Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease.

OBJECTIVES: The impact of autoantibody profiles on prognosis of idiopathic inflammatory myositis associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with Myositis Specific Antibodies (MSA) remains unclear. This retrospective cohort study examines whether serological profiles are associated with mortality and longitudinal lung function change. METHODS: Baseline clinical/demographic characteristics and follow-up lung function of consecutive adult patients with IIM-ILD or Interstitial Pneumonia with Autoimmune Features (IPAF) positive for MSAs were extracted from three hospitals. Univariate and multi-variate Cox-Proportional Hazards analyses were used to compare mortality between autoantibodies. Regression models were used to analyse lung function trends. RESULTS: Of 430 included patients, 81% met IIM criteria, 19% were IPAF-MSA. On univariate analysis, risk factors associated with mortality included higher age, Charlson Co-morbidity Index and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared to anti-MDA5-negativity, anti-MDA5-positivity (MDA5+) was associated with high mortality in the first 3 months (HR 65.2. 95%CI 14.1, 302.0), while no significant difference was seen thereafter (HR 0.55, 95%CI 0.14, 2.28). On multi-variate analysis, combined anti-synthetase antibodies carried a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in anti-Jo1 + (HR 0.61, 95%CI 0.4-0.87) and increased in anti-PL7+ patients (HR 2.07, 95%CI 1.44-2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards. CONCLUSIONS: Among autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ confer higher mortality risks. Survivors of an early peak of mortality in anti-MDA5+ disease appear to have a favourable prognosis.

Multidisciplinary approach to connective tissue disease (CTD) related pleural effusions: a four-year retrospective evaluation.

BACKGROUND: CTD-related pleural effusions are rare and challenging to diagnose. Our lung inflammation service (with expertise in rheumatology, interstitial lung disease and respiratory failure) works closely with the pleural team. This study aims to review the multidisciplinary approach to CTD-related pleural effusions at a tertiary centre. METHODS: All patients with CTD-related pleural effusions at St Thomas' Hospital, London were included. Retrospective data were collected from Dec 2013 to 2016. RESULTS: The lung inflammation service performed an expert clinical assessment and targeted investigations. 11 patients (ages 23-77) were identified with CTD related pleural disease. 9 (82%) patients were given a new CTD diagnosis, with pleural disease as the first manifestation. The range of conditions were: rheumatoid arthritis [3] ,IgG4-related disease [2] ,adult Still's disease [2] ,vasculitis [1] ,SLE [1] ,drug-induced lupus [1] ,and Behcet's [1]. The pleural team review took place 1 day (median) after referral. 73% of diagnoses (8 patients) were achieved with local anaesthetic pleural interventions (a combination of: aspiration, drain, or percutaneous biopsy). This included 1 patient who required no pleural intervention. 1 required medical thoracoscopy, and 2 underwent thoracic surgery. Diagnoses were made by integrating all available evidence such as clinical assessment, imaging, and autoimmune serology. No diagnosis was achieved by pleural cytology or histology analysis alone. 8 (73%) were commenced on prednisolone acutely (vasculitis, SLE, drug-related lupus, 1 patient with rheumatoid arthritis, Behcet's, 2 patients with Adult Still's disease, 1 patient with IgG4-related disease). Of these 8, one patient with rheumatoid arthritis received IV methylprednisolone beforehand, one patient with IgG4-related disease was weaned off prednisolone to methothrexate, two patients with Adult Still's disease were on colchicine as well, and one patient with Behcet's was on cyclophosphamide as well. 7 (64%) were managed as outpatients; 4 required admission. The median time from pleural review to diagnosis was 53 days. CONCLUSIONS: Diagnosis can be challenging in patients presenting with pleural disease as the first manifestation of a CTD. We recommend a multidisciplinary approach in management.

Lesson of the month: selective use of cyclophosphamide in pregnancy for severe autoimmune respiratory disease.

We present the cases of two pregnant women who developed severe respiratory compromise in mid pregnancy, one due to rapidly progressive interstitial lung disease associated with mixed connective tissue disease and one secondary to diffuse alveolar haemorrhage due to antiglomerular basement membrane disease. Both were treated with high-dose steroids followed by pulsed intravenous cyclophosphamide. Both women went onto have live births although one baby was growth restricted and preterm. Neither baby had any evidence of congenital abnormalities.

