Electronic Integrated Management of Childhood Illness (eIMCI): a randomized controlled trial to evaluate an electronic clinical decision-making support system for management of sick children in primary health care facilities in South Africa.

BACKGROUND: Electronic clinical decision-making support systems (eCDSS) aim to assist clinicians making complex patient management decisions and improve adherence to evidence-based guidelines. Integrated management of Childhood Illness (IMCI) provides guidelines for management of sick children attending primary health care clinics and is widely implemented globally. An electronic version of IMCI (eIMCI) was developed in South Africa. METHODS: We conducted a cluster randomized controlled trial comparing management of sick children with eIMCI to the management when using paper-based IMCI (pIMCI) in one district in KwaZulu-Natal. From 31 clinics in the district, 15 were randomly assigned to intervention (eIMCI) or control (pIMCI) groups. Computers were deployed in eIMCI clinics, and one IMCI trained nurse was randomly selected to participate from each clinic. eIMCI participants received a one-day computer training, and all participants received a similar three-day IMCI update and two mentoring visits. A quantitative survey was conducted among mothers and sick children attending participating clinics to assess the quality of care provided by IMCI practitioners. Sick child assessments by participants in eIMCI and pIMCI groups were compared to assessment by an IMCI expert. RESULTS: Self-reported computer skills were poor among all nurse participants. IMCI knowledge was similar in both groups. Among 291 enrolled children: 152 were in the eIMCI group; 139 in the pIMCI group. The mean number of enrolled children was 9.7 per clinic (range 7-12). IMCI implementation was sub-optimal in both eIMCI and pIMCI groups. eIMCI consultations took longer than pIMCI consultations (median duration 28 minutes vs 25 minutes; p = 0.02). eIMCI participants were less likely than pIMCI participants to correctly classify children for presenting symptoms, but were more likely to correctly classify for screening conditions, particularly malnutrition. eIMCI participants were less likely to provide all required medications (124/152; 81.6% vs 126/139; 91.6%, p= 0.026), and more likely to prescribe unnecessary medication (48/152; 31.6% vs 20/139; 14.4%, p = 0.004) compared to pIMCI participants. CONCLUSIONS: Implementation of eIMCI failed to improve management of sick children, with poor IMCI implementation in both groups. Further research is needed to understand barriers to comprehensive implementation of both pIMCI and eIMCI. (349) CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov ID: BFC157/19, August 2019.

Climate footprint assessment of plastic waste pyrolysis and impacts on the Danish waste management system.

Increased plastic recycling is necessary to reduce environmental impacts related to manufacturing and end-of-life of plastic products, however, mechanical recycling (MR) - currently the most widespread recycling option for plastic waste - is limited by quality requirements for inputs and reduced quality of outputs. In this study, pyrolysis of plastic waste is assessed against MR, municipal solid waste incineration (MSWI) and fuel substitution through climate footprint assessment (CFA) based on primary data from pyrolysis of plastic waste sourced from Danish waste producers. Results of the CFA are scaled to the Danish plastic waste resource in an impact assessment of current Danish plastic waste management, and scenarios are constructed to assess reductions through utilization of pyrolysis. Results of the CFA show highest benefits utilizing pyrolysis for monomer recovery (-1400 and -4800 kg CO2e per ton polystyrene (PS) and polymethyl methacrylate (PMMA), respectively) and MR for single polymer polyolefins (-1000 kg CO2e per ton PE). The two management options perform similarly with mixed plastic waste (200 kg CO2e per ton plastic waste). MSWI has the highest impact (1600-2200 kg CO2e per ton plastic waste) and should be avoided when alternatives are available. Scaling the results of the CFA to the full Danish plastic waste resource reveals an impact of 0.79 Mt CO2e in year 2020 of current plastic waste management. Utilizing pyrolysis to manage MR residues reduces the system impact by 15%. Greater reductions are possible through increased separation of plastic from residual waste. The best performance is achieved through a combination of MR and pyrolysis.

