transcriptome level, orally administered ZED1227 effectively prevented gluten-induced intestinal damage and inflammation, providing molecular-level evidence that TG2 inhibition is an effective strategy for treating CeD. ZED1227 treatment preserved transcriptome signatures associated with mucosal morphology, inflammation, cell differentiation and nutrient absorption to the level of the gluten-free diet group. Nearly half of the gluten-induced gene expression changes in CeD were associated with the epithelial interferon-γ response. Moreover, data suggest that deamidated gluten-induced adaptive immunity is a sufficient step to set the stage for CeD pathogenesis. Our results, with the limited sample size, also suggest that individuals with CeD might benefit from an HLA-DQ2/HLA-DQ8 stratification based on gene doses to maximally eliminate the interferon-γ-induced mucosal damage triggered by gluten.

Immunomodulatory Functions of Adipose Mesenchymal Stromal/Stem Cell Derived From Donors With Type 2 Diabetes and Obesity on CD4 T Cells.

For adipose stromal/stem cell (ASCs)-based immunomodulatory therapies, it is important to study how donor characteristics, such as obesity and type 2 diabetes (T2D), influence ASCs efficacy. Here, ASCs were obtained from 2 groups, donors with T2D and obesity (dASCs) or nondiabetic donors with normal-weight (ndASCs), and then cultured with anti-CD3/CD28-stimulated allogeneic CD4 T cells. ASCs were studied for the expression of the immunomodulators CD54, CD274, and indoleamine 2, 3 dioxygenase 1 (IDO) in inflammatory conditions. CD4 T cells cultured alone or in cocultures were assessed to evaluate proliferation, activation marker surface expression, apoptosis, the regulatory T cells (Tregs; CD4+ CD25high FOXP3+) frequency, and intracellular cytokine expression using flow cytometry. Modulation of T-cell subset cytokines was explored via ELISA. In inflammatory conditions, the expression of CD54, CD274, and IDO was significantly upregulated in ASCs, with no significant differences between ndASCs and dASCs. dASCs retained the potential to significantly suppress CD4 T-cell proliferation, with a slightly weaker inhibitory effect than ndASCs, which was associated with significantly reduced abilities to decrease IL-2 production and increase IL-8 levels in cocultures. Such attenuated potentials were significantly correlated with increasing body mass index. dASCs and ndASCs comparably reduced CD4 T-cell viability, HLA-DR expression, and interferon-gamma production and conversely increased CD69 expression, the Tregs percentage, and IL-17A production. Considerable amounts of the immunomodulators prostaglandin E2 (PGE2) and IL-6 were detected in the conditioned medium of cocultures. These findings suggest that ASCs obtained from donors with T2D and obesity are receptive to the inflammatory environment and able to modulate CD4 T cells accordingly.

Transdermal oestradiol and exercise in androgen deprivation therapy (ESTRACISE): protocol.

OBJECTIVE: To report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise. STUDY DESIGN AND METHODS: The primary endpoint of this open-label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT-induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality of life. The trial will recruit high-risk PCa patients (n = 310) undergoing external beam radiation therapy with adjuvant subcutaneous ADT. Participants will be stratified and randomized in a 1:1 ratio to either the E2 + ADT arm or the ADT-only control arm. Additionally, a subset of patients (n = 120) will be randomized into a supervised exercise programme. RESULTS: The primary outcome is assessed according to the efficacy of E2 in mitigating the deterioration of Expanded Prostate Cancer Index Composite sexual function domain scores. Secondary outcomes are assessed according to the occurrence of ADT-induced adverse effects, safety and tolerability of E2, impact of E2 with or without exercise on physical performance, body composition, bone mineral density, muscle size, systematic biomarkers, and quality of life. CONCLUSION: The ESTRACISE study's innovative design can offer novel insights about the benefits of E2 gel, and the substudy can reinforce the benefits resistance training and deliver valuable new novel insights into the synergistic benefits of E2 gel and exercise, which are currently unknown. TRIAL REGISTRATION: The protocol has been registered in euclinicaltrials.eu (2023-504704-28-00) and in clinicaltrials.gov (NCT06271551).