Interventional therapies in acute pulmonary embolus-current trends and future directions.

Venous thromboembolic disease presenting with acute pulmonary embolus (PE) can be treated in a variety of ways from anticoagulation as an outpatient to surgical embolectomy with many new interventional therapies being developed. Mortality in these patients can be as high as 50% and many of these treatments are also considered to be high risk. Early involvement of a multidisciplinary team and patient risk stratification can aid management decisions in these complex patients who can suddenly deteriorate.In this review, we summarise the evidence behind new and developing interventional therapies in the treatment of high and intermediate-high risk PE including catheter-directed thrombolysis, pharmacomechanical thrombolysis, thromboaspiration and the growing role of extracorporeal membrane oxygenation in the stabilisation and management of this cohort of patients.

Steroid exposure and outcome in COVID-19 pneumonia.

Background: Corticosteroids are used to treat COVID-19 pneumonia. However, the optimal dose is unclear. This study describes the association between corticosteroid exposure with disease severity and outcome in COVID-19 pneumonia. Methods: This is a single-centre retrospective, observational study including adult ICU patients who received systemic corticosteroids for COVID-19 pneumonia between March 2020 and March 2021. We recorded patient characteristics, disease severity, total steroid exposure, respiratory support and gas exchange data, and 90-day mortality. Results: We included 362 patients. We allocated patients to groups with increasing disease severity according to the highest level of respiratory support that they received: high-flow nasal oxygen or continuous positive airway pressure (HFNO/CPAP) in 12.7%, invasive mechanical ventilation (IMV) in 61.6%, and extracorporeal membrane oxygenation (ECMO) in 25.7%. For these three groups, the median (inter-quartile range [IQR]) age was 61 (54-71) vs 58 (50-66) vs 46 (38-53) yr, respectively (P<0.001); median (IQR) APACHE (Acute Physiology and Chronic Health Evaluation) II scores were 12 (9-15) vs 14 (12-18) vs 15 (12-17), respectively (P=0.006); the median (IQR) lowest P a O 2 /FiO2 ratio was 15.1 (11.8-21.7) vs 15.1 (10.7-22.2) vs 9.5 (7.9-10.9) kPa, respectively (P<0.001). Ninety-day mortality was 9% vs 27% vs 37% (P=0.002). Median (IQR) dexamethasone-equivalent exposure was 37 (24-62) vs 174 (86-504) vs 535 (257-1213) mg (P<0.001). 'Pulsed' steroids were administered to 26% of the IMV group and 48% of the ECMO group. Patients with higher disease severity who received pulse steroids had a higher 90-day mortality. Conclusions: Corticosteroid exposure increased with the severity of COVID-19 pneumonia. Pulsed dose steroids were used more frequently in patients receiving greater respiratory support. Future studies should address patient selection and outcomes associated with pulsed dose steroids in patients with severe and deteriorating COVID-19 pneumonia.

Veno-venous extracorporeal membrane oxygenation in coronavirus disease 2019: a case series.

BACKGROUND: The use of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in severe hypoxaemic respiratory failure from coronavirus disease 2019 (COVID-19) has been described, but reported utilisation and outcomes are variable, and detailed information on patient characteristics is lacking. We aim to report clinical characteristics, management and outcomes of COVID-19 patients requiring VV-ECMO, admitted over 2 months to a high-volume centre in the UK. METHODS: Patient information, including baseline characteristics and clinical parameters, was collected retrospectively from electronic health records for COVID-19 VV-ECMO admissions between 3 March and 2 May 2020. Clinical management is described. Data are reported for survivors and nonsurvivors. RESULTS: We describe 43 consecutive patients with COVID-19 who received VV-ECMO. Median age was 46 years (interquartile range 35.5-52.5) and 76.7% were male. Median time from symptom onset to VV-ECMO was 14 days (interquartile range 11-17.5). All patients underwent computed tomography imaging, revealing extensive pulmonary consolidation in 95.3%, and pulmonary embolus in 27.9%. Overall, 79.1% received immunomodulation with methylprednisolone for persistent maladaptive hyperinflammatory state. Vasopressors were used in 86%, and 44.2% received renal replacement therapy. Median duration on VV-ECMO was 13 days (interquartile range 8-20). 14 patients died (32.6%) and 29 survived (67.4%) to hospital discharge. Nonsurvivors had significantly higher d-dimer (38.2 versus 9.5 mg·L-1, fibrinogen equivalent units; p=0.035) and creatinine (169 versus 73 µmol·L-1; p=0.022) at commencement of VV-ECMO. CONCLUSIONS: Our data support the use of VV-ECMO in selected COVID-19 patients. The cohort was characterised by high degree of alveolar consolidation, systemic inflammation and intravascular thrombosis.

