Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration: isrctn.org Identifier: ISRCTN16912075.

Use of the HoloLens2 Mixed Reality Headset for Protecting Health Care Workers During the COVID-19 Pandemic: Prospective, Observational Evaluation.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has led to rapid acceleration in the deployment of new digital technologies to improve both accessibility to and quality of care, and to protect staff. Mixed-reality (MR) technology is the latest iteration of telemedicine innovation; it is a logical next step in the move toward the provision of digitally supported clinical care and medical education. This technology has the potential to revolutionize care both during and after the COVID-19 pandemic. OBJECTIVE: This pilot project sought to deploy the HoloLens2 MR device to support the delivery of remote care in COVID-19 hospital environments. METHODS: A prospective, observational, nested cohort evaluation of the HoloLens2 was undertaken across three distinct clinical clusters in a teaching hospital in the United Kingdom. Data pertaining to staff exposure to high-risk COVID-19 environments and personal protective equipment (PPE) use by clinical staff (N=28) were collected, and assessments of acceptability and feasibility were conducted. RESULTS: The deployment of the HoloLens2 led to a 51.5% reduction in time exposed to harm for staff looking after COVID-19 patients (3.32 vs 1.63 hours/day/staff member; P=.002), and an 83.1% reduction in the amount of PPE used (178 vs 30 items/round/day; P=.02). This represents 222.98 hours of reduced staff exposure to COVID-19, and 3100 fewer PPE items used each week across the three clusters evaluated. The majority of staff using the device agreed it was easy to set up and comfortable to wear, improved the quality of care and decision making, and led to better teamwork and communication. In total, 89.3% (25/28) of users felt that their clinical team was safer when using the HoloLens2. CONCLUSIONS: New technologies have a role in minimizing exposure to nosocomial infection, optimizing the use of PPE, and enhancing aspects of care. Deploying such technologies at pace requires context-specific information security, infection control, user experience, and workflow integration to be addressed at the outset and led by clinical end-users. The deployment of new telemedicine technology must be supported with objective evidence for its safety and effectiveness to ensure maximum impact.

The tuberculous pleural effusion.

Pleural tuberculosis (TB) is a common entity with similar epidemiological characteristics to pulmonary TB. It represents a spectrum of disease that can variably self-resolve or progress to TB empyema with severe sequelae such as chronic fibrothorax or empyema necessitans. Coexistence of and progression to pulmonary TB is high. Diagnosis is challenging, as pleural TB is paucibacillary in most cases, but every effort should be made to obtain microbiological diagnosis, especially where drug resistance is suspected. Much attention has been focussed on adjunctive investigations to support diagnosis, but clinicians must be aware that apparent diagnostic accuracy is affected both by the underlying TB prevalence in the population, and by the diagnostic standard against which the specified investigation is being evaluated. Pharmacological treatment of pleural TB is similar to that of pulmonary TB, but penetration of the pleural space may be suboptimal in complicated effusions. Evidence for routine drainage is limited, but evacuation of the pleural space is indicated in complicated disease. Educational aims: To demonstrate that pleural TB incorporates a wide spectrum of disease, ranging from self-resolving lymphocytic effusions to severe TB empyema with serious sequelae.To emphasise the high coexistence of pulmonary TB with pleural TB, and the importance of obtaining sputum for culture (induced if necessary) in all cases.To explore the significant diagnostic challenges posed by pleural TB, and consequently the frequent lack of information about drug sensitivity prior to initiating treatment.To highlight the influence of underlying TB prevalence in the population on the diagnostic accuracy of adjunctive investigations for the diagnosis of pleural TB.To discuss concerns around penetration of anti-TB medications into the pleural space and how this can influence decisions around treatment duration in practice.

Autologous Blood Patch Pleurodesis for Secondary Spontaneous Pneumothorax: A Narrative Review, a Retrospective Case Series and State of Play in the UK.

INTRODUCTION: Treatment of prolonged air leak due to secondary spontaneous pneumothorax is challenging. Autologous blood patch pleurodesis (ABPP) is a treatment option. Previous evidence is reliant on single-centre series and underpowered trials and is mostly described in air leaks post cardiothoracic intervention. There are no United Kingdom (UK) wide data. METHODS: Members of the UK Pleural Society were surveyed for their practice and for patients who underwent blood patch. There were 16 respondents from 333 members. Twelve had performed the procedure, and six had kept records and could submit data. Basic demographics, intervention and clinical details of patients were then collected. The study was sponsored by the Audit Department of Northumbria Healthcare NHS Foundation Trust (reference 8124), and Caldicott Clearance for data sharing was provided by the Trust's Information Goverance Board (reference C4221). There was no requirement for informed consent. RESULTS: Data for 12 patients that received ABPP between 2014 and 2022 in six respiratory centres were assessed. The aetiology of the secondary pneumothoraces was mostly due to chronic obstructive pulmonary disease and end-stage interstitial lung disease. The patients had a median age of 75 years. The median air leak time before ABPP was 17 days. A total of 50-100 ml of blood was used for ABPP. Five patients had two attempts at ABPP. Air leak resolved in six patients (50%). Four patients had pleural apposition prior to ABPP. Four patients were diagnosed with hospital-acquired pneumonia following ABPP. CONCLUSION: This is the only UK-wide retrospective case series of ABPP of 'medical' patients with secondary pneumothorax. There is widespread variation in care. No formal conclusions can be drawn, and much larger robust datasets are required. An application has been made to the European Respiratory Society to incorporate ABPP within the International Collaborative Effusion database.

Sarcoidosis following COVID infection: A case series.

Here we describe three cases of sarcoidosis which were diagnosed following COVID infection. Treating clinicians should consider post-COVID-19 sarcoidosis in their differential, as it represents a potentially treatable cause of persistent symptomatology.

Chest CT features and functional correlates of COVID-19 at 3 months and 12 months follow-up.

Long-term pulmonary sequelae of Coronavirus 2019 (COVID-19) remain unclear. Thus, we aimed to establish post-COVID-19 temporal changes in chest computed tomography (CT) features of pulmonary fibrosis and to investigate associations with respiratory symptoms and physiological parameters at 3 and 12 months' follow-up. Adult patients who attended our initial COVID-19 follow-up service and developed chest CT features of interstitial lung disease, in addition to cases identified using British Society of Thoracic Imaging codes, were evaluated retrospectively. Clinical data were gathered on respiratory symptoms and physiological parameters at baseline, 3 months, and 12 months. Corresponding chest CT scans were reviewed by two thoracic radiologists. Associations between CT features and functional correlates were estimated using random effects logistic or linear regression adjusted for age, sex and body mass index. In total, 58 patients were assessed. No changes in reticular pattern, honeycombing, traction bronchiectasis/bronchiolectasis index or pulmonary distortion were observed. Subpleural curvilinear lines were associated with lower odds of breathlessness over time. Parenchymal bands were not associated with breathlessness or impaired lung function overall. Based on our results, we conclude that post-COVID-19 chest CT features of irreversible pulmonary fibrosis remain static over time; other features either resolve or remain unchanged. Subpleural curvilinear lines do not correlate with breathlessness. Parenchymal bands are not functionally significant. An awareness of the different potential functional implications of post-COVID-19 chest CT changes is important in the assessment of patients who present with multi-systemic sequelae of COVID-19 infection.

Recovering from COVID-19: lessons learnt from an intensive secondary care follow-up service.

In response to the first COVID-19 surge in 2020, secondary care outpatient services were rapidly reconfigured to provide specialist review for disease sequelae. At our institution, comprising hospitals across three sites in London, we initially implemented a COVID-19 follow-up pathway that was in line with expert opinion at the time but more intensive than initial clinical guidelines suggested. We retrospectively evaluated the resource requirements for this service, which supported 526 patients from April 2020 to October 2020. At the 6-week review, 193/403 (47.9%) patients reported persistent breathlessness, 46/336 (13.7%) desaturated on exercise testing, 167/403 (41.4%) were discharged from COVID-19-related secondary care services and 190/403 (47.1%) needed 12-week follow-up. At the 12-week review, 113/309 (36.6%) patients reported persistent breathlessness, 30/266 (11.3%) desaturated on exercise testing and 150/309 (48.5%) were discharged from COVID-19-related secondary care services. Referrals were generated to multiple medical specialties, particularly respiratory subspecialties. Our analysis allowed us to justify rationalising and streamlining provisions for subsequent COVID-19 waves while reassured that opportunities for early intervention were not being missed.

Symptomatic, biochemical and radiographic recovery in patients with COVID-19.