Assessment of a novel BLOOMY score for predicting mortality in hospitalised adults with bloodstream infection.

PURPOSE: A German multicentre study BLOOMY was the first to use machine learning approach to develop mortality prediction scores for bloodstream infection (BSI) patients, but the scores have not been assessed in other cohorts. Our aim was to assess how the BLOOMY 14-day and 6-month scores estimate mortality in our cohort of 497 cases with BSI. METHODS: Clinical data, laboratory data, and patient outcome were gathered retrospectively from patient records. The scores were calculated as presented in the BLOOMY study with the exception in the day of the evaluation. RESULTS: In our cohort, BLOOMY 14-day score estimated death by day 14 with an area under curve (AUC) of 0.87 (95% Confidence Interval 0.80-0.94). Using ≥ 6 points as a cutoff, sensitivity was 68.8%, specificity 88.1%, positive predictive value (PPV) 39.3%, and negative predictive value (NPV) 96.2%. These results were similar in the original BLOOMY cohort and outweighed both quick Sepsis-Related Organ Failure Assessment (AUC 0.76) and Pitt Bacteraemia Score (AUC 0.79) in our cohort. BLOOMY 6-month score to estimate 6-month mortality had an AUC of 0.79 (0.73-0.85). Using ≥ 6 points as a cutoff, sensitivity was 98.3%, specificity 10.7%, PPV 25.7%, and NPV 95.2%. AUCs of 6-month score to estimate 1-year and 5-year mortality were 0.80 (0.74-0.85) and 0.77 (0.73-0.82), respectively. CONCLUSION: The BLOOMY 14-day and 6-month scores performed well in the estimations of mortality in our cohort and exceeded some established scores, but their adoption in clinical work remains to be seen.

Measured levels of positive transglutaminase 2 antibodies are not associated with presentation or incidental endoscopic findings at celiac disease diagnosis.

OBJECTIVES: It has been suggested that celiac disease could be diagnosed non-invasively in adults with transglutaminase antibody (TGA) levels >10x upper limit of normal (ULN). It is, however, unclear if high values signify more advanced disease and higher risk of co-morbidities. We investigated the association between the TGA levels, clinical characteristics and non-celiac endoscopic findings. METHODS: Medical data on 450 celiac disease patients at diagnosis were collected. They were further divided into those with high positive (>10x ULN, n = 164), moderately positive (1-10x ULN, n = 219), and negative (n = 67) TGA. RESULTS: Median age of patients was 50 years and 60% were women. Patients with negative TGA were older (median age 58 vs. 51 vs. 46 years respectively, p = 0.002) and had more often weight loss (27% vs. 10% vs. 9%, p < 0.001) and abdominal pain or dyspepsia (40% vs 27% vs. 22%, p = 0.017) than did those with moderately positive/high TGA. The groups did not differ in sex, BMI, or other symptoms. Major endoscopic findings included one esophageal adenocarcinoma presenting with dysphagia, six esophagitis, three gastric ulcers, and 39 H. Pylori or other active gastritis. High, moderately positive or negative TGA levels were not associated with these findings in crude or age-adjusted analyses. CONCLUSIONS: Presentation was similar in patients with moderate or high levels of TGA, whereas patients with negative TGA were different. The level of TGA was not associated with incidental endoscopic findings and the only malignancy presented with an alarm symptom atypical to celiac disease.

Measurement practices of alanine aminotransferase in children: Temporal changes and etiology for increased values.

