Abbreviations Full term COVID-19 coronavirus disease 2019 SARS-CoV-2 Severe acute respiratory syndrome corona virus 2

Introduction:In late December 2019, a cluster of pneumonia cases of unknown aetiology were reported in Wuhan, Hubei Province, Central China. The causative agent was subsequently identified as the novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV). The coronavirus disease 2019 (COVID-19) was eventually declared as a global pandemic by the World Health Organisation (WHO), having been detected in over 72 countries worldwide, with Europe and the United States now deemed the viral epicentres [1].Healthcare professionals (HCP) are considered high risk due to a multitude of factors including exposure to higher viral loads [2] and aerosolisation [3,4]. The rising number of deaths amongst healthcare professionals and burden of sick leave secondary to self-isolation, raises significant safety concerns during patient assessment and management. This is particularly of concern when undertaking droplet and aerosol generating procedures (AGP), although the evidence is derived largely from low quality studies [6]. Postulated mechanisms thought to generate aerosol and droplets include laryngeal activity (speech & coughing), high velocity gas flow, and cyclical opening and closure of distal airway. These have been found to generate particles in a range of sizes, increasing the viral load in confined spaces, and possibly increasing transmission risk.Recent literature suggests an increased risk posed to otorhinolaryngologists, as diagnostic, interventional and therapeutic procedures involving the upper aerodigestive tract, paranasal sinuses and middle ear exposes HCPs to both direct and indirect transmission of SARS-CoV-2 [7]. At the point of formulating this article, elective clinical workload has been reduced within the United Kingdom. Two-week-wait clinics have continued due to the prevalence and rising incidence of head and neck cancers [8], albeit at a significantly reduced capacity due to lengthened infection control measures.We describe a novel and cost-effective safety adjunct when undertaking flexible nasendoscopy (FNE) within ward/ outpatient settings.

OBJECTIVE: The general public’s knowledge of the risk factors for head and neck cancer is lacking. The otolaryngology clinic population level of awareness has not yet been reported in the literature. DESIGN: Individual cohort study SETTING: Tertiary academic center PARTICIPANTS: We conducted an anonymous survey of all patients presenting to otolaryngology clinic to assess knowledge of head and neck cancer risk factors. MAIN OUTCOME MEASURES: The main outcome measures were percentage of correct responses for each cancer risk factor and comparison of percent correct between cancer and non-cancer patients. RESULTS: A total of 510 patients were enrolled in the study including 69 patients (13.5%) with a history of head and neck cancer. The most well recognized risk factors by all patients were cigarettes (83.7%) and chewing tobacco (77.5%). Twenty-nine percent of patients correctly identified alcohol as a risk factor. Additional risk factors were poorly recognized. Cancer patients had a similar or better correct response rate than non-cancer patients except for chewing tobacco (68.1% vs 78.9% respectively). CONCLUSION: The general otolaryngology clinic population, especially patients with a history of head and neck cancer, demonstrated improved knowledge of some risk factors for head and neck cancer, but insufficient awareness of alcohol and HPV transmissible behaviors.

