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Joé Diederich,1– 3 Kurt E Müller3 1Center for General, Clinical Environmental and Functional Medicine, Colmar-Berg, Luxembourg; 2University of Luxembourg, Faculty of Science, Technology and Medicine, Department of Life Sciences and Medicine, Esch-sur-Alzette, Luxembourg; 3Master of Science Program for Preventive and Functional Medicine, Dresden International University, Dresden, GermanyCorrespondence: Joé Diederich, Center for General, Clinical Environmental and Functional Medicine, 4b, Avenue G. Smith, L-7740, Colmar-Berg, Luxembourg, Tel +352 268866-1, Fax +352 268866-66, Email diederichjoe@gmail.comPurpose: Endodontic inflammation typically results from root canal infections and sensitizations to filling materials after root canal treatment (RCT), potentially leading to systemic inflammation and disease. We therefore aimed to characterize the inflammatory alterations after RCT as well as the inflammatory molecule levels following tooth extraction or renewed RCT.Patients and Methods: All (a total of 2585) walk-in patients with or without RCT history were included in this retrospective study. During the 3-year observation period, blood levels of RANTES/CCL5 (regulated on activation, normal T-cell expressed and secreted/chemotactic cytokine ligand 5), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-10 (IL-10) were measured before and after tooth extraction or renewed RCT. Control patients did not undergo any dental treatment.Results: A total 49.38% of patients had a history of at least one RCT. In RCT patients, RANTES/CCL5 values were significantly reduced by both tooth extraction (p=0.03) and renewed dental RCT (p=0.038), while a non-significant increase was observed in untreated patients. TNF-α levels were reduced by tooth extraction (p=0.014) but not by renewed RCT and no intervention. CRP levels were not significantly changed by either treatment. Tooth extraction significantly lowered IFN-γ levels (p=0.003), while in control patients, IFN-γ levels did not change. IL-10 levels were non-significantly reduced by tooth extraction (p=0.061). In a subcohort of RCT patients, the lymphocyte transformation test revealed an allergic reaction to at least one of the root filling materials in 39.46% of patients, with raw gutta percha (56%) and eugenol (19%) being frequent triggers.Conclusion: Here, we demonstrate the involvement of root-treated teeth in inflammatory processes, as tooth extraction and renewed RCT could significantly reduce individual cytokine levels. Our data support the use of biomarkers for in vivo monitoring of treatment success.Keywords: endodontically treated teeth, root canal, inflammation, thioether/mercaptans, RANTES/CCL5, root canal filling materials

Joé Diederich,1 Hendrik Schwagten,2 Georges Biltgen,3 Johann Lechner,4 Kurt E Müller5 1Center for General, Clinical Environmental and Functional Medicine, Colmar-Berg, Luxembourg; 2Private Practice, Center for Biological Dentistry, Luxembourg-City, Luxembourg; 3Private Practice, Center for Biological Dentistry, Diekirch, Luxembourg; 4Private Practice, Centre for Integrative Dentistry, Munich, Germany; 5Dermatology, Clinical Environmental Medicine, Functional Medicine, Preventive Medicine, Dresden International University, Kempten, GermanyCorrespondence: Joé Diederich, 4b, Avenue G. Smith, Colmar-Berg, L-7740, Luxembourg, Tel +352 268866-1, Fax +352 268866-66, Email diederichjoe@gmail.comPurpose: The presence of bone marrow defects of the jawbone (BMDJ) is associated with increased levels of inflammatory cytokines such as RANTES/CCL5. The purpose of this study was to analyze if BMDJ therapy under real-world conditions reduces RANTES/CCL5 serum levels in BMDJ patients.Patients and Methods: During this retrospective study, 113 BMDJ patients received either no treatment (n = 57), BMDJ surgery (n = 25), tooth extraction (n = 20), or root canal treatment (n = 11). Serum concentrations of RANTES/CCL5, C-reactive protein (CRP), and Tumor Necrosis Factor-α (TNF-α) were assessed before and after treatment (interventional group) and at the beginning and end of the study period (control group). Statistical analyses of the results were performed by the two-sample t-test and Bonferroni post hoc test with ANOVA for multiple comparisons.Results: BMDJ were detected in all patients with 4.42 ± 2.75 BMDJ findings per patient. RANTES/CCL5 levels were significantly reduced by any treatment when compared to no treatment (p < 0.001; effect size d = 0.90). This effect was most pronounced in the BMDJ surgery group (p < 0.001; effect size d = 1.30). In contrast, RANTES/CCL5 serum concentrations further increased in untreated patients. Mean duration between pre- and post-treatment RANTES/CCL5 measurements was 22.86 ± 19.36 weeks, with no correlation with RANTES/CCL5 levels in any interventional group or in the total sample (p = 0.104).Conclusion: BMDJ surgery, tooth extraction, and root canal treatment significantly reduce RANTES/CCL5 serum concentrations in BMDJ patients, with surgery being most beneficial. Further research is required to establish regular RANTES/CCL5 assessments as part of an improved diagnosis, monitoring, and evaluation of therapy success in BMDJ patients.Keywords: bone marrow defect of the jawbone, osteolysis, osteonecrosis of the jaw, RANTES, dental

Joé Diederich,1 Hendrik Schwagten,2 Georges Biltgen,3 Johann Lechner,4 Kurt E Müller5 1Center for General, Clinical Environmental and Functional Medicine, Colmar-Berg, Luxembourg; 2Private Practice, Center for Biological Dentistry, Luxembourg-City, Luxembourg; 3Private Practice, Center for Biological Dentistry, Diekirch, Luxembourg; 4Private Practice, Centre for Integrative Dentistry, Munich, Germany; 5Dermatology, Clinical Environmental Medicine, Functional Medicine, Preventive Medicine, Dresden International University, Kempten, GermanyCorrespondence: Joé Diederich, 4b, Avenue G. Smith, Colmar-Berg, L-7740, Luxembourg, Tel +352 268866-1, Fax +352 268866-66, Email diederichjoe@gmail.com

Abstract Adaptive designs allow planned modifications based on data accumulating within a study. The promise of greater flexibility and efficiency stimulates increasing interest in adaptive designs from clinical, academic, and regulatory parties. When adaptive designs are used properly, efficiencies can include a smaller sample size, a more efficient treatment development process, and an increased chance of correctly answering the clinical question of interest. However, improper adaptations can lead to biased studies. A broad definition of adaptive designs allows for countless variations, which creates confusion as to the statistical validity and practical feasibility of many designs. Determining properties of a particular adaptive design requires careful consideration of the scientific context and statistical assumptions. We first review several adaptive designs that garner the most current interest. We focus on the design principles and research issues that lead to particular designs being appealing or unappealing in particular applications. We separately discuss exploratory and confirmatory stage designs in order to account for the differences in regulatory concerns. We include adaptive seamless designs, which combine stages in a unified approach. We also highlight a number of applied areas, such as comparative effectiveness research, that would benefit from the use of adaptive designs. Finally, we describe a number of current barriers and provide initial suggestions for overcoming them in order to promote wider use of appropriate adaptive designs. Given the breadth of the coverage all mathematical and most implementation details are omitted for the sake of brevity. However, the interested reader will find that we provide current references to focused reviews and original theoretical sources which lead to details of the current state of the art in theory and practice.