Prevalence of and risk factors for self-reported menstrual changes following COVID-19 vaccination: a Danish cohort study.

STUDY QUESTION: Are there some characteristics that render individuals more susceptible to report menstrual changes following the Coronavirus disease 2019 (COVID-19) vaccination? SUMMARY ANSWER: We found that 30% of menstruating women reported menstrual changes following COVID-19 vaccination and several potential risk factors including stress, vaccine concerns, severe COVID-19 infection, and immediate vaccine symptoms were associated with these reports. WHAT IS KNOWN ALREADY: Studies suggest that COVID-19 vaccination might temporarily prolong menstrual cycle length by less than 1 day. Specific characteristics may trigger menstrual changes in temporal relation to the vaccination simply by chance or render women more vigilant to potential menstrual changes after being vaccinated. However, research investigating potential risk factors for reporting menstrual changes following COVID-19 vaccination is limited. STUDY DESIGN, SIZE, DURATION: A population-based Danish cohort study. Data were collected from May 2021 to December 2021 as a part of the BiCoVac Cohort with the aim of examining non-specific effects following COVID-19 vaccination. The main study population included 13 648 menstruating women aged 16-65 years who completed all surveys, received their first dose of a COVID-19 vaccine during the data collection period, and completed questions related to their menstrual cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: Potential risk factors included 14 biological, physical, or psychological measures. Information on most potential risk factors was self-reported and collected before the participants' first COVID-19 vaccination. Information about any menstrual change following COVID-19 vaccination was self-reported at the end of the data collection period. Logistic regression analyses were used to estimate crude and adjusted odds ratios (ORs) with 95% CIs for the association between each potential risk factor and reporting menstrual changes following COVID-19 vaccination. MAIN RESULTS AND THE ROLE OF CHANCE: Any menstrual change following COVID-19 vaccination was reported by 30% of menstruating women. Most of the potential risk factors were associated with reports of menstrual changes following COVID-19 vaccination. In particular, higher odds were found among women who reported ≥5 immediate vaccine symptoms; OR 1.67 [1.50-1.86], had had a prior severe COVID-19 infection; OR 2.17 [1.40-3.35], had a high-stress level at baseline; OR 1.67 [1.32-2.10], or were concerned about COVID-19 vaccines prior to vaccination; OR 1.92 [1.50-2.45]. Lower odds were found among women with regular menstrual cycles using hormonal contraception; OR 0.71 [0.65-0.78]. LIMITATIONS, REASONS FOR CAUTION: We were unable to address the causal effect of COVID-19 vaccination on the reported menstrual changes, as information about menstrual changes was not available among non-vaccinated women. WIDER IMPLICATIONS OF THE FINDINGS: The study identified several potential risk factors for reporting menstrual changes following COVID-19 vaccination. Further studies are needed to establish causal associations and the clinical impact of self-reported menstrual changes. STUDY FUNDING/COMPETING INTEREST(S): The BiCoVac data collection was funded by TrygFonden (id-number: 153678). No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.

Testicular torsion and subsequent testicular function in young men from the general population.

STUDY QUESTION: Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population? SUMMARY ANSWER: In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle. WHAT IS KNOWN ALREADY: Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group. STUDY DESIGN, SIZE, DURATION: A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed. LIMITATIONS, REASONS FOR CAUTION: A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences. WIDER IMPLICATIONS OF THE FINDINGS: Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

HIV-related stigma among healthcare providers working within infectious diseases and gynecology and obstetrics at a large teaching hospital in Denmark.