Data on alanine aminotransferase (ALT) measurement practices and diagnoses associated with increased values are limited. We evaluated these issues by collecting ALT measurements from 1- to 16-year-old patients investigated in 1992-2018 in a tertiary center. Diagnoses were gathered in 2008-2018. Altogether 145,092 measurements from 28,118 children were taken 42% undergoing repeated testing. Testing increased from 21/1000 to 81/1000 children and the prevalence of elevated values fluctuated between 18% and 26%. An increase was seen especially in emergency care and departments of rheumatology, gastroenterology, hemato-oncology, and psychiatry. Common acute causes associated with elevated ALT were infections (45%), hemato-oncologic conditions (17%), and external reasons (13%), whereas autoimmune diseases (28%), psychiatric conditions (14%), and metabolic-dysfunction associated steatotic liver disease (10%) were common chronic causes. In conclusion, ALT testing increased 3.9-fold while the proportion of increased values remained stable, indicating that increased testing was justified. However, in some departments the testing efficiency was low.

Alanine aminotransferase cutoffs for the pediatric fatty liver disease: Major impact of the reference population.

OBJECTIVES AND STUDY: The often-recommended alanine aminotransferase (ALT) cutoffs (girls 21 U/l, boys 25 U/l) are based on a NHANES cohort. A novel concept of metabolic dysfunction associated steatotic liver disease (MASLD) emphasizes the role of ALT. We tested the prevalence of increased ALT and MASLD in children with overweight or obesity applying population-based and NHANES-based cut-offs. METHODS: Six- to seventeen-year-old children underwent data collection in a prospective Physical Activity and Nutrition in Children (PANIC) study. ALT 95th percentiles were calculated from 1167 separate measurements considering various confounders. Test cohort comprised 1044 children with overweight/obesity. RESULTS: ALT values increased at puberty onset (p = 0.031) and correlated negatively with age in girls (r = -0.222, p < 0.001). Particularly overall and central obesity increased ALT, whereas underweight or metabolic abnormalities had smaller effect. After applying the tested exclusions, the age-related ALT 95th percentiles were 24-29 U/l for girls and 29-32 U/l for boys. In 6-8-year-old children with overweight/obesity, the prevalence of increased ALT and MASLD were 21.6% and 2.4% with age-specific PANIC cutoffs. In older children, when NHANES-based cutoffs were used, there was a trend for higher prevalence of increased ALT and MASLD in all age groups for both sexes, reaching significance for increased ALT in 12-16-year-old boys (NHANES 63.5%, 95% confidence interval [CI]: 56.4%-70.0% vs. PANIC 47.1%, 95% CI [40.1%-54.2%]) and 9-11-year-old girls (60.0% [49.4%-69.8%] vs. 31.8% [22.8%-42.3%]), respectively. Increased ALT/MASLD were more common in boys than in girls, and in boys these increased with age, whereas in girls these peaked at age 9-12 years. CONCLUSION: A reference population impacts on the prevalence of increased ALT and MASLD. Considering this help optimizing screening while avoiding unnecessary investigations and surveillance. The prospective part of this study is registered in clinicaltrials.gov; identifier NCT01803776.

Psychological well-being of children and adolescents with inflammatory bowel disease.

OBJECTIVES: Prior studies on the psychological well-being in pediatric inflammatory bowel disease (PIBD) have reported controversial results. Our aim was to compare the psychological well-being and lifestyle factors in patients with PIBD and their controls and to assess the role of contributing disease characteristics. METHODS: This cross-sectional study included 60 PIBD patients aged 6-17 years (26 with Crohn's disease [CD], 34 with ulcerative colitis [UC] or unclassified colitis [IBD-U]) from two university hospitals in Finland, and their age- and sex-matched healthy controls. Psychological well-being was assessed with three measures: a questionnaire on overall psychological well-being (PSWB) and for adolescents also Beck Depression Inventory (BDI Ia) and Perceived Stress Scale (PSS). In addition to disease characteristics and pain, we assessed physical activity, sleep, screen time, and social well-being. RESULTS: Controls were more likely of stressing more (odds ratio [OR] = 3.67, 95% confidence interval [95% CI] 95% CI = 1.02-13.14), but other measures of psychological well-being did not differ statistically significantly between patients and controls. In CD, a clinically more active disease associated with inferior psychological well-being in adolescents (BDI [ρ = 0.63, p = 0.021], PSS [ρ = 0.70, p = 0.008], PSWB [ρ = 0.56, p = 0.049]). Longer time from diagnosis correlated with better psychological well-being on BDI (ρ = -0.39, p = 0.024) and PSS (ρ = -0.38, p = 0.034). Lifestyle was more sedentary in PIBD (less physical activity in children OR = 0.82, 95% CI = 0.68-0.99 and more screen time in adolescents OR = 1.18, 95% CI = 1.00-1.40). CONCLUSION: Although the clinical features of PIBD are potentially a burden for psychological well-being, many young patients cope well with their disease. Individual variation in well-being is remarkable, making supportive measures challenging.