Abstract Background To compare the diagnostic accuracy of two continuous screening tests, a common approach is to test the difference between the areas under the receiver operating characteristic (ROC) curves. After study participants are screened with both screening tests, the disease status is determined as accurately as possible, either by an invasive, sensitive and specific secondary test, or by a less invasive, but less sensitive approach. For most participants, disease status is approximated through the less sensitive approach. The invasive test must be limited to the fraction of the participants whose results on either or both screening tests exceed a threshold of suspicion, or who develop signs and symptoms of the disease after the initial screening tests. The limitations of this study design lead to a bias in the ROC curves we call paired screening trial bias. This bias reflects the synergistic effects of inappropriate reference standard bias, differential verification bias, and partial verification bias. The absence of a gold reference standard leads to inappropriate reference standard bias. When different reference standards are used to ascertain disease status, it creates differential verification bias. When only suspicious screening test scores trigger a sensitive and specific secondary test, the result is a form of partial verification bias. Methods For paired screening tests with bivariate normally distributed scores, we give formulae and programs to quantify the effect of paired screening trial bias on a paired comparison of area under the curves. We fix the prevalence of disease, and the chance a diseased subject manifests signs and symptoms. We derive the formulas for true sensitivity and specificity, and those for the sensitivity and specificity observed by the study investigator. Results The observed area under the ROC curves is quite different from the true area under the ROC curves. The typical direction of the bias is a strong inflation in sensitivity, paired with a concomitant slight deflation of specificity. Conclusion In paired trials of screening tests, when area under the ROC curve is used as the metric, bias may lead researchers to make the wrong decision as to which screening test is better.

Background: Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection (HAI). HAP is associated with a high burden of morbidity and mortality, but the diagnosis is difficult to establish and the incidence uncertain., Methods: Patients aged ≥ 18 years hospitalised with radiologically verified non-ventilator hospital acquired pneumonia (NV-HAP) during 2018 were retrospectively identified at Drammen Hospital, a Norwegian general hospital. Infectious Diseases Society of America and the American Thoracic Society's definition of HAP was used., Results: In total 119 cases of NV-HAP were identified among 27,701 admissions. The incidence was 4.3 per 1000 admissions and 1.2 per 1000 patient-days. The median age was 74 years, 63% were male and median Charlson comorbidity index was 5. Coronary heart disease (42%) was the most common comorbidity. Median length of stay was 17.2 days. A blood culture was obtained in 53.8% of patients, while samples from lower airways were seldom obtained (10.9%). In-hospital mortality was 21%, accumulated 30-day mortality was 27.7% and accumulated 1-year mortality was 39.5%. Thirty-day readmission rate among survivors was 39.4%., Conclusion: NV-HAP was present in approximately 1 in 250 hospitalisations, most had multiple comorbidities, and 1 in 5 died in hospital. Although thorough microbiological sampling is recommended when NV-HAP is suspected, our data indicate that airway sampling is infrequent in clinical practice. Our findings underscore the need to develop microbiological diagnostic strategies to achieve targeted antimicrobial treatment that may improve patient outcomes and reduce broad-spectrum antibiotic usage.

Six hundred fifty-nine farms in three regions of Germany (North: n = 240, East: n = 247, and South: n = 172) were included in the study, which aims at determining the association of management-related risk factors with farm-level lameness in German dairy herds. For each risk factor, a generalised linear regression model with negative binomial distribution and logit link was built. Results showed that cows housed in deep-bedded cubicles had a lower risk of being lame than cows housed in other cubicle types. A larger cubicle width was associated with a lower risk of being lame. Feeding a total mixed ration was associated with lower lameness prevalence (compared to feeding a partial mixed ration or single components). For first lactation cows, lameness assessment performed daily (compared to less than daily) and during other work tasks (compared to lameness assessment as a separate work task) were associated with lower risk for lameness. Finally, the present study provided evidence for crucial associations of management-related risk factors with lameness in German dairy cows, especially in the fields of cubicle design, feeding management, and lameness assessment.

Objectives: This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years)., Methods: Cases from 21 centers worldwide diagnosed with VEOIBD (2008-2018), with minimum 2 years of follow-up, were retrospectively reviewed., Results: The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2-18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all)., Conclusions: Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course., (Copyright © 2024 by the American Academy of Pediatrics.)

