Pre-registered controlled comparison of auditory function reveals no difference between hospitalised adults with and without COVID-19.

OBJECTIVE: Several viruses are known to have a negative impact on hearing health. The global prevalence of COVID-19 means that it is crucial to understand whether and how SARS-CoV2 affects hearing. Evidence to date is mixed, with studies frequently exhibiting limitations in the methodological approaches used or the populations sampled, leading to a substantial risk of bias. This study addressed many of these limitations. DESIGN: A comprehensive battery of measures was administered, including lab-based behavioural and physiological measures, as well as self-report instruments. Performance was thoroughly assessed across the auditory system, including measures of cochlear function, neural function and auditory perception. Hypotheses and analyses were pre-registered. STUDY SAMPLES: Participants who were hospitalised as a result of COVID-19 (n = 57) were compared with a well-matched control group (n = 40) who had also been hospitalised but had never had COVID-19. RESULTS: We find no evidence to support the hypothesis that COVID-19 is associated with deficits in auditory function on any auditory test measure. Of all the confirmatory analyses, only the self-report measure of hearing decline indicated any difference between groups. CONCLUSION: Results do not support the hypothesis that COVID-19 infection has a significant long-term impact on the auditory system.

Conventional oxygen therapy versus CPAP as a ceiling of care in ward-based patients with COVID-19: a multi-centre cohort evaluation.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is commonly used for respiratory failure due to severe COVID-19 pneumonitis, including in patients deemed not likely to benefit from invasive mechanical ventilation (nIMV). Little evidence exists demonstrating superiority over conventional oxygen therapy, whilst ward-level delivery of CPAP presents practical challenges. We sought to compare clinical outcomes of oxygen therapy versus CPAP therapy in patients with COVID-19 who were nIMV. METHODS: This retrospective multi-centre cohort evaluation included patients diagnosed with COVID-19 who were nIMV, had a treatment escalation plan of ward-level care and clinical frailty scale ≤ 6. Recruitment occurred during the first two waves of the UK COVID-19 pandemic in 2020; from 1st March to May 31st, and from 1st September to 31st December. Patients given CPAP were compared to patients receiving oxygen therapy that required FiO2 ≥0.4 for more than 12 hours at hospitals not providing ward-level CPAP. Logistic regression modelling was performed to compare 30-day mortality between treatment groups, accounting for important confounders and within-hospital clustering. FINDINGS: Seven hospitals provided data for 479 patients during the UK COVID-19 pandemic in 2020. Overall 30-day mortality was 75.6% in the oxygen group (186/246 patients) and 77.7% in the CPAP group (181/233 patients). A lack of evidence for a treatment effect persisted in the adjusted model (adjusted odds ratio 0.84 95% CI 0.57-1.23, p=0.37). 49.8% of patients receiving CPAP-therapy (118/237) chose to discontinue it. INTERPRETATION: No survival difference was found between using oxygen alone or CPAP to treat patients with severe COVID-19 who were nIMV. A high patient-initiated discontinuation rate for CPAP suggests a significant treatment burden. Further reflection is warranted on the current treatment guidance and widespread application of CPAP in this setting. FUNDING: L Pearmain is supported by the MRC (MR/R00191X/1). TW Felton is supported by the NIHR Manchester Biomedical Research Centre.

An update on interstitial lung disease.

Interstitial lung diseases are a complex group of conditions that cause inflammation and scarring of the lung interstitium. This article discusses the diagnosis and management of common interstitial lung diseases including idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, connective tissue disease associated-interstitial lung disease, sarcoidosis and drug-induced interstitial lung disease. A multidisciplinary approach to diagnosis of interstitial lung disease is the gold standard; key history and examination features, blood panel, pulmonary function tests, high resolution computed tomography imaging, and when required bronchoalveolar lavage and lung biopsy results are discussed to reach a multidisciplinary consensus diagnosis. Advances, including the development of the disease-modifying anti-fibrotic medications nintedanib and pirfenidone, continue to shape the future management of interstitial lung disease. A holistic approach to the care of patients with interstitial lung disease is paramount, as they often have a high symptom burden and considerable palliative care needs.

