Germline HAVCR2/TIM-3 Checkpoint Inhibitor Receptor Deficiency in Recurrent Autoinflammatory Myocarditis.

Myocarditis can be caused by viral infection, drug reaction or general inflammatory condition. To provide understanding on inflammatory myocarditis, we describe clinical, genetic, and immunological properties of a young male patient who suffered from recurrent myocarditis episodes since the age of four years. Electrocardiography, troponin I/T, echocardiography, myocardial magnetic resonance imaging and histological findings were consistent with recurrent myocarditis episodes. Homozygous c.245 A > G p.Tyr82Cys pathogenic variant in Hepatitis A Virus Cellular Receptor 2 (HAVCR2) gene encoding T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) receptor was found. Peripheral blood mononuclear cells were collected when the patient was asymptomatic; CD4+ and CD8+ T lymphoblasts, CD56+ natural killer cells and CD14+ monocytes were negative for surface TIM-3 expression. In vitro, TLR4 mediated interleukin-1ß (IL-1ß) response was high after LPS/ATP stimulation. Clinical symptoms responded to IL-1 receptor antagonist anakinra. TIM-3 p.Tyr82Cys CD4+ and CD8+ T cell proliferation in vitro was unrestrained. Findings on IL-2, interferon gamma, regulatory T cells, signal transducer and activator of transcription (STAT) 1, 3 and 4 phosphorylation, and PD-1 and LAG-3 checkpoint inhibitor receptor analyses were comparable to controls. We conclude that TIM-3 deficiency due to homozygous HAVCR2 c.245 A > G p.Tyr82Cys pathogenic variant in the patient described here is associated with autoinflammatory symptoms limited to early onset recurrent febrile myocarditis. Excessive IL-1ß production and defective regulation of T cell proliferation may contribute to this clinical condition responsive to anakinra treatment.

Comparison of remote learning methods to on-site teaching -randomized, controlled trial.

BACKGROUND: In the digitalized world, there is a need for developing new online teaching and learning methods. Although audio and video recordings are increasingly used in everyday learning, little scientific evidence is available on the efficacy of new online methods. This randomized trial was set out to compare the learning outcomes of online and classroom teaching methods in training healthcare students to diagnose breathing difficulties in children. METHODS: In total, 301 students of medicine (N = 166) and nursing (N = 135) volunteered to participate in this total sampling study in 2021-2022. The students were randomized into four groups based on teaching methods: classroom teaching (live, N = 72), streamed classroom teaching (live-stream, N = 77), audio recording (podcast, N = 79) and video recording (vodcast, N = 73). Each 45-minute lesson was taught by the same teachers and used the same protocol. The students participated an online test with their own electronic device at three distinct time points: prior to any teaching (baseline), immediately after teaching (final test), and five weeks later (long-term memory test). The test consisted of 10 multiple-choice questions on recognizing breathing difficulties from real-life videos of breathing difficulties in pre-school age. The test results scale ranged from - 26 to 28 points. Statistical analyses were performed using ANOVA multiple comparison and multiple regression tests. RESULTS: The mean scores (SD) of the final tests were 22.5 (5.3) in the vodcast, 22.9 (6.1) in the live, 20.0 (5.6) in the podcast (p < 0.05 vs. live) and 20.1 (6.8) in the live-stream group. The mean difference of test scores before and after the lesson improved significantly (p < 0.05) in all study groups, with 12.9 (6.5) in the vodcast, 12.6 (5.6) in the live, 10.9 (7.0) in the live-stream and 10.4 (6.9) in the podcast group. The improvement in test scores was significantly higher in the vodcast (p = 0.016) and the live (p = 0.037) groups than in the podcast group. No significant differences were found between the other groups. However, there was a nonsignificant difference towards better results in the vodcast group compared to the live-stream group. CONCLUSIONS: While the new online teaching methods produce learning, only video learning is comparable to team teaching in classrooms.

Nationwide infection control strategy lowered seasonal respiratory infection rate: occupational health care perspective during the COVID-19 epidemic in Finland.