Lameness in dairy cows is an expression of pain most likely originating from a claw disorder, causing impaired animal wellbeing and substantial economic losses for farmers. The aim of this study was to investigate the effects of access to pasture, time spent on pasture, and season on farm level lameness prevalence. The survey was part of a cross-sectional observational study, in which farms in three regions of Germany (North, East and South) were visited by study veterinarians. On each farm (total: 659, N: 240, E: 247, S: 172), management data were recorded, and cows were scored for locomotion, according to Sprecher. Median farm-level lameness prevalence (Score 3/5 or higher) was 29.4% (IQR: 18.7% - 42.0%), and 8.2% (IQR: 3.7% - 14.0%) for severe lameness (Score 4/5 or higher). Farm-level lameness prevalence continuously decreased with increasing time spent on pasture (up to approximately 10 hours per cow per day). On farms that did not offer their cows access to pasture lameness prevalence did not show a seasonal variation. On farms where cows had pasture access for up to three hours per day lameness prevalence peaked in autumn. In contrast, on farms offering their cows access to pasture beyond three hours per day the peak of lameness was observed in spring. Our results revealed that even short periods of pasture access of at least two hours per cow and day (on average per year) are beneficial for the locomotion of dairy cows., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tillack et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: Extraintestinal manifestations are frequent in patients with inflammatory bowel disease and have a negative impact on quality of life. Currently, however, there is no evidence available to determine which drug should be recommended for these patients beyond anti-tumour necrosis factor [anti-TNF] treatment. We aimed to analyse the frequency of new extraintestinal manifestations and the behaviour of pre-existing extraintestinal manifestations during advanced therapy., Methods: We conducted a systematic search on November 15, 2022, and enrolled randomized controlled trials, cohorts, and case series reporting the occurrence and behaviour of extraintestinal manifestations in patients with inflammatory bowel disease receiving advanced therapy [non-TNF inhibitor biologicals and JAK inhibitors]. Proportions of new, recurring, worsening, and improving extraintestinal manifestations were calculated with 95% confidence intervals [CIs]. The risk of bias was assessed with the QUIPS tool., Results: Altogether, 61 studies comprising 13,806 patients reported eligible data on extraintestinal manifestations. The overall proportion of new extraintestinal manifestations was 8% [95% CI, 6-12%] during advanced therapy. There was no significant difference between the frequency of new extraintestinal manifestations during vedolizumab and ustekinumab therapy [11%, 95% CI, 8-15% vs 6%, 95% CI, 3-11%, p = 0.166]. The improvement of pre-existing manifestations was comparable between vedolizumab- and ustekinumab-treated patients, except for joint involvement [42%, 95% CI, 32-53% vs 54%, 95% CI, 42-65%, p = 0.029]., Conclusion: The proportion of new extraintestinal manifestations was low during advanced therapy. Furthermore, the improvement of pre-existing manifestations was comparable between advanced therapies, except for pre-existing joint manifestations., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Objectives: Antibiotic-impregnated shunts seem to be beneficial in preventing bacterial infections and decreasing mortality by effectively inhibiting microbial growth in the shunt system and reducing the risk of shunt-associated infections. This study aimed to evaluate the efficacy of antibiotic-impregnated shunt catheters (AISC) in reducing the incidence of bacterial shunt infection in patients with hydrocephalus., Methods: The protocol was registered on PROSPERO. A meta-analysis was conducted by searching 3 databases (PubMed, Scopus, CENTRAL) for relevant randomized controlled trials and observational studies. We included all studies published until November 2022 in any language. The primary outcome was the rate of bacterial infections, whereas the rate of shunt failure was our secondary endpoint. Odds ratios (OR) with 95% CI were calculated using a random-effects model., Results: A total of 27 articles with 27 266 shunt operations were included in this study. The results indicated that using AISC is significantly associated with reduction in infections (OR = 0.42; 95% CI: 0.33-0.54). Regarding shunt failure, there was a tendency in favor of AISC use (OR = 0.73; 95% CI: 0.51-1.06)., Conclusion: Our study provided evidence that AISC is significantly associated with the reduction in the rate of bacterial ventriculoperitoneal-shunt infection. In addition, there was a tendency toward AISC to decrease shunt failure compared with the standard shunt., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

From 2016 to 2020, the "PraeRi" study, conducted by three German veterinary universities, was aimed at enhancing animal health and welfare in dairy farms. With 765 dairy farms visited and 101,307 animals examined, this study provided a basis for improving animal health and welfare. The study population comprised three different regions representing a broad variety of characteristics. To ensure representative estimates, a sample size of 250 farms was determined for each region, employing a stratified sampling plan based on farm size. According to the information provided by the farmers, the most commonly occurring disease in their herds was mastitis without general disorder (14.2% to 16.3% of the herd-depending on the region). For most disorders, prevalence data were lowest for the region South compared with the two remaining regions. Multivariable regression analyses were performed to identify risk factors for various target variables, and the results were communicated through individual reports and benchmarking flyers to participating farmers. The authors encountered challenges in management and communication due to the project's size in terms of personnel, data, and farms examined. Harmonizing data management and hypothesis testing across all involved parties added complexity.

Perinatal mortality (PM) is a common issue on dairy farms, leading to calf losses and increased farming costs. The current knowledge about PM in dairy cattle is, however, limited and previous studies lack comparability. The topic has also primarily been studied in Holstein-Friesian cows and closely related breeds, while other dairy breeds have been largely ignored. Different data collection techniques, definitions of PM, studied variables and statistical approaches further limit the comparability and interpretation of previous studies. This article aims to investigate the factors contributing to PM in two underexplored breeds, Simmental (SIM) and Brown Swiss (BS), while comparing them to German Holstein on German farms, and to employ various modelling techniques to enhance comparability to other studies, and to determine if different statistical methods yield consistent results. A total of 133,942 calving records from 131,657 cows on 721 German farms were analyzed. Amongst these, the proportion of PM (defined as stillbirth or death up to 48 hours of age) was 6.1%. Univariable and multivariable mixed-effects logistic regressions, random forest and multimodel inference via brute-force model selection approaches were used to evaluate risk factors on the individual animal level. Although the balanced random forest did not incorporate the random effect, it yielded results similar to those of the mixed-effect model. The brute-force approach surpassed the widely adopted backwards variable selection method and represented a combination of strengths: it accounted for the random effect similar to mixed-effects regression and generated a variable importance plot similar to random forest. The difficulty of calving, breed and parity of the cow were found to be the most important factors, followed by farm size and season. Additionally, four significant interactions amongst predictors were identified: breed-calving ease, breed-season, parity-season and calving ease-farm size. The combination of factors, such as secondiparous SIM breed on small farms and experiencing easy calving in summer, showed the lowest probability of PM. Conversely, primiparous GH cows on large farms with difficult calving in winter exhibited the highest probability of PM. In order to reduce PM, appropriate management of dystocia, optimal heifer management and a wider use of SIM in dairy production are possible ways forward. It is also important that future studies are conducted to identify farm-specific contributors to higher PM on large farms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zablotski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Despite medical advances, individuals with cerebral palsy (CP) face significant respiratory challenges, leading to heightened hospitalization rates and early mortality among this population. We hypothesize that integrating supplementary respiratory therapy into standard rehabilitation will result in significant improvements in pulmonary function, enhanced respiratory muscle strength, and an overall increase in the quality of life among pediatric patients with CP., Methods: A systematic search of literature across five databases was conducted, and random-effects meta-analyses were performed to assess the impact of supplementary respiratory therapy on (a) pulmonary function: forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FVC/FEV1 ratio, peak expiratory flow (PEF), and (b) respiratory muscle strength: maximal inspiratory and expiratory pressure (MIP, MEP), and (c) quality of life. Certainty of evidence was determined by the GRADE assessment., Results: Analysis of data from 11 eligible randomized controlled trials revealed clinically meaningful changes in pulmonary function. We found a relevant mean difference (MD) in absolute PEF of 0.50 L/s (95% confidence interval (CI): 0.19; 0.82 p = 0.0107). The certainty of the evidence ranged from moderate to high., Conclusions: This study presents current evidence on the impact of various supplementary respiratory therapies for CP patients classified under gross motor function classification level I-IV, demonstrating clinically meaningful improvements in pulmonary function and respiratory muscle strength. These improvements suggest the potential for an enhanced quality of life. Our findings hold the promise of serving as a foundational reference for potential revisions to conventional rehabilitation care, incorporating supplementary respiratory therapy.