HIV-related stigma experienced in healthcare settings may be particularly detrimental to people with HIV (PWH). This study aims to examine the drivers of stigma and enacted HIV-related stigma among healthcare providers working in HIV and non-HIV care at a large teaching hospital in Denmark. In total, 162 providers working in gynecology and obstetrics, and 57 providers working in infectious diseases completed the "Measuring HIV stigma and discrimination among health facility staff" questionnaire. Compared to providers working in infectious diseases, providers working in gynecology and obstetrics had less training in infection control, HIV, and stigma, and although their level of worry and negative attitudes toward PWH was overall low, they were more like to use extra precaution measures (e.g., double gloves) when caring for PWH (20% versus 0%). Addressing HIV-related stigma in healthcare is important, as any amount of HIV-related stigma from providers has the potential to compromise the patients' engagement in care and health outcomes.

Pre-eclampsia screening in Denmark (PRESIDE): national validation study.

OBJECTIVES: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for pre-eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. METHODS: This was a prospective study of women with a singleton pregnancy attending for their first-trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre-eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre-eclampsia diagnosis, was recorded. Pre-eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen-positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. RESULTS: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1-33.9) years. The majority were white (95%), naturally conceiving (90%), non-smokers (97%) and had no family history of pre-eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2-26.6) kg/m2 . A complete risk assessment including maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A was available for 8156 women (92.9%). In these women, UtA-PI was measured bilaterally with a median value of 1.58 (IQR, 1.27-1.94) and the median resting MAP of 80.5 (IQR, 76.1-85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre-eclampsia, including 55 (0.7%) cases of pre-eclampsia with delivery < 37 weeks of gestation and 16 (0.2%) cases of pre-eclampsia with delivery < 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A had a DR of 77.4% (95% CI, 57.6-97.2%) for pre-eclampsia with delivery < 34 weeks, 66.8% (95% CI, 54.4-79.1%) for pre-eclampsia with delivery < 37 weeks and 44.1% (95% CI, 38.5-49.7%) for pre-eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre-eclampsia with delivery < 34 weeks and 19.6% of women with pre-eclampsia with delivery < 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA-PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9-84.1%) for PE with delivery < 34 weeks and 45.2% (95% CI, 32.0-58.5%) for PE with delivery < 37 weeks. CONCLUSION: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A predicted 77.4% of cases with pre-eclampsia with delivery < 34 weeks and 66.8% of cases with pre-eclampsia with delivery < 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Association of QRS-T angle and Late Gadolinium Enhancement in patients with a Clinical Suspicion of Myocarditis.

Objective: To investigate the association of a wide QRS-T angle on the surface ECG and late gadolinium enhancement on contrast-enhanced cardiovascular magnetic (CMR) imaging in patients with clinically suspected myocarditis. Background: Diagnosis and risk stratification in patients with suspected myocarditis is particularly challenging due to a great spectrum of clinical presentations. Late gadolinium enhancement (LGE) visualizes myocardial necrosis and fibrosis in patients with biopsy-proven myocarditis. The presence or absence of late gadolinium enhancements in these patients is prognostically meaningful. The QRS-T angle from the surface ECG, on the other hand, may serve as a simple and easily available risk marker in suspected myocarditis. Methods: We enrolled 97 consecutive patients that were referred to CMR imaging for a clinical suspicion of myocarditis. All patients obtained a standardized digital 12-lead ECG for the calculation of the QRS-T angle and underwent contrast-enhanced CMR imaging. Patients were divided into two groups according to the absence or presence of LGE on CMR. Results: 78 of 97 patients with suspected myocarditis had LGE on CMR. Patients with LGE had wider QRS-T angles as compared to the patient group without LGE (53.95-47.5 vs. 26.2-21.2; p<0.001). The sensivity, specificity, negative predictive value and positive predictive value for a QRS-T angle above 90 degrees for LGE positive myocarditis were 16.5%, 100%, 24.7%, and 100%, respectively. Conclusion: A wide QRS-T angle of 90 degrees or more is linked to myocardial fibrosis or necrosis (late gadolinium enhancement) in patients with suspected myocarditis.

Danish translation and validation of the Self-reported foot and ankle score (SEFAS) in patients with ankle related fractures.