The quality of life of frequently vs. infrequently screened HPV vaccinated women.

PURPOSE: Cervical lesions caused by human papillomavirus (HPV) are related to decreased quality of life (QoL) of women. Also, cervical cancer (CC) screening can cause psychological adverse effects. It has been assumed that by decreasing the HPV-related disease burden, HPV vaccinations would increase the QoL. This study compares the effect of CC screening on QoL of HPV vaccinated women in two different screening protocols. METHODS: A total of 753 HPV16/18 vaccinated women were randomized to frequent (22/25/28 years of age) and infrequent (28 years of age) CC screening arms. QoL questionnaires (EQ VAS, RAND 36, amended CECA 10) were sent at the age of 28. RESULTS: Median EQ VAS scores were 80 (Q1-Q3 75-90) in both screening arms. Mean RAND 36 scores of frequently and infrequently screened women were 78.13/81.64 in Physical role functioning domain and, respectively, 77.93/80.18 in Pain, 69.10/69.12 in General Health, 54.67/53.61 in Energy, 83.72/85.11 in Social functioning, 69.53/69.68 in Emotional role functioning, and 68.16/69.29 in Emotional well-being domain. Among women with a self-reported history of Pap cytology abnormalities, overall mean scores of amended CECA 10 were 69.52/72.07, and among women with a self-reported history of genital warts, 60.09/66.73, respectively. CONCLUSION: There was no significant difference in the QoL of HPV vaccinated women between the two CC screening arms. Women were mostly satisfied with the screening experience despite the screening frequency. This information is important for the future screening program planning as we need to reach the best possible balance with screening benefits and harms. TRIAL REGISTRATION NUMBER: NCT02149030, date of registration 29/5/2014.

Maternal gestational hypertension, smoking and pre-eclampsia are associated with metabolic dysfunction-associated fatty liver disease in overweight offspring.

INTRODUCTION: Due to a steep increase in obesity, metabolic dysfunction-associated fatty liver disease (MAFLD) has also become the most common chronic hepatic condition among children and adolescents. Various maternal and pregnancy-related factors have also been implicated in the development of MAFLD, but human studies remain scarce. MATERIAL AND METHODS: Comprehensive data of 460 overweight or obese children aged 2-16 years were collected and combined with data on selected maternal and pregnancy-related factors for a case-control study. MALFD was defined as alanine aminotransferase >2× upper limit of normal. Children with and without MAFLD were compared regarding to the study variables and multivariable regression analysis was utilized. RESULTS: Median age of the study children was 11.8 (quartiles 9.1-14.2) years; 44% were girls and 17.8% had MAFLD. Children with MAFLD were older (12.7 vs. 11.6 years, p = 0.002), while the groups did not differ age-standardized body mass index (BMI-SDS) or gender. Factors associated with MAFLD in a multivariable model considering also the offspring's present BMI-SDS, sex, and maternal prepregnancy overweight, were child's older age (odds ratio [OR] 1.16, 95% confidence interval [CI]: 1.06-1.28), maternal gestational smoking (OR 2.01, 95% CI: 1.16-3.47), gestational hypertension (OR 3.44, 95% CI: 1.08-11.0) and pre-eclampsia (OR 2.93, 95% CI: 1.15-7.45). There was no significant association between MAFLD and maternal BMI, birth anthropometrics or perinatal complications. CONCLUSIONS: Maternal smoking, gestational hypertension and pre-eclampsia were associated with MAFLD among overweight or obese children. Further prospective studies are needed to verify causal relationships.

