Optimal diagnostic strategies for pleural diseases and identifying high-risk patients.

INTRODUCTION: Pleural diseases encompass a broad range of conditions with diverse and heterogenous etiologies. Diagnostics in pleural diseases thus represents a challenging field with a wide array of available testing to distinguish between the numerous causes of pleural disease. Nonetheless, deploying best practice diagnostics in this area is essential in reducing both duration o the investigation pathway and symptom burden. AREAS COVERED: This article critically appraises the optimal diagnostic strategies and pathway in patients with pleural disease, reviewing the latest evidence and key practice points in achieving a treatable diagnosis in patients with pleural disease. We also cover future and novel directions that are likely to influence pleural diagnostics in the near future. PubMed was searched for articles related to pleural diagnostics (search terms below), with the date ranges including June 2012 to June 2022. EXPERT OPINION: No single test will ever be sufficient to provide a diagnosis in pleural conditions. The key to reducing procedure burden and duration to diagnosis lies in personalizing the investigation pathway to patients and deploying tests with the highest diagnostic yield early (such as pleural biopsy in infection and malignancy). Novel biomarkers may also allow earlier diagnostic precision in the near future.

What can we Learn from Patients who Died from Covid-19 Following Escalation to a Respiratory High Dependency Unit for Trial of Non-Invasive Respiratory Support?

Background: Covid-19 infection is associated with significant risk of death, particularly in older, comorbid patients. Emerging evidence supports use of non-invasive respiratory support (CPAP and high-flow nasal oxygen [HFNO]) in this context, but little is known about its use in patients receiving end-of-life care. Methods: This was a retrospective study of 33 patients who died of Covid-19 on the Respiratory High Dependency Unit at the John Radcliffe Hospital, Oxford between 28/03/20 and 20/05/20. Data was sourced via retrospective review of electronic patient records and drug charts. Results: Patients dying from Covid-19 on the Respiratory HDU were comorbid with median Charlson Comorbidity Index 5 (IQR 4-6); median age 78 (IQR 72-85). Respiratory support was trialled in all but one case with CPAP being the most common form of first line respiratory support (84.8%) however, was only tolerated in 44.8% of patients. Median time to death was 10.7 days from symptom onset (IQR 7.5-14.6) and 4.9 days from hospital admission (IQR 3.1-8.3). 48.5% of patients remained on respiratory support at the time of death. Conclusions: End-of-life care for patients with Covid-19 remains a challenge. Patients tend to be frail and comorbid with a rapid disease trajectory. Non-Invasive Respiratory Support may play a key role in symptom management in select patients, however, further work is needed in order to identify patients who will most benefit from Respiratory Support and those for whom withdrawal may prevent unnecessary distress at the end of life or potential prolongation of suffering.

CT appearances of pleural infection: analysis of the Second Multi-centre Intra-pleural Sepsis Trial (MIST 2) cohort.

AIM: To determine the prevalence of pleural abnormalities and describe the computed tomography (CT) features observed in a well-characterised population of patients with pleural infection. MATERIALS AND METHODS: A retrospective study of a subgroup of patients from the Second Multi-centre Intra-pleural Sepsis Trial (MIST 2) trial was carried out. Patients were diagnosed with pleural infection on robust clinical criteria. CT examinations were assessed by three observers independently for the presence of predefined features. Planned subgroup comparisons of patients with and without evidence of parenchymal infection were performed. RESULTS: Eighty-one patients were included. Parietal pleural thickening and enhancement were seen in 98.7% of patients. Visceral pleural changes were observed in most, including several previously undescribed features. Consolidation was observed in 61.7% of patients and there was a significant association of parenchymal consolidation with CT evidence of small airways infection (p<0.001) and visceral pleural thickening and enhancement (p<0.05). Features of parenchymal infection were absent in one third of patients. CONCLUSION: This study provides a comprehensive account of the parietal pleural, visceral pleural, and parenchymal changes of pleural infection on CT. Parenchymal infection is absent in a significant proportion of patients with pleural infection, suggesting that a pneumonic process may not be necessary for the development of pleural infection.

COVID-19 in the least developed, fragile, and conflict-affected countries - How can the most vulnerable be protected?

The relentless spread of coronavirus disease 2019 (COVID-19) and its penetration into the least developed, fragile, and conflict-affected countries (LDFCAC) is a certainty. Expansion of the pandemic will be expedited by factors such as an abundance of at-risk populations, inadequate COVID-19 mitigation efforts, sheer inability to comply with community mitigation strategies, and constrained national preparedness. This situation will reduce the benefits achieved through decades of disease control and health promotion measures, and the economic progress made during periods of global development. Without interventions, and as soon as international travel and trade resume, reservoirs of COVID-19 and other vaccine-preventable diseases in LDFCAC will continue 'feeding' developed countries with repeated infection seeds. Assuring LDFCAC equity in access to medical countermeasures, funds to mitigate the pandemic, and a paradigm change in the global development agenda, similar to the post-World War II Marshall Plan for Europe, are urgently needed. We argue for a paradigm change in strategy, including a new global pandemic financing mechanism for COVID-19 and other future pandemics. This approach should assist LDFCAC in gaining access to and membership of a global interdisciplinary pandemic taskforce to enable in-country plans to train, leverage, and maintain essential functioning and also to utilize and enhance surveillance and early detection capabilities. Such a task force will be able to build on and expand research into the management of pandemics, protect vulnerable populations through international laws/treaties, and reinforce and align the development agenda to prevent and mitigate future pandemics. Lifting LDFCAC from COVID-related failure will offer the global community the best economic dividends of the century.

All Hands on Deck: A synchronized whole-of-world approach for COVID-19 mitigation.

The COVID-19 pandemic can no longer be mitigated by a nationwide approach of individual nations alone. Given its scale and accelerating expansion, COVID-19 requires a coordinated and simultaneous Whole- of-World approach that galvanizes clear global leadership and solidarity from all governments of the world. Considering an 'all hands-on deck' concept, we present a comprehensive list of tools and entities responsible for enabling them, as well a conceptual framework to achieve the maximum impact. The list is drawn from pandemic mitigation tools developed in response to past outbreaks including influenza, coronaviruses, and Ebola, and includes tools to minimize transmission in various settings including person-to-person, crowd, funerals, travel, workplace, and events and gatherings including business, social and religious venues. Included are the roles of individuals, communities, government and other sectors such as school systems, health, institutions, and business. While individuals and communities have significant responsibilities to prevent person-to-person transmission, other entities can play a significant role to enable individuals and communities to make use of the tools. Historic and current data indicate the role of political will, whole-of-government approach, and the role of early introduction of mitigation measures. There is also an urgent need to further elucidate the immunologic mechanisms underlying the epidemiological characteristics such as the low disease burden among women, and the role of COVID-19 in inducing Kawasaki-like syndromes in children. Understanding the role of and development of anti-inflammatory strategies based on our understanding of pro-inflammatory cytokines (IL1, IL-6) is also critical. Similarly, the role of oxygen therapy as an anti-inflammatory strategy is evident and access to oxygen therapy should be prioritized to avoid the aggravation of COVID-19 infection. We highlight the need for global solidarity to share both mitigation commodities and infrastructure between countries. Given the global reach of COVID-19 and potential for repeat waves of outbreaks, we call on all countries and communities to act synergistically and emphasize the need for synchronized pan-global mitigation efforts to minimize everyone's risk, to maximize collaboration, and to commit to shared progress.

Pulmonary nodules: Assessing the imaging biomarkers of malignancy in a "coffee-break".

INTRODUCTION: Although nodule volumetry is a recognized biomarker of malignancy in pulmonary nodules (PNs), caution is needed in its interpretation because of variables such as respiratory volume variation and inter-scan variability of up to 25%. CT Texture Analysis (CTTA) is a potential independent biomarker of malignancy but inter-scan variability and respiratory volume variation has not been assessed. METHODS: In this prospective cohort study, 40 patients (20 with an indeterminate PN and 20 with pulmonary metastases) underwent two LDCTs within a 60-min period (the "Coffee-break") with the aim of assessing the repeatability of CTTA and semi-automated volume measurements. Texture features were extracted from each automatic contoured region surrounding the PN. Patients were also randomized to two inspiratory control groups: normal breath hold, and controlled lung volume to study the influence of inspiratory control on these measurements. RESULTS: The mean difference in volume between the two scans was 6.3%,SD:29.9%. The textural features displayed 95% CI below ±17.8%, and were less variable than nodule volume (95%CI ±â€¯28.9%). All features had high repeatability, calculated by the concordance correlation coefficient, (0.84 ≤ CCC ≤ 0.99). All measurements were more repeatable for the controlled lung volume group than the normal breath-hold group. CONCLUSION: CTTA repeatability was comparable to automatic volumetric measurements, and appears to be improved using controlled volume breath holding.

A retrospective validation study of three models to estimate the probability of malignancy in patients with small pulmonary nodules from a tertiary oncology follow-up centre.

