The triumvirate of NF-κB, inflammation and cytokine storm in COVID-19.

The coronavirus disease (COVID-19) has once again reminded us of the significance of host immune response and consequential havocs of the immune dysregulation. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) inflicts severe complications to the infected host, including cough, dyspnoea, fever, septic shock, acute respiratory distress syndrome (ARDs), and multiple organ failure. These manifestations are the consequence of the dysregulated immune system, which gives rise to excessive and unattended production of pro-inflammatory mediators. Elevated circulatory cytokine and chemokine levels are accompanied by spontaneous haemorrhage, thrombocytopenia and systemic inflammation, which are the cardinal features of life-threatening cytokine storm syndrome in advanced COVID-19 diseases. Coronavirus hijacked NF-kappa B (NF-κB) is responsible for upregulating the expressions of inflammatory cytokine, chemokine, alarmins and inducible enzymes, which paves the pathway for cytokine storm. Given the scenario, the systemic approach of simultaneous inhibition of NF-κB offers an attractive therapeutic intervention. Targeted therapies with proteasome inhibitor (VL-01, bortezomib, carfilzomib and ixazomib), bruton tyrosine kinase inhibitor (acalabrutinib), nucleotide analogue (remdesivir), TNF-α monoclonal antibodies (infliximab and adalimumab), N-acetylcysteine and corticosteroids (dexamethasone), focusing the NF-κB inhibition have demonstrated effectiveness in terms of the significant decrease in morbidity and mortality in severe COVID-19 patients. Hence, this review highlights the activation, signal transduction and cross-talk of NF-κB with regard to cytokine storm in COVID-19. Moreover, the development of therapeutic strategies based on NF-κB inhibition are also discussed herein.

Burnout in trauma and orthopaedic surgeons: can the UK military stress management model help?

The recent coronavirus disease (COVID-19) pandemic has increased doctors' stresses at work and at home, putting them at increased risk of burnout. Considering this, we recently conducted the British Orthopaedic Association (BOA) Burnout and Wellbeing Survey which showed that, from 1298 respondents (approximately 25% of the membership of the BOA), 40% reported burnout and a further 50% were just below the threshold. The burnout rates were found to be higher in Black, Asian and minority ethnic (BAME), female and LGBTQ+ groups (45.6%) compared to white, heterosexual males (33.6% - p < 0.001) and also higher in trainees (49.1%) and associate specialists (52.1%) compared to consultants (35.7% - p < 0.001). We discuss what can be learned from the experience of the UK Armed Forces in their programme for stress management, their mental resilience training and their campaign to destigmatize mental wellbeing, that may mitigate burnout in our profession. We also put forward the case for appropriate resources to be allocated to tackling burnout in orthopaedic doctors and introduce the BOA's Wellbeing Initiative.

A novel mathematical model for COVID-19 with remedial strategies.

Coronavirus (COVID-19) outbreak from Wuhan, Hubei province in China and spread out all over the World. In this work, a new mathematical model is proposed. The model consists the system of ODEs. The developed model describes the transmission pathways by employing non constant transmission rates with respect to the conditions of environment and epidemiology. There are many mathematical models purposed by many scientists. In this model, " α E " and " α I ", transmission coefficients of the exposed cases to susceptible and infectious cases to susceptible respectively, are included. " δ " as a governmental action and restriction against the spread of coronavirus is also introduced. The RK method of order four (RK4) is employed to solve the model equations. The results are presented for four countries i.e., Pakistan, Italy, Japan, and Spain etc. The parametric study is also performed to validate the proposed model.

Microbial contamination of powered air purifying respirators (PAPR) used by healthcare staff during the COVID-19 pandemic: an in situ microbiological study.

BACKGROUND: Powered air purifying respirators (PAPR) are an option for healthcare workers requiring respiratory protection during the current COVID-19 pandemic; they are shared between multiple people. PAPR hoods are intended for multiple uses by a single user and may pose an infection risk between wearers. METHODS: Internal components of PAPR hoods and corrugated air supply hoses were swabbed for evidence of bacterial, fungal, common respiratory viruses and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) contamination. RESULTS: Twenty-five PAPR hoods were swabbed; 10 (40%) returned positive results. Bacterial growth was detected on six PAPR; five of the PAPR tested positive for fungal growth; all tested negative for SARS-CoV-2 and common respiratory viruses. CONCLUSIONS: Bacteria and fungi can remain on internal components of PAPR hoods and air supply hoses despite following recommended disinfection procedures. PAPR hoods have the potential to act as fomites, cross-infecting wearers, and patients. Current guidelines for disinfecting PAPR hoods may not be effective for use in high risk healthcare environments.

Should nasogastric tube insertion during the COVID-19 pandemic be considered as an aerosol-generating procedure?

Nasogastric tubes are used frequently in surgical patients for bowel decompression, provision of enteral nutritional support and preventing aspiration of gastric contents. There is no conclusive research into the risk of COVID-19 transmission associated with nasogastric tube insertion, although evidence from the severe acute respiratory syndrome outbreak appears to suggest that there is no increased risk of transmission. However, close contact with a COVID-19 patient, especially those displaying respiratory symptoms, is likely to increase the risk of transmission. Nasogastric tube insertion requires increased time spent at a patient's bedside and can also cause pharyngeal irritation, resulting in coughing. In addition, the nasogastric tube can expose the healthcare worker to potentially infectious saliva. Therefore, there is a clear need for increased evidence regarding the risk of transmission associated with nasogastric tube insertion, to ensure that such risks can be mitigated.

Practical strategies to manage cancer patients during the COVID-19 pandemic: Saudi Oncology Pharmacy Assembly Experts recommendations.

PURPOSE: During COVID-19 pandemic, cancer patients are considered one of the most vulnerable to infection since they tend to have advanced age, multiple comorbidities, and are often immunosuppressed by their cancer or therapy. Hence, the Saudi Oncology Pharmacy Assembly has issued recommendations to reduce the frequency of cancer patients' visits to oncology centers during the pandemic while maintaining the access to cancer therapy and minimize the risk of exposure to coronavirus disease. MATERIALS AND METHODS: A qualitative methodological approach was conducted in April 2020 using a virtual panel discussion for collection of recommendations. RESULTS: A total of 12 expert oncology pharmacy practitioners shared their knowledge and experiences in managing oncology patients during the COVID-19 pandemic. The participants recognized many fundamental recommendations that were already applied in many cancer centers since the start of the COVID-19 outbreak. On that basis, the panelists developed eight practice-related recommendations for action, with a main focus on cancer treatment modification. CONCLUSIONS: In conclusion, delivering cancer care during the COVID-19 pandemic carries significant challenges. This paper addressed suggestions to properly manage cancer patients during difficult times. Implementing changes in practice mandates a national collaborative effort from different sectors to guarantee the quality and continuity of care. The SOPA expert panel developed these recommendations, to ultimately contribute in maintaining access to cancer therapy while minimizing the risk of COVID-19 exposure.