Compliance with CPR quality guidelines and survival after 30 days following out-of-hospital cardiac arrest. A retrospective study.

BACKGROUND: Our study assessed the quality of cardiopulmonary resuscitation (CPR) given by emergency medical services in Southern Ostrobothnia Finland, as is advised in the international guidelines. The goal was to evaluate the current quality of CPR given to patients who suffered an out-of-hospital cardiac arrest and to examine possible measures for improving emergency medical services. METHODS: A retrospective study was conducted on out-of-hospital cardiac arrest patients in Southern Ostrobothnia, Finland, during a three-year period. Confounding caused by each patient's individual medical history was addressed by calculating Charlson Comorbidity Index (CCI), a score describing individual's risk for death in 10 years. The Utstein analysis and the CPR metrics were acquired from the medical records hospital district in question and analysed in an orderly manner using SPSS. Descriptive statistics are presented as mean (SD) and median [IQR]. RESULTS: We found that of the 349 patients, 144 (41%) received ROSC, 96 (28%) survived to the hospital and 51 (15%) survived for at least 30 days. CPR metrics data were available for 181 patients. CCIs were 3.0 versus 5.0 (p = .157) for the ones who did and those who did not survive at least 30 days. Correspondingly, following metrics were as follows: Mean compression depth was 5.1 (1.3) versus 5.6 (0.8) cm (p = .088), median 28 [18;40] versus 40 [26;54]% of the compressions were in target depth (p = .015) and median compression rate was 113 [109;119] versus 112 [108;120] min-1 (p = .757). The median no-flow fraction was 5.1 [2.8;7.1] versus 3.7 [2.5;5.5] s (p = .073). Ventricular fibrillation (OR 8.74, 95% CI 2.89-26.43, p < .001), public location (OR 3.163, 95% CI 1.03-9.69, p = .044) and compression rate of 100-110/min (OR 7.923, 95% CI 2.11-29.82, p = .002) were related to survival. CONCLUSION: Patients who suffered out-of-hospital cardiac arrest in Southern Ostrobothnia received CPR that met the international CPR quality target values. The proportion of unintentional pauses during CPR was low and the 30-day survival rate exceeded the international average.

Traumatic cervical spinal cord injury: Comparison of two different blood pressure targets on neurological recovery.

BACKGROUND: Controversy exists whether blood pressure augmentation therapy benefits patients suffering from spinal cord injury (SCI). This retrospective comparative study was designed to assess the impact of two different mean arterial pressure (MAP) targets (85-90 mmHg vs. 65-85 mmHg) on neurological recovery after traumatic cervical SCI. METHODS: Fifty-one adult patients with traumatic cervical SCI were retrospectively divided into two groups according to their intensive care unit (ICU) MAP targets: 85-90 mmHg (higher MAP group, n = 32) and 65-85 mmHg (lower MAP group, n = 19). Invasive MAP measurements were stored as 2-min median values for 3-7 days. The severity of SCI (AIS grade and neurological level) was evaluated upon ICU stay and during rehabilitation. Neurological recovery was correlated with individual mean MAP values and with the proportion of MAP values ≥85 mmHg upon the first 3 days (3d-MAP%≥85 ). RESULTS: The initial AIS grades were A 29.4%, B 17.6%, C 31.4%, and D 21.6%. AIS grade improved in 24 patients (47.1%). During ICU care, 82.0% and 36.8% of the measured MAP values reached ≥85 mmHg in the higher and the lower MAP groups, respectively (p < .001). The medians of individual mean MAP values were different between the groups (90.2 mmHg vs. 81.4 mmHg, p < .001). Similarly, 3d-MAP%≥85 was higher in the higher MAP group (85.6% vs. 50.0%, p < .001). However, neurological recovery was not different between the groups, nor did it correlate with individual mean MAP values or 3d-MAP%≥85 . CONCLUSION: The currently recommended MAP target of 85-90 mmHg was not associated with improved outcomes compared to a lower target in patients with traumatic cervical SCI in this cohort.