Key points: Positional paroxysmal nystagmus-vestibular dysfunction, vascular factor, middle ear diseases, Central pathways, infectious factorKey words: positional, paroxysmal nystagmus, cupulolithiasis, labyrinthitis.Introduction. Short-term accompanied by severe dizziness, large-scale nystagmus, which occurs when the patient is laid on his back with a simultaneous turn of the head to the side and tilt back, is called positional paroxysmal nystagmus (PPN) [2,3,6]. This symptom is an important and often the only objective sign of vestibular dysfunction. PPN, first described by Bárány (1921), is observed in various diseases and injuries of the inner ear, organic processes in the posterior cranial fossa, functional disorders of the nervous system, endocrine disorders, diseases of the cardiovascular system, lesions of the cervical spine [1,3,5,8].PPN is a sign of the presence of cupulolithiasis, i.e. the formation of sediment with a high relative density in the posterior and semicircular channel of the labyrinth. Possible causes of cupulolithiasis include age-related degenerative changes in the vestibular part of the labyrinth, concussion of the inner ear with skull injuries, acute and chronic purulent otitis media, surgical interventions on the stirrups, violations of blood supply to the inner ear [4,7].In addition, many authors consider the presence of chronic infection in the body to be an important reason for the appearance of PPN overlay. disorders that occur in the practice of an otorhinolaryngologist are often caused by the presence of an infectious focus (including acute or chronic otitis, sinusitis, tonsillitis) or (due to the wide spread of vascular pathology) disorders of the blood supply to the labyrinth and its pathways and centers.The aim of the study was to study the influence of vascular and infectious factors on the development of positional paroxysmal nystagmus.Materials and methods of research. This study is devoted to a comparative assessment of the value of infectious and vascular factors in the Genesis of PPN. We observed 548 patients with impaired function, including 311 women and 237 men aged 15 to 74 years, who were inpatient treatment at the clinic No. 1 of the Samarkand medical Institute and 45 of them had foci of chronic infection: chronic tonsillitis (19), chronic polypous sinusitis (12). chronic cholecystitis (8), chronic adnexitis (6). PPN was observed in 101 of 548 patients. Chronic focal infection was significantly more common in individuals who had this type of infection (14 out of 101), but in 37 out of 101 patients, it was not possible to link the occurrence of paroxysmal nystagmus with the presence of foci of chronic infection in the body.Result of discussion. We divided all the patients under our supervision into 3 groups. Group 1 included patients with vascular disorders: atherosclerosis (46), hypertension (50), cervical osteochondrosis with artery syndrome (63), Meniere’s disease (84), vegetative-vascular dystonia (115); group 2 patients with complications of acute and chronic purulent otitis media: with various forms of the labyrinth (109), otogenic intracranial complications (18 patients), group 3 63 patients with combination of vascular pathology of middle ear diseases. The data is presented in table 1.Table 1 shows data on the frequency of paroxysmal nystagmus in patients of the above-mentioned 3 groups. Thus, in patients of group I, PPN was significantly more common (P<0.01) than in patients of group 2. However, this symptom was most often observed in a combination of vascular pathology and middle ear diseases. Obviously, the occurrence in this group of patients can be explained by a violation of the blood supply to the ear and the impact of a pathological process located in the middle ear on the ear labyrinth.To determine the strength and reliability of the influence of diseases of the SOSU: the system of pathological processes in the middle ear in the Genesis of PPN in patients, we applied the method of analysis. Since violations of the function of the vestibular analyzer are observed mainly in cerebral forms of vascular pathology, we can distinguish the following gradations of the degree of intensity of the influence of the vascular factor the occurrence of paroxysmal nystagmus: 1) cerebral form of hypertension, cerebral atherosclerosis, cervical osteochondrosis with artery syndrome, vegetative-vascular dystonia with pronounced phenomena of fundus spasm (A1); 2) cardinal and cardiocerebral forms of hypertension, atherosclerosis with a predominant lesion of the carotid arteries, vegetative-vascular dystonia without pronounced signs of impaired tone of the brain vessels (A2). It is obvious that the presence of a purulent focus, especially destructive processes in the temporal bone, is a greater danger of damage to the inner ear and its conducting pathways and centers than scarring changes in the tympanic cavity (adhesive otitis, tympanosclerosis). Therefore, it is also advisable to distinguish the following gradations or degrees of intensity of the influence of factor (B) (features of the pathological process in the middle ear) on the frequency of nystagmus laying:1) purulent chronic epithympanitis (B1); 2) chronic mesotimpanitis (B2); 3) cicatricial changes in the tympanic cavity (tympanosclerosis, adhesive otitis), scars of the eardrums (B3). The data is presented in table 2.Data on the influence of factors A and B on the detection rate in 63 individuals with various forms of vascular pathology combined with diseases of the middle ear are shown in table 2, which is the basis of a two-factor uneven dispersion complex for qualitative characteristics.The influence of factor A and the total influence of organized factors (A+AB+ AB) are statistically significant (P<0.01). The influence of factor B (features of the pathological process in the middle ear) in 63 patients suffering from vascular diseases in combination with lesions of the middle ear was statistically insignificant, which may depend on a relatively small number of observations.The data obtained by us indicate that changes in the vascular system were the main leading factor in the origin of PPN in patients of this group.Based on the above, the following conclusions are obtained:1. in the origin of PPN, vascular disorders are predominant in comparison with the influence of foci of infection, including those located in the temporal bone.2. in patients suffering from positional labyrinth syndrome and PD, it is advisable to prescribe means that regulate vascular tone and blood supply to the inner ear.

Objective: This meta-analysis aimed to systematically estimate the prevalence of comorbid bronchiectasis in patients with asthma and to summarize its clinical impact. Data sources: Embase, PubMed, and Cochrane Library electronic databases were searched to identify relevant studies published from inception until March 2020. Study Selection: Studies were included if bronchiectasis was identified by high-resolution computed tomography. Outcomes included prevalence of bronchiectasis and its association with demographic characteristics and indicators of asthma severity, including results of lung function tests and number of exacerbations. Results: Five observational studies with 839 patients were included. Overall, the mean prevalence of bronchiectasis in patients with asthma was 36.6% (307/839). Patients with comorbid bronchiectasis had lower forced expiratory volume (FEV1)/forced vital capacity (FVC) (MD: -2.71; 95% CI: -3.72 to -1.69) and more frequent exacerbations (MD: 0.68; 95% CI: 0.03 to 1.33) than those with asthma alone, there was no significant difference of sex, duration of asthma and serum levels of immunoglobulin(Ig)Es between asthmatic patients with or without bronchiectasis. Conclusion: The presence of bronchiectasis in patients with asthma was associated with greater asthma severity. There are important therapeutic implications of identifying bronchiectasis in asthmatic patients.

Rationale, aims and objectives: The diversity of safety signals (e.g., case reports, animal studies and observational studies) makes the assessment of the (un-)safety of a drug a formidable challenge. While frequentist viewpoints to uncertain inference struggle in aggregating these signals, the more flexible Bayesian approaches seem better suited for this quest. Artificial Intelligence (AI) offers great promise to these approaches for information retrieval, decision support and leaning probabilities from data. E-Synthesis is a Bayesian framework for drug safety assessments build on philosophical principles and considerations. It aims to aggregate all the available information, in order to provide a Bayesian probability of a drug causing an adverse reaction. We delineate and assess ways in which AI can support E-Synthesis. Results: We find that AI can help with information retrieval, usability (graphical decision making aids), learning Bayes factors from historical data, assessing quality of information and determining conditional probabilities for the so-called “indicators” of causation for E-Synthesis. Conclusions: Properly applied, AI can help the transition of philosophical principles and considerations concerning evidence aggregation for drug safety to a tool that can be used in practise.

INTRODUCTION Otolaryngology is one of the branch where endoscopes is being widely used nowadays to perform different surgeries. Ear surgeries are of special interest among the ENT surgeons. It has several advantages compared to the microscopes. METHODS 60 patients underwent endoscopic transcanal myringoplasty by the postgraduate residents under direct supervision of same consultants, using temporalis facia graft. RESULTS The overall success rate in terms of graft uptake was 86.67 % and the AB gap closure 0f <10 DB in 63.3% of cases and 10-20 DB in 33.3%. CONCLUSION Endoscopic myringoplasty was found to be equally effective, less morbid and very cost effective than the microscopic myringoplasty. This was applicable irrespective of the size of the perforation and condition of the middle ear(Dry/Wet) in our centre

Viral vectors have a great potential for gene delivery, but manufacturing at pharmaceutical scale is a big challenge for the industry. The baculovirus-insect cells system is one of the most scalable platforms to produce clinical grade recombinant Adeno-Associated Virus (rAAV) vectors, however, the standard procedure to generate recombinant baculovirus based on Tn7 transposition is time consuming and still suffers technical constraints. Indeed, we recently shown that baculoviral sequences adjacent to the AAV ITRs are preferentially encapsidated into the rAAV vector particles. This observation raised concern about safety for clinical applications due to the presence of bacterial and antibiotic resistance coding sequences with Tn7-mediated system for the construction of recombinant baculoviruses. Here, we investigated a faster and safer method to generate baculovirus reagents based on homologous recombination (HR) for its use in rAAV manufacturing compared to the Tn7-based system. First, we confirmed the functionality of inserted cassette and the absence of undesirable genes into HR-derived baculoviral genomes. Strikingly, we found that the exogenous cassette shown an increased stability over passages when using HR system. Finally, we tested these materials to produce rAAV vectors. The baculoviruses originated from either system lead to high rAAV vector genome yields, with the advantage for the HR method being that the rAAV lots are exempted of undesirable gentamycin and kanamycin genes derived sequences which provides an additional level of safety for the manufacturing of rAAV vectors. Overall, this study highlights the importance of the upstream process and starting biologic materials to generate safer rAAV biotherapeutic products.

BACKGROUND AND PURPOSE: Pharmacological treatments are unavailable to patients with cocaine use disorders. Efforts to develop pharmacotherapies have led to the study of cannabidiol, a constituent of the C. sativa plant. However, the specific effects and mechanisms of action of cannabidiol in a rodent model of extinction-based abstinence and drug seeking relapse remain unclear. EXPERIMENTAL APPROACH: In this study, cannabidiol was provided during extinction training to male CD-1 mice trained to self-administer cocaine. We evaluated the reinstatement of cocaine seeking induced by cues, stress, and drug priming. To ascertain the participation of CB1 receptors in these behavioural changes, we administered the neutral CB1 antagonist AM4113 before each reinstatement session. KEY RESULTS The results document that cannabidiol did not modulate extinction learning. After cannabidiol treatment, increased levels of CB1 receptor protein were found in the prelimbic and orbitofrontal parts of the prefrontal cortex, as well as in the ventral striatum; an effect paralleled by a reduction of ∆FosB accumulation and increased GluR2 AMPA receptor subunits. Furthermore, cue-induced reinstatement of cocaine seeking was prevented in cannabidiol-treated mice. Unexpectedly, cannabidiol facilitated stress-induced reinstatement of cocaine-maintained responding. Cocaine-primed reinstatement remained unaltered by cannabidiol. Both, the blockade of cue-induced reinstatement and the facilitation of stress-induced reinstatement were abolished by AM4113 in cannabidiol-treated mice. CONCLUSION AND IMPLICATIONS: Our results reveal a series of complex CB1-related changes induced by cannabidiol with opposite implications for the reinstatement of cocaine seeking behaviour that may limit therapeutic opportunities.

Background and Purpose: Repetitive epileptic seizures trigger massive neuronal death. Therefore, neuroprotection plays a role in preventing neuronal death and inversely suppresses seizure generation. Additionally, some studies have shown ferroptosis, featured by lipid peroxidation (a dominant form of oxidative stress in the brain), is of paramount importance in epileptic seizures. Lapatinib can play a first-line anti-tumor role by targeting oxidative stress and a recent work illustrates the improvement of encephalomyelitis in rodent models after lapatinib treatment. We hypothesize whether lapatinib can protect against ferroptosis in epileptic seizures via regulating lipid peroxidation. Experimental Approach: The epileptic behavior of the mice was recorded after intracranial injection of KA. Western blot and RT-qPCR were used to detect the protein expression of 4-hydroxynonenal (4-HNE) and glutathione peroxidase 4 (GPX4) and the mRNA expression of prostaglandin endoperoxide synthase 2 (PTGS2) in vivo and in vitro. The level of lipid reactive oxygen species (lipid ROS) in cells pretreated with lapatinib was analyzed by flow cytometry. Key Results: Lapatinib remarkably prevented KA-induced epileptic seizures in mice and ferroptosis was involved in the neuroprotection of lapatinib. Compared with the model group, western blot showed that lapatinib significantly upregulated the levels of GPX4. In the ferroptotic cell death model, lapatinib exerted neuroprotection via up-regulating GPX4. Treatment with Ras-selective lethal small molecule 3 (RSL3), a selective GPX4 inhibitor abrogated its anti-ferroptotic potential. Conclusions and Implications: These results illustrated that lapatinib has neuroprotective potential against KA-triggered epileptic seizures via suppressing GPX4-dependent ferroptosis.

Haemorrhagic cystitis is a life-threatening condition in which the transitional epithelium and blood vessels of the bladder necrose leading to severe haematuria, abdominal pain and voiding lower urinary tract symptoms. Aetiology includes chemotherapy (cyclophosphamide, ifosfamide, busulfan), radiotherapy or infectious agents. We present a paediatric case of a 15-year-old boy with medulloblastoma who developed haemorrhagic cystitis following cisplatin chemotherapy. All other causes were ruled out and it is therefore likely that the agent in this case was cisplatin, which has never had haemorrhagic cystitis reported as a side effect. We also suggest a mechanism for urothelial injury centred around OCT-2 receptors.

Objective: As an aerosol generating procedure (AGP), mastoidectomy in the COVID-19 era requires healthcare workers to wear personal protective equipment (PPE); UK guidelines recommend an FFP-3 mask and full-face visor. The aim of this study was to examine the effect of wearing PPE on the view achieved using the operating microscope. Methods: Using the operating microscope, ENT surgeons were asked to view a target so that it filled the entire operating field. The distance between the surgeon’s eye and the microscope was recorded and subsequently measured with the surgeon wearing a range of PPE. In each PPE condition, surgeons scored the visibility of the target; scores were used to calculate the visible area of the surgical field. Results: Eleven surgeons took part, generating 51 eye-microscope and target-view scores. Distance from the eye to the microscope inversely correlated with diameter and area visible (Pearson correlation coefficient -0.983 and -0.894 respectively; p<0.001). Use of PPE increased the eye-microscope distance and reduced the surgical view. The median area visible wearing the FFP-3 mask and full-face visor was 4% (range 4 – 16%). Conclusion: PPE consisting of an FFP-3 mask and full-face visor is incompatible with use of the operating microscope, with less than 10% of the surgical field visible in most cases. Solutions that allow for concurrent use of the operating microscope and drill during mastoid surgery are urgently required so that surgeons are adequately protected from COVID-19 transmission.

Treating twenty-five cases of chronic resistant otitis externa with fluticasone propionate (Flixonase®): a case series Utilising Flixonase® in treatment of chronic otitis externaKey points:Chronic cases of otitis externa, resistant to conventional treatments are notoriously difficult to treat, with resolution in these cases challenging.Guidelines suggest the use of corticosteroid in chronic otitis externa, however, there is no specific advice on which corticosteroid to utilise.Our case-series demonstrates the potential benefit of fluticasone propionate in patients who have previously failed a multitude of conventional management options.Despite the limitations of our study, our experience highlights a gap in the literature and suggest fluticasone propionate as an exciting and potentially important tool in the arsenal of the otolaryngologist.

How Can Internet Technologies Help Hospital to Curb COVID-19: PUMCH Experience from ChinaQianyu Zhuang1,2, Guoqiang Sun1, Feng Zhang1, Jianguo Zhang2, Liluan You1, Si Chen1, Ke Zeng1, Xiaoyang Meng1, Wen Li1, Yue Peng2, Peng Peng1,3, Weiguo Zhu1,4*, Mingwei Qin5, Mingyan Chen6, Bingshui Hu7, Hui Pan8Department of information managementDepartment of OrthopedicsDepartment of Obstetrics and GynaecologyDepartment of Primary Care and Family MedicineTelemedicine centerPublicity DepartmentOutpatient departmentMedical administration department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P.R. China

Background: In pulmonary hypertension (PH), the development of dilatation and the right ventricular failure are signs of accelerated progression of the disease, resulting in an increased risk of cardiac death and right ventricular failure. Even the non-invasive assessment of the systolic blood pressure in the pulmonary artery by echocardiography does not provide a measure of ventricle-pulmonary interaction. Some studies showed that the potential use of echocardiography to evaluate indirectly the pulmonary vascular resistance (PVR) and the acceleration time of pulmonary outflow (ACTPO) could be a good, correlated, indirect measure. Methods: We decided to use a parameter that contained information related to pulmonary artery pressure (sPAP) and pulmonary vascular resistance. We called it PAPs/ACTPO ratio [strength/surface unit]/[time]. We aimed to study this parameter in apparently healthy subjects to code the normal range. From January 2017 to December 2018, 60 normal volunteer subjects and 63 patients with systemic scleroderma (Ssc)(60F,3M), 27 with PH and 36 without PH at two-dimensional echocardiographic/Doppler evaluation. Results: In normal subjects, we found a mean sPAP/ACTPO ratio of 0.26 indicative of an optimal pulmonary arterial ventricle coupling and biventricular function. The data derived from the analysis of the patients with Ssc showed that those presenting pre-capillary PH at cardiac catheterization had a sPAP/ACTPO ratio of 0.40 ± 0.05. There was a significant correlation between sPAP/ACTPO with Walk Distance (WD) and PVR but not with TAPSE. Interobserver variability was lower than 5%.

Objective Carbon dioxide (CO2) is used by many endoscopic vein harvesting systems to facilitate visualisation and dissection by creating a subcutaneous tunnel. We aim to investigate the potential detrimental effect of CO2 insufflation, on endothelial structural and functional viability of human saphenous vein (HSV). Method We performed an ex vivo experiment on HSV segments (n = 40) by applying CO2 for 40 minutes at 6 – 12 mmhg in a specially designed chamber and compared it with controls (n = 40). We have investigated the level of endothelial damage by Calcein/Propidium iodide (PI) Live/Dead assay. Functional viability of HSV was assessed by Ca2+ (FLUO3 AM) and nitric oxide (DAF-FM) specific indicators for calcium mobilisation and endothelial nitric oxide synthase related nitric oxide (NO) production. Results CO2 did not cause any immediate structural endothelial damage and there was no statistical difference between control and CO2 groups (Calcein p = 0.27 and PI p = 0.98). After CO2 exposure and bradykinin stimulation, Ca2+ mobilisation was significantly attenuated (p = 0.013) and NO generation was also markedly reduced in endothelial cells, without reaching statistical significance (p = 0.078). Conclusion We believe these results are purely due to CO2 insufflation, which can compromise the entire length of vein graft. However, more research is required to establish, whether these findings are transient in nature or they have long term implications on graft survival and clinical outcome.

Title Value of oesophagoscopy and bronchoscopy in diagnosis of synchronous malignancies in patients with head and neck squamous cell carcinomas: a 10-year single center experience in Chinese population. Objectives Routine screening of patients with head and neck squamous cell carcinomas (HNSCCs) for synchronous malignancies using oesophagoscopy and bronchoscopy had been controversial. The aim of this study is therefore to find out the rate of synchronous malignancies in patients with primary HNSCCs, the risk factors for its occurrence and the effectiveness of oesophagoscopy and bronchoscopy in a single center with Chinese population. Method A retrospective review of medical records was conducted from July 2008 to June 2018 in a tertiary referral center in Hong Kong. All patients with newly diagnosed HNSCCs were screened with oesophagoscopy and bronchoscopy at the time of diagnosis and therefore all patients were included in the study. The incidence of synchronous malignancies along the aerodigestive tract and the yield of oesophagoscopy and bronchoscopy were studied. Result Of the 702 patients included in the study, the overall rate of synchronous malignancies was 8.3% (58/702), with the rate of synchronous esophageal and lung malignancies being 5.8% (41/702) and 0.85% (6/702) respectively. 14 out of the 41 esophageal malignancies were only detectable with esophagoscopy. Only one of the synchronous lung malignancies was detectable by bronchoscopy. Risk factors for synchronous malignancies include male gender, smokers, drinkers and primary hypopharyngeal cancer. Conclusion Oesophagoscopy is essential for detecting synchronous esophageal malignancies in patients with HNSCC especially in male patients, smokers, drinkers and primary hypopharyngeal cancer patients. Bronchoscopy had a low yield for synchronous lung malignancies and can be potentially replaced by imaging techniques.

Objective: To investigate the correlation of prepregnancy dietary inflammatory index (DII) with obstetric outcomes in women with endometriosis. Design: Prospective cohort study Setting: Japan Population: We identified 88,398 Japanese women (n=85,149 without endometriosis and n=3,249 with endometriosis) who were recruited in the Japan Environment and Children’s study (JECS) between January 2011 and March 2014. Methods: Participants were categorised according to DII quintiles (Q1 and Q5 were the most pro-inflammatory and most anti-inflammatory groups, respectively) and stratified according to the presence or absence of endometriosis. Women with endometriosis were further categorised based on conceptions after assisted reproductive technology. Main outcomes were preterm birth (PTB) and low birth weight (LBW) infant. A multiple logistic regression model was used to estimate the effect of anti-inflammatory diet on PTB before 37 or 34 weeks and LBW <2500 g or 1500 g. Results: In women with endometriosis without ART, Q5 significantly decreased the risk of PTB before <34 weeks (aOR 0.25, 95% CI 0.07–0.83) and LBW <1500 g (aOR 0.07, 95% CI 0.01–0.60). Conclusions: This study suggested a distinctive effect of anti-inflammatory diet on more severe obstetrics outcomes, specifically PTB before 34 weeks and LBW <1500 g, among women with endometriosis. Moreover, preconception lifestyle may improve perinatal mortality and morbidity among women with endometriosis. Funding: None

Aim: CQ and HCQ are currently being investigated worldwide for their clinical efficacy against COVID-19, however a major concern regarding these drugs remains their safety profile. The aim of the present study was to identify potential safety signals of CQ and HCQ use, in the period prior to their repurpose as COVID-19 treatment options analyzing safety data retrieved from the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database. Methods: We performed a disproportionality analysis of all available FAERS data between the first quarter of 2004 and December 2019 using the OpenVigil2.1-MedDRA software. Disproportionality was quantified using the reporting odds ratio (ROR) and its 95% confidence interval (CIs). The reporting mortality of CQ and HCQ was also investigated Results: The dataset contained 6,635,356 reports. Based on the comparison of the RORs, significant differences were observed between CQ and HCQ for most of the adverse events: cardiomyopathy, cardiac arrhythmias, retinal disorders, corneal disorders, hearing disorders, headache, hepatic disorders, severe cutaneous reactions, musculoskeletal disorders and cytopenia. Only CQ was significantly associated with psychotic disorders, suicide and self-injury, convulsions, peripheral neuropathy and decreased appetite. In multivariable logistic regression, outcome death was more frequently associated with CQ users, generally older females, with co-reported suicide and self-injury, cardiomyopathy, cardiac arrhythmias and decreased appetite. Discussion: Our results suggest that HCQ has a safer clinical profile compared to CQ, especially regarding cardiotoxicity and thus could serve as a safer therapeutic approach in COVID-19. However, until more real-world and RCTs’ data are available, close supervision is strongly recommended.

We describe the case of a 59-year old female affected by aortic extensive endocarditis with communication between aortic annulus and right cavities, treated with double pericardial patch reconstruction and rapid-deployment aortic valve prosthesis implantation.

Pleuropulmonary blastoma (PPB) is the most common primary lung tumor of childhood and is associated with somatic or germline DICER1 variants. Recurrent PPB, especially with brain metastases, are difficult to treat and survival is poor. Comprehensive genomic analyses of PPB have been limited in number and depth. The cases presented here identified additional oncogenic drivers from tumor sequencing that could be modulating tumor progression and response to therapy outside of known DICER1 mutations highlighting the need for upfront genomic analysis on all patients with PPB.

Background and objectives: Children with Hodgkin lymphoma (HL) and Human Immunodeficiency Virus (HIV) have low 5 year overall survival rates in South Africa, home to the world’s largest HIV population. We aimed to explore factors impacting on survival in children with HIV and HL by comparing those with and without HIV, and to determine long term survival. Methods: A retrospective study was conducted to determine survival rates and prognostic factors in South African children and adolescents with HL. Univariate risk factor analysis was performed to analyse prognostic factors. Results: Between January 2000 and December 2010, 271 children and adolescents with HL were eligible for analysis. Compared to the 242 HIV-uninfected patients, the 29 HIV-infected patients were younger (median 7.2 vs 10.0 years, p=0.052) and more likely to present with Stage IV disease (p=0.000) The 5-year overall survival rate (OS) of HIV-infected patients of 49% versus 84% for HIV-uninfected patients (p=0.001) appeared to be associated with hypoalbuminaemia (<20g/dL) and a CD4 percentage of <15%. Causes of death in the HIV-infected group included disease progression (6/14), infection (4/14), unknown (3/14) and second malignancy (1/14). The 10-year OS was 45% in the HIV-infected cohort and 79% in the HIV-uninfected cohort (p=0.000). Conclusion: HIV-infected children with HL experience increased mortality due to opportunistic and nosocomial infections. Particular attention should be paid to children and adolescents with hypoalbuminaemia and low CD4 percentages at diagnosis to lower treatment-related mortality. Aggressive supportive care of children with HIV and HL may improve survival.

The FastDesign protocol in the molecular modeling program Rosetta iterates between sequence optimization and structure refinement to stabilize de novo designed protein structures and complexes. FastDesign has been used previously to design novel protein folds and assemblies with important applications in research and medicine. To promote sampling of alternative conformations and sequences, FastDesign includes stages where the energy landscape is smoothened by reducing repulsive forces. Here, we discover that this process disfavors larger amino acids in the protein core because the protein compresses in the early stages of refinement. By testing alternative ramping strategies for the repulsive weight, we arrive at a scheme that produces lower energy designs with more native-like sequence composition in the protein core. We further validate the protocol by designing and experimentally characterizing over 4000 proteins and show that the new protocol produces higher stability proteins.

4 cases have been reported from a tertiary referral hospital in Tehran, of which 3 have confirmed COVID-19 infection and one has been highly suspicious. The cases describe different cardiovascular presentations that can be linked to COVID-19 infection, including myocardial infarction, in-stent restenosis, myopericarditis and tamponade, and aortic dissection.