Borna disease is a progressive meningoencephalitis caused by spillover of the Borna disease virus 1 (BoDV-1) to horses and sheep and has gained attention due to its zoonotic potential. New World camelids are also highly susceptible to the disease; however, a comprehensive description of the pathological lesions and viral distribution is lacking for these hosts. Here, the authors describe the distribution and severity of inflammatory lesions in alpacas ( n = 6) naturally affected by this disease in comparison to horses ( n = 8) as known spillover hosts. In addition, the tissue and cellular distribution of the BoDV-1 was determined via immunohistochemistry and immunofluorescence. A predominant lymphocytic meningoencephalitis was diagnosed in all animals with differences regarding the severity of lesions. Alpacas and horses with a shorter disease duration showed more prominent lesions in the cerebrum and at the transition of the nervous to the glandular part of the pituitary gland, as compared to animals with longer disease progression. In both species, viral antigen was almost exclusively restricted to cells of the central and peripheral nervous systems, with the notable exception of virus-infected glandular cells of the Pars intermedia of the pituitary gland. Alpacas likely represent dead-end hosts similar to horses and other spillover hosts of BoDV-1., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Biological agents have transformed the management of inflammatory bowel disease (IBD). However, intestinal resection is still unavoidable in complicated IBD. It is still under debate whether antitumor necrosis factor (TNF)-α is related to higher postoperative complications in children with IBD. Therefore, we aimed to analyze data on preoperative anti-TNF-α and postoperative complications in pediatric IBD., Methods: We conducted a systematic literature search in 4 databases for studies that compared the incidence of postoperative complications between children with IBD who received anti-TNF-α treatment within 12 weeks prior to intestinal resection and who did not receive anti-TNF-α before the operation. To analyze this question, pooled odds ratios (ORs) were calculated with 95% confidence intervals (CIs). Odds ratios higher than 1 mean higher complication rate among children treated with preoperative anti-TNF-α, whereas an OR lower than 1 means lower complication rate. The I² value was calculated to measure the strength of the between-study heterogeneity, where a smaller percentage means the lower heterogeneity., Results: We found 8 eligible articles with 526 pediatric patients with IBD. The primary outcome was the overall complication. The pooled OR of overall complications was 1.38 (95% CI, 0.10-18.76; P = .65; I2 = 34%) in contrast, the OR of infectious and noninfectious complications were 0.59 (95% CI, 0.21-1.69; P = .16; I2 = 0%) and 0.48 (95% CI, 0.18-1.25; p = .09; I2 = 0%), although both showed a nonsignificant result., Conclusion: There is no significant association between preoperative anti-TNF-α therapy and postoperative complications in children with IBD after intestinal resection. However, the evidence is low due to the low number of studies investigating this question., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of the present study was to evaluate the associations between milk recording data, body condition score (BCS), housing factors, management factors, and lameness in freestall-housed dairy cows in 3 structurally different regions in Germany. These regions substantially vary regarding herd size, breeds, access to pasture, farm management (family run or company owned), and percentage of organic farms. The data used was collected in a large cross-sectional study from 2016 to 2019. A total of 58,144 cows from 651 farms in 3 regions of Germany (North, East, and South) was scored for locomotion and body condition. Additionally, data on milk yield, milk composition, breed, age, as well as information on housing and management were retrieved. One mixed-logistic regression model was fitted per region to evaluate the association of the data with the target variable "lame" and to allow for a comprehensive reflection across different kinds of farming types. In all regions, undercondition (BCS lower than recommended for the lactation stage; North: odds ratio [OR] 2.15, CI 1.96-2.34; East: OR 2.66, CI 2.45-2.88; South: OR 2.45, CI 2.01-2.98) and mid-lactation stage (102-204 d in milk; North: OR 1.15, CI 1.05-1.27; East: OR 1.24, CI 1.17-1.32; South: OR 1.38, CI 1.18-1.62) were associated with higher odds for lameness, whereas overcondition (BCS higher than recommended for the lactation stage; North: OR 0.51, CI 0.44-0.60; East: OR 0.51, CI 0.48-0.54; South: OR 0.65, CI 0.54-0.77) and parity of 1 or 2 was associated with lower odds (parity 1 = North: OR 0.32, CI 0.29-0.35; East: OR 0.19, CI 0.18-0.20; South: OR 0.28, CI 0.24-0.33; parity 2 = North: OR 0.51, CI 0.47-0.46; East: OR 0.41, CI 0.39-0.44; South: OR 0.49, CI 0.42-0.57), irrespective of the regional production characteristics. Low energy-corrected milk yield was associated with higher odds for lameness in South and North (North: OR 1.16, CI 1.05-1.27; South: OR 1.43, CI 1.22-1.69). Further factors such as pasture access for cows (North: OR 0.64, CI 0.50-0.82; and South: OR 0.65, CI 0.47-0.88), milk protein content (high milk protein content = North: OR 1.34, CI 1.18-1.52; East: OR 1.17, CI 1.08-1.28; low milk protein content = North: OR 0.79, CI 0.71-0.88; East: OR 0.84, CI 0.79-0.90), and breed (lower odds for "other" [other breeds than German Simmental and German Holstein] in East [OR 0.47, CI 0.42-0.53] and lower odds both for German Holstein and "other" in South [German Holstein: OR 0.62, CI 0.43-0.90; other: OR 0.46, CI 0.34 - 0.62]) were associated with lameness in 2 regions, respectively. The risk of ketosis (higher odds in North: OR 1.11, CI 1.01-1.22) and somatic cell count (higher odds in East: increased (>39.9 cells × 1,000/mL): OR 1.10; CI 1.03-1.17; high (>198.5 cells × 1,000/mL): OR 1.08; CI 1.01-1.06) altered the odds for lameness in 1 region, respectively. Cows from organic farms had lower odds for lameness in all 3 regions (North: OR 0.18, CI 0.11-0.32; East: OR 0.39, CI 0.28-0.56; South: OR 0.45, CI 0.29-0.68). As the dairy production systems differed substantially between the different regions, the results of this study can be viewed as representative for a wide variety of loose-housed dairy systems in Europe and North America. The consistent association between low BCS and lameness in all regions aligns with the previous literature. Our study also suggests that risk factors for lameness can differ between geographically regions, potentially due to differences in which dairy production system is predominantly used and that region-specific characteristics should be taken into account in comparable future projects., (© 2023, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Lameness in dairy cows poses a significant challenge to improving animal well-being and optimizing economic efficiency in the dairy industry. To address this, employing automated animal surveillance for early lameness detection and prevention through activity sensors proves to be a promising strategy. In this study, we analyzed activity (accelerometer) data and additional cow-individual and farm-related data from a longitudinal study involving 4860 Holstein dairy cows on six farms in Germany during 2015-2016. We designed and investigated various statistical models and chose a logistic regression model with mixed effects capable of detecting lameness with a sensitivity of 77%. Our results demonstrate the potential of automated animal surveillance and hold the promise of significantly improving lameness detection approaches in dairy livestock.