No difference was found between double-bundle and single-bundle anterior cruciate ligament reconstructions in terms of osteoarthritis at 15-year follow-up.

PURPOSE: The purpose of the study was to determine whether the grade of osteoarthritis (OA) is higher with single-bundle (SB) or double-bundle (DB) anterior cruciate ligament (ACL) reconstruction. The hypothesis was that there will be no difference in the grade of OA between the techniques. METHODS: This study was a randomised controlled trial (RCT) with a follow-up period of 15 years. Patients were randomly assigned to either the SB group (n = 78) or the DB group (n = 75). Surgical techniques were anatomic, and the rehabilitation protocol was standardised. Evaluation included Kellgren-Lawrence (KL) difference and absolute OA results. OA was defined as a KL grade of at least 2. RESULTS: At 15-year follow-up, information was available on 101 patients (66%), of whom 56 (37%) were accepted in the final statistical analysis. No difference was found between the SB and DB techniques in terms of KL difference or absolute OA results. Significantly less OA was found in the contralateral knee (21%) than in the reconstructed knee (59%) (p < 0.001). Patients with meniscal tears who underwent partial meniscal resection during ACL reconstruction had a significantly higher rate of OA changes (82%) compared with patients with isolated ACL tears (33%) (p < 0.001). A longer delay between initial injury and surgery did not appear to affect the severity of the KL classification. CONCLUSION: At 15-year follow-up, no difference was found between the DB and SB techniques in terms of OA. LEVEL OF EVIDENCE: Level I.

Double-bundle anterior cruciate ligament reconstruction resulted in better International Knee Documentation Committee objective grading at fifteen year follow-up compared to single-bundle reconstruction.

PURPOSE: The aim of this prospective randomized study was to evaluate whether the use of the anatomic double-bundle (DB) method for anterior cruciate ligament (ACL) reconstruction results in better clinical outcomes and a lower incidence of graft failure compared with the anatomic single-bundle (SB) method. The hypothesis was that DB ACL reconstruction would result in a lower incidence of graft failure. METHODS: Patients were randomly assigned to either the SB group (n = 78) or the DB group (n = 75). Evaluation included clinical testing, subjective assessments, functional testing, and International Knee Documentation Committee (IKDC) objective grading. Surgical techniques were anatomic, and the rehabilitation protocol was standardized. RESULTS: At 15-year follow-up, information was available on 100 patients (65%), of whom 55 (36%) were accepted in the final statistical analysis. There were almost three times as many graft failures in the SB group, but the result wasn´t statistically significant. Subjective assessments, knee stability (KT -1000 and pivot shift), range of motion (ROM), and functional one leg hop test showed no statistically significant differences between the groups. However, DB ACL reconstruction resulted in better International Knee Documentation Committee objective grading (P < 0.001). CONCLUSION: At the 15-year follow-up, double-bundle surgery resulted in significantly better International Knee Documentation Committee objective grading compared to single-bundle surgery.

Characteristics of chronic ulcer patients by gender and ulcer aetiology from a multidisciplinary wound centre.

Chronic ulcer patients form a heterogenous group of patients with various medical backgrounds. Cost-effective targeted treatment necessitates more knowledge about specific features related to different subgroups of ulcer patients. Hence, this study aimed to characterize ulcer patients according to gender and ulcer aetiology. A total of 946 consecutively recorded chronic ulcer patients in the Tampere Wound Registry (TWR) were included and data were gathered from the TWR and patient medical records. Comparisons were made between males and females and patients with venous-, arterial or mixed-, diabetic foot-, pressure- and atypical ulcers. Male patients were found to have diabetes, hypercholesterolemia and obesity significantly more often than females (59.2% vs. 39.6%; p < 0.001, 46.5% vs. 33.3%; p = 0.001, 42.7% vs. 35.9%; p = 0.017 respectively), whereas autoimmune diseases were more common among females (30.6% vs. 15.6%; p < 0.001). Recurrence of ulcers was most common among patients with venous ulcers (p < 0.001) and multimorbidity among those with diabetic foot ulcers (p < 0.001). To conclude, males with chronic ulcers would benefit particularly from lifestyle advice, multidisciplinary treatment should be targeted specifically at those with diabetic and arterial or mixed ulcers and preventive measures at those with venous ulcers.

