Letter to the Editor, BJOG Exchange

The factors responsible for the spectrum of COVID-19 disease severity and the genesis and nature of protective immunity against COVID-19 remain elusive. Multiple studies have investigated the immune responses to COVID 19 in various populations, including those without evidence of COVID 19 infection. Information regarding innate and adaptive immune responses to the novel SARS-CoV-2 has evolved rapidly. Here, data are accumulating defining disease phenotypes that aid in rational and informed development of new therapeutic approaches for the treatment of patients infected with SARS-CoV-2 and the development of novel vaccines. In this article, we summarize data on important innate immune responses including cytokines, specifically IL-6 and complement, and explore potential treatments. We also examine adaptive immune responses and derivative therapeutics such as monoclonal antibodies directed at spike proteins. Finally, we explore data on real-time assessments of adaptive immune responses which include CD4+/CD8+ T-cells, NKT-cells, memory B-cells, and T-follicular cells with specificities for COVID-19 peptides in infected individuals and normals. Data of two novel vaccines have been released, both showing >95% efficacy in preventing SARS-CoV-2 infection. Analysis of humoral and cellular responses to the vaccines will determine the robustness and durability of protection. In addition, long-term assessment of SARS-CoV-2 memory B and T-cell mediated immune responses in patients recovering from an infection or those with cross-reactive immunologic memory will help to define risk for future SARS-CoV infections. Finally, patients recovering from SARS-CoV-2 infection may experience prolonged immune activation likely due to T-cell exhaustion. This will be an important new frontier for study.

Trans-catheter PFO closure is typically done utilizing femoral access for both ICE and device deployment. We hereby report the first two cases of PFO closure through the jugular veins guided by ICE from the arm in patients without any femoral options.

Background: H1-antihistamines (AHs) are widely used for the treatment of allergic diseases, being one of the most commonly prescribed classes of medications in Pediatrics. Newer-generation AHs are associated with fewer adverse effects compared to first-generation. However, their relative harms in the pediatric population still need scrutiny. Methods: We performed a systematic review of randomized controlled trials (RCTs) which included comparisons of safety parameters between an orally administered newer-generation AH with another AH (first- or second- generation), montelukast or placebo in children aged≤12 years. We searched MEDLINE and CENTRAL, independently extracted data on study population, interventions, adverse events (AEs) and treatment discontinuations, and assessed the methodological quality of the included RCTs using the Cochrane’s risk of bias tool. Results: Fourty-five RCTs published between 1989 and 2017 met eligibility criteria. The majority of RCTs included school-aged children with allergic rhinitis and had a follow-up period of up to a month. Four RCTs reported serious AEs in patients receiving a newer-generation AH, but only two patients experienced a possibly drug-related serious AE. The occurrence of AEs, drug-related AEs and treatment discontinuations due to AEs varied between RCTs. Most AEs reported were of mild intensity. Indirect evidence indicates that cetirizine is more sedating than the other newer-generation AHs. Conclusion: Our findings confirm that newer-generation AHs have a favorable safety and tolerability profile. However, we could not draw firm conclusions regarding the comparative safety profile of the newer-generation AHs due to the paucity of head-to-head RCTs, variation in definitions and reporting of AEs, and short follow-up duration.

Introduction: Children with allergy may increase a chance to sensitize the allergic pollens with several environmental changes. Purpose of this study was to investigate the correlation with alternation of pollination associated with meteorological changes and increased sensitization rate of pollen allergens of children in Seoul metropolitan area, Korea. Methods: There were recruited 8,295 children who visited the pediatric allergic clinics at Hanyang University Seoul and Guri Hospital for allergy symptoms from January 1st, 1998 to December 31st, 2019. The pollen was collected by Burkard 7 days-sampler in 2 hospitals during the study. Meteorological data was investigated from Korea Meteorological Administration. Results: Allergic sensitization of oak, hazel, and alder pollens had the highest rate of increase among major tree pollens, an increase of 0.28% annually. The sensitization rate to pollen was increased with younger age group yearly. The duration of pollen season was 98 days in 1998, but 140 days in 2019. The duration of the pollen seasons and pollen sensitization rate to trees were positively correlated. The relationship between the sensitization rate to pollens and accumulated temperature were also correlated, positively. Conclusions: This study demonstrates the correlation between the weather changes and consequent changes of pollen seasons with increasing the sensitization rate to allergic pollens in children in Seoul metropolitan area. In addition, there was an increase in the sensitization rate in younger age group from year to year. Continuous changes in distribution of pollens raised from meteorological changes are expected from now on.