Early clinical experiences with nintedanib in three UK tertiary interstitial lung disease centres.

BACKGROUND: Nintedanib has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF). It was approved by the National Institute for Health and Care Excellence (NICE) in January 2016 for IPF patients with a forced vital capacity (FVC) of 50-80% in the United Kingdom (UK). AIM: To report real world data about our early clinical experience using nintedanib in 187 patients with a multi-disciplinary (MDT) diagnosis of IPF in a manufacturer funded patient in need scheme (three UK centres) prior to NICE approval. METHODS: All patients with a MDT diagnosis of IPF from December 2014 to January 2016 commenced on nintedanib were included. Demographic details, adverse events (AEs) and where available lung function results were retrospectively collected from clinical letters. RESULTS: 187 patients (76% males) with a median age of 72 years (49-89) were treated with nintedanib. The average pre-treatment FVC was 81.1 ± 19.8% and diffusion capacity of the lungs for carbon monoxide was 43.9 ± 15% (n = 82). Fifty percent of patients started nintedanib because they were ineligible for pirfenidone due to an FVC > 80%. The median treatment course was 8 ± 4 months. The majority of patients experienced 1-3 AEs with nintedanib (52%, n = 97). The most frequent AEs were diarrhoea (50%), nausea (36%), reduced appetite (24%), tiredness (20%) and gastro-oesophageal reflux (18%). The majority of AEs resulted in no change in treatment (64%, n = 461). 21% (n = 150) of AEs resulted in a dose reduction and 13% (n = 94) necessitated discontinuation of treatment. 1 in 5 patients discontinued treatment either temporarily or on a permanent basis during the monitoring period. In a select cohort of patients, a statistically significant greater proportion of patients remained stable or improved and a lower proportion declined, as depicted by FVC changes of > 5% after nintedanib commencement (P < 0.05 using Chi squared test). CONCLUSIONS: Nintedanib is well tolerated and has an acceptable safety profile. Only 8% of those reporting diarrhoea discontinued treatment either on a temporary or permanent basis. There were no signals with respect to increased cardiovascular morbidity or major bleeding risk. This is in keeping with the INPULSIS clinical trial findings but in a real world cohort.

Crossing the bridge to VATS lobectomy.

Introduction The impact of the introduction of video assisted thoracoscopic surgery (VATS) on the management of lung cancer 20 years ago has been well documented. However, the uptake of VATS lobectomy in surgical practice worldwide has been slower than expected. We believe that this is partly due to a lack of consensus on how this procedure should be integrated into training programmes. We present our initial experience with a newly developed training model, which could help bridge the divide between open and VATS lobectomy. Methods Two surgical registrars were initiated into this model, supervised by a single consultant. All cases were performed using a standardised three-port anterior approach with systematic lymph node dissection. Both registrars were scrubbed for each case, alternating as first surgeon and assistant, with the supervising consultant operating the camera. Results Over a 6-month period, 22 lung resections for non-small cell lung carcinoma were performed as VATS lobectomies. Thirteen of them were upper lobectomies. There were no emergency conversions to open surgery. The mean operative time for the registrars was 155 minutes compared with 140 minutes for consultant-led operations (p=0.22). There was no perioperative mortality. The most common postoperative complications were atrial fibrillation (4 cases) and prolonged air leak (3 cases). Conclusions VATS lobectomy involves a team approach. Especially in upper lobectomies, the assistant surgeon plays a significant role in the operation, often helping with the dissection as well as stapling of the bronchial and vascular structures. With a team consisting of two trainees and a supervising surgeon, the teaching process becomes more intuitive and is accelerated. This should reduce the learning curve considerably and improve safety during training.

The evolution of intraoperative conversion in video assisted thoracoscopic lobectomy.