BACKGROUND: The Self-reported Foot and Ankle Score (SEFAS) is a patient-reported outcome measure used to evaluate foot and ankle disorders. The purpose of this study was to translate, cross-culturally adapt and validate the Danish language version of the SEFAS in patients with ankle-related fractures. METHODS: Forward-backward translation, cross-cultural adaption and validation were performed. In total, 125 patients completed the SEFAS-DK and the Danish version of American Orthopaedic Foot and Ankle Score (AOFAS-DK) at three time points after the date of fracture. The evaluation was performed according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. RESULTS: The intra-class correlation coefficient (ICC) level of the SEFAS-DK total score was 0.93 (95% confidence interval [CI]: 0.88-0.96). Cronbach's alpha (CA) for the SEFAS-DK was 0.93, while the floor and ceiling effect at week 6 post-injury was 22.4%. Construct validity was correlated with the AOFAS, and >75% of the pre-defined hypotheses could be confirmed. Responsiveness was analysed using longitudinal data. The minimal clinical important change (MCIC) showed that the SEFAS-DK detects changes in physical function over time. CONCLUSION: The Danish version of the SEFAS showed overall good reliability, validity and responsiveness. SEFAS-DK can be used to evaluate physical function in patients with ankle-related fractures. LEVEL OF EVIDENCE: level II, prospective cohort study.

QRS-T-angle in Patients with ST-Segment Elevation Myocardial Infarction (STEMI) - a Comparison with Cardiac Magnetic Resonance Imaging.

Background: The QRS-T angle from the surface EKG is a promising prognostic marker in patients with coronary artery disease. Cardiovascular magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) offers high resolution imaging of myocardial damage. We investigated the association of the QRS-T angle and the extent of myocardial damage as assessed by LGE in patients with acute ST-segment myocardial infarction (STEMI) Methods: 169 patients with STEMI obtained a standardized digital 12-lead EKG on admission for the calculation of the QRS-T angle and underwent CMR imaging for analysis of infarct size by LGE within the first week. Patients were divided into groups: (1) abnormal QRS-T angle ≥ 90 degree and (2) QRS-T angle < 90 degree. Results: Patients with a QRS-T angle of 90 degree or more had larger infarcts (36.5±12.4 vs. 13.3±9.5; p<0.001) and lower ejection fraction (42.9±12.1% vs. 50.6±10.6%; p<0.001). Conclusion: The extent of myocardial damage as measured by the gold standard LGE is associated with a larger QRS-T angle calculated from the surface EKG.

Desmoplastic Small Round Cell Tumor: Imaging Pattern of Disease at Presentation.

OBJECTIVE: The purpose of this study is to evaluate the clinical, pathologic, and multimodality cross-sectional imaging features of a cohort of 94 patients with desmoplastic small round cell tumor (DSRCT). MATERIALS AND METHODS: This retrospective study of 94 patients with pathologically verified DSRCT was conducted at a tertiary cancer center between 2001 and 2013. Epidemiologic, clinical, pathologic, and imaging findings were recorded. Tumor size, location, and shape and the distribution pattern of metastases at presentation were analyzed. RESULTS: DSRCT most often occurred in young patients (median age, 21.5 years; range, 5-53 years), showing a marked predominance in male patients (86 male patients vs eight female patients). Eighty nine-patients (95%) were white (defined in this study as white or Hispanic), four were African American, and one was of Asian descent. Most patients had symptoms, with abdominal pain noted as the most common symptom. At initial presentation, 85 patients (90%) had multifocal disease, nodular disease, diffuse omental and peritoneal disease, or a combination of these conditions. Thirty-eight patients (40%) had diaphragmatic involvement. Thirty-two patients (34%) had liver metastases, and 49 patients (52%) had retroperitoneal involvement in the form of implants, tumoral extension, or nodal involvement. With regard to thoracic findings, 33 patients (35%) had nodal disease, 17 (18%) had pleural effusions, and only two (2%) had lung metastases at presentation. Twelve patients (13%) had calcified lesions. CONCLUSION: DSRCT is a rare, multifocal peritoneal malignancy with frequently disseminated abdominal disease at presentation. In the abdomen, disease most commonly involves the omentum and peritoneum, followed by the retroperitoneum. The liver is the most common solid visceral metastatic site. A substantial number of patients have diaphragmatic involvement. In the thorax, nodal and pleural involvement is more common than lung involvement.

