Objectives. To investigate the obstetrical management of cancer in pregnancy and to determine adverse pregnancy and neonatal outcomes. Design. A register-based nationwide historical prospective cohort study. Setting and population. We assessed all pregnancies (N = 4,071,848) in Denmark from 1 January 1973 to 31 December 2018. Methods. We linked data on maternal cancer, obstetrical, and neonatal outcomes. Exposure was defined as pregnancies exposed to maternal cancer (n = 1,068). The control group comprised pregnancies without cancer. The groups were compared using logistic regression analysis and adjusted for potential confounders. Main outcome Measures. The primary outcome was the iatrogenic termination of the pregnancy (induced abortions/labor induction or elective caesarean section). Secondary outcomes were adverse neonatal outcomes. Results. More women with cancer in pregnancy, as compared to the control group, experienced first-trimester induced abortion; adjusted odds ratio (aOR) 3.7 (95% CI 2.8─4.7), second-trimester abortion; aOR 9.0 (6.4─12.6), iatrogenic preterm delivery; aOR 10.9 (8.1─14.7), and iatrogenic delivery below 32 gestational weeks; aOR 16.5 (8.5─32.2). Neonates born to mothers with cancer in pregnancy had a higher risk of respiratory distress syndrome; aOR 1.5 (1.2─2.0), but not of low birth weight; aOR 0.6 (0.4─0.8), admission to neonatal intensive care unit more than seven days; aOR 1.4 (1.1─1.9), neonatal infection; aOR 0.9 (0.5─1.5) nor neonatal mortality; aOR1.3 (0.6─2.6). Conclusion. Cancer in pregnancy implies an increased risk of iatrogenic termination of pregnancy and iatrogenic premature birth. Neonates born to mothers with cancer in pregnancy had no increased risk of severe adverse neonatal outcomes.

Objective To investigate the association between the maternal lipid profile in early pregnancy and embryonic growth. Design Prospective population-based cohort study. Setting Rotterdam, the Netherlands. Population We included 1474 women from the Generation R(otterdam) Study. Methods The maternal lipid profile was defined as total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), remnant cholesterol, non-high-density (non-HDL-c) lipoprotein cholesterol concentrations and the triglycerides/high-density lipoprotein (TG/HDL-c) ratio. Additionally, maternal glucose concentrations were assessed. Associations were studied with linear regression models, adjusted for confounding factors: maternal age, pre-pregnancy BMI, parity, educational level, ethnicity, smoking and folic acid supplement use Main Outcome Measures Crown-rump length (CRL). Results Triglycerides and remnant cholesterol concentrations are positively associated with embryonic growth (fully adjusted models, 0.17 SDS: 95% CI 0.03 ; 0.30, and 0.17 SDS: 95% CI 0.04 ; 0.31, respectively). These associations were not present in women with normal weight (triglycerides and remnant cholesterol: fully adjusted model, 0.44 SDS: 95% CI 0.15 ; 0.72). Associations between maternal lipid concentrations and embryonic growth were not attenuated after adjustment for glucose concentrations. Total cholesterol, HDL-c, LDL-c, non-HDL-c concentrations and the TG/HDL-c ratio were not associated with embryonic growth. Conclusions Higher triglycerides and remnant cholesterol concentrations in early pregnancy are associated with increased embryonic growth, most notably in overweight women. Keywords Pregnancy, Cholesterol, Low-density lipoprotein (LDL-c), High-density lipoprotein (HDL-c), Triglycerides, Intrauterine development, Fetal growth, Early pregnancy Tweetable abstract The maternal lipid profile in pregnancy is associated with embryonic growth.

Background: Bronchopulmonary dysplasia (BPD) is the most common cause of chronic lung disease in children born prematurely. There is little information about the epidemiology and severity of BPD places with high altitude. This study aimed to evaluate the frequency of BPD severity levels and the associated risk factors with severity in a cohort of preterm newborns ≤34 weeks of gestational age born in Rionegro, Colombia Materials and methods: We carried out a retrospective analytical cohort of preterm newborns without major malformations from Rionegro, Colombia between 2011-2018 admitted to neonatal intensive unit at high altitude (2200m above sea level). The main outcomes were the incidence and severity of bronchopulmonary dysplasia. Results: The bronchopulmonary dysplasia incidence was 25.7% (95% CI, 21.6-29.9). Bronchopulmonary dysplasia was moderate in 62.1% of patients and severe in 26.7%. After modeling regression analysis, the final variables associated with BPD severity levels were: sepsis (OR 2.37 CI 95% 1.04-5.40) and pulmonary hypertension (OR 3.79 CI95% 1.19-12). Conclusion: The incidence of BPD was higher and similar to cities with higher altitudes. In our population, the variables associated with BPD severity levels were: duration of oxygen therapy and pulmonary hypertension. It is necessary to increase the awareness of risk factors, the effect of clinical practices, and early recognition of bronchopulmonary dysplasia to reduce morbidity in patients with this pathology.

