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Introduction: Immunoglobulin A vasculitis (IgAV) in adults has a variable disease course, with patients often developing gastrointestinal and renal involvement and thus contributing to higher mortality. Due to understudied molecular mechanisms in IgAV currently used biomarkers for IgAV visceral involvement are largely lacking. Our aim was to search for potential serum biomarkers based on the skin transcriptomic signature. Methods: RNA sequencing analysis was conducted on skin biopsies collected from 6 treatment-naïve patients (3 skin only and 3 renal involvement) and 3 healthy controls (HC) to get insight into deregulated processes at the transcriptomic level. 15 analytes were selected and measured based on the transcriptome analysis (adiponectin, lipopolysaccharide binding protein (LBP), matrix metalloproteinase-1 (MMP1), C-C motif chemokine ligand (CCL) 19, kallikrein-5, CCL3, leptin, C-X-C motif chemokine ligand (CXCL) 5, osteopontin, interleukin (IL)-15, CXCL10, angiopoietin-like 4 (ANGPTL4), SERPIN A12/vaspin, IL-18 and fatty acid-binding protein 4 (FABP4)) in sera of 59 IgAV and 22 HC. Machine learning was used to assess the ability of the analytes to predict IgAV and its organ involvement. Results: Based on the gene expression levels in the skin, we were able to differentiate between IgAV patients and HC using principal component analysis (PCA) and a sample-to-sample distance matrix. Differential expression analysis revealed 49 differentially expressed genes (DEGs) in all IgAV patient’s vs. HC. Patients with renal involvement had more DEGs than patients with skin involvement only (507 vs. 46 DEGs) as compared to HC, suggesting different skin signatures. Major dysregulated processes in patients with renal involvement were lipid metabolism, acute inflammatory response, and extracellular matrix (ECM)-related processes. 11 of 15 analytes selected based on affected processes in IgAV skin (osteopontin, LBP, ANGPTL4, IL-15, FABP4, CCL19, kallikrein-5, CCL3, leptin, IL-18 and MMP1) were significantly higher (p-adj < 0.05) in IgAV serum as compared to HC. Prediction models utilizing measured analytes showed high potential for predicting adult IgAV. Conclusion: Skin transcriptomic data revealed deregulations in lipid metabolism and acute inflammatory response, reflected also in serum analyte measurements. LBP, among others, could serve as a potential biomarker of renal complications, while adiponectin and CXCL10 could indicate gastrointestinal involvement.

Supplemental Digital Content is Available in the Text.Blagus, R, Jurak, G, Starc, G, and Leskošek, B. Centile reference curves of the SLOfit physical fitness tests for school-aged children and adolescents. J Strength Cond Res37(2): 328–336, 2023—The study provides sex- and age-specific centile norms of Slovenian children and youth. Physical fitness was assessed using the SLOfit test battery on population data, including 185,222 children, aged 6–19 years, measured in April and May 2018. Centile curves for both sexes and 12 test items were constructed using the generalized additive models for location, scale, and shape (GAMLSS). Boys generally achieved higher scores in most of the physical fitness tests, except in stand and reach, but this was not consistent throughout childhood and adolescence, nor did it pertain to the entire range of performance. Girls outperformed boys in the arm-plate tapping test throughout childhood; the poorest performing girls outperformed the poorest performing boys in the 600-m run, 60-m dash, backward obstacle course, and standing broad jump. The shapes and trends of physical fitness curves adequately reflect the effects of growth and development on boys' and girls' physical performance. Comparing the existing reference fitness curves showed that Slovenian children and adolescents display higher fitness levels than their peers from other countries. This study provides the most up-to-date sex- and age-specific reference fitness centile curves of Slovenian children, which can be used as benchmark values for health and fitness monitoring and surveillance systems.