A systematic review and meta-analysis of functional outcomes and complications following external fixation or open reduction internal fixation for distal intra-articular tibial fractures: an update.

PURPOSE: To conduct a systematic review and meta-analysis comparing physical function and complications following DIATF surgery with external fixation (EF) or open reduction internal fixation (ORIF). METHOD: A search was conducted using PubMed, Embase, Cochrane CENTRAL, Open Grey and Orthopaedic Proceedings. Studies with a level of evidence of I-III on patients (≥ 18 years) with DIATFs operated on with either EF or ORIF were included. A total of 3814 studies were identified. The Cochrane Risk of Bias Tool for randomised controlled trials and the ROBINS-I tool for nonrandomised studies were used to assess risk of bias. RESULTS: Nine studies with 478 patients, 271 ORIF and 197 EF met the inclusion criteria. The mean follow-up ranged from 12 to 38 months. The meta-analysis showed a higher incidence of superficial wound infections (RR = 2.94, 95% CI 1.62-5.34, p = 0.0004) and malunions (RR = 2.62, 95% CI 1.27-5.43, p = 0.009) in the EF group compared to the ORIF group. Also worse physical function was associated with the EF group. However, the overall evidence was low. CONCLUSION: This systematic review is the first to report on physical function following DIATF surgery. In general, decreased physical function was reported. The meta-analysis showed lower incidence of superficial wound infection and malunion rates in the ORIF group. Heterogeneity was low. In conclusion, this review reports lower complication rates following ORIF for DIATF. The overall evidence was limited, and therefore, the authors cannot recommend ORIF to be superior to EF treatment for DIATF. More multi-centre studies with larger sample sizes are needed to assess long-term physical function and complications following DIATF surgery. LEVEL OF EVIDENCE: Level 1.

Concomitant sensitization to legumin, Fag e 2 and Fag e 5 predicts buckwheat allergy.

BACKGROUND: Buckwheat (Fagopyrum esculentum) has become increasingly popular as a healthy food in Europe. However, for sensitized individuals, consumption can cause anaphylactic reactions. The aim of this study was to identify individual well-characterized buckwheat allergens for component-resolved diagnosis. METHODS: Patients were selected by positive skin prick test to buckwheat and divided into two groups: (1) sensitized to buckwheat without clinical symptoms and (2) buckwheat allergy. Buckwheat proteins were extracted from raw buckwheat seeds, purified applying a combination of protein precipitation and chromatographic methods, and analyzed by IgE immunoblotting and ELISA. RESULTS: Buckwheat-allergic patients had a significantly larger median skin prick test weal diameter for buckwheat than the sensitized group and the positive control. Also, IgE immunoblotting clearly showed a distinct pattern in sera from allergic patients when compared to sensitized individuals. Several IgE-reactive proteins were purified from crude buckwheat extract, namely legumin (Fag e 1 plus its large subunit), Fag e 2 (2S albumin), and newly identified Fag e 5 (vicilin-like) as well as hevein-like antimicrobial peptides, designated Fag e 4. All four allergens showed superior diagnostic precision compared to extract-based ImmunoCAP with high sensitivity as well as high specificity. CONCLUSIONS: Patients with clinical symptoms clearly show a distinct allergen recognition pattern. We characterized a buckwheat vicilin-like protein as a new relevant marker allergen, designated Fag e 5. Additionally, another new allergen, Fag e 4, potentially important for cross-reactivity to latex was added to the allergen panel of buckwheat. Further, our data show that the full-length legumin comprising both, large and small subunit should be applied for component-resolved diagnosis. Our data indicate that concomitant sensitization to legumin, Fag e 2 and Fag e 5, predicts buckwheat allergy.