Objectives: The association between obesity and gastroesophageal reflux disease (GERD) is well-established in adults; however, data in pediatric population is scarce. Our study aimed to assess the association between GERD and health-related quality of life (HRQoL) in overweight children., Methods: From April to August of 2020, we included children aged 7-18 years who attended the Endocrinological Outpatient Clinic at the Paediatric Institute, University of Debrecen, Hungary. The participants completed two questionnaires: the Pediatric Gastroesophageal Reflux Disease Symptom Questionnaire (PGSQ) and the HRQoL questionnaire (PedsQL). Based on the criteria of the World Health Organization (WHO), the patients were categorized into two groups: an overweight or obese group and a group with normal weight., Results: A total of 107 children (51 % female, mean age 13.2 years, 46 % overweight or obese) completed the questionnaires. The median PGSQ score was similar in both groups (4.0 (IQR: 1.0-7.8) vs. 3.0 (IQR: 1.0-7.0), p=0.6). However, the total PedsQL score was significantly lower in the children with overweight or obesity compared to those with normal weight (80.1 (71.1-91.0) vs. 88.0 (76.1-94.6), p=0.031). The PedsQL score was lower among overweight patients with GERD symptoms than that of normal-weight patients without GERD symptoms., Conclusions: Our findings highlight the importance of raising awareness about GERD to enhance the HRQoL and prevent long-term complications in obese children., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Real-world data of children with inflammatory bowel disease (IBD) after SARS-CoV-2 vaccination are needed., Method: This prospective, observational study evaluate antibody kinetics of children with IBD 6 months after immunization with COVID-19 mRNA vaccine., Results: 24 children with IBD were included, 22 received immunosuppressive treatment. After five weeks the spike protein antibody level was positive in 95% of the cases. After six months all participants had seropositivity results, though the titre was decreasing., Conclusion: These data show the effectiveness of SARS-CoV2 immunization and the antibody decay over time, that highlight the importance of booster vaccines., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: In the TRANS-IBD clinical trial, the outcomes are measured with selected validated questionnaires. Cross-cultural and age adaptations of the Self-Efficacy Scale for adolescents and young adults (IBD-SES), the Transition Readiness Assessment Questionnaire (TRAQ), and the Self-Management and Transition Readiness Questionnaire (STARx) were performed. Methods: Linguistic and cultural adaptation was carried out with the usage of reliability coefficients (Cronbach's α coefficients, Spearman's rank correlation), and with confirmatory factor analysis (CFA; root Mean Square Error of Approximation [RMSEA], Comparative Fit Index [CFI], and Tucker-Lewis Index [TLI]). Results: 112 adolescents participated in the study (45.5% male, mean age 17 ± 1.98 years). CFA was acceptable in the IBD-SES and the TRAQ. Internal consistency was acceptable in IBD-SES and good in TRAQ (0.729; 0.865, respectively). Test-retest reliability was good in IBD-SES, but below the acceptable threshold in TRAQ (ρ = 0.819; ρ = 0.034). In STARx tools, RMSEA showed poor fit values, CFI and TLI were below acceptable fit values, and internal consistency was not satisfied (0.415; 0.693, respectively), while test-retest reliabilities were acceptable (ρ = 0.787; ρ = 0.788, respectively). Conclusions: Cross-cultural, age-specific adaptation was successfully completed with IBD-SES and TRAQ. Those are comparable to the original validated versions. The adaption of the STARx tools was not successful.

Background: Poor outcome of inflammatory bowel disease (IBD) is associated with malnutrition. Our aim was to compare body composition (BC) and physical activity (PA) between patients with IBD and healthy controls, and to assess the changes in BC, PA and health related quality of life (HRQoL) in children with IBD during anti-TNF therapy., Methods: 32 children with IBD (21 with Crohn's disease (CD), (age: 15.2 ± 2.6 years, 9 male) and 11 with ulcerative colitis (UC), (age: 16.4 ± 2.2 years, 5 male) participated in this prospective, observational follow up study conducted at Semmelweis University, Hungary. As control population, 307 children (age: 14.3 ± 2.1) (mean ± SD) were included. We assessed BC via bioelectric impedance, PA and HRQoL by questionnaires at initiation of anti-TNF therapy, and at two and six months later. The general linear model and Friedman test were applied to track changes in each variable., Results: During follow-up, the fat-free mass Z score of children with CD increased significantly (-0.3 vs 0.1, p = 0.04), while the BC of patients with UC did not change. PA of CD patients was lower at baseline compared to healthy controls (1.1 vs. 2.4), but by the end of the follow up the difference disappeared., Conclusions: The fat-free mass as well as PA of CD patients increased during the first six months of anti-TNF treatment. As malnutrition and inactivity affects children with IBD during an important physical and mental developmental period, encouraging them to engage in more physical activity, and monitoring nutritional status should be an important goal in patient care., (© 2022. The Author(s).)