The role of split-thickness skin grafting in the treatment of vasculitic and pyoderma gangrenosum ulcers in a multidisciplinary wound centre.

Vasculitic and pyoderma gangrenosum ulcers are traditionally treated with immunosuppressants, and the role of surgery in the treatment of these atypical ulcers remains unclear. This study aimed to investigate the need for surgical intervention as well as the outcome and safety of skin grafting in the treatment of 46 patients with vasculitic ulcers and 34 with pyoderma gangrenosum ulcers using data recorded in the validated Wound Registry. Of the 80 patients with atypical ulcers, 14% (n = 11) were treated surgically; these patients were older (p = 0.039), had lower mobility status (p = 0.002), and more often pulmonary diseases, rheumatoid arthritis, and previous arterial procedures (p = 0.007; p = 0.031; p = 0.031, respectively) than those treated conservatively. Of 181 ulcers, 15% (n = 27) were surgically treated, 78% once and 22% multiple times. During follow-up, 92.3% of both surgically and conservatively treated ulcers with available data healed. Of the surgically treated ulcers, median healing time after first surgical procedure was 96 days, and post-surgical complications were considered mild or unrelated to surgery. Our results suggest that if surgery is indicated, skin grafting is a safe and efficient treatment method provided that multidisciplinary approach is applied.

Paediatric asthma hospitalisations continue to decrease in Finland and Sweden between 2015 and 2020.

We previously reported a decreasing incidence of paediatric asthma hospitalisations in Finland, but a rather stable trend in Sweden, between 2005 and 2014. We now aimed to investigate the incidence of paediatric asthma hospitalisations in these countries between 2015 and 2020, using Finland's National Hospital Discharge Register and Sweden's National Patient Register, which cover all hospitalisations in the respective countries. From 2015 to 2019, the incidence of paediatric asthma hospitalisations decreased by 36.7% in Finland and by 39.9% in Sweden and are increasingly approaching parity. In 2020, despite differences in COVID-19-related restrictions, asthma hospitalisations decreased by over 40%, thus warranting future research on the subject.

Thyroid function test variability and cardiovascular morbidity in hyperthyroidism.

OBJECTIVE: The variability of thyroid function tests (TFTs) during antithyroid drug (ATD) therapy and its association with adverse health outcomes have not been previously studied. The aim of this study was to evaluate the association of TFT variability and cardiovascular morbidity during ATD therapy. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Hyperthyroid patients (n = 394) treated with ATD therapy at Tampere University Hospital between March 2016 and December 2018 were followed up for a median time of 1.5 years (interquartile range 0.8-2.0). The coefficients of variation (CVs) of the follow-up thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) measurements were determined. The associations of TFT variability and baseline clinical factors with cardiovascular disease (CVD) -associated hospital visits were assessed with logistic regression analyses. RESULTS: In the multivariable analyses, age (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.03-1.09), male gender (OR: 2.33, 95% CI: 1.03-5.28) and fT4-CV (OR: 1.02, 95% CI: 1.01-1.04) were independent risk factors for cardiovascular morbidity, whereas baseline positive thyrotropin receptor antibodies (TRAbs) were associated with lower cardiovascular morbidity (OR: 0.29, 95% CI: 0.14-0.61). When the patients with baseline TRAb positivity were studied separately, fT4-CV was associated with cardiovascular morbidity (OR: 1.03, 95% CI: 1.00-1.05). CONCLUSIONS: During ATD therapy, fT4 variability is associated with an increased cardiovascular morbidity. Although positive TRAbs are associated with a lower cardiovascular morbidity compared with hyperthyroidism with negative autoantibodies, the variability of fT4 is associated with cardiovascular morbidity also in patients with positive TRAbs.

