Backgroud The long-term outcomes of this combined procedure remain elusive. This meta-analysis aimed to assess the long-term efficacy and safety of combined procedure. Methods PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from the establishment of databases to 1 January 2021. Studies on the long-term (defined as a mean follow-up of approximately 12 months or longer) efficacy and safety outcomes of combined ablation and LAAC were included for meta-analysis. Results A total of 16 studies comprising 1,428 patients were included in the meta-analysis. The pooled long term freedom rate from atrial arrhythmia was 0.66 (95% confidence interval [CI], 0.59-0.71), long-term successful rate sealing of LAAC was 1.00 (95% CI, 1.00-1.00), and ischemic stroke/transient ischemic attack/systemic embolism during follow-up was 0.01 (95% CI, 0.00-0.02). Meanwhile, the rates of peri-procedural adverse events included phrenic nerve palsy, intracoronary air embolus, device embolization, peri-procedural death of 0.00 (95% CI, 0.00-0.00), procedure-related bleeding events of 0.03 (95% CI, 0.02-0.04), and pericardial effusion requiring or not requiring intervention of 0.00 (95% CI, 0.00-0.01). Moreover, the rates of long-term adverse events rate included device dislocation, intracranial bleeding, and pericardial effusion requiring or not requiring intervention, and all-cause mortality of 0.00 (95% CI, 0.00-0.00), device embolization of 0.01 (95% CI, 0.00-0.01), and other bleeding events of 0.01 (95% CI, 0.00-0.03). Conclusion This meta-analysis suggests that the strategy of combined atrial ablation and LAAC is effective and safe during long-term follow-up

Objectives As we pass the anniversary of the declaration of a global pandemic by the World Health Organisation, it invites us to reflect upon the inescapable changes that coronavirus has wrought upon ENT and, in particular, rhinological practice. As it remains unclear when we will globally emerge from the shadow of COVID-19, a critical analysis of the evidence base on both the assessment and mitigation of risk is vital for ENT departments worldwide. This article presents a systematic review of the literature examining articles which consider either the quantification of risk or strategies to mitigate risk specifically in the setting of rhinological surgery. Design Systematic literature review. Results The literature search yielded a total of 3406 returns with 24 articles meeting eligibility criteria. A narrative synthesis stratified results into two broad themes: those which made an assessment as to the aerosolisation of droplets during sinus surgery, further subdivided into work which considered macroscopically visible droplets and that which considered smaller particles, and those studies which examined the mitigation of this risk. Conclusion Studies considering the aerosolisation of both droplets and smaller particles suggest endonasal surgery carries significant risk. Whilst results both highlight a range of innovative adjunctive strategies and support suction as an important variable to reduce aerosolisation, appropriate use of personal protective equipment (PPE) should be considered mandatory for all healthcare professionals involved in rhinological surgery given studies have demonstrated that close adherence to PPE use is effective at preventing COVID-19 infection.

Adoptive cell immunotherapy with chimeric antigen receptor (CAR) T cell has brought a revolutionary means of treatment for aggressive diseases such as hematologic malignancies and solid tumors. Over the last decade, FDA approved three types of CAR-T cells against CD19 hematologic malignancies, including Tisagenlecleucel (Kymriah), Axicabtagene ciloleucel (Yescarta), and Brexucabtagene autoleucel (Tecartus). Despite outstanding results gained from different clinical trials, CAR-T cell therapy is not free from side effects and toxicities, and needs careful investigations and improvements. Gene-editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9) system has emerged as a promising tool to address some of the CAR-T therapy hurdles. Using CRISPR/Cas9 technology, CAR expression as well as other cellular pathways can be modified in various ways to enhance CAR-T cell’s anti-tumor function and persistence in immunosuppressive tumor microenvironment. CRISPR/Cas9 technology can also be utilized to reduce CAR-T cells toxicity and side effects. Hereby, we discuss the practical challenges and hurdles related to the accuracy, efficiency, efficacy, safety and delivery of CRISPR/Cas9 technology to the genetically engineered-T cells. Combining of these two state-of-the-art technologies, CRISPR/Cas9 and CAR-T cells, the field of oncology has an extraordinary opportunity to enter a new era of immunotherapy, which offers novel therapeutic options for different types of tumors.