Changes in sensitization rates in patients with asthma and/or rhinitis in China between 2008 and 2018: a national cross-sectional studyWanjun Wang1*, Jianhong Wang2*, Guihua Song3*, Hua Xie4*, Xiaoping Lin4*, Ruonan Chai4*, Rongfei Zhu5*, Yong He6*, Jun Tang7*, Junge Wang8*, Jinghua Yang9*, Lili Zhi10*, Lin Wu11*, Yan Jiang12*, Xiaoqin Zhou13*, Dongming Huang14*, Ning Wang15*, Rui Xu16*, Yuan Gao17*, Zhimin Chen18*, Jinling Liu18*, Xiaoli Han19*, Guolin Tan20*, Jinzhun Wu21*, Deyu Zhao22*, Jianjun Chen23*, Xiwei Zhang24*, Mengrong Li24*, Yuemei Sun25*, Yi Jiang26*, Weitian Zhang27*, Qianhui Qiu28*, Chuanhe Liu29*, Jie Yin30*, Guodong Hao31*, Huabin Li32*, Yongsheng Xu33*, Shaohua Chen34*, Hua Zhang35, Shi Chen36, Juan Meng37, Dan Zeng38, Wei Tang39, Chuangli Hao40, Jing Li1†, Nanshan Zhong1†, for the China Alliance of Research on Respiratory Allergic Disease*Contributed equally†Joint corresponding authors1 National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University;2 The First People’s Hospital of Yibin, Sichuan;3 The First Affiliated Hospital of Henan University of Traditional Chinese Medicine;4 General Hospital of Northern Theater Command;5 Tongji Hospital, Tongji Medical College, Huazhong University of Science&Technology;6 The Affiliated Hospital of Medical School, Ningbo University;7 Foshan First people’s hospital;8 Beijing Hospital of Traditional Chinese Medicine;9 GuangDong Provincial Hospital of Chinese Medicine;10 The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases;11 Hangzhou Hospital of Traditional Chinese;12 The Affiliated Hospital of Qingdao University;13 Hubei Province Maternal and Child Health Hospital;14 Boai Hospital of Zhongshan City;15 Xi’an Children’s Hospital;16 The First Affiliated Hospital of Sun-Yat University;17 The First Affiliated Hospital of Zhengzhou University;18 Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health;19 Hebei General Hospital;20 Third Xiangya Hospital of Central South University;21 The Women and Children’s Hospital affiliated to Xiamen University;22 Children’s Hospital of Nanjing Medical University;23 Union hospital of Tongji medical college;24 The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University;25 Yu Huang Ding Hospital;26 The First Hospital of Shanxi Medical University;27 Shanghai Jiao Tong University Affiliated Sixth People’s Hospital;28 Zhujiang Hospital of Southern Medical University;29 Children’s Hospital Capital Institute of Pediatrics;30 Chengdu First People’s Hospital;31 Tangshan Gongren Hospital;32 ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University;33 Children’s Hospital of Tianjin University;34 Guangdong Provincial People’s Hospital;35 The First Affiliated Hospital of Xinjiang Medical University;36 Hainan provincial people’s Hospital;37 West China Hospital of Sichuan University;38 Chongqing General Hospital, University of Chinese Academy of Sciences;39 Ruijin Hospital of Shanghai Jiaotong University;40 Children’s Hospital of Soochow University.

Objective: Otitis media (OM) is a common disease in childhood, but much less prevalent in adults, where it, however, tends to have a less benign course. The incidence of OM in children has decreased in recent years, which might be partly explained by the introduction of watchful waiting strategies, and by the introduction of conjugate pneumococcal vaccination (PCV) in children. Adult OM has been sparsely studied, and it is not known whether a herd immunity effect has been achieved after the introduction of PCV. Watchful waiting is usually not considered in adult OM patients. The purpose of this study was to use a national database to investigate the incidence of adult OM in Sweden during the last 20 years. Design: The yearly number of patients aged 20 and over, admitted to hospital with OM was obtained through a national database from 2000 to 2019. The corresponding numbers for outpatients were obtained between 2005 and 2019. Main outcome measures: incidence of acute otitis media in adults in in- and outpatient care. Results: Incidence rates decreased steadily during the study period. Comparing data on hospitalised patients from 2016-2019 to 2005-2008 (PCV was introduced in 2009), the incidence rate ratio was 0.49 (95% CI 0.45-0.53); p<0.0001. The corresponding figures for outpatients were 0.62 (95% CI 0.61-0.63); p<0.0001. The decrease in hospital admissions was most pronounced among younger patients, whereas the opposite was true for outpatient visits. Conclusions: There has been a continuous decrease in incidence of adult patients admitted to hospital with OM in Sweden during the last twenty years. Outpatient visits for OM have declined since 2009.

Objective: To study the risk of CD for each gestational week among ongoing pregnancies of nulliparous women at term. Design: A retrospective, population-based cohort study from January 1, 2016, through December 31, 2017 Setting: a French perinatal network of the Yvelines district, France Population: 11 308 nulliparous women with a singleton fetus in a cephalic presentation and delivered at term (≥37-week +0 day) Methods: for each week of gestation at term, we defined ongoing pregnancies as all pregnancies undelivered at the start of each week. Regression models adjusted by maternal characteristics and hospital status were used to compare the CD risk between ongoing pregnancies and the pregnancies delivered the preceding week. The same methods were applied to subgroups defined by the mode of labor onset. Main outcome measure: The caesarean delivery rate (CD) Results: Ongoing pregnancies > 40 weeks+0 days were associated with a higher risk of CD compared with pregnancies delivered the previous week: 24.3% in ongoing pregnancies ≥ 40 weeks +0 days versus 19.9% in deliveries between 39 weeks +0 days and 39 weeks+6 days (Odd ratio adjusted of 1.28, 95%CI [1.15-1.44]; 30.4% in ongoing pregnancies ≥ 41 weeks +0 days versus 19.6% in deliveries between 40 weeks +0 days and 40 weeks+6 days (OR 1.73, 95%CI [1.51-1.96]). This was also shown for all modes of labor onset and in every maternity unit. Conclusions: CD rates increased starting at 40 weeks +0 days in ongoing pregnancies, regardless of the mode of labor onset.