BACKGROUND: Respiratory infection is the 4th most common reason for absence from work in Finland. There is limited knowledge of how social distancing affects the spread of respiratory infections during respiratory epidemics. We assessed the effect of nationwide infection control strategies against coronavirus disease in 2020 on various respiratory infections (International Statistical Classification of Diseases and Related Health Problems code J06) in occupational outpatient clinics. METHODS: We used occupational healthcare data of respiratory infection J06 diagnoses from 2017 to 2020 obtained from the largest health service provider in Finland. The data was divided into three 252 day-long pieces and was weekday-matched and smoothed by 7-day-moving average. The difference in the J06 diagnosis rate between the follow-up years was measured using Pearson correlation. Possible confounding by sex, age, and region was investigated in a stratified analysis. Confounding by respiratory syncytial virus was analysed using nationwide data of confirmed cases obtained from the national registry. RESULTS: In the second quarter of 2020, the trend in the daily number of J06 diagnoses was significantly different from the follow-up years 2019 and 2018. The number of J06 diagnoses peaked between March and April 2020 with roughly 2-fold higher count compared to normal. The timing of these peaks matched with the government issued infection control strategies and lockdowns. Based on stratified analysis, the increase in the number of J06 diagnoses was not confounded by region, age, or sex. Moreover, the rapid increase in the number of J06 diagnoses was not governed by the respiratory syncytial virus. CONCLUSION: Nationwide infection control strategies were effective to slow down the spread of common respiratory infectious diseases in the occupational population.

Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray?

The role of the microbiota in multiple autoimmune diseases, including juvenile idiopathic arthritis (JIA) has earned substantial attention in the last 10 years. Increasing evidence suggests that the microbiota's link to JIA begins in early childhood, as early life events that influence the nature of the microbiota also appear to influence disease risk. In this review, we discuss these early life events including mode of delivery, infant feeding practice, antibiotics exposure, and other events and their impacts on the microbiota and on disease risk; reported abnormalities of the microbiota in children with JIA; mechanisms by which an altered microbiota at birth and later on in childhood may influence disease risk; and the prospects for therapeutic alteration of the microbiota in children with JIA.

MMP-10 and TIMP-1 as indicators of severe sepsis in adult hematological patients with febrile neutropenia.

Commonly used indicators of sepsis are nonspecific and insufficient for predicting the course of febrile neutropenia (FN) in hematological patients. We analyzed data from 91 adult FN patients who received intensive chemotherapy for acute myeloid leukemia or autologous stem cell transplantation. Compared to patients with non-severe sepsis, patients with severe sepsis had significantly higher serum levels of tissue inhibitor of metalloproteinases-1 on the day of first occurrence of fever (day 0: 172 vs. 112 µg/L, p= .002) and for the two following days (day 1: 219 vs. 128 µg/L, p< .001; day 2: 443 vs. 128 µg/L, p= .001), and significantly higher serum levels of matrix metalloproteinase-10 on day 1 (1975 vs. 876 ng/L, p= .001) and day 2 (2020 vs. 841 ng/L, p< .001). We conclude that the measurement of these biomarkers may be useful in predicting the severity of sepsis in FN patients.

Cow's Milk Allergy in Infancy and Later Development of Juvenile Idiopathic Arthritis: A Register-Based Case-Control Study.

We examined the association between cow's milk allergy (CMA) and juvenile idiopathic arthritis (JIA). The material for this case-control study was collected from national registers of all children born in Finland between 2000 and 2010 and diagnosed with JIA (n = 1,298) and age-, sex-, and place-matched controls (n = 5,179). We identified 235 children with CMA; 66 of these children also had JIA. A conditional logistic regression analysis was performed to evaluate the association between CMA and JIA and to test whether exposure to antibiotics would be a covariate for this association. In boys (but not in girls), a diagnosis of CMA and the use of hypoallergenic formula in infancy were associated with the later development of JIA (odds ratio = 2.4, 95% confidence interval: 1.6, 3.6). The association was most evident in boys who were diagnosed with JIA before age 3 years or diagnosed with CMA with predominantly gastrointestinal symptoms. There was no statistically significant additive interaction between CMA and antibiotic exposure in the later development of JIA. These associations may reflect impaired maturation of intestinal immunity and integrity in boys with a risk of JIA. Predisposing factors related to JIA pathogenesis seem to display a sex-linked disparity.