Objective: To investigate the symptomatic relief and functional preservation of a novel surgical strategy combined with triple semicircular canal occlusion and endolymphatic sac decompression in patients with intractable Meniere’s disease. Design: Retrospective analysis. Setting: Patients with intractable Meniere’s disease in the Department of Otolaryngology Head & Neck in the Second Affiliated Hospital of Nanchang University between July 2015 and June 2019. Participants: Data from 46 patients diagnosed with Meniere’s disease, and underwent surgery Methods: Triple semicircular canal occlusion combined with endolymphatic sac decompression was performed in all patients with intractable Meniere’s disease. Pre- and postoperative vertigo attacks, hearing levels, tinnitus, aural fullness, and equilibrium function rehabilitation were analyzed at defined time points during follow-up. Results: A significant vertigo control rate was observed in all patients postoperatively. The overall control rate of vertigo postoperatively was 100% in the entire follow-up, with a complete control rate of 97.8% and a substantial control rate of 2.2%. The rate of hearing preservation was 54.35%, and all patients suffering from hearing deterioration were at stages III and IV. The rate of tinnitus and aural fullness alleviation was 65.8% and 100%, respectively. Four patients failed to regain the equilibrium function postoperatively. Conclusion: Combining triple semicircular canal occlusion with endolymphatic sac decompression is an efficient strategy for vertigo control in patients with intractable Meniere’s disease. Patients in advanced stages suffered more from hearing function deterioration. Hearing preservation and tinnitus alleviation warrant further investigation.

Background: Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA), a subset of ANCA, are associated with a multisystem vasculitis affecting small blood vessels in the body. A handful of adult patients who developed vasculitis post-COVID-19 infection have been reported. Although COVID-19 infection has been shown to drive an exaggerated immune response in the pediatric population, such as MIS-C (multisystem inflammatory syndrome in children), only one case of vasculitis following COVID-19 infection has been reported previously in children. Case presentation: Seventeen-year-old male with a past medical history of COVID-19 pneumonia two months prior presented with acute kidney injury/failure and diffuse alveolar hemorrhage (DAH). Rheumatologic workup revealed P-ANCA and Myeloperoxidase (MPO) positivity. Kidney biopsy showed necrotizing glomerulonephritis with limited immune complex deposition. Subsequently, he was treated with pulse steroids, plasmapheresis, and ultimately started on cyclophosphamide. Conclusions: To our knowledge, this report presents the second reported pediatric case of P-ANCA / MPO vasculitis following COVID-19 infection.

RT-PCR is currently the standard diagnostic method to detect symptomatic and asymptomatic individuals infected with SARS-CoV-2. However, RT-PCR results are not immediate and may falsely be negative before an infected individual sheds viral particle in the upper airway where swabs are collected. Infected individuals emit volatile organic compounds (VOCs) in their breath and sweat that are detectable by trained dogs. Here we evaluate the diagnostic accuracy of dog detection against SARS-CoV-2 infection. Fifteen dogs previously trained at two centres in Australia were presented to axillary sweat specimens collected from known SARS-CoV-2 human cases and non-cases. The true infection status of the cases and non-cases were confirmed based on RT-PCR results as well as clinical presentation. Across dogs, the overall diagnostic sensitivity (DSe) was 95.6% (95%CI: 93.6%-97.6%) and diagnostic specificity (DSp) was 98.1% (95%CI: 96.3%-100.0%). The DSp decreased significantly with non-case specimens sourced from UAE ( P-value < 0.001). The location of evaluation did not impact the detection performances. The accuracy of detection varied across dogs and experienced dogs revealed a marginally better DSp ( P-value = 0.003). The potential and limitations of this alternative detection tool are discussed.

Developing media to sustain cell growth and production is an essential and ongoing activity in bioprocess development. Modifications to media can often address host or product-specific challenges, such as low productivity or poor product quality. For other applications, systematic design of new media can facilitate the adoption of new industrially relevant alternative hosts. Despite manifold existing methods, common approaches for optimization often remain time and labor intensive. We present here a novel approach to conventional media blending that leverages stable, simple, concentrated stock solutions to enable rapid improvement of measurable phenotypes of interest. We applied this modular methodology to generate high-performing media for two phenotypes of interest: biomass accumulation and heterologous protein production, using high-throughput, milliliter-scale batch fermentations of Pichia pastoris as a model system. In addition to these examples, we also created a flexible open-source package for modular blending automation on a low-cost liquid handling system to facilitate wide use of this method. Our modular blending method enables rapid, flexible media development, requiring minimal labor investment and prior knowledge of the host organism, and should enable developing improved media for other hosts and phenotypes of interest.