The power of the Mediator complex-Expanding the genetic architecture and phenotypic spectrum of MED12-related disorders.

MED12 is a member of the large Mediator complex that controls cell growth, development, and differentiation. Mutations in MED12 disrupt neuronal gene expression and lead to at least three distinct X-linked intellectual disability syndromes (FG, Lujan-Fryns, and Ohdo). Here, we describe six families with missense variants in MED12 (p.(Arg815Gln), p.(Val954Gly), p.(Glu1091Lys), p.(Arg1295Cys), p.(Pro1371Ser), and p.(Arg1148His), the latter being first reported in affected females) associated with a continuum of symptoms rather than distinct syndromes. The variants expanded the genetic architecture and phenotypic spectrum of MED12-related disorders. New clinical symptoms included brachycephaly, anteverted nares, bulbous nasal tip, prognathism, deep set eyes, and single palmar crease. We showed that MED12 variants, initially implicated in X-linked recessive disorders in males, may predict a potential risk for phenotypic expression in females, with no correlation of the X chromosome inactivation pattern in blood cells. Molecular modeling (Yasara Structure) performed to model the functional effects of the variants strongly supported the pathogenic character of the variants examined. We showed that molecular modeling is a useful method for in silico testing of the potential functional effects of MED12 variants and thus can be a valuable addition to the interpretation of the clinical and genetic findings.

Omalizumab prevents anaphylaxis and improves symptoms in systemic mastocytosis: Efficacy and safety observations.

BACKGROUND: Patients with systemic mastocytosis (SM) may suffer from mast cell (MC) mediator-related symptoms insufficiently controlled by conventional therapy. Omalizumab is an established treatment in other MC-driven diseases, but experiences in SM are limited. OBJECTIVE: To assess the efficacy and safety of omalizumab in SM. METHODS: In our patient cohort, we evaluated all SM patients treated with omalizumab. A physician global assessment of type and severity of symptoms was performed at baseline, at 3 and 6 months and at latest follow-up. Quality of life was assessed by visual analogue scale. S-tryptase and KIT D816V allele burden were monitored. RESULTS: A total of 14 adult SM patients (10 ISM, 2 BMM, 1 SSM, and 1 ASM-AHN) received omalizumab with a median duration of 17 months (range: 1-73 months). One patient was excluded due to concomitant cytoreductive therapy. In the remaining 13 patients, we observed a significant reduction in symptoms, with complete symptom control in five (38.5%), major response in three (23.1%), and a partial response in three (23.1%) patients, whereas two patients (15.4%) withdrew due to subjective side-effects at first dose. The treatment was most effective for recurrent anaphylaxis and skin symptoms, less for gastrointestinal, musculoskeletal, and neuropsychiatric symptoms. Patient-reported quality of life showed significant improvement. No significant changes in s-tryptase/KIT D816V allele burden were observed. No severe adverse events were recorded. CONCLUSIONS: Omalizumab appears to be a promising treatment option in SM, effectively preventing anaphylaxis and improving chronic MC mediator-related symptoms, insufficiently controlled by conventional therapy. Controlled studies are needed to substantiate findings.

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

The urgent need for a harmonized severity scoring system for acute allergic reactions.

The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.

The Allergic Rhinitis and its Impact on Asthma (ARIA) score of allergic rhinitis using mobile technology correlates with quality of life: The MASK study.

Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires.

Transfer of innovation on allergic rhinitis and asthma multimorbidity in the elderly (MACVIA-ARIA) - EIP on AHA Twinning Reference Site (GARD research demonstration project).

The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults.