TB PCR in BAL and EBUS-TBNA samples for the diagnosis of pulmonary and mediastinal lymph node TB: retrospective TRiBE study.

INTRODUCTION: The role of Xpert Ultra in bronchoalveolar lavage (BAL) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples for pulmonary and mediastinal lymph node tuberculosis (TB) remains unclear. METHODS: This was a retrospective observational service evaluation at a tertiary TB centre in a low-incidence setting. The diagnostic indices of Xpert Ultra, smear and culture (with cytology for EBUS-TBNA samples) were compared with culture positivity or a composite reference standard of clinical TB diagnosis. Trace readouts, a new category of results for Xpert Ultra indicating low bacillary load, were analysed in two ways as a true positive or true negative result. 282 BAL and 139 EBUS-TBNA samples were included in the analysis. RESULTS: BAL: sensitivity with 95% CI against culture-confirmed pulmonary TB from BAL samples for Xpert Ultra (trace as positive) was 0.91 (0.82 to 0.98), Xpert Ultra (trace as negative) was 0.76 (0.69 to 0.83), smear was 0.38 (p=0.0009) and culture was 1.00 (0.91 to 1.00). Specificities for all the tests were ≥0.99 (0.98 to 1.00). The addition of smear to Xpert Ultra did not improve the diagnostic accuracy.EBUS-TBNA: sensitivity against culture-confirmed TB from EBUS-TBNA samples for Xpert Ultra (trace as positive) was 0.71 (0.63 to 0.78), Xpert Ultra (trace as negative) was 0.59 (0.54 to 0.63), smear was 0.12 (p=0.002), culture was 1.00 (0.89 to 1.00), cytology was 0.87 (0.76 to 0.98) and rapid on-site evaluation of cytology (ROSE) was 0.92 (0.78 to 1.00). Specificities were 0.99 (0.97 to 1.00), 0.99 (0.97 to 1.00), 1.00 (0.98 to 1.00), 1.00 (0.98 to 1.00), 0.67 (0.67 to 0.68) and 0.42, respectively. CONCLUSION: Xpert Ultra had a significantly higher sensitivity compared with smear in both BAL and EBUS-TBNA samples. Xpert Ultra had a lower sensitivity compared with culture but comparable specificity with results being available within <24 hours. Trace readings in our low-incidence setting were associated with culture positivity in all BAL samples.

M ycobacterium avium complex genomics and transmission in a London hospital.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are environmental microorganisms and opportunistic pathogens in individuals with pre-existing lung conditions such as cystic fibrosis (CF) and non-CF bronchiectasis. While recent studies of Mycobacterium abscessus have identified transmission within single CF centres as well as nationally and globally, transmission of other NTM species is less well studied. METHODS: To investigate the potential for transmission of the Mycobacterium avium complex (MAC) we sequenced 996 isolates from 354 CF and non-CF patients at the Royal Brompton Hospital (London, UK; collected 2013-2016) and analysed them in a global context. Epidemiological links were identified from patient records. Previously published genomes were used to characterise global population structures. RESULTS: We identified putative transmission clusters in three MAC species, although few epidemiological links could be identified. For M. avium, lineages were largely limited to single countries, while for Mycobacterium chimaera, global transmission clusters previously associated with heater-cooler units (HCUs) were found. However, the immediate ancestor of the lineage causing the major HCU-associated outbreak was a lineage already circulating in patients. CONCLUSIONS: CF and non-CF patients shared transmission chains, although the lack of epidemiological links suggested that most transmission is indirect and may involve environmental intermediates or asymptomatic carriage in the wider population.

Educational opportunities for postgraduate medical trainees during the COVID-19 pandemic: deriving value from old, new and emerging ways of learning.

The COVID-19 pandemic has had a significant impact on postgraduate medical training across all specialties. Although some traditional learning opportunities have been curtailed, there have been numerous examples of highly valuable educational experiences that have arisen during this time. Here, from a trainee perspective, we consider the educational merits of the re-emergence of 'firm-based' teams, new online learning opportunities, use of digital technologies and the rise of telephone clinics and new COVID-19 clinical services. As health services continue to recover from surges in COVID-19 cases, it is important to reflect on and recognise the value of these educational experiences so that helpful elements can be retained and embedded into training programmes for the benefit of both trainees and patients.

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

Treatment of COVID-19-exacerbated asthma: should systemic corticosteroids be used?

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a new rapidly spreading infectious disease. Current guidance from the World Health Organization (WHO) highlights asthmatics as a high-risk group for severe illness from COVID-19. Viruses are common triggers of asthma exacerbations and the current SARS-CoV-2 pandemic raises several questions regarding the optimum management strategies. Here, we discuss the contentious issue of whether the mainstay therapy systemic corticosteroids should be used in the routine management of COVID-19-associated asthma exacerbations. Recent guidance from the WHO has advised against the use of corticosteroids if COVID-19 is suspected due to concerns that these agents may impair protective innate antiviral immune responses. This may not be appropriate in the unique case of asthma exacerbation, a syndrome associated with augmented type 2 inflammation, a disease feature that is known to directly inhibit antiviral immunity. Corticosteroids, through their suppressive effects on type 2 inflammation, are thus likely to restore impaired antiviral immunity in asthma and, in contrast to non-asthmatic subjects, have beneficial clinical effects in the context of SARS-CoV-2 infection.

Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial.

Importance: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. Objective: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age. Design, Setting, and Participants: Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. Interventions: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. Main Outcomes and Measures: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. Results: Among 638 infants (mean, 26 weeks' gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks' postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). Conclusions and Relevance: Among premature infants younger than 28 weeks' gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

Right-sided endocarditis: eustachian valve and coronary sinus involvement.

Infective endocarditis in patients with intravenous drug use commonly involves right-sided heart valves. Eustachian valve (EV) endocarditis is not commonly seen given the valve's infrequent presence. Involvement of the coronary sinus (CS) with endocarditis is also an unusual finding. We present a case with echocardiographic findings consistent with EV endocarditis along with CS involvement, which appropriately responded to antibiotics.

Development of a Chest Wall Protector Effective in Preventing Sudden Cardiac Death by Chest Wall Impact (Commotio Cordis).

OBJECTIVE: Commotio cordis, sudden death with chest impact, occurs clinically despite chest wall protectors worn in sports. In an experimental model of commotio cordis, commercially available chest wall protectors failed to prevent ventricular fibrillation (VF). The goal of the current investigation was to develop a chest wall protector effective in the prevention of commotio cordis. DESIGN: In the Tufts experimental model of commotio cordis the ability of chest protectors to prevent VF was assessed. Impacts were delivered with a 40-mph lacrosse ball, timed to the vulnerable period for VF. INTERVENTION: A chest wall protector or no chest wall protector (control) was randomly assigned to be placed over the chest. Four iterative series of 2 to 4 different chest wall material combinations were assessed. Materials included 3 different foams (Accelleron [Unequal Technologies, Glen Mills, PA], closed cell high density foam; Airilon [Unequal Technologies, Glen Mills, PA], closed cell low density soft foam; and an open cell memory foam) that were adhered to a layer of TriDur (Unequal Technologies, Glen Mills, PA), a flexible elastomeric coated aramid that was bonded to a semirigid polypropylene polymer (ImpacShield, Unequal Technologies, Glen Mills, PA). MAIN OUTCOME MEASURE: Induction of VF by chest wall impact was the primary outcome. RESULTS: Of 80 impacts without chest protectors, 43 (54%) resulted in VF. Ventricular fibrillation with chest protectors ranged from a high of 60% to a low of 5%. Of 12 chest protectors assessed, only 3 significantly lowered the risk of VF compared with impacts without chest protectors. These 3 chest protectors were combinations of Accelleron, Airilon, TriDur, and ImpacShield of different thicknesses. Protection increased linearly with the thicker combinations. CONCLUSIONS: Effective protection against VF with chest wall protection can be achieved in an experimental model of commotio cordis. CLINICAL RELEVANCE: Chest protector designs incorporating these novel materials will likely be effective in the prevention of commotio cordis on the playing field.

Deep Learning Auto-Segmentation Network for Pediatric Computed Tomography Data Sets: Can We Extrapolate From Adults?