Background: Gut microbiota alterations have been reported in hospitalized COVID-19 patients, with reduced alpha diversity and altered microbiota composition related to respiratory failure. However, data regarding gut microbiota and mortality are scarce., Methods: Rectal swabs for gut microbiota analyses were collected within 48 h after hospital admission (baseline; n = 123) and three-month post-admission (n = 50) in a subset of patients included in the Norwegian SARS-CoV2 cohort study. Samples were analysed by sequencing the 16S rRNA gene. Gut microbiota diversity and composition at baseline were assessed in relation to need for intensive care unit (ICU) admission during hospitalization. The primary objective was to investigate whether the ICU-related gut microbiota was associated with 60-day mortality., Results: Gut microbiota diversity (Shannon index) at baseline was lower in COVID-19 patients requiring ICU admission during hospitalization than in those managed in general wards. A dysbiosis index representing a balance of enriched and reduced taxa in ICU compared with ward patients, including decreased abundance of butyrate-producing microbes and enrichment of a partly oral bacterial flora, was associated with need of ICU admission independent of antibiotic use, dexamethasone use, chronic pulmonary disease, PO 2 /FiO 2 ratio, C-reactive protein, neutrophil counts or creatinine levels (adjusted p < 0.001). The ICU-related dysbiosis index at baseline correlated with systemic inflammation and was associated with 60-day mortality in univariate analyses (Hazard ratio 3.70 [2.00-8.6], p < 0.001), as well as after separate adjustment for covariates. At the three-month follow-up, the dysbiosis index remained elevated in ICU patients compared with ward patients (adjusted p = 0.007)., Conclusions: Although our data should be regarded as exploratory due to low number of clinical end points, they suggest that gut microbiota alterations during hospitalization could be related to poor prognosis after severe COVID-19. Larger studies of gut involvement during COVID-19 in relation to long-term clinical outcome are warranted. Trial registration NCT04381819 . Retrospectively registered May 11, 2020., (© 2023. The Author(s).)

The present work evaluates sampling protocols, storage procedures, and DNA purification methods for Leishmania spp. detection and quantification in different biological samples. The efficiency of three preservation solutions, a phosphate buffer solution, an ethylenediaminetetraacetic acid (EDTA) buffer solution, and 70% ethanol, was compared in combination with three DNA extraction protocols: a commercial silica column kit, salting-out protein precipitation, and organic extraction with phenol-chloroform. Tissue samples from BALB/c mice experimentally infected with Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, or Leishmania (Leishmania) infantum were stored in the three preservation solutions and subsequently subjected to the three different DNA extraction methods. The extracted DNA was then used in real-time polymerase chain reaction (PCR) assays for the detection and quantification of parasite ribosomal small subunit DNA targets as well as mammalian glyceraldehyde-3-phosphate dehydrogenase (gapdh) targets. The results of the optimized protocols showed that the DNA extraction method did not influence test quality, but DNA from samples preserved with the EDTA buffer solution produced higher amounts of target amplicons. Based on these results, we concluded that samples from suspected cases of leishmaniasis for submission to molecular diagnostic procedures should be preferentially preserved in EDTA, followed by any one of the DNA purification methods evaluated.

Background: Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited. We thus investigated the levels of these chemokines in COVID-19 patients., Methods: Serial blood samples were obtained from patients hospitalized with COVID-19 (n = 414). Circulating CCL19 and CCL21 levels during hospitalization and 3-month follow-up were analyzed. In vitro assays and analysis of RNAseq data from public repositories were performed to further explore possible regulatory mechanisms., Results: A consistent increase in circulating levels of CCL19 and CCL21 was observed, with high levels correlating with disease severity measures, including respiratory failure, need for intensive care, and 60-day all-cause mortality. High levels of CCL21 at admission were associated with persisting impairment of pulmonary function at the 3-month follow-up., Conclusions: Our findings highlight CCL19 and CCL21 as markers of immune dysregulation in COVID-19. This may reflect aberrant regulation triggered by tissue inflammation, as observed in other chronic inflammatory and autoimmune conditions. Determination of the source and regulation of these chemokines and their effects on lung tissue is warranted to further clarify their role in COVID-19., Clinical Trials Registration: NCT04321616 and NCT04381819., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Malnutrition and inflammatory bowel disease (IBD) are interrelated conditions. Our aim was to assess the prevalence of malnutrition, to compare anthropometric parameters in the evaluation of nutritional status in pediatric IBD, and to investigate the association between anthropometric parameters and disease activity indices (AI). Pediatric patients with newly diagnosed IBD recorded between 2010 and 2016 in the Hungarian Pediatric IBD Registry were included in this cross-sectional study. Body weight, body mass index (BMI), weight-for-height, and ideal body weight percent (IBW%) were analyzed. Pearson linear and non-linear correlations and polynomial regression analyses were performed to assess correlation between nutritional status and AI. p-values < 0.05 were considered significant. Anthropometric data of 1027 children with IBD (Crohn’s disease (CD): 699; ulcerative colitis (UC): 328; mean age 13.7 years) were analyzed. IBW% identified more obese patients than BMI both in CD (7.02% vs. 2.28%) and UC (12.17% vs. 5.48%). Significant negative correlation was found among anthropometric parameters and AI in CD. In contrast, polynomial regression analysis revealed a U-shaped correlation curve between IBW% and AI in UC. Our findings show that obesity has a bimodal association with disease activity in pediatric UC. Furthermore, IBW% was more useful to identify obese pediatric patients with IBD.

Background: The lungs are the organ most likely to sustain serious injury from coronavirus disease 2019 (COVID-19). However, the mechanisms for long-term complications are not clear. Patients with severe COVID-19 have shorter telomere lengths and higher levels of cellular senescence, and we hypothesized that circulating levels of the telomere-associated senescence markers chitotriosidase, β-galactosidase, cathelicidin antimicrobial peptide and stathmin 1 (STMN1) were elevated in hospitalized COVID-19 patients compared to controls and could be associated with pulmonary sequelae following hospitalization., Methods: Ninety-seven hospitalized patients with COVID-19 who underwent assessment for pulmonary sequelae at three-month follow-up were included in the study. β-Galactosidase and chitotriosidase were analysed by fluorescence; stathmin 1 and cathelicidin antimicrobial peptide were analysed by enzyme immuno-assay in plasma samples from the acute phase and after three-months. In addition, the classical senescence markers cyclin-dependent kinase inhibitor 1A and 2A were analysed by enzyme immuno-assay in peripheral blood mononuclear cell lysate after three months., Results: We found elevated plasma levels of the senescence markers chitotriosidase and stathmin 1 in patients three months after hospitalization with COVID-19, and these markers in addition to protein levels of cyclin-dependent kinase inhibitor 2A in cell lysate, were associated with pulmonary pathology. The elevated levels of these markers seem to reflect both age-dependent (chitotriosidase) and age-independent (stathmin 1, cyclin-dependent kinase inhibitor 2A) processes., Conclusions: We suggest that accelerated ageing or senescence could be important for long-term pulmonary complications of COVID-19, and our findings may be relevant for future research exploring the pathophysiology and management of these patients.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Hypokalemia in dairy cows, which is characterized by too low serum potassium levels, is a severe mineral disorder that can be life threatening. In this paper, we explore different originating conditions of hypokalemia-reduced potassium intake, increased excretion, acid-base disturbances, and increased insulin-by using a dynamic mathematical model for potassium balance in non-lactating and lactating cows. The simulations confirm observations described in literature. They illustrate, for example, that changes in dietary intake or excretion highly effect intracellular potassium levels, whereas extracellular levels vary only slightly. Simulations also show that the higher the potassium content in the diet, the more potassium is excreted with urine. Application of the mathematical model assists in experimental planning and therefore contributes to the 3R strategy: reduction, refinement and replacement of animal experiments., (© 2022. The Author(s).)