Aim: The risk-benefit profile of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (Covid-19) is still a matter of debate. With growing evidence on the protective effect of this group of commonly used antihypertensives in Covid-19, we aimed to thoroughly investigate the association between the use of major classes of antihypertensive medications and Covid-19 outcomes in comparison with the use of ACEIs and ARBs. Methods: We conducted a population-based study in patients with pre-existing hypertension in the UK Biobank. Multivariable logistic regression analysis was performed adjusting for a wide range of confounders. Results: The use of either beta-blockers (BBs), calcium-channel blockers (CCBs), or diuretics was associated with a higher risk of Covid-19 hospitalization compared to ACEI use (adjusted OR, 1.63; 95% CI, 1.40 to 1.90) and ARB use (adjusted OR, 1.50; 95% CI, 1.27 to 1.77). The risk of 28-day mortality among Covid-19 patients was also increased among users of BBs, CCBs or diuretics when compared to ACEI users (adjusted OR, 1.64; 95% CI, 1.23 to 2.19) but not when compared to ARB users (adjusted OR, 1.18; 95% CI, 0.87 to 1.59). However, no associations were observed when the same analysis was conducted among hospitalized Covid-19 patients only. Conclusion: Our results suggest protective effects of blocking of the renin-angiotensin-aldosterone system on Covid-19 hospitalization and mortality among patients with pharmaceutically treated hypertension, which should be addressed by randomized controlled trials. If confirmed, this finding could have high clinical relevance for treating hypertension during the SARS-CoV-2 pandemic.

BJOG-21-0722 Statistical associations versus causal inference.Øjvind Lidegaard, professor 11Department of Gynaecology, Rigshospitalet, University of Copenhagen, DenmarkMany clinicians are of the opinion that observational studies may provide only “statistical associations”, but not “causal inference”. And further, that only randomized designs ensure causal interpretation. For the same reason, many medical journals have made rules for all observational studies finding significant statistical associations to be presented as just “associations” often emphasizing that a causal inference is not possible.I hereby sign up to the growing group of epidemiologists, who are of the opinion that just well confounder controlled observational studies are the very design most often providing convincing evidence of a causal interference. Prospective cohort studies better than retrospective case-control studies, but even the latter design has given us important knowledge of risk factors of rare clinical outcomes such as thrombotic diseases, a long list of cancers, obstetrical complications, including latest stillbirths.In a new original Swedish study, Heiddis Valgeirsdottir et al. demonstrate in a nationwide historical follow-up study, that women with polycystic ovary syndrome (PCOS) once pregnant have a 50% increased risk of experiencing stillbirth, as compared to women without PCOS (1). Further, that the rate ratio of stillbirth between women with and without PCOS increased by increasing gestational age, peaking at 42 weeks with 4.3 deaths per 1000 ongoing pregnancies in women with PCOS versus 1.0 deaths per 1000 ongoing pregnancies in women without PCOS.Any such association should certainly be controlled for a long list of potential confounders, the most important being maternal age, calendar year, parity, hypertensive disorders, diabetes, and educational length. Adiposity (BMI) was undertaken in an additional adjustment, because this covariate correctly could be considered as both a confounder (adiposity being a risk factor for stillbirth, and PCOS women more often being adipose), but also as a mediator; women with PCOS are more likely to develop adiposity due to their PCOS. The authors chose carefully to present the BMI adjusted results as the main results, thereby if anything underestimating the risk of stillbirths in women with PCOS.This is far from the first contribution from Scandinavian National Health Registers, identifying and quantifying risk factors for different diseases. We should always be aware that some unknown or unmeasured potential confounders not being controlled for, could reduce (or enhance) the results, and that other research groups should confirm the Swedish findings. A causal inference was made more likely with a suggested biomedical mechanism by which PCOS could confer such a risk. But already with this new carefully provided observational evidence, we should reasonably consider pregnant women with PCOS not to go too far beyond term, to prevent stillbirths in this group, which according to the study results accounts about 5% of all stillbirths. A pragmatic first recommendation could be induction of women with PCOS at 41 gestational weeks.Valgeirsdottir H et al. BJOG 2021; 128: xxx-xxx.

Background: Although women are encouraged to achieve good diet quality in preconception and pregnancy, the benefits on perinatal outcomes have not been established. Objective: To systematically review and quantify the association between diet quality and adverse perinatal outcomes. Search strategy: Medline, Embase, Food Science and Technology Abstracts and CINAHL were searched up to 5th March 2020. Selection criteria: Two authors independently screened, selected and coded relevant prospective cohort studies. Data collection and analysis: Thirty-three studies (315,431 participants) were included in the meta-analysis. Odds ratios and mean differences from individual studies were pooled using random-effects models. Main Results: The pooled results for the association between diet quality and excessive (OR: 0.91; 95 CI: 0.76, 1.10) or inadequate (OR: 0.90; 95 CI: 0.70, 1.17) gestational weight gain were not statistically significant. Women in the top tertile of diet quality scores during prepregnancy or pregnancy had a lower risk of gestational diabetes (OR: 0.77; 95 CI: 0.65, 0.90), hypertensive disorders of pregnancy (OR: 0.87; 95 CI: 0.83, 0.92), preterm birth (OR: 0.77; 95 CI: 0.66, 0.89), small for gestational age (OR: 0.88; 95 CI: 0.79, 0.99) and low birth weight (OR: 0.60; 95 CI: 0.37, 0.99) compared to those in the bottom tertile. No studies were found for delivery mode. Conclusions: Data from prospective cohort studies support the potential of improving maternal diet quality in the effort to prevent adverse perinatal outcomes. Funding: Canadian Institutes of Health Research HLT 151517, National Natural Sciences Foundation of China No. 81661128010 Keywords: Diet quality, perinatal outcomes.