AIM: To estimate the probability of malignancy in small pulmonary nodules (PNs) based on clinical and radiological characteristics in a non-screening population that includes patients with a prior history of malignancy using three validated models. MATERIALS AND METHODS: Retrospective data on clinical and radiological characteristics was collected from the medical records of 702 patients (379 men, 323 women; range 19-94 years) with PNs ≤12 mm in diameter at a single centre. The final diagnosis was compared to the probability of malignancy calculated by one of three models (Mayo, VA, and McWilliams). Model accuracy was assessed by receiver operating characteristics (ROC). The models were calibrated by comparing predicted and observed rates of malignancy. RESULTS: The area under the ROC curve (AUC) was highest for the McWilliams model (0.82; 95% confidence interval [CI]: 0.78-0.91) and lowest for the Mayo model (0.58; 95% CI: 0.55-0.59). The VA model had an AUC of (0.62; 95% CI: 0.47-0.64). Performance of the models was significantly lower than that in the published literature. CONCLUSIONS: The accuracy of the three models is lower in a non-screening population with a high prevalence of prior malignancy compared to the papers that describe their development. To the authors' knowledge, this is the largest study to validate predictive models for PNs in a non-screening clinically referred patient population, and has potential implications for the implementation of predictive models.

Effectiveness of chemical pleurodesis in spontaneous pneumothorax recurrence prevention: a systematic review.

OBJECTIVES: Spontaneous pneumothorax is a common pathology. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second occurrence. This study comprehensively reviews the existing literature regarding chemical pleurodesis efficacy. DESIGN: We systematically reviewed the literature to identify relevant randomised controlled trials (RCTs), case-control studies and case series. We described the findings of these studies and tabulated relative recurrence rates or ORs (in studies with control groups). Meta-analysis was not performed due to substantial clinical heterogeneity. RESULTS: Of 560 abstracts identified by our search strategy, 50 were included in our systematic review following screening. Recurrence rates in patients with chest tube drainage only were between 26.1% and 50.1%. Thoracoscopic talc poudrage (four studies (n=249)) provided recurrence rates of between 2.5% and 10.2% with the only RCT suggesting an OR of 0.10 compared with drainage alone. In comparison, talc administration during video-assisted thoracic surgery (VATS) from eight studies (n=2324) recurrence was between 0.0% and 3.2%, but the RCT did not demonstrate a significant difference compared with bleb/bullectomy alone. Minocycline appears similarly effective post-VATS (recurrence rates 0.0-2.9%). Prolonged air leak and recurrence prevention using tetracycline via chest drain (n=726) is likely to provide recurrence rates between 13.0% and 33.3% and autologous blood patch pleurodesis (n=270) between 15.6% and 18.2%. CONCLUSIONS: Chemical pleurodesis postsurgical treatment or via thoracoscopy appears to be most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised trials or other comparative studies.

Molecular cloning and expression pattern of oriental river prawn (Macrobrachium nipponense) nitric oxide synthase.

Nitric oxide synthase (NOS) produces nitric oxide (NO) by catalyzing the conversion of l-arginine to l-citrulline, with the concomitant oxidation of nicotinamide adenine dinucleotide phosphate. Recently, various studies have verified the importance of NOS invertebrates and invertebrates. However, the NOS gene family in the oriental river prawn Macrobrachium nipponense is poorly understood. In this study, we cloned the full-length NOS complementary DNA from M. nipponense (MnNOS) and characterized its expression pattern in different tissues and at different developmental stages. Real-time quantitative polymerase chain reaction (RT-qPCR) showed the MnNOS gene to be expressed in all investigated tissues, with the highest levels observed in the androgenic gland (P < 0.05). Our results revealed that the MnNOS gene may play a key role in M. nipponense male sexual differentiation. Moreover, RT-qPCR revealed that MnNOS mRNA expression was significantly increased in post-larvae 10 days after metamorphosis (P < 0.05). The expression of this gene in various tissues indicates that it may perform versatile biological functions in M. nipponense.

Spatial Variation of Arsenic in Soil, Irrigation Water, and Plant Parts: A Microlevel Study.

Arsenic pollution became a great problem in the recent past in different countries including Bangladesh. The microlevel studies were conducted to see the spatial variation of arsenic in soils and plant parts contaminated through ground water irrigation. The study was performed in shallow tube well command areas in Sadar Upazila (subdistrict), Faridpur, Bangladesh, where both soil and irrigation water arsenic are high. Semivariogram models were computed to determine the spatial dependency of soil, water, grain, straw, and husk arsenic (As). An arsenic concentration surface was created spatially to describe the distribution of arsenic in soil, water, grain, straw, and husk. Command area map was digitized using Arcview GIS from the "mouza" map. Both arsenic contaminated irrigation water and the soils were responsible for accumulation of arsenic in rice straw, husk, and grain. The accumulation of arsenic was higher in water followed by soil, straw, husk, and grain. Arsenic concentration varied widely within command areas. The extent and propensity of arsenic concentration were higher in areas where high concentration of arsenic existed in groundwater and soils. Spherical model was a relatively better and appropriate model. Kriging method appeared to be more suitable in creating interpolated surface. The average arsenic content in grain was 0.08-0.45 mg/kg while in groundwater arsenic level it ranged from 138.0 to 191.3 ppb.

