In patients with moderate-to-severe COVID-19 pneumonia, an aberrant post-viral alveolitis with excessive inflammatory responses and immunothrombosis underpins use of immunomodulatory therapy (eg, corticosteroids and interleukin-6 receptor antagonism). By contrast, immunosuppression in individuals with mild COVID-19 who do not require oxygen therapy or in those with critical disease undergoing prolonged ventilation is of no proven benefit. Furthermore, a window of opportunity is thought to exist for timely immunosuppression in patients with moderateto-severe COVID-19 pneumonia shortly after clinical presentation. In this Viewpoint, we explore the shortcomings of a universal immunosuppression approach in patients with moderate-to-severe COVID-19 due to disease heterogeneity related to ongoing SARS-CoV-2 replication, which can manifest as RNAaemia in some patients treated with immunotherapy. By contrast, immunomodulatory therapy has overall benefits in patients with rapid SARS-CoV-2 clearance, via blunting of multifaceted, excessive innate immune responses in the lungs, potentially uncontrolled T-cell responses, possible autoimmune responses, and immunothrombosis. We highlight this therapeutic dichotomy to better understand the immunopathology of moderate-to-severe COVID-19, particularly the role of RNAaemia, and to refine therapy choices.

Recruitment and retention of doctors is a priority for the Irish healthcare service, with many leaving to work in regions with more favourable conditions. Aligning flexible training options with other jurisdictions may be an effective means of improving working conditions. We sought to assess possible improvements to the existing system and to review barriers to flexible training. We carried out a survey using ‘Survey Monkey’ and disseminated it to 1557 basic specialist (BST) and higher specialist trainee (HST) doctors of the Institute of Medicine, 3500 members of the Irish Medical Organisation (IMO), and across social media. There were 854 respondents; 303 (35.5%) BST, 352 (41.2%) HST, 125 (14.6%) non-training doctors, unknown, n = 74. The response rate was approximately 15–23%. Non-consultant doctors identified a preference for access to flexible training (n = 849, 99.4%), with 82.2 of doctors reporting that they would consider applying (n = 702). Most (92.4%) considered the current provision of 16 whole-time equivalent positions as inadequate (n = 789). Of doctors who would not apply for flexible training, themes identified included a perceived negative impact on their career, not meeting eligibility criteria, prolonged training, and salary implications. Suggestions for improving the system included expanding the number of places available, removing eligibility criteria, job sharing options, and the provision of regional training schemes. Access to flexible training should be a priority for the healthcare service, which may enhance recruitment and retention. A majority of our sample of non-consultant doctors identified a preference for access to flexible training options.

The first pillar of the End-TB Strategy is “early diagnosis and prompt treatment”. Nevertheless, long delays in starting tuberculosis (TB) treatment are reported. We aimed to describe the demographics and clinical features of TB in the west of Ireland and better understand the delays in treatment. We conducted a retrospective chart review of all patients diagnosed with active TB who attended the Galway University Hospital (GUH) TB clinic from 2014 to 2018. Eighty-five patients were diagnosed with TB and attended our clinic. Ten (12%) patients were receiving immunosuppressive therapy, 8 (9%) had drug resistance, and 41 (48%) had extra-pulmonary disease. Patients with extra-pulmonary disease had a longer length of stay before treatment (11 vs. 4 days; p = 0.006). Patients older than 55 had a longer length of stay before (16 vs. 5 days, p = 0.0001) and during (36 vs. 11 days, p = 0.004) treatment and were readmitted more frequently than younger patients. A total of 36% of patients were born outside Ireland. Non-Irish patients were younger (mean age 35 vs 48; p = 0.004) and more frequently had drug resistance (19% vs. 4%, p = 0.02). The median time from symptom onset to hospital presentation was 76 days (IQR 35–146 days) and the median time from first hospital presentation to TB treatment was 11 days (IQR 5–51 days). TB patients experienced long symptom durations in the community prior to presentation. Many TB patients experienced delays in diagnosis and treatment following presentation. Both pre-hospital and in-hospital delays need to be addressed in order to ‘End-TB’.