Wild equids can harvest multiple-host infectious agents that are able to affect other wildlife species, but also domestic animals and humans. The contact between wild and domestic equids is constantly increasing due to the depletion of natural areas, climate and land-usage changes, which could result in burdensome epidemics. Nevertheless, currently there is a lack of adequate epidemiological data from zebra. Three electronic databases were searched from 10 to 20 March 2021 for publications reporting bacterial, viral and protozoan infections in zebra. Data for a total of 12 nominal variables were extracted from reviewed papers to undergo a qualitative analysis on microbial infections in zebra. Prevalence-reporting studies were subjected to meta-analysis for estimating the pooled prevalence and seroprevalence of infectious agents in wild zebra populations. We identified 29 pathogen species and the most represented were Equine Herpesvirus 1 and 9, Bacillus anthracis, African Horse Sickness virus and Theileria equi. They were reported from all the three zebra species, both in captivity and wilderness. Pooled seroprevalences were estimated for the equine Orbiviruses AHSV (70%; 95%CI: 35-96%) and EEV (21%; 95%CI: 8-38%) and for the equine α -Herpesviruses EHV-1 (72%; 95%CI: 43-93%), EHV-4 (40%; 95%CI: 0-100%) and EHV-9 (58%; 95%CI: 9-98%), and pooled prevalences for the equine piroplasms T. equi (100%; 95%CI: 94-100%) and B. caballi (8%; 95%CI: 0-28%). Zebra is most probably a reservoir from which AHSV, EHV-1 and T. equi can be transmitted to horse populations, potentially causing disastrous epidemics. Zebra can also harvest zoonotic pathogens like B. anthracis, A. phagocytophylum, CCHFV and T. brucei. Other agents like EHV-9, BPV-1 and BPV-2 have the potential to spread from zebra to other wild endangered animal species. We conclude that zebra is an important host for multiple and dangerous pathogens. Alert and epidemiological research should be increased on infectious agents of zebra.

Thrombotic events are common during COVID-19 infection. Aspirin might be beneficial. Objective: Systematic review and meta-analysis of deaths in users and non-users of aspirin. Data sources: Pubmed Medline, Google scholar, Clinicaltrials.gov, Cochrane, to June 8, 2021, Study selection: Studies providing adjusted or matched evaluation of association of exposure to aspirin and death in COVID-19 patients were included. Data extraction and synthesis: Data were used as published, as Odds ratio, hazard ratio or relative risks and 95% CI from which log(OR) and SE were recalculated. These were entered in an inverse variance odds ratios random-effects model, using RevMan 5.4 (the Cochrane Collaboration). Main outcomes and measure: The prespecified outcome studied was death. Results: Nine studies (8 observational, one interventional) included 14989 patients exposed to aspirin and 15857 unexposed. Overall Odds Ratio of death in aspirin exposed patients in a random effects model was 0.63, 95% confidence interval [0.40-0.99], I2 94%. Using a fixed-effect model did not change much the result (0.76 [0.71-0.81], removing the Recovery trial (OR 0.43 [0.38-0.49], I271%, or the two largest studies (0.66 [0.47-0.93], I2 38%) reduced heterogeneity without materially altering the results. The funnel plot showed no evident publication bias Conclusion: this meta-analysis suggests that the use of aspirin may be associated with a lower risk of death in COVID-19. Considering the results of the Recovery Study, it would appear preferable to continue aspirin in patients who have a non-covid indication, but possibly useless to add it if they don’t.

Foot-and-mouth disease (FMD) is widely distributed in Sudan where outbreaks occur on an annual basis especially during the winter months (December-February). This study aimed to increase our understanding of the epidemiological patterns of FMD in Sudan and connections to neighbouring countries by characterising the genetic sequences of FMD viruses (FMDV) collected from seven Sudanese states over a 10-year period (between 2009 and 2018). FMDV was detected in 91 of the 265 samples using an antigen-detection ELISA. Three serotypes were detected: O (46.2%), A (34.1%), and SAT 2 (19.8%). Fifty-three of these samples were submitted for sequence analyses, generating sequences that were characterised as belonging to O/EA-3 (n=18), A/AFRICA/G-IV (n=23) and SAT 2/VII/Alx-12 (n=12) viral lineages. Phylogenetic analyses provided evidence that FMDV lineages were maintained within Sudan, and also highlighted epidemiological connections to FMD outbreaks reported in neighbouring countries in East and North Africa (such as Ethiopia and Egypt). This study motivates continued FMD surveillance in Sudan to monitor the circulating viral lineages and broader initiatives to improve our understanding of the epidemiological risks in the region.