INTRODUCTION Unplanned conversion to thoracotomy remains a major concern in video assisted thoracoscopic surgery (VATS) lobectomy. This study aimed to investigate the development of a VATS lobectomy programme over a five-year period, with a focus on the causes and consequences of unplanned conversions. METHODS A single centre retrospective review was performed of patients who underwent complete anatomical lung resection initiated by VATS between January 2010 and April 2015. RESULTS In total, 1,270 patients underwent a lobectomy in the study period and 684 (53.9%) of these were commenced thoracoscopically. There were 75 cases (10.9%) with unplanned conversion. The proportion of lobectomies started as VATS was significantly higher in the second half of the study period (2010-2012: 277/713 [38.8%], 2013-2015: 407/557 [73.1%], p<0.001). The conversion rate dropped initially from 20.4% (11/54) in 2010 to 9.9% (15/151) in 2013 and then remained consistently under 10% until 2015. Conversions were most commonly secondary to vascular injury (26/75, 34.7%). Patients undergoing unplanned conversion had a longer length of stay than VATS completed patients (9 vs 6 days, p<0.001). There was a higher incidence of respiratory failure (10/75 [14.1%] vs 23/607 [3.8%], p<0.001) and 30-day mortality (7/75 [9.3%] vs 6/607 [1.0%], p=0.003) in patients with unplanned conversion than in those with completed VATS. CONCLUSIONS As our VATS lobectomy programme developed, the unplanned conversion rate dropped initially and then remained constant at approximately 10%. With increasing unit experience, it is both safe and technically possible to complete the majority of lobectomy procedures thoracoscopically.

Summary of the British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults.

Flexible bronchoscopy is an essential, established and expanding tool in respiratory medicine. Its practice, however, needs to be safe, effective and for the right indications to maximise clinical utility. This guideline is based on the best available evidence and is a revised update of the British Thoracic Society guideline on diagnostic flexible bronchoscopy.

Diesel exhaust particles override natural injury-limiting pathways in the lung.

Induction of effective inflammation in the lung in response to environmental and microbial stimuli is dependent on cooperative signaling between leukocytes and lung tissue cells. We explored how these inflammatory networks are modulated by diesel exhaust particles (DEP) using cocultures of human monocytes with epithelial cells. Cocultures, or monoculture controls, were treated with DEP in the presence or absence of LPS or flagellin. Production of cytokines was explored by Western blotting and ELISA; cell signaling was analyzed by Western blotting. Here, we show that responses of epithelial cells to DEP are amplified by the presence of monocytes. DEP amplified the responses of cellular cocultures to very low doses of TLR agonists. In addition, in the presence of DEP, the responses induced by LPS or flagellin were less amenable to antagonism by the physiological IL-1 antagonist, IL-1ra. This was paralleled by the uncoupling of IL-1 production and release from monocytes, potentially attributable to an ability of DEP to sequester or degrade extracellular ATP. These data describe a model of inflammation where DEP amplifies responses to low concentrations of microbial agonists and alters the nature of the inflammatory milieu induced by TLR agonists.

Syntheses, crystal structures, and magnetic properties of metal-organic hybrid materials of Cu(II): effect of a long chain dicarboxylate backbone, and counteranion in their structural diversity.

Eight new metal-organic hybrid materials of Cu(II) have been synthesized by using flexible glutarate/adipate as a bridging ligand, 2,2'-bipyridine/1,10-phenanthroline as a chelating ligand, and BF4-/ClO4-/Cl- as a counteranion. These materials are characterized by single-crystal X-ray diffraction analyses and variable temperature magnetic measurements. Out of them, complexes 1, 3, 5, and 8 crystallize in the triclinic system with space group P. Complexes 2, 4, 6, and 7 crystallize in the monoclinic system with space group P21/n (2, 4), P21/c (6), and C2 (7). The structural analysis reveals that bridging glutarate gives rise to dinuclear and tetranuclear species, whereas the adipate dianion leads to octanuclear, one-dimensional and two-dimensional polymeric complexes, although they have been prepared under similar conditions. Supramolecular architectures of higher dimensionality have been achieved through H-bonding and pi-pi interaction. In all the complexes, the bridging and/or counteranions as well as chelating ligand have a vital role in directing the solid-state structure. A variable temperature (2-300 K) magnetic susceptibility study discloses the antiferromagnetic coupling for all of the complexes.

Comparison of the effect of sodium hyaluronate (Ophthalin) and hydroxypropylmethylcellulose (HPMC-Ophtal) on corneal endothelium, central corneal thickness, and intraocular pressure after phacoemulsification.

PURPOSE: To prospectively evaluate the effects of 2% hydroxypropyl-methylcellulose (HPMC-Ophtal) and sodium hyaluronate 1% (Ophthalin) on intraocular pressure, corneal thickness, and endothelial cell loss in small incision cataract surgery with implant. METHODS: A total of 110 patients undergoing routine phacoemulsification with implant received either 2% hydroxypropyl methylcellulose or sodium hyaluronate 1% as ophthalmic viscosurgical device. Pre- and postoperative slitlamp examination, intraocular pressure measurement (preoperatively and at 1-4 hours, 1 day, and 7 days postoperatively), ultrasonic pachymetry (preoperatively and at 1 week, 4-6 weeks, and 12 weeks post operatively), and corneal endothelial cell count (preoperatively and 12 weeks postoperatively) were performed. Data were analyzed using two-way analysis of variance. RESULTS: All measurements were comparable between the two groups preoperatively. Intraocular pressure was significantly lower in the Ophthalin group at 1 day post operatively, while no significant difference was found between the two groups on the 1-4 hours and 7 days examination. The central corneal thickness was not significantly different between the two groups at any postoperative visit . However, the mean cell density demonstrated a significant fall of 11.76% for Ophthalin and 4.27% for HPMC-Ophtal at 12 weeks post-operatively, the difference between the two being significant (p=0.009). CONCLUSIONS: 2% Hydroxypropyl methylcellulose, compared with sodium hyaluronate 1%, is superior in protecting the corneal endothelial cells, has the same effect on central corneal thickness, and is associated with slightly higher intraocular pressure 1 day post operatively. It compares favorably with sodium hyaluronate 1% and can be used as an effective and cheaper alternative in routine small incision cataract surgery with implant.

Effect of training on patient outcomes following lobectomy.

BACKGROUND: Little is known about the effect of surgical training on outcomes in thoracic surgery. The impact of surgeon training on outcomes following lung resection was examined, focusing on lobectomy as a marker operation. METHODS: 328 consecutive patients who underwent lobectomy at our institution between 1 October 2001 and 30 June 2003 were studied. Data were collected prospectively during the patient's admission as part of routine clinical practice and validated by a designated audit officer. Patient characteristics and postoperative outcomes were compared between trainee led and consultant led operations. RESULTS: In 115 cases (35.1%) the operation was performed by a trainee thoracic surgeon as the first operator. There were no significant differences in patient characteristics between the two groups. In-hospital mortality was similar for operations led by trainees and consultants (3.5% and 2.8%, respectively; p > 0.99). Outcomes in the two groups did not differ significantly with respect to respiratory, cardiovascular, renal, neurological, chest infection, bleeding, and gastrointestinal complications. Survival rates at 1 year were 82.6% for procedures led by trainees compared with 81.7% for procedures led by consultants (p = 0.83). CONCLUSIONS: With appropriate supervision, trainee thoracic surgeons can perform lobectomies safely without compromising short or intermediate term patient outcome.

Rare azido-bridged manganese(II) systems: syntheses, crystal structures, and magnetic properties.

Two new polymeric azido-bridged manganese complexes of formulas [Mn(N3)2 (bpee)]n (1) and {[Mn(N3)(dpyo)Cl(H2O)2](H2O)}n (2) [bpee, trans-1,2-bis(4-pyridyl)ethylene; dpyo, 4,4'-dipyridyl N,N'-dioxide] have been synthesized and characterized by single-crystal X-ray diffraction analysis and low-temperature magnetic study. Both the complexes 1 and 2 crystallize in the triclinic system, space group P1, with a = 8.877(3) A, b = 11.036(3) A, c = 11.584(4) A, alpha = 72.62(2) degrees, beta = 71.06(2) degrees, gamma = 87.98(3) degrees, and Z = 1 and a = 7.060(3) A, b = 10.345(3) A, c = 11.697(4) A, alpha = 106.86(2) degrees, beta = 113.33(2) degrees, gamma = 96.39(3) degrees, and Z = 2, respectively. Complex 1 exhibits a 2D structure of [-Mn(N3)2-]n chains, connected by bpee ligands, whose pyridine rings undergo pi-pi and C-H...pi interactions. This facilitates the rare arrangement of doubly bridged azide ligands with one end-on and two end-to-end (EO-EE-EE) sequence. Complex 2 is a neutral 1D polymer built up by [Mn(N3)(dpyo)Cl(H2O)2] units and lattice water molecules. The metals are connected by single EE azide ligands, which are arranged in a cis position to the Mn(II) center. The 1D zipped chains are linked by H-bonds involving lattice water molecules and show pi-pi stacking of dpyo pyridine rings to form a supramolecular 2D layered structure. The magnetic studies were performed in 2-300 K temperature range, and the data were fitted by considering an alternating chain of exchange interactions with S = 5/2 (considered as classical spin) with the spin Hamiltonians H = -Ji sigma(S(3i)S(3i+1) + S(3i+1)S(3i+2)) - J2 sigmaS(3i-1)S(3i) and H = -Ji sigmaS(2i)S(2i+1) - J2 sigmaS(2i+1)S(2i+2) for complexes 1 and 2, respectively. Complex 2 exhibits small antiferromagnetic coupling between the metal centers, whereas 1 exhibits a new case of topological ferromagnetism, which is very unusual.

Can pneumonectomy for non-small cell lung cancer be avoided? An audit of parenchymal sparing lung surgery.

BACKGROUND: Lung cancer resection rates are suboptimal in the UK. Pneumonectomy has a higher perioperative mortality risk than lobectomy. To increase resection rates and improve outcomes we have implemented a policy of parenchymal sparing surgery for tumours involving a main stem bronchus. METHODS: In a prospective 4 year study of 119 consecutive patients operated upon by a single surgeon the perioperative course, pathology and survival were compared for 81 patients undergoing pneumonectomy and 38 patients in whom pneumonectomy was avoided by bronchoplastic+/-angioplastic procedures. RESULTS: The rate of pneumonectomy decreased significantly with increasing experience with parenchymal sparing surgery (R(2)=0.98, P<0.001) with 21 of the last 30 patients (70%) avoiding pneumonectomy. There were no significant inter-group differences in patient characteristics, perioperative course or outcome. One-year survival was 64% after pneumonectomy and 73% after sleeve lobectomy. However the perioperative loss of respiratory function was significantly lower in the patients in whom pneumonectomy was avoided (P=0.0003). CONCLUSIONS: Pneumonectomy can be avoided in a large proportion of patients with non-small cell lung cancer of a main stem bronchus without adversely affecting outcome but with preservation of lung function

Effect of prior steroid treatment on temporal artery biopsy findings in giant cell arteritis.

AIM: To examine the effect of up to 6 weeks of corticosteroid treatment on the positive temporal artery biopsy rate in giant cell arteritis (GCA). METHODS: Prospective comparative clinical study of 11 patients meeting the American College of Rheumatology criteria for diagnosis of GCA. Patients underwent temporal artery biopsy within 1 week, at 2-3 weeks, or after 4 weeks of corticosteroid treatment. RESULTS: Overall, nine of 11 (82%) patients had positive temporal artery biopsies. Six of seven (86%) biopsies performed after 4 or more weeks of steroid treatment were positive. CONCLUSION: Temporal artery biopsy is useful several weeks after institution of steroids.

Quantification of relative afferent pupillary defects induced by posterior sub-Tenon's, peribulbar, and retrobulbar anaesthetics.

AIMS: The effect of local anaesthetics on optic nerve function can be investigated by quantifying the relative afferent pupillary defect (RAPD). METHODS: The study compared the depth of induced RAPD following posterior sub-Tenon's, retrobulbar, and peribulbar local anaesthetics using crossed polarising filters before cataract surgery (time 1 = 5 minutes), immediately after surgery (time 2 = 42 minutes (av)), and once again on the ward (time 3 = 107 minutes (av)). RESULTS: All patients developed a RAPD. There was no significant difference in the depth of RAPD between the groups at any one time period. The peribulbar group had a significantly steeper decay in RAPD from time 1 to time 2 (p = 0.014). This effect was reduced when the shorter operation time for this group was entered as a cofactor (p = 0.063). By time 3 the RAPDs for all groups had decayed similarly so that no differences could be detected. CONCLUSION: All three anaesthetic methods caused a similar level of disruption to optic nerve conduction immediately following administration and at the time of day case discharge.

Ensuring complete absence of Ce(IV) and measurement of the stability constant of the fluoride complex of Ce(III).

Literature survey revealed a wide variation in the measured stability constant values of the aqueous fluoride complexes of trivalent cerium. This could be due to inadequate care for full conversion and maintenance of the oxidation state of cerium to trivalent state. In the present work quinhydrone has been used to ensure complete absence of Ce(IV) and the stability constant of CeF(2+) in 1 M NaClO(4) has been measured potentiometrically using a fluoride ion selective electrode. Log beta(1) obtained in this work was 2.936+/-0.024 and fitted well with the general trend of stability constants of the lanthanide (rare earths) fluorides in aqueous solution.

Emergency reinstitution of cardiopulmonary bypass following cardiac surgery: outcome justifies the cost.

OBJECTIVE: Crash back on bypass (crash-BOB) is occasionally required in the resuscitation of patients developing life-threatening complications following cardiac surgery. This study aims to determine the incidence, aetiology and cost-effectiveness of such intervention. METHODS: Retrospective review of all crash-BOB patients over 5.5 years at one hospital. RESULTS: The incidence of crash-BOB was 0.8% and occurred at a mean of 7 h post-operatively (range 1 h-20 days). Pre-operative Parsonnet scores were similar to the overall population of patients undergoing surgery in our institution (mean score 10; range 0-45). The original cardiac operations were coronary revascularization (39), valve surgery (12) and others (4). Indications for crash-BOB were cardiac arrest (23), bleeding (20), hypotension (7), ischaemia (1) and others (4). Of the 55 patients, 20 died on the operating table. Of the remaining 35, a further 12 died in hospital. Overall survival was therefore 42%. Where crash-BOB was for bleeding, 17 of 20 patients (85%) survived to leave theatre, of whom 11 patients (55%) left hospital alive. In the 35 non-bleeders, only 18 (51%) survived crash-BOB and 12 (34%) left hospital alive. Sixteen patients required a second period of aortic cross-clamping of whom 13 (81%) survived to leave theatre, and 11 (69%) left hospital alive. Conversely, of nine patients in whom no specific diagnosis was found during crash-BOB, only two (22%) survived the procedure and none survived to hospital discharge. Multiple logistic regression identified pre-operative Parsonnet score (P=0.045) and the need for aortic cross-clamping to deal with an identified surgical problem (P=0.03) as significant predictors of hospital survival. Indication for crash-BOB (bleeder/non-bleeder) failed to reach significance (P=0.08). Age, sex, intra-aortic balloon pump use at the primary procedure, and time following the primary procedure to crash-BOB were not identified as predictors of hospital survival. Of the 23 hospital survivors, three patients suffered a stroke post-operatively and made a good functional recovery prior to discharge. Two patients developed sternal wound dehiscence requiring surgical rewiring. At follow-up (mean 3 years, range 1-6 years), 19 patients were in NYHA class I and four were in class II. Crash-BOB patients required an average of 8 extra intensive care days and 2 extra ward days. The total cost of these resources was pound164900 (including theatre time, cardiopulmonary bypass and intra-aortic balloon pump use). This was equivalent to pound7170 per life saved. CONCLUSIONS: Crash-BOB occurred in 0.8% of cases and was associated with a survival to discharge of 42%, and a justifiable cost of only pound7170 per life saved. Establishing an accurate diagnosis for the cause of clinical deterioration resulting in crash-BOB intervention was important, and the need for a further period of aortic cross-clamping did not preclude a favourable outcome.