PURPOSE: Artificial intelligence (AI)-based auto-segmentation models hold promise for enhanced efficiency and consistency in organ contouring for adaptive radiation therapy and radiation therapy planning. However, their performance on pediatric computed tomography (CT) data and cross-scanner compatibility remain unclear. This study aimed to evaluate the performance of AI-based auto-segmentation models trained on adult CT data when applied to pediatric data sets and explore the improvement in performance gained by including pediatric training data. It also examined their ability to accurately segment CT data acquired from different scanners. METHODS AND MATERIALS: Using the nnU-Net framework, segmentation models were trained on data sets of adult, pediatric, and combined CT scans for 7 pelvic/thoracic organs. Each model was trained on 290 to 300 cases per category and organ. Training data sets included a combination of clinical data and several open repositories. The study incorporated a database of 459 pediatric (0-16 years) CT scans and 950 adults (>18 years), ensuring all scans had human expert ground-truth contours of the selected organs. Performance was evaluated based on Dice similarity coefficients (DSC) of the model-generated contours. RESULTS: AI models trained exclusively on adult data underperformed on pediatric data, especially for the 0 to 2 age group: mean DSC was below 0.5 for the bladder and spleen. The addition of pediatric training data demonstrated significant improvement for all age groups, achieving a mean DSC of above 0.85 for all organs in every age group. Larger organs like the liver and kidneys maintained consistent performance for all models across age groups. No significant difference emerged in the cross-scanner performance evaluation, suggesting robust cross-scanner generalization. CONCLUSIONS: For optimal segmentation across age groups, it is important to include pediatric data in the training of segmentation models. The successful cross-scanner generalization also supports the real-world clinical applicability of these AI models. This study emphasizes the significance of data set diversity in training robust AI systems for medical image interpretation tasks.

IL-1α is required for T cell-driven weight loss after respiratory viral infection.

Respiratory viral infections remain a major cause of hospitalization and death worldwide. Patients with respiratory infections often lose weight. While acute weight loss is speculated to be a tolerance mechanism to limit pathogen growth, severe weight loss following infection can cause quality of life deterioration. Despite the clinical relevance of respiratory infection-induced weight loss, its mechanism is not yet completely understood. We utilized a model of CD 8+ T cell-driven weight loss during respiratory syncytial virus (RSV) infection to dissect the immune regulation of post-infection weight loss. Supporting previous data, bulk RNA sequencing indicated significant enrichment of the interleukin (IL)-1 signaling pathway after RSV infection. Despite increased viral load, infection-associated weight loss was significantly reduced after IL-1α (but not IL-1ß) blockade. IL-1α depletion resulted in a reversal of the gut microbiota changes observed following RSV infection. Direct nasal instillation of IL-1α also caused weight loss. Of note, we detected IL-1α in the brain after either infection or nasal delivery. This was associated with changes in genes controlling appetite after RSV infection and corresponding changes in signaling molecules such as leptin and growth/differentiation factor 15. Together, these findings indicate a lung-brain-gut signaling axis for IL-1α in regulating weight loss after RSV infection.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD): Epidemiology, diagnosis and multidisciplinary management.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause significant disease in both immunocompromised and immunocompetent individuals. The incidence of NTM pulmonary disease (NTM-PD) is rising globally. Diagnostic challenges persist and treatment efficacy is variable. This article provides an overview of NTM-PD for clinicians. We discuss how common it is, who is at risk, how it is diagnosed and the multidisciplinary approach to its clinical management.

Objective assessment of control compared with clinical triple office control score in children with intermittent exotropia.

Poor control of intermittent exotropia may be used as an indication for surgery. However, control fluctuates during the day and from day to day. The standardized triple office control score (mean of three scores on a 6-point ordinal scale) is representative of repeated assessments throughout the day, but lacks validation against an objective measure of eye movements. We report the agreement between the triple office control score measured by the referring eyecare professional and lab-measured vergence instability using an EyeLink video eye tracker. Near and distance triple office control scores were moderately correlated with vergence instability. Near, but not distance, triple office control score was moderately correlated with the percentage of time intermittent exotropia was manifest during EyeLink recording. Larger triple office control scores for intermittent exotropia provide a meaningful description of larger vergence instability, supporting its use in clinical decisions and as a measure in clinical trials.

Efficacy and Safety of an Upfront RotaTripsy Strategy in the Treatment of De Novo and In-Stent Restenosis Cases.

BACKGROUND: Use of both rotational atherectomy (RA) and intravascular lithotripsy (IVL)-the "RotaTripsy" technique-offers a potentially synergistic calcium-modification strategy that can treat both luminal and abluminal calcification. An upfront RotaTripsy strategy using an undersized burr in large-caliber coronaries also offers the advantage of facilitating IVL catheter passage while being able to undertake the procedure with a 6-Fr system. METHODS: Consecutive patients with heavily calcified lesions on angiographic or intravascular imaging and large target-vessel caliber (≥3 mm) who underwent an upfront RA followed by IVL between July 2021 and January 2022 were included in this study. Study aims were to evaluate periprocedural efficacy and safety. RESULTS: Of the 21 patients included, RotaTripsy was used for treatment of de novo lesions in 12 patients (57%) and for in-stent-restenosis in 9 patients (43%). Seven cases of in-stent restenosis (ISR) involved 2 layers of stents. Mean reference vessel diameter was 3.67 ± 0.46 mm and baseline diameter stenosis was 77.4 ± 11.3%. Average RA burr-to-artery ratio was 0.43 ± 0.05 and IVL balloon-to-artery ratio was 0.93 ± 0.06, with IVL balloon crossing the lesion in all cases following RA. Procedural success was attained in 20 of 21 cases; 1 periprocedural complication (a death related to coronary perforation following stent postdilation) was recorded. CONCLUSIONS: An upfront RotaTripsy strategy is associated with a high degree of procedural success in de novo lesions and ISR cases by facilitating the use of a smaller burr-to-artery ratio and smaller-bore vascular access. Larger studies are required to further evaluate the potential benefits of an upfront RotaTripsy strategy from a safety and cost-benefit perspective.

Ticagrelor or prasugrel versus clopidogrel in patients undergoing percutaneous coronary intervention for chronic coronary syndromes.

BACKGROUND: Potent P2Y12 inhibitors such as ticagrelor and prasugrel are superior to clopidogrel in acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). Whether this benefit extends to a patient population with chronic coronary syndromes (CCS) is unclear. AIMS: We sought to compare the safety and efficacy of prasugrel and ticagrelor versus clopidogrel in patients undergoing PCI for CCS. METHODS: Consecutive patients undergoing PCI for CCS at a tertiary centre between 2014 and 2019 who were discharged on prasugrel or ticagrelor were compared with those on clopidogrel. The primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularisation at 1 year. RESULTS: Overall, 11,508 patients were included in the study (ticagrelor/prasugrel n=2,860 [24.9%], clopidogrel n=8,648 [75.1%]) with an increasing frequency of potent P2Y12 inhibitor use over the study period (ptrend<0.001). Clopidogrel was used more frequently in patients with multimorbid risk factors, whereas anatomical or procedural complexity was associated with ticagrelor/prasugrel use (left main PCI, bifurcation PCI, number of lesions, rotational atherectomy). No difference in the incidence of death or MI was noted across the groups (ticagrelor/prasugrel vs clopidogrel: 2.7% vs 3.1%, adjusted hazard ratio [adjHR] 0.86, 95% confidence interval [CI]: 0.62-1.17; p=0.33) or secondary outcomes including bleeding (adjHR 0.75, 95% CI: 0.46-1.21; p=0.23) on propensity score stratification analysis. Additionally, no difference in the primary outcome was observed across subgroups, including those undergoing complex PCI. CONCLUSIONS: Ticagrelor and prasugrel are increasingly used in patients with CCS undergoing PCI with similar 1-year efficacy and safety when compared to clopidogrel. Whether use of these agents can be beneficial in patients undergoing PCI for CCS with a high thrombotic and low bleeding risk warrants further study.

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.

Nontuberculous Mycobacterial Pulmonary Disease: Clinical Epidemiologic Features, Risk Factors, and Diagnosis: The Nontuberculous Mycobacterial Series.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) continues to impose a significant clinical burden of disease on susceptible patients. The incidence of NTM-PD is rising globally, but it remains a condition that is challenging to diagnose and treat effectively. This review provides an update on the global epidemiologic features, risk factors, and diagnostic considerations associated with the management of NTM-PD.

The role of wirelessly observed therapy in improving treatment adherence.

Wirelessly observed therapy (WOT) offers a novel way of monitoring treatment adherence. In this article, we provide an overview of how this technology works and discuss the evidence for its clinical effectiveness in tuberculosis, hepatitis C virus infection, mental health and cardiovascular disease. We consider the acceptability of WOT to patients as well as potential issues relating to patient autonomy and data protection. We highlight the current limited data on its economic impact and reflect on its future role in patient care.

British Thoracic Society survey of the career intentions of respiratory medicine specialty trainees in the UK.

There were respiratory consultant post vacancies in 82% of surveyed UK hospitals in 2021. Understanding respiratory trainees' career intentions is vital to plan and train a future respiratory workforce. In 2020, the British Thoracic Society surveyed trainee members (n=144) to assess career plans and perceived barriers and facilitators when applying for consultant posts. Most trainees (79, 55.6%) report intending to pursue UK-based posts with general internal medicine responsibilities. Consultant applications are influenced by location, hospital type, previous local experience and availability of subspecialty posts. Insufficient guidance is available regarding consultant applications.