Objective There is a lack of studies comparing Procalcitonin (PCT), C-reactive protein (CRP) and white blood cell (WBC) levels in the differential diagnosis of acute bacterial, viral, and mycoplasmal respiratory infections. It is necessary to explore the correlation between above markers and different types of acute respiratory tract infections (ARTI). Methods 108 children with confirmed bacterial infection were regarded as group A, 116 children with virus infection were regarded as group B, and 122 children with mycoplasma infection were regarded as group C. The levels of PCT, CRP and WBC of the three groups were detected and compared. Results The levels of PCT, CRP and WBC in group A were significantly higher than those in groups B and C (P <0.05). The positive rate of combined detection of PCT, CRP and WBC was significantly higher than that of single detection. There was no significant difference of PCT, CRP and WBC levels between the group of Gram-positive (G+) bacteria infection and Gram-negative (G-) bacteria infection (P >0.05). ROC curve results showed that the area under the curve (AUC) of PCT, CRP and WBC for the diagnosis of bacterial respiratory infections were 0.65, 0.55, and 0.58, respectively. Conclusions PCT, CRP and WBC can be used as effective indicators for the identification of acute bacterial or no-bacterial infections in children. The levels of PCT and CRP have higher differential diagnostic value than that of WBC in infection, and the combined examination of the three is more valuable in clinic.

Background: Aspergillus fumigatus and other fungal species are common pathogens isolated in CF patients and they lead to a variety of diseases like ABPA and invasive aspergillosis. Aims and Objectives: To study the prevalence of Aspergillus colonization, sensitization and ABPA in our cohort of CF patients. Also, to study the various risk factors for Aspergillus colonization and ABPA in these patients. Methodology: This was a observational study in which 30 patients of cystic fibrosis between 0 to 18 years were enrolled visiting a tertiary care hospital in north India during January 2019 till December 2020. Data was collected on pre-structured proforma on cough swab and sputum c/s for bacteria and fungus, skin prick test for Aspergillus fumigatus, total IgE, Aspergillus specific IgE, Aspergillus specific IgG, galactomannan and CXR. Prevalence of Aspergillus colonization, sensitization and ABPA was calculated, Odds ratio for all the postulated risk factors for Aspergillus colonization and ABPA were calculated and further Chi square test was applied to check association of ABPA with pulmonary exacerbation. Results: Patients enrolled were between the age group of 4 months till 18 years of age with the median age being 4.75 years (IQR: 2.25 -11.75). 16.67% (n=5), 36.67% (n=11) of the patients enrolled in our study were colonized and sensitized with Aspergillus fumigatus respectively. While, 23.34% (n=7) of the patients had ABPA. We found positive association of Aspergillus colonization with multiple risk factors under study, in the following order of decreasing odds ratio, inhaled antibiotics (OR: 4.75) followed by use of azithromycin (OR: 3.5), inhaled corticosteroids (OR: 2.6), and atopy (OR: 1.3). Conclusion: Aspergillus fumigatus is a common colonizer in patients of cystic fibrosis (16.67%), and can lead to an inflammatory response and ABPA (23.34%). Use of azithromycin, inhaled antibiotics, inhaled corticosteroids and atopy increases the chances of Aspergillus colonization.

Background: Serological tests are a powerful tool in the monitoring of infectious diseases and the detection of host immunity. However, manufacturers often provide diagnostic accuracy data generated through biased studies and the performance in clinical practice is essentially unclear.  Objectives: We aimed to determine the diagnostic accuracy of various serological testing strategies for (a) identification of patients with previous coronavirus disease-2019 (COVID-19) and (b) prediction of neutralizing antibodies against SARS-CoV-2 in real-life clinical settings.  Methods: We prospectively included 2’573 consecutive health-care workers and 1’085 inpatients with suspected or possible previous COVID-19 at a Swiss University Hospital. Various serological immunoassays based on different analytical techniques (enzyme-linked immunosorbent assays, ELISA; chemiluminescence immunoassay, CLIA; electrochemiluminescence immunoassay, ECLIA; lateral-flow immunoassay, LFI), epitopes of SARS-CoV-2 (nucleocapsid, N; receptor-binding domain, RBD; extended RBD, RBD+; S1 or S2 domain of the spike [S] protein, S1/S2), and antibody subtypes (IgG, pan-Ig) were conducted. A positive real-time PCR test from a nasopharyngeal swab was defined as previous COVID-19. Neutralization assays with live SARS-CoV-2 were performed in a subgroup of patients to assess neutralization activity (n=201).  Results: The sensitivity to detect patients with previous COVID-19 was ≥85% in anti-N ECLIA (86.8%) and anti-S1 ELISA (86.2%). Sensitivity was 84.7% in anti-S1/S2 CLIA, 84.0% in anti-RBD+ LFI, 81.0% in anti-N CLIA, 79.2% in anti-RBD ELISA, and 65.6% in anti-N ELISA. The specificity was 98.4% in anti-N ECLIA, 98.3% in anti-N CLIA, 98.2% in anti-S1 ELISA, 97.7% in anti-N ELISA, 97.6% in anti-S1/S2 CLIA, 97.2% in anti-RBD ELISA, and 96.1% in anti-RBD+ LFI. The sensitivity to detect neutralizing antibodies was ≥85% in anti-S1 ELISA (92.7%), anti-N ECLIA (91.7%), anti-S1/S2 CLIA (90.3%), anti-RBD+ LFI (87.9%), and anti-RBD ELISA (85.8%). Sensitivity was 84.1% in anti-N CLIA, and 66.2% in anti-N ELISA. The specificity was ≥97% in anti-N CLIA (100%), anti-S1/S2 CLIA (97.7%), and anti-RBD+ LFI (97.9%). Specificity was 95.9% in anti-RBD ELISA, 93.0% in anti-N ECLIA, 92% in anti-S1 ELISA, and 65.3% in anti-N ELISA. Diagnostic accuracy measures were consistent among subgroups.  Conclusions: The diagnostic accuracy of serological tests for SARS-CoV-2 antibodies varied remarkably in clinical practice, and the sensitivity to identify patients with previous COVID-19 deviated substantially from the manufacturer’s specifications. The data presented here should be considered when using such tests to estimate the infection burden within a specific population and determine the likelihood of protection against re-infection.