BACKGROUND: The symptoms, radiography, biochemistry and healthcare utilisation of patients with COVID-19 following discharge from hospital have not been well described. METHODS: Retrospective analysis of 401 adult patients attending a clinic following an index hospital admission or emergency department attendance with COVID-19. Regression models were used to assess the association between characteristics and persistent abnormal chest radiographs or breathlessness. RESULTS: 75.1% of patients were symptomatic at a median of 53 days post discharge and 72 days after symptom onset and chest radiographs were abnormal in 47.4%. Symptoms and radiographic abnormalities were similar in PCR-positive and PCR-negative patients. Severity of COVID-19 was significantly associated with persistent radiographic abnormalities and breathlessness. 18.5% of patients had unscheduled healthcare visits in the 30 days post discharge. CONCLUSIONS: Patients with COVID-19 experience persistent symptoms and abnormal blood biomarkers with a gradual resolution of radiological abnormalities over time. These findings can inform patients and clinicians about expected recovery times and plan services for follow-up of patients with COVID-19.

Birt-Hogg-Dubé syndrome presenting with spontaneous pneumothorax and extensive pulmonary cysts in the absence of skin lesions or renal pathology.

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition which classically manifests with skin lesions such as fibrofolliculomas, pulmonary cysts that predispose to spontaneous pneumothorax and an increased risk of developing renal cell carcinoma. We describe the case of a patient who presented with a spontaneous pneumothorax on a background of multiple lung cysts, in the absence of cutaneous fibrofolliculomas and renal tumours. A germline mutation in the folliculin FLCN gene was subsequently identified, confirming BHD syndrome. Our case highlights the importance of considering a broad differential diagnosis for the cause of a spontaneous pneumothorax in the presence of unexplained cystic lung disease and emphasises the value of maintaining a high index of clinical suspicion for inherited causes of pneumothoraces.

Postoperative diffuse alveolar haemorrhage: insidious negative pressure or sevoflurane induced?

Negative pressure pulmonary oedema is well described in the literature as an uncommon but recognised complication of general anaesthe sia; negative pressure diffuse alveolar haemorrhage is a rarer consequence. We report a case of massive haemoptysis following elective general anaesthesia using a laryngeal mask airway device and sevoflurane anaesthetic maintenance. The patient had no obvious signs of laryngospasm or other cause of upper airway obstruction perioperatively. We explore the possibility that the haemoptysis was caused by clinically unapparent negative pressure generation, but also ask whether the anaesthetic agent should be considered as a culprit.

Pleural tuberculosis: a key differential diagnosis for pleural thickening, even without obvious risk factors for tuberculosis in a low incidence setting.

We report the case of a 64-year-old woman, presenting with pleuritic chest pain and weight loss. She had a previous history of breast malignancy and no clear risk factors for tuberculosis (TB). Initial investigations showed a right-sided pleural effusion and pleural thickening suggestive of malignancy, which would have been in keeping with the clinical presentation. Initial pleural biopsy showed features suggestive of possible TB infection, though no growth on cultures. A repeat biopsy was negative on initial microscopy, but was culture positive for Mycobacterium tuberculosis, also identifying isoniazid resistance. This case highlights that TB remains an important differential even in the absence of classical risk factors, and illustrates the diagnostic challenges it poses. It also highlights the value of culture positivity in identification of drug resistance and facilitation of appropriate treatment.

Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach.

INTRODUCTION: Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue. METHODS AND ANALYSIS: Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12 h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken. IMPLICATIONS: Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes. ETHICS AND DISSEMINATION: This study was approved by the West London National Research Ethics Committee (12/LO/1101). The study findings will be presented at conferences and will be reported in peer-reviewed journals.

Interactions of androgens, green tea catechins and the antiandrogen flutamide with the external glucose-binding site of the human erythrocyte glucose transporter GLUT1.

This study investigates the effects of androgens, the antiandrogen flutamide and green tea catechins on glucose transport inhibition in human erythrocytes. These effects may relate to the antidiabetogenic effects of green tea. Testosterone, 4-androstene-3,17-dione, dehydroepiandrosterone (DHEA) and DHEA-3-acetate inhibit glucose exit from human erythrocytes with half-maximal inhibitions (Ki) of 39.2+/-8.9, 29.6+/-3.7, 48.1+/-10.2 and 4.8+/-0.98 microM, respectively. The antiandrogen flutamide competitively relieves these inhibitions and of phloretin. Dehydrotestosterone has no effect on glucose transport, indicating the differences between androgen interaction with GLUT1 and human androgen receptor (hAR). Green tea catechins also inhibit glucose exit from erythrocytes. Epicatechin 3-gallate (ECG) has a Ki ECG of 0.14+/-0.01 microM, and epigallocatechin 3-gallate (EGCG) has a Ki EGCG of 0.97+/-0.13 microM. Flutamide reverses these effects. Androgen-screening tests show that the green tea catechins do not act genomically. The high affinities of ECG and EGCG for GLUT1 indicate that this might be their physiological site of action. There are sequence homologies between GLUT1 and the ligand-binding domain (LBD) of hAR containing the amino-acid triads Arg 126, Thr 30 and Asn 288, and Arg 126, Thr 30 and Asn 29, with similar 3D topology to the polar groups binding 3-keto and 17-beta OH steroid groups in hAR LBD. These triads are appropriately sited for competitive inhibition of glucose import at the external opening of the hydrophilic pore traversing GLUT1.