Systemic Lupus Erythematosus and Antiphospholipid Antibody Syndrome.

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease, characterized by an antibody response to nucleic antigens and involvement of any organ system. Pulmonary manifestations are frequent and include pleuritis, acute lupus pneumonitis, chronic interstitial lung disease, alveolar hemorrhage, shrinking lung syndrome, airway disease, pulmonary hypertension (PH), and thromboembolic disease. The antiphospholipid antibody syndrome (APLAS) is a systemic autoimmune disorder where different prothrombotic factors interact to induce arterial and venous thrombosis. The most common pulmonary manifestations are pulmonary thromboembolism and PH. This review will focus on the clinical presentation, diagnosis, and management of the SLE- and APLAS-associated pulmonary conditions.

Pulmonary and paradoxical embolism with platypnoea-orthodeoxia.

This article outlines the case of a 62-year-old man who presented with a deep vein thrombosis, pulmonary embolus and right middle cerebral artery territory ischaemic stroke in association with a patent foramen ovale with right-to-left shunting. Despite anticoagulation, he was noted to have desaturation and tachypnoea when upright, without other symptoms or cardiovascular compromise, that resolved on lying down. The article describes the syndrome of platypnoea-orthodeoxia, characterized by breathlessness, hypoxia and/or cyanosis while in the upright position that improves on lying down, its relationship to this case, and its resolution by closure of the patent foramen ovale.

Modernising morning report: innovation in teaching and learning.

BACKGROUND: Over recent years there has been a shift in undergraduate medical education, from predominantly passive, didactic teaching methods to facilitating learning by focusing on the management of common scenarios, through the means of problem- and case-based learning. CONTEXT: Case-based learning and peer-led teaching are often overlooked at postgraduate level, despite the continuing demonstrated success of these methods in fostering independent reasoning and problem-solving skills that are vital for newly qualified doctors to develop. When trying to strike a balance between educational needs and service provision, it is essential to identify and implement efficient, effective approaches to optimise learning opportunities. INNOVATION: We have adapted the pre-existing framework of the American 'Morning Report' to suit the needs of today's junior doctors, creating a system of providing case-based learning paired with peer-led teaching. IMPLICATIONS: We evaluated the educational model through a focus group session, and found that our Morning Report was a unique environment where junior doctors feel comfortable engaging with group case-based teaching, with the support and encouragement of senior consultants, reinforced with online case summaries and blog resources.

Is cardiopulmonary exercise testing a useful test before esophagectomy?

BACKGROUND: Cardiopulmonary exercise (CPX) testing may identify patients at high risk of postoperative cardiopulmonary morbidity and mortality. This study aims to assess the utility of CPX testing before esophagectomy. METHODS: Between January 2004 and October 2006, 78 consecutive patients (64 men) with a median age of 65 years (range, 40 to 81 years) underwent CPX testing before esophagectomy (50% transhiatal; 50% transthoracic). Measured variables included anaerobic threshold (AT) and maximum oxygen uptake at peak exercise (VO2peak). Outcome measures were postoperative morbidity and mortality, length of hospital stay, and unplanned intensive therapy unit admission. RESULTS: Cardiopulmonary complications occurred in 33 (42%) patients and noncardiopulmonary complications in 19 (24%). One in-hospital death (1.3%) occurred, and 13 patients (17%) required an unplanned intensive therapy unit admission. The level of VO2peak was significantly lower in patients with postoperative cardiopulmonary morbidity (p = 0.04). The area under a receiver operating characteristic curve was 0.63 (95% confidence interval [CI], 0.50 to 0.76) for the VO2peak and 0.62 (95% CI, 0.49 to 0.75) for AT. An AT cutoff of 11 mL/kg/min was a poor predictor of postoperative cardiopulmonary morbidity. CONCLUSIONS: Although the VO2peak was significantly lower in those patients who developed cardiopulmonary complications, CPX testing is of limited value in predicting postoperative cardiopulmonary morbidity in patients undergoing esophagectomy.