Objective: To investigate the appropriate drug therapy based on a novel classification system for adenoids based on their appearance. Methods: We used fiberoptic nasal endoscopy to determine the degree and appearance of adenoid hypertrophy (AH). The adenoids were divided into three types: edematous type, common type, and fibrous type. In adenoid tissues, the eosinophils were counted. Immunohistochemistry and western blot were done to determine the expression of CysLTR1, CysLTR2, CGR-α, and CGR-β in different types of adenoids. Results: 70.67% (106/150) AH patients with AR, and of them 68% (72/106) of adenoids were the edematous type. The expression of CGR-α and CGR-β and eosinophil count were higher in the edematous type but not in common and fibrous types. The expression of the leukotriene receptor was stable in all types. There was a positive correlation between eosinophil count in the blood and in the adenoid tissue. Conclusion: AR was the risk factor for the development of AH. Leukotriene receptor antagonist was an important drug for the treatment of AH. The glucocorticoid was only useful in the edematous type. Therefore, for AH patients with AR, patients with edematous type adenoids and/or patients with increased eosinophils in blood routine choose nasal glucocorticoid combined with leukotriene receptor antagonist is appropriate. On the contrary, leukotriene receptor antagonists alone can be selected to treat AH.

Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been described to partially overlap with Kawasaki disease (KD) with regard to clinical symptoms, but they are unlikely to share the same disease entity. We conducted a systematic review and meta-analysis to characterize the laboratory parameters of MIS-C compared with those of KD and Kawasaki disease shock syndrome (KDSS). Databases were searched for studies on laboratory parameters of MIS-C (hematology, inflammatory markers, cardiac markers and biochemistry) through May 31, 2021. Twelve studies with 3073 participants yielded 969 MIS-C patients. In terms of hematology, MIS-C patients had lower levels of leukocytes, absolute lymphocyte count and platelet count (PLT) than KD patients and had similar absolute neutrophil count (ANC) and hemoglobin (Hb) levels. In terms of inflammatory markers, MIS-C patients had higher levels of C-reactive protein, D-dimer and ferritin than KD patients and had similar levels of procalcitonin and ESR. In terms of cardiac markers, MIS-C patients had higher CPK levels than KD patients. The levels of NT-proBNP, troponin and AST were not significantly different between MIS-C and KD patients. In terms of biochemistry, MIS-C patients had lower levels of albumin, sodium and ALT and higher levels of creatinine than KD patients. In addition, MIS-C patients had lower levels of PLT, Hb and ESR and higher levels of ANC than KDSS patients. Measurement of laboratory parameters might assist clinicians with accurate evaluation of MIS-C and further mechanistic research.

The dynamic of SARS-CoV-2 and other respiratory virus in children and adolescents is relevant in clinical context. There are few studies comparing clinical course in COVID-19 (coronavirus disease) and other respiratory virus in pediatric patients. The aim of this study was to compare demographics and clinical features, exams abnormalities, and outcomes in SARS-CoV-2 and other respiratory virus infections in a pediatric population. This was a single-center prospective study, between April 17 to September 30, 2020. We evaluated 76 pediatric COVID-19 and 157 other respiratory virus infections. Rhinovirus occurred in 132/157(84%). COVID-19 patients were significantly older, had more fever (69% versus 50%; p=0.01), pneumonia (22% versus 5%; p<0.01), myalgia (29% versus 8%; p=0.001), headache (31% versus 14%; p=0.01) and worse outcomes than those with other respiratory virus infections. Our data emphasizes differences in clinical presentation and outcomes between pediatric COVID-19 and rhinovirus infections.

Background: Air pollutants induce the increase of inflammatory components in the lungs and the decrease in pulmonary function. Genetic polymorphisms may modify the inflammatory and immunological response to the inhalation of those pollutants. Objective: To investigate effect modification by GST and TNF-α polymorphisms in the association between particulate matter (PM10) and lung function. Methods: This is a cross-sectional epidemiological study with 112 asthmatic children aged 6 to 14 years old. GSTM1, GSTT1, GSTP1, and TNF-α polymorphisms were genotyped using the polymerase chain reaction (PCR) technique. Spirometry tests were conducted. We tested associations using generalized linear models, adjusting for confounding variables. The effect modification of the genetic polymorphisms was assessed, including the genotypes and pollutants. Results: In carriers of the TNF-α-308 GA or AA genotypes, we found a reduction of 11.5% (95% CI: -19.08, -3.30) in FEV1 in the current exposure to PM10 and a reduction of 10.46% (95% CI: -14.91, -5.77) for the 5-day cumulative exposure. The TNF-α-1031 TT genotype was associated with a decline in FEV1 and FEF25-75% for the cumulative exposure to PM10. The GSTP1 wild-type genotype was associated with a decrease in FEF25-75% of 23.45% (95% CI; -30.6, -15.56) and in FEV1 of 13% (95% CI; -15.21, -10.74). We found that among GSTT1 null children, the cumulative exposure to PM10 was also associated with a reduction in FEV1, FVC, and FEF25-75%. Conclusion: Genetic polymorphism in GST and TNF-α may modify the association between particulate matter and pulmonary function in asthmatic children and adolescents.