Objectives(1) To develop reference values for health-related fitness in European children and adolescents aged 6–18 years that are the foundation for the web-based, open-access and multilanguage fitness platform (FitBack); (2) to provide comparisons across European countries.MethodsThis study builds on a previous large fitness reference study in European youth by (1) widening the age demographic, (2) identifying the most recent and representative country-level data and (3) including national data from existing fitness surveillance and monitoring systems. We used the Assessing Levels of PHysical Activity and fitness at population level (ALPHA) test battery as it comprises tests with the highest test–retest reliability, criterion/construct validity and health-related predictive validity: the 20 m shuttle run (cardiorespiratory fitness); handgrip strength and standing long jump (muscular strength); and body height, body mass, body mass index and waist circumference (anthropometry). Percentile values were obtained using the generalised additive models for location, scale and shape method.ResultsA total of 7 966 693 test results from 34 countries (106 datasets) were used to develop sex-specific and age-specific percentile values. In addition, country-level rankings based on mean percentiles are provided for each fitness test, as well as an overall fitness ranking. Finally, an interactive fitness platform, including individual and group reporting and European fitness maps, is provided and freely available online (www.fitbackeurope.eu).ConclusionThis study discusses the major implications of fitness assessment in youth from health, educational and sport perspectives, and how the FitBack reference values and interactive web-based platform contribute to it. Fitness testing can be conducted in school and/or sport settings, and the interpreted results be integrated in the healthcare systems across Europe.

Background: The purpose of our analysis was to compare the results of treatment in patients who underwent resection for colorectal carcinoma. Methods: In the period from 1/1/1991 to 31/12/2000 1478 patients with colorectal carcinoma underwent potentially curative resection. We divided them into two 5-year period groups according to different treatment regimes. The 5-year net survival rate was estimated, where the net survival is the probability of survival derived solely from the cancer-specific hazard. Results: In a 10-year period, we resected 1478 patients. The 5-year net survival rate for R0-resected patients with colon cancer increased from 76.3 to 85.2% between the periods 1991–1995 and 1995–2000. The 5-year net survival rate for R0-resected patients with rectal cancer also increased from 67.5 to 73% in the same period. Conclusion: A comparison of the 5-year net survival rate for R0-resected patients with colorectal cancer increased in the last period from 1995 to 2000 compared with the period from 1991 to 1995. In multivariate analysis, early stage at diagnosis and adjuvant chemotherapy was both associated with better net survival after surgery with curative intent. The improvement of net survival is potentially the result of combination of better surgical and adjuvant therapy.

IMPORTANCE: Multiple erythema migrans (MEM) has been suggested as a risk factor for unfavorable antibiotic treatment outcome compared with solitary erythema migrans (EM). However, no direct comparison of early Lyme borreliosis manifested as MEM with solitary EM has been undertaken. OBJECTIVE: To investigate the potential differences in clinical course and treatment outcome between MEM and solitary EM. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted from June 1, 2010, to October 31, 2015, at the University Medical Center Ljubljana, Slovenia. Data were analyzed from June 1, 2017, to January 3, 2018. Of the 778 consecutive adult patients with early Lyme borreliosis evaluated, 200 patients with MEM and 403 patients with solitary EM were enrolled. Patients were asked to refer a family member or a friend of similar age (±5 years) without a history of Lyme borreliosis to serve as a control participant. Clinical course and posttreatment outcome of MEM were compared with those of solitary EM. Outcome was assessed at 14 days and at 2, 6, and 12 months after enrollment. At each visit, patients completed a written questionnaire about their symptoms; controls completed the same questionnaire. Nonspecific symptoms reported by patients and controls without a history of Lyme borreliosis were compared. MAIN OUTCOMES AND MEASURES: The proportion of patients with incomplete response at 12 months after enrollment and the associated 2-sided 95% CI for the difference between MEM and solitary EM were estimated using the normal approximation with continuity correction. RESULTS: A total of 200 patients with MEM and 403 patients with solitary EM were included. Among the 200 patients with MEM, 94 (47.0%) were males and 106 (53.0%) were females, with a median (interquartile range [IQR]) age of 47 (35-58) years. Among the 403 patients with solitary EM, 182 (45.2%) were males and 221 (54.8%) were females, with a median (IQR) age of 55 (42-62) years. Patients with MEM reported Lyme borreliosis–associated constitutional symptoms at enrollment more often than those with solitary EM (93 [46.5%]; 95% CI, 39.4-53.7 vs 96 [23.8%]; 95% CI, 19.7-28.3; P < .001). During the initial 6 months after treatment, the proportion of patients with incomplete response was higher in the MEM group than in the solitary EM group (14 days: 62 of 193 [32.1%] vs 72 of 391 [18.4%]; P < .001; 2 months: 38 of 193 [19.7%] vs 55 of 394 [14.0%]; P = .28; 6 months: 29 of 182 [15.9%] vs 31 of 359 [8.6%]; P = .02). However, at the 12-month visit, the outcome was comparable: 10 of 170 (5.9%) patients with MEM vs 20 of 308 (6.5%) patients with solitary EM showed incomplete response (−0.6; 95% CI, –5.5 to 4.3; P = .95). The frequency of nonspecific symptoms in patients was similar to that in controls. CONCLUSIONS AND RELEVANCE: The long-term outcome at 12 months after treatment was comparable, regardless of dissemination. Follow-up of at least 12 months after treatment is thus recommended for future studies that investigate post–Lyme borreliosis symptoms.