Patients after liver transplantation have an increased risk to develop haematologic neoplasias. Information how to treat these patients in the context of immunosuppression is sparse. Here, we report two patients with polycythemia vera (PV) and myelofibrosis (MF) on ruxolitinib after liver transplantation.

Objective: To characterize viscoelastic testing profiles of children with multisystem inflammatory syndrome in children (MIS-C). Methods: This single-center retrospective review included 30 patients diagnosed with MIS-C from January 1 to September 1, 2020. Thromboelastography (TEG) with platelet mapping was performed in 19 (63%) patients and compared to age- and gender- matched controls via Student’s t-test and Wilcoxon rank sum test. Pearson’s and Spearman correlation were used to assess relationships between TEG parameters and inflammatory markers. Results: Patients with MIS-C had abnormal TEG results compared to controls, including decreased K time (1.1 vs. 1.7 min, P<0.01), increased alpha angle (75.0 vs. 65.7 degrees, P<0.01), increased maximum amplitude (70.8 vs. 58.3 mm, P<0.01), and decreased Ly-30 (1.1 vs. 3.7%, P=0.03); consistent with increased clot formation rate and strength, and slower fibrinolysis. TEG maximum amplitude was moderately correlated with erythrocyte sedimentation rate (r=0.60, P=0.02), initial platelet count (r=0.67, P<0.01), and peak platelet count (r=0.51, P=0.03). TEG alpha angle was moderately correlated with peak platelet count (r=0.54, P=0.02). 17 (57%) patients received aspirin (ASA) and anticoagulation, 5 (17%) received only ASA, and 3 (10%) received only anticoagulation. No patients had a thrombotic event. 6 (20%) patients had a bleeding event, none of which was major. Conclusions: Patients with MIS-C had evidence of hypercoagulability on TEG. Increased erythrocyte sedimentation rate and platelets were associated with higher clot strength. Treatment with ASA or anticoagulation was well tolerated. Further multi-center study is required to characterize the rate of thrombosis and optimal thromboprophylaxis algorithm in this patient population.

Porcine epidemic diarrhea virus (PEDV) produces infection in pigs characterized by vomiting and diarrhea. PEDV is transmitted via oral-fecal and a very low oral dose is enough to infect susceptible pigs, causing devastating consequences in production. A 10,000-sow farrow-to-wean farm located in northwest Mexico was infected with PEDV. After the observation of the first clinical signs, an outbreak investigation take into place to determine the most probably source of infection. A systematic collection of samples including rectal swabs, gestation and lactation feed, surface swabs from the interior or feed bins and many points of the feed truck delivering the implicated feed was performed. Samples were tested for PEDV polymerase chain reaction (PCR). Positive PCR results showed the evidence of PEDV RNA in lactating feed, the interior walls of the feed bins and in the interior of the auger boom of the feed truck. This, connected with the location of first clinical signs point that the most probably incursion of PEDV in to this breeding herd was contaminated feed. This paper shows how feed or feed transport can be a potential source of PEDV infection in farms and highlight the importance of stablishing biosecurity programs to mitigate the risk of PEDV infections.

Ravitch technique of chest correction has been considered, although invasive, as safe and efficacious surgical method. We describe a case of 35-year-old woman with cardiac tamponade and in cardiogenic shock due to exceptional late complication after pectus excavatum reconstruction by means of classic Ravitch technique 19 years earlier. This very late adverse event was caused by broken metal sternal wire that injured the wall of the ascending aorta. Patient underwent salvage repair of this segment of aorta in cardiopulmonary bypass. Postoperative course and post-discharge 3-year follow-up have been uneventful.

This paper is concerned with the initial-boundary value problem for a nonlinear parabolic equation with a small parameter. The existence of a boundary layer as the parameter goes to zero is obtained together with the estimation on the thickness of the boundary layer. The main result extends an earlier work of Frid and Shelukhin (1999).