Introduction. Dietary habits in developing countries are characterized in the last decades by low intake of fruits, vegetables, and high consumption of sweetened drinks. Most of the evidence linking carbohydrate intake and asthma comes from children over 6 years of age. The aim of this study was to examine the association of macronutrient intake with the severity of wheezing exacerbation in children aged 2 to 6 years Methods. We performed a prospective cohort study that included all children aged 2 to 6 years hospitalized by a wheezing exacerbation in two tertiary centers in Rionegro, Colombia. Dietary data were collected using a food frequency questionnaire (FFQ) validated in the Colombian population. Gina classification of acute wheezing in children 5 years and younger was to define the severity of the wheezing Results During the study period, 228 cases of patients with wheezing exacerbation were included. Wheezing severity was dose-dependently associated with protein and carbohydrate-rich intake. The variables included in the multivariable analysis included reactive C protein, smoking at home, atopic dermatitis, protein, and carbohydrate-rich food intake Conclusion High carbohydrate-rich food intake was associated with severity of wheezing exacerbation adjusted by other known risk factors such as atopic, smoking, and reactive C protein. Also, we found a negative association of severity of wheezing exacerbation with high protein-rich food intake adjusted by the factors mentioned above. This evidence should motivate the development of public health policies to control the consumption of sugar-rich products in children under 6 years of age.

A case of acute necrotising pancreatitis following the second dose of Pfizer-BioNTech COVID-19 mRNA vaccineAs of 22 June 2021, there have been about 400,000,000 doses of the Pfizer-BioNTech COVID-19 mRNA vaccine administered world-wide. At this time, 176 cases of pancreatitis have been reported in pharmacovigilance reports submitted to the WHO.1 No epidemiological link between the Pfizer-BioNTech COVID-19 mRNA vaccine and pancreatitis has been reported. We report a case of acute necrotising pancreatitis following the second dose of the Pfizer-BioNTech COVID-19 mRNA vaccine. This case has been reported to the New Zealand Pharmacovigilance Centre and the patient has consented to publication of the case report.A 43-year-old, NZ European male was diagnosed with acute necrotising pancreatitis 10 hours following the administration of his second Pfizer-BioNTech COVID-19 mRNA vaccine. He has a background of atopy with seasonal rhinitis, eczema and asthma, all of which are ‘mild’. He takes no regular medications and takes as needed melatonin 2 mg nocte, cetirizine 10 mg for hay fever, and betamethasone and emollient cream for dermatitis. He has no family history of note and works in a senior professional role. He drinks six standard units of alcohol per week, has never been a tobacco smoker and does not use recreational drugs – and his employer undertakes regular drug testing.He had a previous episode of pancreatitis in 2011, precipitated by high alcohol intake during a holiday abroad. He is otherwise previously well. There is no family history of note, his father was a smoker and died of lung cancer in his 60s, his mother is well, he has two siblings and three children all of whom are well. He is not aware of any diseases of note in his extended family.In May 2021 he received his second dose of Pfizer-BioNTech COVID-19 mRNA vaccine, he was well at that time. Four hours after the dose he had two 330ml bottles of 5% alcohol beer with his dinner. Six hours after the dose he became unwell with nausea, epigastric pain, and vomiting. Ten hours after the dose blood tests on admission to hospital included: white cell count 18.5 x109/L (4 - 11), neutrophils 15.5 x109/L (1.9 - 7.5), lymphocytes 0.8 x109/L (1.0 - 4.0), CRP <3 mg/L (<5), lipase 23,750 U/L (10 – 70), and triglycerides 3.3 mmol/L. Acute pancreatitis was diagnosed. An ultrasound scan showed pancreatitis without evidence of cholelithiasis. He subsequently deteriorated and a computer tomography (CT) scan on 17 May, day 9 of the illness, showed severe necrotising pancreatitis with collections.During the admission under a specialist hepatobiliary surgical team, known causes of pancreatitis were excluded including: steroid use, trauma, family history of autoimmune conditions, and infection. He did not have the risk factors of obesity, smoking or heavy alcohol consumption. He had the risk factor of a previous episode of acute pancreatitis. The incidence of pancreatitis in New Zealand Europeans in this age group is approximately 50 per 100,000 per year.2 Idiopathic cases represent about 15% of these.Using the Naranjo criteria, the pancreatitis being ’caused’ by the Pfizer-BioNTech COVID-19 mRNA vaccine score was 6 ‘probable’.3 Clinical case discussion (including a hepatobiliary surgeon, gastroenterologist and clinical pharmacologist) concluded that while idiopathic pancreatitis could not be excluded, the onset of symptoms and findings were consistent with an acute precipitating event around the time the second vaccine dose was administered.In addition to the 176 cases reported in VigiBase™, searches of PubMed and Google Scholar™ identified two published case reports of pancreatitis following the Pfizer-BioNTech COVID-19 mRNA vaccine. These were following administration of the first dose of the Pfizer-BioNTech COVID-19 mRNA vaccine. In one case symptoms developed several hours after vaccine administration and the other several days after vaccine administration.4,5Acute pancreatitis is a rare in patients with COVID-19 but characteristic patterns of illness have been reported.6 This raises the possibility that an immune response to either the virus or the vaccine could have common sequalae.This case of acute pancreatitis was temporally associated with the Pfizer-BioNTech COVID-19 mRNA vaccine suggesting a causal link. The characteristics of pancreatitis cases associated with the Pfizer-BioNTech COVID-19 mRNA vaccine should be examined to see if a consistent pattern is present.VigiAccess™ http://www.vigiaccess.org/ - accessed June 24, 2021.Pendharkar SA, Mathew J, Zhao J, Windsor JA, Exeter J, Petrov MS. Ethnic and geographic variations in the incidence of pancreatitis and post- pancreatitis diabetes mellitus in New Zealand: a nationwide population- based study. 2017;130(1450):14.Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther . 1981;30(2):239-245. doi:10.1038/clpt.1981.154Cieślewicz A, Dudek M, Krela-Kaźmierczak I, Jabłecka A, Lesiak M, Korzeniowska K. Pancreatic Injury after COVID-19 Vaccine—A Case Report. Vaccines . 2021;9(6):576. doi:10.3390/vaccines9060576Parkash O, Sharko A, Farooqi A, Ying GW, Sura P. Acute Pancreatitis: A Possible Side Effect of COVID-19 Vaccine. Cureus . Published online April 28, 2021. doi:10.7759/cureus.14741Bircakova B, Bruha R, Lambert L, Grusova G, Michalek P, Burgetova A. A bimodal pattern of the onset of COVID-19 related acute pancreatitis supports both the cytotoxic and immune-related pathogenesis – a systematic review. Scand J Gastroenterol . 2021;56(7):870-873. doi:10.1080/00365521.2021.1922751