Migratory and non-migratory passerine birds can carry several pathogens, including parasites, which may cause significant diseases in birds, other animal species and humans. Parasites have been shown to negatively impact many populations of wildlife, and this may become more significant with global temperature changes. This study was performed to investigate the prevalence of intestinal parasites in faecal samples of European passerines. Intestinal parasites identified were statistically associated with passerines phylogenetic classification, migratory habits (migratory, non-migratory) and the type of diet (omnivorous, insectivorous and granivorous). A total of 385 passerines of 42 species were captured and their droppings collected. The prevalence of parasites in faecal samples of passerines was 15.6%. Intestinal parasites were identified in 50/309 (16.2%) migratory passerines and 10/76 (13.2%) non-migratory passerines using the faecal flotation method. Coccidia were most often identified parasites; they were more likely to be present in an omnivorous bird species (p = 0.02). Syngamusspp. was more likely to be detected in omnivorous passerines (p = 0.04). Tits (p = 0.01) and finches (p = 0.006) were less likely to have intestinal parasites present in their faecal samples than passerines classified in other phylogenetic clades. Tits (p = 0.02) and finches (p = 0.008) were also less likely to have coccidia present in their faecal samples. Phylogeny was associated with the presence of parasites in faecal samples of passerines (p = 0.03). The prevalence of parasites, however, was not associated with the migration habit of passerines, but to the type of diet (p = 0.04). Our analysis suggests that the diversity of feeding sources of omnivore passerines exposes them to infection with intestinal parasites to a greater extent than granivore or insectivore passerines.

•We introduced restrictive interventions for some antibiotics in ambulatory care.•The change in antibiotic consumption before and after the interventions was evaluated by interrupted time series method.•Consumption of restrictive antibiotics decreased more than that of non-restrictive antibiotics.•Restrictive interventions had a significantly greater impact on consumption 3 years post-intervention than after 12 years.•The combination of restrictive and regulative interventions had an important impact on the costs of antibiotics.

The purpose of the present study was to determine the incidence of inflammatory bowel disease (IBD) and its subgroups in children in northeastern Slovenia (NE Slovenia) during the period 2002–2010, and to assess the phenotypic characteristics at the diagnosis and during the follow-up.

The purpose of the present study was to determine the incidence of inflammatory bowel disease (IBD) and its subgroups in children in northeastern Slovenia (NE Slovenia) during the period 2002–2010, and to assess the phenotypic characteristics at the diagnosis and during the follow-up. A retrospective investigation was conducted on a cohort of newly diagnosed children and adolescents with IBD ages 0 to 18 years between 2002 and 2010 and residing in NE Slovenia. The phenotypic characteristics were determined at presentation and during follow-up. The location of Crohn disease (CD) and ulcerative colitis (UC) was assessed according to the Paris classification at diagnosis, and later in patients who had a follow-up period >2 years. The type of therapy at diagnosis and during follow-up, and the need for surgery were determined. The study covered approximately one-third of the total pediatric population (0–18 years). In total, 107 cases of IBD were diagnosed during the study period. The mean annual incidence (per 100,000) was 7.6 (95% confidence interval [CI] 6.3–9.2) for all IBD, 4.6 (95% CI 3.6–5.9) for CD, and 2.8 (95% CI 1.9–3.8) for UC. The incidences of total IBD, CD, and UC increased from 5.7 (3.8–8.2), 3.9 (2.3–6.1), and 1.8 (0.8–3.5) in the period 2002–2004, respectively, to 8.9 (6.3–12.2), 5.0 (3.1–7.6), and 3.4 (1.9–5.6) in the period 2008–2010, respectively. During the follow-up, the proportion of complicated CD disease behavior (stricturing/penetrating) had doubled. A total of 18.5% of patients with CD underwent bowel surgery. The incidence of childhood IBD in the northeastern part of the country is high and comparable with that reported from the developed western countries of Europe, and is probably still increasing. This increase may be the result of changes in the lifestyle, especially in dietary habits during the last 20 years.