New drug therapies for COPD.

Clinical trials with new drugs for chronic obstructive pulmonary disease (COPD) have been performed. Viruses exacerbate COPD and bacteria may play a part in severe COPD; therefore, antibiotic and antiviral approaches have a sound rationale. Antiinflammatory approaches have been studied. Advances in understanding the molecular basis of other processes have resulted in novel drugs to target reactive oxidant species, mucus, proteases, fibrosis, cachexia, and muscle wasting, and accelerated aging. Studies with monoclonal antibodies have been disappointing, highlighting the tendency for infections and malignancies during treatment. Promising future directions are lung regeneration with retinoids and stem cells.

Performance of Xpert MTB/RIF in the diagnosis of tuberculous mediastinal lymphadenopathy by endobronchial ultrasound.

RATIONALE: The Xpert (GeneXpert) MTB/RIF, an integrated polymerase chain reaction assay, has not been systematically studied in extrapulmonary and in particular mediastinal tuberculosis (TB). OBJECTIVES: To investigate the performance of Xpert MTB/RIF in the diagnosis of intrathoracic nodal TB in a large tertiary urban medical center in the UK. METHODS: We collected clinical, cytological, and microbiological data from two cohorts: 116 consecutive patients referred with mediastinal lymphadenopathy with detailed diagnostic information obtained, and an immediately subsequent second cohort of 52 consecutive patients with microbiologically confirmed mediastinal TB lymphadenopathy. All data were derived between January 2010 and October 2012. All patients underwent endobronchial ultrasound and transbronchial needle aspiration (TBNA). The performance of a single Xpert MTB/RIF assay alongside standard investigations, cytology, and microscopy/culture was evaluated against culture-confirmed TB. MEASUREMENTS AND MAIN RESULTS: Microbiologically confirmed TB mediastinal lymphadenopathy was diagnosed in a total of 88 patients from both cohorts. Three culture-negative cases with associated caseating granulomatous inflammation on TBNA were given a probable diagnosis. A single Xpert MTB/RIF assay demonstrated overall sensitivity for culture-positive TB of 72.6% (62.3-81.0%). Xpert specificity from cohort 1 was 96.3% (89.1-99.1%). The positive predictive value was 88.9% (69.7-97.1%), negative predictive value was 86.5% (76.9-92.1%), and odds ratio was 51.3 (24.0-98.0) for correctly identifying culture-positive disease. Xpert captured all microscopy-positive cases (14 of 14) and the majority of microscopy-negative cases (48 of 71, 67.6%). Among the cases that were culture positive by TBNA, Xpert identified two-thirds of the multiple drug-resistant TB cases, leading to immediate regimen change up to 5 weeks ahead of positive cultures. The use of Xpert combined with cytology increased the sensitivity to 96.6%. CONCLUSIONS: Xpert MTB/RIF provides a rapid, useful, and accurate test to diagnose mediastinal nodal TB in intermediate-incidence settings. The additional use of TBNA cytology further enhances the sensitivity of Xpert. This combination can facilitate rapid risk assessment and prompt TB treatment.

Recurrent vasculitis in cystic fibrosis.

A 22-year-old man presented with recurrent palpable purpuric rash. His clubbing relates to underlying cystic fibrosis (CF) and his rash was identified as CF-related vasculitis, a rare extrapulmonary manifestation of the disease. It occurs predominantly on the lower limbs, mainly over the dorsa of the feet, ankles and tibial surfaces. The rash occurred while the patient had an infective exacerbation of CF (IECF), however, there had also been previous occurrences without worsening of his pulmonary symptoms, to which the rash remitted spontaneously. The patient responded well to immunosuppression, which was given on this admission due to worsening of his CF-related vasculitis. He died 18 months within the onset of his initial rash.

HIV, thrombotic thrombocytopaenic purpura and rituximab in a violent noncompliant patient.

HIV is an increasingly common cause of thrombotic thrombocytopaenic purpura in the United Kingdom. We report a patient with both conditions who presented major therapeutic and ethical challenges. Furthermore, he was recalcitrant to all established therapies, and was, therefore, the first reported HIV patient with thrombotic thrombocytopaenic purpura to receive rituximab.