Molecular cloning and expression analysis of Fem1b from oriental river prawn Macrobrachium nipponense.

Feminization-1 homolog b (Fem1b) is one of the genes essential for male development and play central roles in sex determination of Caenorhabditis elegans. In this study, we cloned and characterized the full-length Fem1b cDNA from the freshwater prawn Macrobrachium nipponense (MnFem1b) in different tissues and at different developmental stages. Real-time quantitative reverse polymerase chain reaction (RT-qPCR) showed that the MnFem1b gene was expressed in all investigated tissues, with the highest expression level found in the testes. The results revealed that the MnFem1b gene might play roles in aspects of development of the male prawn phenotype. The RT-qPCR also revealed that MnFem1b mRNA expression was significantly increased at 10 days after metamorphosis. The expression levels in all investigated tissues showed a certain degree of sexually dimorphism, the expression levels in males were significantly higher than those in females (P < 0.05). Notably, the highest expression of MnFem1b was found in the testes. The expression of MnFem1b in different tissues indicates that it plays multiple biological functions in M. nipponense.

The diagnosis of pleural effusions.

Pleural effusions arise from a variety of systemic, inflammatory, infectious and malignant conditions. Their precise etiological diagnosis depends on a combination of medical history, physical examination, imaging tests and pertinent pleural fluid analyses; including specific biomarkers (e.g., natriuretic peptides for heart failure, adenosine deaminase for tuberculosis, or mesothelin for mesothelioma). Invasive procedures, such as pleuroscopic biopsies, may be required for persistently symptomatic effusions which remain undiagnosed after the analysis of one or more pleural fluid samples. However, whenever parietal pleural nodularity or thickening exist, image-guided biopsies should first be attempted. This review addresses the current diagnostic approach to pleural effusions secondary to heart failure, pneumonia, cancer, tuberculosis and other less frequent conditions.

The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial.

BACKGROUND: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. METHOD: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. RESULTS: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. CONCLUSIONS: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.

The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication.

BACKGROUND: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. METHODS: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. FINDINGS: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001). INTERPRETATION: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response.

Role of CT in assessing pleural malignancy prior to thoracoscopy.

The definitive diagnosis of pleural malignancy depends upon histological confirmation by pleural biopsy. CT is reported to have a high sensitivity and specificity for the diagnosis of malignant pleural disease, and is part of the routine diagnostic workup of these patients. The aim of this study was to assess the sensitivity and specificity of CT in detecting pleural malignancy prior to definitive histology obtained via thoracoscopy in a large cohort of patients with suspected malignant pleural disease. Retrospective review of thoracoscopies between January 2008 and January 2013 at two UK tertiary referral centres: Oxford and Preston. The histological results were compared with the CT reported diagnosis before the procedure. CT scan reports were assessed by independent respiratory physicians as to whether the radiologist concluded evidence of malignant pleural disease or benign features only. 211 (57%) of 370 patients included in the analysis had malignant disease: CT scans were reported as 'malignant' in 144, giving a sensitivity of 68% (95% CI 62% to 75%). Of the 159 patients with benign disease, 124 had CT scans reported as benign: specificity 78% (72% to 84%). The positive predictive value of a malignant CT report was 80% (75% to 86%), with a negative predictive value of 65% (58% to 72%). A significant proportion of patients being investigated for malignant disease will have malignancy despite a negative CT report. The use of CT alone in determining which patients should have invasive pleural biopsies should be re-evaluated, and further studies to define the diagnostic pathway are now required.

Effect of submucosal injection of dexamethasone on postoperative discomfort after third molar surgery: a prospective study.

AIM: To evaluate the relative ability of 4 mg dose of intraoperative dexamethasone, administered submucosally, to reduce the postoperative discomfort after third molar surgery. MATERIALS AND METHODS: A total of 100 patients requiring surgical removal of a single mandibular third molar were included. The experimental group (50) received dexamethasone 4 mg as submucosal injection and control group (50) received no drugs. The maximum interincisal distance and facial contours were measured at baseline and at postsurgery days 2 and 7. The measurement of pain was done using visual analog scale (VAS). RESULTS: None of the patients developed wound infection or any serious postoperative complications. Postoperative edema tended to be less severe on the second postoperative day in the experimental group and the result was statistically significant. There were no significant differences in the reduction of pain and trismus between the two groups studied. CONCLUSION: Submucosal administration of dexamethasone sodium phosphate (4 mg) results in reduction of postoperative edema, comparable with or greater than other routes of administration. Presumably, a higher effective drug concentration at the site of injury without loss due to distribution to other compartments may be achieved, and the submucosal route is convenient for both the surgeon and the patient. CLINICAL SIGNIFICANCE: Submucosal route of administration of dexamethasone (4 mg) is effective in reducing postoperative discomfort after third molar surgeries.