Disease activity and treatment-related toxicity are the most important contributors to poor prognosis in patients with ANCA-associated vasculitis (AAV). Sometimes, it is difficult to distinguish them. We present a case to highlight the challenges in the management of AAV and the complications with immunosuppression.

Background: In children and adolescents, isolated cholestasis rarely is a first clinical sign of severe sepsis. Case: A previously healthy 14-year-old adolescent had severe S. aureus sepsis. Delayed diagnosis required a prolonged antimicrobial treatment. Conclusion: This unique case illustrates the importance of considering jaundice as an early sign of sepsis.

Under-expanded stents in calcific coronary stenoses are a common challenge for interventional cardiologists as we undertake more complex coronary interventions for older population cohorts. It results in short-term and long-term stent failure and adverse patient outcomes. These complex lesions can be treated after many years with intravascular lithotripsy (IVL-Shockwave).

Background: Flaxseed may be beneficial for the management of obesity due to its high content of alpha-linolenic acid, fiber, and lignans. Objective: We aimed to evaluate the effects of Flaxseed consumption on serum lipids, adiponectin, leptin, and weight loss in overweight or obese women. Methods: This randomized controlled clinical trial involved 60 overweight or obese women. Participants were randomly allocated to two groups; a) a balanced diet plus 30 g/day milled Flaxseed and b) a balanced diet plus 30g/day milled rice (as control group), for 12 weeks. Anthropometric indices, serum lipids, leptin, and adiponectin levels were measured at baseline and at the end of intervention. Results: After 12 weeks of intervention, there were significantly higher reductions in waist circumference (WC) and waist to hip ratio (WHR) (both P<0.05) in the flaxseed group compared to the controls. Moreover, adiponectin level was significantly increased in the flaxseed group (17.15±6.1) compared to the controls (16.83±10.5), (P=0.001). However, there were no significant differences in serum lipid levels between the study groups before and after the intervention (all p>0.05). Conclusion: Flaxseed consumption may improve adiposity markers, as well as adiponectin levels Thus, flaxseed consumption could be an adjunctive therapy to attenuate central obesity. Serum lipid profile has not changed significantly after flaxseed consumption. Keywords: obesity, flaxseed, adiponectin, Leptin, blood lipids

Actinomycosis is a rare, indolent and invasive infection caused by Actinomyces species. Pulmonary actinomycosis is very rarely seen in the paediatric population. The classic radiological presentation of thoracic involvement of actinomycosis includes lower lobe consolidation, empyema and periostitis of the ribs. We report a case of endobronchial pulmonary actinomycosis in a child diagnosed on endobronchial biopsy and broncho-alveolar lavage taken during bronchoscopy. Bronchoscopy can be dangerous when performed on these cases, as there is a risk of severe bleeding and large airway obstruction, as was the case with this patient.

African swine fever (ASF), is a serious global concern from an ecological and economic point of view. While it is well established that its main transmission routes comprise contact between infected and susceptible animals and transmission through contaminated carcasses, the specific mechanism leading to its long-term persistence is still not clear. Among others, a proposed mechanism involves the potential role of convalescent individuals, which would be able to shed the virus after the end of the acute infection. Using a spatially explicit, stochastic, individual-based model, we tested: 1) if ASF can persist when transmission occurs only through infected wild boars and infected carcasses; 2) if the animals that survive ASF can play a relevant role in increasing ASF persistence chances; 3) how hunting pressure can affect the ASF probability to persist. The scenario in which only direct and carcass-mediated transmission were contemplated had 52% probability of virus persistence 10 years after the initial outbreak. The inclusion of survivor-mediated transmission corresponded to slightly higher persistence probabilities (57%). ASF prevalence during the endemic phase was generally low, ranging 0.1-0.2%. The proportion of seropositive individuals gradually decreased with time and ranged 4.5 – 6.6%. Our results indicate that direct and carcass-mediated infection routes are sufficient to explain and justify the long-term persistence of ASF at low wild boar density and the ongoing geographic expansion of the disease front in the European continent. During the initial years of an ASF outbreak, hunting should be carefully evaluated as a management tool, in terms of potential benefits and negative side-effects, and combined with an intensive effort for the detection and removal of wild boar carcasses. During the endemic phase, further increasing hunting effort should not be considered as an effective strategy. Additional effort should be dedicated to finding and removing as many wild boar carcasses as possible.