Breast density and the likelihood of malignant MRI-detected lesions in women diagnosed with breast cancer.

OBJECTIVES: To assess whether mammographic breast density in women diagnosed with breast cancer correlates with the total number of incidental magnetic resonance imaging (MRI)-detected lesions and the likelihood of the lesions being malignant. METHODS: Patients diagnosed with breast cancer meeting the EUSOBI and EUSOMA criteria for preoperative breast MRI routinely undergo mammography and ultrasound before MRI at our institution. Incidental suspicious breast lesions detected in MRI are biopsied. We included patients diagnosed with invasive breast cancers between 2014 and 2019 who underwent preoperative breast MRI. One reader retrospectively determined breast density categories according to the 5th edition of the BI-RADS lexicon. RESULTS: Of 946 patients with 973 malignant primary breast tumors, 166 (17.5%) had a total of 175 (18.0%) incidental MRI-detected lesions (82 (46.9%) malignant and 93 (53.1%) benign). High breast density according to BI-RADS was associated with higher incidence of all incidental enhancing lesions in preoperative breast MRIs: 2.66 (95% confidence interval: 1.03-6.86) higher for BI-RADS density category B, 2.68 (1.04-6.92) for category C, and 3.67 (1.36-9.93) for category D compared to category A (p < 0.05). However, high breast density did not predict higher incidence of malignant incidental lesions (p = 0.741). Incidental MRI-detected lesions in the contralateral breast were more likely benign (p < 0.001): 18 (27.3%)/48 (72.7%) vs. 64 (58.7%)/45 (41.3%) malignant/benign incidental lesions in contralateral vs. ipsilateral breasts. CONCLUSION: Women diagnosed with breast cancer who have dense breasts have more incidental MRI-detected lesions, but higher breast density does not translate to increased likelihood of malignant incidental lesions. CLINICAL RELEVANCE STATEMENT: Dense breasts should not be considered as an indication for preoperative breast MRI in women diagnosed with breast cancer. KEY POINTS: • The role of preoperative MRI of patients with dense breasts diagnosed with breast cancer is under debate. • Women with denser breasts have a higher incidence of all MRI-detected incidental breast lesions, but the incidence of malignant MRI-detected incidental lesions is not higher than in women with fatty breasts. • High breast density alone should not indicate preoperative breast MRI.

Long-term outcomes of patients with acute severe ulcerative colitis treated with cyclosporine rescue therapy.

BACKGROUND AND AIMS: The early outcomes of ulcerative colitis (UC) after rescue therapy with cyclosporine A (CyA) are well known. Published data on the safety of this treatment in perioperative use and data on the long-term prognosis are scarce and are investigated here. METHODS: All UC patients treated with CyA in Tampere University Hospital between 2009 and 2018 were reviewed from patient records. RESULTS: A total of 182 patients were included with the median follow-up of 3.8 (range 0-13) years. Of all patients, 139 (76%) responded to CyA. A quarter of the responders achieved long-term remission and used thiopurines as maintenance therapy at the end of follow-up. Altogether 83 (46%) needed further enhancement of treatment with corticosteroids (Cs) and 57 (31%) with biologicals or small molecules. Of the nonresponders 27 (55%) were treated surgically within admission to index flare. Infliximab was used as a third-line rescue therapy for 16 patients of whom four benefitted. The overall colectomy rate in this series was 45%. When compared to Cs alone CyA did not increase the risk for severe postoperative complications in patients treated for severe treatment-refractory UC. CONCLUSION: In conclusion, despite the good initial response to CyA, a large proportion of patients relapsed during long-term follow-up and the colectomy rates remain high. Other therapy attempts after failure of CyA merely postpone surgery in many. We therefore recommend informing patients about the possibility of surgery prior to the initiation of rescue therapy.