Gut microbiota-host interactions and juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis is the most common form of chronic arthritis in children. There is mounting evidence that the microbiota may influence the disease. MAIN BODY: Recent observations in several systemic inflammatory diseases including JIA have indicated that abnormalities in the contents of the microbiota may be factors in disease pathogenesis, while other studies in turn have shown that environmental factors impacting the composition of the microbiota, such as delivery mode and early exposure to antibiotics, affect the risk of chronic inflammatory diseases including JIA. Microbial alterations may predispose to JIA through a variety of mechanisms, including impaired immunologic development, alterations in the balances of pro- versus anti-inflammatory bacteria, and low-grade mucosal inflammation. Additional confirmatory studies of microbiota aberrations and their risk factors are needed, as well as additional mechanistic studies linking these alterations to the disease itself. CONCLUSIONS: The microbiota may influence the risk of JIA and other systemic inflammatory conditions through a variety of mechanisms. Additional research is required to improve our understanding of the links between the microbiota and arthritis, and the treatment implications thereof.

An autochthonous case of cystic echinococcosis in Finland, 2015.

We report a case of pulmonary cystic echinococcosis in a child from eastern Finland with no history of travelling abroad. The cyst was surgically removed and the organism molecularly identified as Echinococcus canadensis genotype G10. This parasite is maintained in eastern Finland in a sylvatic life cycle involving wolves and moose; in the present case, the infection was presumably transmitted by hunting dogs.

Repeated exposure to antibiotics in infancy: a predisposing factor for juvenile idiopathic arthritis or a sign of this group's greater susceptibility to infections?

OBJECTIVE: Previous exposure to antibiotics has been associated with the pathogenesis of several autoimmune diseases. Our objective was to explore whether childhood exposure to antibiotics would be associated with the risk of developing juvenile idiopathic arthritis (JIA). METHODS: The material was collected from national registers containing all children born in 2000-2010 in Finland and diagnosed with JIA by the end of December 2012 (n = 1298) and appropriate controls (n = 5179) matched for age, sex, and place of birth. All purchases of antibiotics were collected from birth until the index date (i.e., the date of special reimbursement for JIA medications). A conditional logistic regression was performed to evaluate the association between the exposure to antibiotics and the risk of JIA. RESULTS: The risk of JIA increased with the number of antibiotic purchases from birth to the index date: for ≥ 1 purchases versus none, OR 1.6, 95% CI 1.3-1.9 with an upward trend in OR (p < 0.001). Antibiotic groups lincosamides and cephalosporins showed the strongest association with JIA (OR 6.6, 95% CI 3.7-11.7, and OR 1.6, 95% CI 1.4-1.8, respectively). Overall exposure to antibiotics before 2 years of age was associated with an increased risk of JIA (OR 1.4, 95% CI 1.2-1.6), with the trend test of OR (p < 0.001). CONCLUSION: Previous early and repeated exposure to antibiotics may predispose individuals to develop JIA. Alternatively, the apparent association may reflect shared susceptibility to infections and JIA.

Pitch-synchronous changes in the anterior cricothyroid space during singing.

Pitch-synchronous changes in the anterior cricothyroid (CT) space were registered with ultrasonography (USG) for ten healthy subjects (5 males, 5 females) during the production of musical fifths throughout the whole voice range. One of the males and one of the females were trained amateur singers, the other subjects were choir singers. The average decrease in CT space per a musical fifth was 1.3-2.4 mm for the males and 1.0-1.8 mm for the females; the average decrease was smaller in the middle of the pitch range for both genders. The results suggest that (1) USG can be used for detection of pitch-synchronous changes in the CT space; (2) these changes are dependent on pitch range; and (3) more trained singers tend to have somewhat smaller changes than less trained subjects at certain frequencies. The results seem to indicate that F0 control mechanism varies according to pitch range and register, and possibly according to individual structure and vocal technique related differences.