Background: T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown., Objectives: To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID-19., Methods: Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID-19 (n = 414) were analyzed for soluble (s) markers of T-cell activation (sCD25) and exhaustion (sTim-3) during hospitalization and follow-up., Results: Both markers were strongly associated with acute respiratory failure, but only sTim-3 was independently associated with 60-day mortality. Levels of sTim-3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months., Conclusion: Our findings suggest prolonged T-cell exhaustion is an important immunological sequela, potentially related to long-term outcomes after severe COVID-19., (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Decades of debate surround the use of intraoperative cholangiography (IOC) during cholecystectomy. To the present day, the role of IOC is controversial as regards decreasing the rate of bile duct injury (BDI). We aimed to review and analyse the available literature on the benefits of IOC during cholecystectomy., Methods: A systematic literature search was performed until 19 October 2020 in five databases using the following search keys: cholangiogra* and cholecystectomy. The primary outcomes were BDI and retained stone rate. To investigate the differences between the groups (routine IOC vs selective IOC and IOC vs no IOC), we calculated weighted mean differences (WMD) for continuous outcomes and relative risks (RR) for dichotomous outcomes, with 95% confidence intervals (CI)., Results: Of the 19,863 articles, 38 were selected and 32 were included in the quantitative synthesis. Routine IOC showed no superiority compared to selective IOC in decreasing BDI (RR = 0.91, 95% CI 0.66; 1.24). Comparing IOC and no IOC, no statistically significant differences were found in the case of BDI, retained stone rate, readmission rate, and length of hospital stay. We found an increased risk of conversion rate to open surgery in the no IOC group (RR = 0.64, CI 0.51; 0.78). The operation time was significantly longer in the IOC group compared to the no IOC group (WMD = 11.25 min, 95% CI 6.57; 15.93)., Conclusion: Our findings suggest that IOC may not be indicated in every case, however, the evidence is very uncertain. Further good quality research is required to address this question., (© 2022. The Author(s).)

Good calf health is crucial for a successfully operating farm business and animal welfare on dairy farms. To evaluate calf health on farms and to identify potential problem areas, benchmarking tools can be used by farmers, herd managers, veterinarians, and other advisory persons in the field. However, for calves, benchmarking tools are not yet widely established in practice. This study provides hands-on application for on-farm benchmarking of calf health. Reference values were generated from a large dataset of the "PraeRi" study, including 730 dairy farms with a total of 13,658 examined preweaned dairy calves. At herd level, omphalitis (O, median 15.9%) was the most common disorder, followed by diarrhea (D, 15.4%) and respiratory disease (RD, 2.9%). Abnormal weight bearing (AWB) was rarely detected (median, 0.0%). Calves with symptoms of more than one disorder at the same time (multimorbidity, M) were observed with a prevalence of 2.3%. The enrolled farms varied in herd size, farm operating systems, and management practices and thus represented a wide diversity in dairy farming, enabling a comparison with similar managed farms in Germany and beyond. To ensure comparability of the data in practice, the reference values were calculated for the whole data set, clustered according to farm size (1-40 dairy cows ( n = 130), 41-60 dairy cows ( n = 99), 61-120 dairy cows ( n = 180), 121-240 dairy cows ( n = 119) and farms with more than 240 dairy cows ( n = 138), farm operating systems (conventional ( n = 666), organic ( n = 64)) and month of the year of the farm visit. There was a slight tendency for smaller farms to have a lower prevalence of disorders. A statistically significant herd-size effect was detected for RD ( p = 0.008) and D ( p < 0.001). For practical application of these reference values, tables, diagrams, and an Excel ® (Microsoft ® ) based calf health calculator were developed as tools for on-farm benchmarking (https://doi.org/10.6084/m9.figshare.c.6172753). In addition, this study provides a detailed description of the colostrum, feeding and housing management of preweaned calves in German dairy farms of different herd sizes and farm type (e.g., conventional and organic)., Competing Interests: Author KB was employed by VetZ GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dachrodt, Bartel, Arndt, Kellermann, Stock, Volkmann, Boeker, Birnstiel, Do Duc, Klawitter, Paul, Stoll, Woudstra, Knubben-Schweizer, Müller and Hoedemaker.)

German dairy farming has intensified markedly in recent years, and the demand for Veterinary Herd Health Management (VHHM) is rising. To protect farms from epidemics, ensure food safety, and prevent developing of antibiotic resistance, VHHM has been anchored in EU law since April 2021. Via an online survey, distributed by different farmers' organizations, dairy farmers were asked about the cooperation with their veterinarian. The aim was to evaluate farm performance as a function of participation in VHHM. From 216 analyzed questionnaires, 106 respondents participated in VHHM. Results showed that farmers who make use of VHHM and consult their veterinarian in decision-making frequently have the highest 305-day milk yield (305dMY), the lowest bulk tank somatic cell counts, and the lowest age at first calving (AFC). However, these farmers tended to have higher replacement rates and a higher mortality of cows in the period up to 60 days in milk (MORT60DIM). Furthermore, respondents who defined VHHM as "evaluation of herd data, strategic planning" had the highest 305dMY compared with those who defined VHHM through one of the different options given ("pregnancy checks and support in reproduction"/"problem solving"). In the multifactorial regression model, VHHM participating farms had a 660-kg higher 305dMY and 1 month less in AFC, compared with farms not participating in VHHM. However, within the VHHM participants, no association between VHHM practices and performance parameters was found. Further research is needed, to find out if tailored advice of the VHHM approach may show effect herein., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ries, Jensen, Müller, Thöne-Reineke and Merle.)

Lameness is one of the most challenging problems in the dairy industry. Control is impeded because farmers often underestimate the number of lame cows. The objectives of this study were to assess German farmers' awareness of lameness in their herds and to determine the associations between farmers' awareness and their management practices, farm characteristics as well as with farmers' education, personality traits and attitudes. As a part of a large cross-sectional study, veterinarians visited farms in three structurally different regions of Germany: north ( n = 253), east ( n = 252), and south ( n = 260). The cows ( n = 84,998) were scored for locomotion and farmers were asked to estimate the number of cows that were lame or did not walk soundly. The ratio of farmers' estimated prevalence and the veterinarians' observed prevalence (Farmer's Detection Index; FDI) was calculated. The median lameness prevalence assessed by the veterinarians was 23.1, 39.1, and 23.2%, and the median prevalence of lame cows estimated by the farmers was 9.5, 9.5, and 7.1% in the north, east, and south, respectively. On average, farmers were conscious of only 45.3% (north), 24.0% (east), and 30.0% (south) of their lame cows. Farmers managing their herds according to organic principles had a higher FDI than farmers who managed their herds conventionally. Surprisingly, no significant associations between FDI and factors concerning claw health management could be detected. Therefore, increased awareness did not seem to be necessarily linked to improved management. Moreover, the FDI was not significantly associated with farmers' education or herd size. In the south, more extraverted farmers had a lower FDI. Those farmers who totally agreed with the statement, "I am satisfied with my herd's health," had a lower FDI than farmers who disagreed or were undecided. Moreover, farmers who disagreed or were undecided with the statement, "It affects me to see a cow in pain" had a higher FDI than those farmers who agreed to the statement. The results indicate that poor awareness of lameness was linked to the farmers' attitude and personality. Therefore, new approaches concerning the consultation regarding lameness control, such as the use of Motivational Interviewing, might be useful in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jensen, Oehm, Campe, Stock, Woudstra, Feist, Müller, Hoedemaker and Merle.)

Background: Patients with inflammatory bowel disease (IBD) have a high risk for infection. Pneumonia related to influenza and pneumococcal infection is one of the most common infection-related complications in IBD., Aims: To evaluate the immunogenicity of pneumococcal and influenza vaccination in patients with IBD receiving different treatments., Methods: We searched four databases for studies evaluating seroprotection and seroconversion rates after influenza or pneumococcal vaccination in IBD on 20th October 2020. In the meta-analysis, odds ratios (OR) were calculated with 95% confidence intervals (CI)., Results: We included twelve studies (1429 patients with IBD) in this meta-analysis. The seroconversion rate after pneumococcal vaccination and the seroprotection rate after influenza vaccination were not significantly lower in patients receiving conventional immunosuppressive treatment compared to the non-immunosuppressed patients. Meanwhile, the seroconversion rate following pneumococcal vaccine was significantly lower in patients with anti-TNF mono- or combination therapy (OR = 0.28, CI: 0.15-0.53, and OR = 0.27, CI: 0.15-0.49, respectively). In the analysis of patients with IBD on conventional immunosuppressive monotherapy versus anti-TNF therapy, the seroprotection rate after influenza immunization did not differ between patients receiving either anti-TNF mono-or combination therapy (OR = 1.45, CI: 0.62-3.38 and OR = 0.91, CI: 0.37-2.22, respectively)., Conclusion: Our data suggest that the immunization against Pneumococcus and influenza is safe and immunogenic despite immunosuppression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Context: Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction., Objective: Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed., Methods: In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action., Results: From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P < 0.0001; target 1.4-2.5 nmol/L). Body-weight-for-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P = 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P = 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) µmol/L (mean increase 7 µmol/L; 95% CI, 6-9; P < 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported., Conclusions: Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential of Triac for MCT8 deficiency., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Veterinary Herd Health Management plays an important role in veterinary medicine on dairy farms and has also been mandatory at the European Union level since April 21, 2021. Despite the increasing importance of VHHM, little is known about the extent of utilization of VHHM by dairy farmers and their view on this type of collaboration. Therefore, this cross-sectional study aimed to determine the status quo of the currently practiced VHHM in Germany. For this purpose, an online survey was conducted among dairy farmers in November and December 2020. From 216 analyzed questionnaires, about half ( n = 106) of the surveyed dairy farmers used VHHM at different scopes. However, regardless of the group, the term "veterinary herd health management" generally was given most relative importance by the participants as a veterinary service for herd fertility improvement, rather than the actual definition of a holistic approach. In contrast to this, the actual motivation of the VHHM participants, to take part in such a program was primarily based on the desire to safeguard animal health by employing preventive measures, that is, to avoid the occurrence of diseases via improved management and to improve farm performance (and profitability). Dairy farmers who opted for VHHM tended to manage larger higher yielding herds than those who did not. Additionally, the farmers in latter farms were more likely to make joint animal health decisions with their veterinarians. Using a latent class analysis, two groups of farmers among farms that were not currently using VHHM were identified, one of which expressed great interest in using VHHM while the other did not. Since the new legal basis makes the topic even more relevant than before, dairy farmers, animals, and veterinarians might benefit from the study to exploit hidden opportunities for VHHM collaboration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ries, Jensen, Müller, Thöne-Reineke and Merle.)

Objectives: According to the Porto criteria, upper endoscopy and ileocolonoscopy with histology for patients with pediatric inflammatory bowel disease (pIBD) are recommended with small bowel imaging (SBI). We aimed to evaluate the adherence to the Porto criteria and biopsy sampling practice and to evaluate the diagnostic yield of magnetic resonance enterography (MRE) first time in a nationwide pIBD inception cohort. Methods: Newly diagnosed pIBD cases (ages 0-18 years) are registered in the prospective, nationwide Hungarian Paediatric IBD Registry (HUPIR). We analyzed the diagnostic workup of patients recorded between the 1st of January 2007 and the 31st of December 2016. Results: Data for diagnostic workup was available in 1,523 cases. Forty percent of the cases had complied with the Porto criteria. Adherence to the Porto criteria increased significantly from 20 to 57% ( p < 0.0001) between 2007 and 2016. The most frequent reason for the incomplete diagnostic work-up was the lack of small bowel imaging (59%). In 2007, 8% of cases had a biopsy from all segments, and this rate reached 51% by 2016 ( p < 0.0001). We analyzed the diagnostic yield of MRE in 113 patients (10.1%), who did not have any characteristic lesion for Crohn's disease. The MRE was positive for the small bowel in 44 cases (39%). Conclusions: Adherence to the Porto criteria increased significantly during the 10-year period. This is the first study that reports multiple biopsy sampling as the less accepted recommendation. The diagnostic yield of MRE in patients without characteristic lesion for Crohn's disease is 39%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Müller, Dezsőfi, Cseh, Szűcs, Vass, Nemes, Kadenczki, Tárnok, Szakos, Guthy, Kovács, Karoliny, Czelecz, Tokodi, Tomsits and Veres.)