The COVID-19 pandemic is a public health emergency of unprecedented scale. The surge in clinical cases of patients with severe respiratory illness has overwhelmed the traditional capacity of healthcare systems worldwide. Continuous Positive Airway Pressure (CPAP) delivered through Non-Invasive Ventilation (NIV) has been shown to be useful in caring for patients with COVID-19. In particular patients with early stage milder acute hypoxemic respiratory failure can benefit from NIV CPAP therapy, though there is an acknowledged risk of COVID-19 aerosolization with traditional circuit use. Furthermore, given the surge in clinical care demand, there is an acute global shortage of ventilators, including NIV devices and therefore innovative methods are needed to increase NIV capacity and ameliorate infectious aerosolization. This paper outlines an emergency use modified dual NIV CPAP Circuit that uses a 3D printed splitter designed to work with traditional international NIV CPAP tubing standards and a 3D printed respiratory face mask knuckle to allow for distal expiratory breath exhalation through a viral filter rather than through an open to air proximal valve, which is the traditional NIV CPAP configuration. We expect that this work will increase global NIV CPAP capacity and ameliorate aerosolization of COVID-19 in patients undergoing therapy in an emergency scenario.

The necessity for palliative surgery in transposition of the great vessels is indicated and the basic haemodynamics of the condition are outlined. The clinical picture of infants with transposition is divided into three types, and a method of surgical treatment is suggested for the two most common types. Our technique of investigation and treatment is described and the reasons for our choice of therapy are discussed. The results of cases operated upon are presented.

The COVID19 pandemic is a public health emergency of unprecedented scale. The surge in clinical cases of patients with severe respiratory illness has overwhelmed the traditional capacity of healthcare systems worldwide. Continuous Positive Airway Pressure (CPAP) delivered through Non-Invasive Ventilation (NIV) has been shown to be useful in caring for patients with COVID19. In particular patients with early stage milder acute hypoxemic respiratory failure can benefit from NIV CPAP therapy, though there is an acknowledged risk of COVID19 aerosolization with traditional circuit use. Furthermore, given the surge in clinical care demand, there is an acute global shortage of ventilators, including NIV devices and therefore innovative methods are needed to increase NIV capacity and ameliorate infectious aerosolization. This work outlines an emergency use modified dual NIV CPAP Circuit that uses a 3D printed splitter designed to work with traditional international NIV CPAP tubing standards and a 3D printed respiratory face mask knuckle to allow for distal expiratory breath exhalation through a viral filter rather than through an open to air proximal valve, which is the traditional NIV CPAP configuration. We expect that this work will increase global NIV CPAP capacity and ameliorate aerosolization of COVID19 in patients undergoing therapy in an emergency scenario.

Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. Methods An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. Results The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. Conclusions The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.

Severe COVID-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). This is distinct from HLH associated with immunodeficiency states termed primary HLH -with radically different therapy strategies in both situations. COVID-19 infection with MAS typically occurs in subjects with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. We provide a model for the classification of MAS to stratify the MAS-like presentation in COVID-19 pneumonia and explore the complexities of discerning ARDS from MAS. We discuss the potential impact of timing of anti-cytokine therapy on viral clearance and the impact of such therapy on intra-pulmonary macrophage activation and emergent pulmonary vascular disease.

Chronic obstructive pulmonary disease (COPD) is increasing in prevalence and accounts for up to 10% of acute emergency medical hospital admissions and 2% of nonsurgical referrals to the intensive care unit (ICU). Acute admission with COPD is associated with as high as an 11% acute mortality and 43% 1-year m ortality, and a 50% readmission rate within 6 months. While it is difficult to predict the acute outcome of ICU admissions in COPD, late failure of ward-based care, comorbidities and severe disease may aid in establishing appropriate ceilings of care. Pharmacologic treatment remains corticosteroids, nebulized bronchodilators, and antibiotics. Oxygen should be titrated in a controlled manner in COPD to oxygen saturation of 88–90%. This has been shown to reduce mortality. Noninvasive ventilation has evolved into the most effective treatment for acute hypercapnic respiratory failure, with better outcome in mortality and length of stay compared with invasive ventilation. Clinicians must be aware of barotrauma and dynamic hyperinflation when using positive pressure ventilation in COPD. High-flow nasal oxygen is evolving as an effective therapy to assist extubation as well as treat acute respiratory failure in COPD. Further studies are required. End-of-life decisions can be assisted by early discussion in those with severe disease, especially with comorbid illness, and in those with prolonged intubation over 72 hours and failed extubation. Some studies have shown that patients with COPD describe same or improved quality of life after invasive ventilation in the ICU; so it can be difficult to predict impact and outcomes.

BACKGROUND:Mycobacterium goodii is a rapidly growing nontuberculous mycobacterium which has been associated with several infections including cellulitis, osteomyelitis, lymphadenitis, infected pacemakers and bursitis but it is a rare cause of respiratory infection.CASE PRESENTATION:In this case report we describe a 51-year-old woman who presented with a 6-week history of non-productive cough, pleuritic chest pain and weight loss. She had a history of gastric adenocarcinoma managed with a distal oesophagectomy and total gastrectomy and consequentially suffered severe post-operative gastric reflux. Initial cultures were negative but following a VATS lung biopsy Mycobacterium goodii was cultured and histology revealed an organising pneumonia. Treatment was with a prolonged course of steroids, amikacin and meropenem followed by oral ciprofloxacin and doxycycline. Ongoing gastric dysmotility and weight loss showed clinical improvement with a novel approach of a combination of prokinetics and somatostatin analogues controlling risk of repeat aspiration and improving symptom control.CONCLUSIONS:This is an unusual case of organising pneumonia related to Mycobacterium goodii infection and highlights the importance of mycobacterial culture in unusual and unresolving cases of organising pneumonia. The importance of controlling symptoms related to gastric dysmotility and aspiration is also addressed.

Diffuse parenchymal lung diseases comprise a heterogeneous group of disorders with varying clinical, physiologic, radiographic and pathologic presentations. Age of onset varies considerably. Interstitial lung abnormalities, and in particular, idiopathic pulmonary fibrosis (IPF), occur much more commonly in older persons. In recent years, advances have been made in understanding IPF pathogenesis and changes have occurred in relation to how IPF is managed.

A 57-year-old special Olympics athlete presented with subacute onset dyspnoea. Baseline investigations revealed troponin T rise and an abnormal ECG, which prompted coronary angiography. This was unremarkable, as was his transthoracic echocardiography (TTE). He re-presented 7 months later with progressive dyspnoea associated with significant weight loss, peripheral oedema and intermittent fevers. Examination revealed bilateral fine end-inspiratory crackles, peripheral oedema and fever. Investigations revealed elevated troponin T and raised inflammatory markers. ECG remained unchanged, whereas TTE revealed mild global impairment of left ventricular function. Chest radiography was suggestive of extensive interstitial lung disease, which was confirmed by high resolution CT. Presence of interstitial lung disease and myocarditis raised the suspicion of a systemic inflammatory condition. Subsequently, an autoimmune screen was positive for anti-Jo-1 antibody associated with antisynthetase syndrome. He was treated with high-dose steroids and rituximab with dramatic symptomatic improvement and immediate fall in troponin T level.

Background: This study aims to examine the predictive and prognostic implications of C-reactive protein (CRP) and clinically relevant baseline variables in determining treatment indication and disease progression in a large clinical cohort of patients with stable sarcoidosis. Methods: A retrospective observational study of 328 sarcoidosis patients attending a regional tertiary referral centre over a 26-year period was performed. Clinical, biochemical, radiological and physiological data were analysed according to a clinically relevant dichotomous cutpoint of CRP. Multiple models of logistic regression were used to determine independent predictors of outcome as defined by indication for treatment with corticosteroids, radiological deterioration and physiological progression. Results: 328/409 (80.2%) sarcoidosis patients had baseline serum CRP measured and were suitable for inclusion. Baseline CRP was elevated in 154 (47%). 178 (54.3%) were prescribed corticosteroid treatment during the disease course. Physiological deterioration was demonstrated in 48 (14.6%) patients and radiological progression in 59 (17.9%) patients. High baseline CRP was strongly associated with Lofgren's syndrome (p=< 0.001) and reduced FVC% predicted (p=0.012). High CRP was found to be a negative predictor of radiological progression (p=0.046). In a sub-analyses of patients without Lofgren's syndrome (n=223), patients with high baseline CRP were almost twice as likely to receive corticosteroid treatment, OR 1.89 (95% CI 1.04-3.55). Low baseline DLCO% independently predicted the need for corticosteroid treatment (p=< 0.001) and physiological decline (p=0.045). Conclusions: Elevated baseline CRP in sarcoidosis is associated with a good prognosis and is a negative predictive indicator of radiological progression. In patients without Lofgren's syndrome, high CRP and low DLCO% at presentation may identify a subset of patients more likely to develop physiological progression who may benefit from early systemic treatment.