Background: Denosumab is a monoclonal antibody approved for the treat-ment of postmenopausal osteoporosis. The withdrawal of denosumab produc-es an abrupt loss of bone mineral density and may cause multiple vertebral fractures (MVF). Objective: To study the clinical, biochemical and densitometric characteristics in a large series of postmenopausal women who suffered MVF after deno-sumab withdrawal. Likewise, we try to identify those factors related to the presence of a greater number of vertebral fractures (VF). Patients and Methods: 56 patients (54 women) who suffered MVF after re-ceiving denosumab at least for 3 consecutive years and abruptly suspended it. A clinical examination was carried out. Biochemical bone remodeling markers (BBRM) and bone densitometry at the lumbar spine and proximal femur were measured. VF were diagnosed by MRI, X-ray or both at dorsal and lumbar spine. Results: 56 patients presented a total of 192 VF. 41 patients (73.2%) had not previously suffered VF. After discontinuation of the drug, a statistically signifi-cant increase in the BBRM was observed. In the multivariate analysis, only the time that denosumab was previously received was associated with the pres-ence of a greater number of VF (p = 0.04). Conclusions: We present the series with the largest number of patients col-lected to date. 56 patients accumulated 192 new VF. After the suspension of denosumab and the production of MVF, an increase in the serum values of the BBRM. The time of denosumab use was the only parameter associated with a greater number of fractures.

Background: Overweight, obesity and lack of sleep quality as inflammatory states are the common problems among college students and the Association of Dietary Inflammatory Index (DII) with these problems among this population is unknown. We aimed to evaluate the relationship of the DII with obesity and sleep quality among Iranian female students. Methods: The present cross-sectional study was conducted in 249 female college students. The Dietary Inflammatory Index (DII) was calculated using a valid and reliable 147-item food frequency questionnaire (FFQ). To assess sleep quality, Pittsburgh Sleep Quality Index (PSQI) was used. Odds Ratio (OR) and 95% Confidence Intervals (CIs) were estimated for anthropometric indices and sleep quality according to DII score. Linear regression was used to estimate the relationship between DII score with sleep and anthropometric indices. Results: There was a significant association evident between DII and sleep quality(> 5 is considered as poor quality of sleep); i.e., the odds ratios between DII quartile 2 vs 1 (unadjusted model: OR= 0.33 (CI: 0.14-0.74), P for trend =0.002; model 1: the fully adjusted OR= 0.31(CI: 0.12-0.78), P for trend = 0.005; model 2:OR=0.30 (CI:0.12-0.78), P for trend = 0.005) to quartile 4(unadjusted model: OR= 1.13(CI: 0.45-2.80); model 1: OR= 1.11(CI: 0.44-2.79); model 2:OR=1.13(CI:0.44-2.87), P for trend = 0.005). Also, odds ratios increased significantly from quartile 2 to quartile 4 in all models for DII and sleep quality. According to the continuous score of DII, there was a significant positive association between DII and sleep quality in all 3 models: unadjusted, model 1, and model 2 (OR= 1.21 (CI: 1.05-1.40), OR= 1.21 (CI: 1.03-1.43), and OR= 1.22 (CI: 1.03-1.44), respectively. Conclusions: In this study, after removing the effect of confounding factors, participants in the highest quartile of DII score had significantly higher PSQI global score.

Background: We investigated the interaction between PPAR-γ Pro12Ala polymorphism and Healthy Eating Index (HEI), Dietary Quality Index-International (DQI-I) and Dietary Phytochemical Index (DPI) on Cardiovascular Disease (CVD) risk factors in patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional study was conducted on 393 diabetic patients. PPAR-γ Pro12Ala was genotyped by PCR-RFLP method. Biochemical markers including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), superoxide dismutase (SOD), C-reactive protein (CRP), total antioxidant capacity (TAC), pentraxin-3 (PTX3), isoprostaneF2α (PGF2α) were measured by standard protocol. FFQ was used for dietary indices (DQI, DPI, HEI) calculation. Results: There was no significant relationship between PPAR-γ Pro12Ala polymorphism and CVD risk factors. The rs1801282-DQI interactions were significant on WC (P= 0.01). Thus, C-allele carriers in the higher tertile of DQI had higher WC compared to GG homozygous. Further, an interaction was observed between PPAR rs1801282 polymorphism and DQI on serum IL-18 level (P = 0.03). Besides, a significant rs1801282-DPI interaction was shown on HDL concentration (P Interaction= 0.04), G allele carriers who were in the highest tertile of DPI, had lower HDL. Moreover, there were significant rs1801282-HEI interactions on ghrelin (P= 0.04) in the crude model and serum leptin (P = 0.02) in the adjusted model. Individuals with (CC, CG) genotypes in the higher tertile of HEI, had lower leptin and ghrelin concentration. Conclusions: Higher dietary indices (DQI, DPI, HEI) may affect the relationship between PPAR-γ Pro12Ala polymorphism and waist circumference and ghrelin, leptin, HDL-c, IL-18 concentration in patients with T2DM. To date, studies on this polymorphism have been shown that this gene can interact with diabetes and different nutritional factors. For the first time, this study provides information on the interaction of dietary indices (DQI, DPI, HEI) and PPAR-γ gene which is functionally effective in nutrient metabolism.

Molecular simulation has emerged as an important sub-field of chemical engineering, due in no small part to the leadership of Keith Gubbins. A characteristic of the chemical engineering molecular simulation community is the commitment to freely share simulation codes and other key software components required to perform a molecular simulation under open-source licenses and distribution on public repositories such as GitHub. Here we provide an overview of open-source molecular modeling software in Chemical Engineering, with focus on the Molecular Simulation Design Framework (MoSDeF). MoSDeF is an open-source Python software stack that enables facile use of multiple open-source molecular simulation engines, while at the same time ensuring maximum reproducibility.

Cardiac surgical patients are often discharged to a rehabilitation facility to complete the convalescence in a protected setting. This care pathway is usually reserved for elderly and fragile patients, with severe and invalidating comorbid conditions. Between March and April 2020, nineteen patients were discharged from our unit to a rehabilitation clinic where a hotbed of SARS-CoV-2 infection was documented on April 17. After the outbreak, all patients underwent screening with real-time PCR on nasal swabs, and 18/19 patients were found positive. Diversely from other observations on perioperative COVID-19 reporting mortality rates of 30-40%, the COVID-19 had a benign course in our cohort: six patients were completely asymptomatic, and only seven patients required hospitalization (no deaths). We describe the baseline, operative and postoperative features of these patients, and present some potential explanations for the surprisingly benign course of the COVID-19 in this cohort.

Background: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. Methods: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. Results: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection, 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. Conclusions: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.

Background and Aims Current guidance advises that at least 90% of anterior cruciate ligament reconstructions are performed as day case operations. Same-day surgery rates achieved by surgical units have significant clinical and financial implications. The primary aim of this multi-centre study was to determine the rate of admission and causes for admissions in patients undergoing anterior cruciate ligament reconstruction. Method Patient documentations were studied for those who underwent an elective anterior cruciate ligament reconstruction between January 2015 and April 2019. Contributing factors related to admission length were investigated and included patient age, gender, body mass index (BMI), operating surgeon, operating hospital, American Society of Anaesthesiology (ASA) grade, and position of the patient on the operating list. Both univariate and multivariate analysis was conducted using the STATA/IC 16.1 statistical package. Results The day surgery rate of anterior cruciate ligament reconstructions were 52% (50/95). Patients positioned later on the operating list were more likely to be admitted post-operatively (OR – 4.49; p=0.002; 95% CI – 1.72-11.69) and this was the only factor associated with admission. A large majority of admitted patients (95.6%) were admitted without a clinical cause and were otherwise safe for same-day discharge. Conclusions The day surgery rate for ACL reconstruction remains low, despite an extremely low complication rate. Reconfiguration of the operating lists and positioning anterior cruciate ligament reconstructions earlier in the day will likely increase the same-day discharge rate.

Microbiome composition data collected through amplicon sequencing are count data on taxa in which the total count per sample (the library size) is an artifact of the sequencing platform and as a result such data are compositional. To avoid library size dependency, one common way of analyzing multivariate compositional data is to perform a principal component analysis (PCA) on data transformed with the centered log-ratio, hereafter called a log-ratio PCA. Two aspects typical of amplicon sequencing data are the large differences in library size and the large number of zeroes. In this paper we show on real data and by simulation that, applied to data that combines these two aspects, log-ratio PCA is nevertheless heavily dependent on the library size. This leads to a reduction in power when testing against any explanatory variable in log-ratio redundancy analysis. If there is additionally a correlation between the library size and the explanatory variable, then the type 1 error becomes inflated. We explore putative solutions to this problem.

Background Past active surveillance have reported prevalence of subclinical RHD amongst school children which are not comparable because of major differences in screening methods. The present study is based on the WHF criteria to assess the prevalence of subclinical carditis due to RHD and elucidate evolution of the disease when these children were placed on appropriate antibiotic prophylaxis and regular follow-up. This is the first large active surveillance study which has been conducted in a single district of India after the publication of WHF criteria and is reporting short-medium term follow-up data. Methods For active surveillance of RHD among urban and rural school children of Bikaner, a random inclusion strategy was adopted. The diagnostic labelling based on the echocardiographic criteria proposed by World Heart Federation was done by a group of experienced cardiologists. The follow up of the patients recruited in to the study was done to ascertain the early evolution of the disease in the presence of appropriate antibiotic prophylaxis. Results A high prevalence of subclinical RHD was noted in the study population. Pathological mitral and/or aortic valves regurgitation was the commonest lesion and significant proportion of cases improved on regular antibiotic prophylaxis. There was no case of fixity of leaflets/ stenosis. Conclusion The prevalence of subclinical RHD and these cases are reversible if appropriate antibiotic prophylaxis is instituted at an early stage.

Necrotising pneumonia complicated by mycotic pseudoaneurysm has been reported very rarely in infancy. Here we present a five month old girl who had an acute life-threatening presentation of cavitatory pneumonia.

Single-stage endovascular treatment of cardiac and vascular diseases with combined endovascular techniques has bee increasingly reported in the contemporary literature. Although more complex cases are currently being treated with such techniques, there are still crucial issues regarding their safety and efficacy.silmutaneous

We describe the demographic, clinical, and laboratory characteristics of children with COVID 19 in comparison with those of not-laboratory-confirmed cases. We conducted a cross-sectional study on the epidemiological, clinical, radiological, and laboratory characteristics, and outcome of 422 children (aged 0–18 years) with suspected and confirmed COVID 19 admitted to the pediatric emergency department from March 23rd to July 23rd, 2020. Of the 422 children with suspected COVID-19 included in this study, COVID-19 was PCR-confirmed in 78 (18.4%). Fever (51.2%) and cough (43.5%) were the most prominent symptoms in children with confirmed cases. The clinical status of the patients with confirmed COVID-19 was significantly milder than that of those with suspected COVID-19. The proportion of COVID-19 pneumonia cases was 44.4%, 5.5%, 18.7%, and 8.5% for the age groups of ≤ 1, 2–6, 7–12, and ≥ 12 years, respectively. Of the 422 children, 128 (30.3%) underwent nasopharyngeal PCR testing for other respiratory viral pathogens; 21 (16.4%) were infected with viral pathogens other than severe acute respiratory syndrome-related coronavirus-2. Only one patient (4.7%) with confirmed COVID-19 had coinfection with respiratory syncytial virus and rhinovirus. The areas under the receiver-operating characteristics curves were 0.812 for WBCs, 0.752 for neutrophils, 0.717 for lactate dehydrogenase, and 0.708 for lymphocyte for predicting COVID-19 (p ≤ 0.001). Fever and cough or other clinical symptoms or signs should not be considered hallmarks of COVID 19. In this study, the WBC, neutrophil, and lymphocyte counts were predictive of COVID-19 positivity.

Pyoderma gangrenosum (PG) being a primary sterile neutrophilic dermatosis, the etiology is still uncertain and it rarely affects children. A high index of suspicion is essential to execute its prompt treatment. To the best of our knowledge this is the first reported case in our country