Background: Uncontrolled chronic rhinosinusitis (CRS) needing consideration of surgery is a growing health problem yet its risk factors at individual level are not known. Our aim was to examine risk factors of revision endoscopic sinus surgery (ESS) at the individual level by using artificial intelligence. Methods: Demographic and visit variables were collected from electronic health records (EHR) of 790 operated CRS patients. The effect of variables on the prediction accuracy of revision ESS was examined at the individual level via machine learning models. Results: Revision ESS was performed to 114 (14.7%) CRS patients. The logistic regression, gradient boosting and random forest classifiers had similar performance (AUC values .746, .745 and .747, respectively) for predicting revision ESS. The best performance was yielded by using logistic regression and long predictor data retrieval time (AUC .809, precision 36%, sensitivity 70%) as compared with data collection time from baseline visit until 0, 3 and 6 months after the baseline ESS (AUC values .668, .717 and .746, respectively). The number of visits, number of days from the baseline visit to the baseline ESS, age, CRS with nasal polyps (CRSwNP), asthma, NERD and immunodeficiency or its suspicion were associated with revision ESS. Age and the number of visits before baseline ESS had non-linear effects for the predictions. Conclusions: Intelligent data analysis found important predictors of revision ESS at the individual level, such as visit frequency, age, Type 2 high diseases and immunodeficiency or its suspicion.

Objective: We developed a research usefulness tool collating published criteria and examined if randomised controlled trials (RCTs) addressing preterm birth were useful. Search Strategy: Cochrane library. Selection Criteria: Published RCTs within 56 preterm birth Cochrane reviews. Data Collection and Analysis: A usefulness tool was developed with eight criteria combining 13 items identified through literature searches and consensus. RCTs were evaluated for compliance with each item by multiple assessors (reviewer agreement 95-98%). Proportions with 95% confidence interval (CI) were calculated and compared for change over time using ≧ 2010 as a cut-off, with relative risks (RR). Main Results: Among 350 selected RCTs, only 38 (11%, 95% CI 8-15%) met half of the usefulness criteria. Compared to trials before 2010, recent trials used composite or surrogate (less informative) outcomes more often (13% vs 25%, RR 1.87, 95% CI 1.19-2.93). Only 17 trials reflected real life (pragmatism) in design (5%, 95% CI 3-8%), with no improvements over time. No trials reported involvement of mothers to reflect patients’ top priorities in question definition or outcomes selection. Recent trials were more transparent with prospective registration (0.5% vs 28%, RR 58, 95% CI 8-420%), availability of protocol (0.5% vs 15%, RR 32, 95% CI 4-237%) and data sharing statements (2% vs 8%, RR 3, 95% CI 1-10%). Conclusion: Clinical trials in preterm birth lacked many usefulness features, with one tenth of trials meeting half of the items evaluated. Use of informative outcomes, patient centeredness, pragmatism and transparency should be key targets for future research planning.

Objective: To describe the burden of influenza among pregnant women and their young infants. Design: Prospective cohort study. Setting: Rural western Kenya. Population: Pregnant women below 31 weeks of gestation and their infants aged 6 months and below Methods: We conducted weekly follow-up until 6 months postpartum to identify acute respiratory illnesses (ARI). We collected nasal/nasopharyngeal and oropharyngeal swabs from mothers/infants with ARI and tested for influenza A and B using polymerase chain reaction. We calculated incidence of laboratory-confirmed influenza per 1,000 person-months. Main outcome measure: Incidence of medically attended influenza illness among pregnant women and its impact on birth outcomes. Results: During June 2015–May 2020, we enrolled 3,026 pregnant women at a median gestational age of 16 weeks (interquartile range [IQR], 13, 18) and followed 2,550 infants. Incidence of laboratory-confirmed influenza during pregnancy (10.3 episodes per 1,000 person-months [95% CI 8.6–11.8]) was 2-fold higher than in the postpartum period (4.0 [95% CI 2.6–5.5]; p<0.01), and significantly higher among HIV-infected pregnant women (15.6 [95% CI 11.0–20.6] vs. 9.1 [95% CI 7.5–10.8]; p<0.01). Incidence among young infants was 4.4 (95% CI 3.0–5.9) and similar among HIV-exposed and HIV-unexposed infants. Conclusion: Our findings suggest a substantial burden of influenza illnesses during pregnancy, with a higher burden among HIV-infected mothers. Kenyan authorities should consider the value of vaccinating pregnant women, especially if HIV-infected. Funding: This work was supported by funding [Grant number GH002133] from the U.S. CDC, through the Influenza Division. Keywords: Burden, influenza, pregnant women, infants