The role of imaging in malignant pleural mesothelioma: an update after the 2018 BTS guidelines.

Malignant pleural mesothelioma (MPM) is a primary malignancy of the pleura and is associated with a poor outcome. The symptoms and signs of malignant mesothelioma present late in the natural history of the disease and are non-specific, making the diagnosis challenging and imaging key. In 2018, the British Thoracic Society (BTS) updated the guideline on diagnosis, staging, and follow-up of patients with MPM. These recommendations are discussed in this review of the current literature on imaging of MPM. It is estimated MPM will continue to cause serious morbidity and mortality in the UK late into the 21st century, and internationally, people continue to be exposed to asbestos. We aim to update the reader on current and future imaging strategies, which could aid early diagnosis of pleural malignancy and provide an update on staging and assessment of tumour response.

Non-invasive methods for estimating mPAP in COPD using cardiovascular magnetic resonance imaging.

PURPOSE: Pulmonary hypertension (PH) is associated with a poor outcome in chronic obstructive pulmonary disease (COPD) and is diagnosed invasively. We aimed to assess the diagnostic accuracy and prognostic value of non-invasive cardiovascular magnetic resonance (CMR) models. METHODS: Patients with COPD and suspected PH, who underwent CMR and right heart catheter (RHC) were identified. Three candidate models were assessed: 1, CMR-RV model, based on right ventricular (RV) mass and interventricular septal angle; 2, CMR PA/RV includes RV mass, septal angle and pulmonary artery (PA) measurements; 3, the Alpha index, based on RV ejection fraction and PA size. RESULTS: Of 102 COPD patients, 87 had PH. The CMR-PA/RV model had the strongest diagnostic accuracy (sensitivity 92%, specificity 80%, positive predictive value 96% and negative predictive value 63%, AUC 0.93, p<0.0001). Splitting RHC-mPAP, CMR-RV and CMR-PA/RV models by 35mmHg gave a significant difference in survival, with log-rank chi-squared 5.03, 5.47 and 7.10. RV mass and PA relative area change were the independent predictors of mortality at multivariate Cox regression (p=0.002 and 0.030). CONCLUSION: CMR provides diagnostic and prognostic information in PH-COPD. The CMR-PA/RV model is useful for diagnosis, the RV mass index and PA relative area change are useful to assess prognosis. KEY POINTS: • Pulmonary hypertension is a marker of poor outcome in COPD. • MRI can predict invasively measured mean pulmonary artery pressure. • Cardiac MRI allows for estimation of survival in COPD. • Cardiac MRI may be useful for follow up or future trials. • MRI is potentially useful to assess pulmonary hypertension in patients with COPD.

A Q methodology study to investigate the experiences of head and neck cancer patients from diagnosis to 1 year.

The experiences of disease and treatment for patients diagnosed with head and neck cancer (H&NC) are known to be important indicators of the quality of care but are represented poorly in the literature. Survival is a major outcome measure to which health-related quality of life (HRQoL) adds detail but outcomes are not fully representative of the patients' experiences because quality of care and reality of treatment are overlooked. This study explored the HRQoL, quality of care and reality of treatment themes using a mixed-methods approach, Q Methodology. In total, 18 participants who were at least 12 months post-diagnosis rank-ordered 45 prepared statements to reflect their own experiences of H&NC. After the statements had been sorted, the participants reviewed the order in an interview to clarify experiences. The statements become a way of facilitating the discussion because the participant can explain the position of specific statements that are notable for them. The ranking was factor-analysed case-wise and five factors provided the best conceptual fit: meaning and attachment to illness; overwhelmed by the cancer; surviving or not; change and recovery; and keep control for the greater good of others. The findings suggest there are distinct ways that H&NC patients experience the disease and its treatment. The concept of the experience being different and defined for individuals has practical implications at a clinical level and is a way of ensuring care is truly patient-centred.

CT features of pulmonary arterial hypertension and its major subtypes: a systematic CT evaluation of 292 patients from the ASPIRE Registry.

We evaluated the prevalence and prognostic value of CT-pulmonary angiographic (CTPA) measures in 292 treatment naive patients with pulmonary arterial hypertension (PAH). Pulmonary artery calcification (13%) and thrombus (10%) were exclusively seen in PAH-congenital heart disease. Oesophageal dilation (46%) was most frequent in PAH-systemic sclerosis. Ground glass opacification (GGO) (41%), pericardial effusion (38%), lymphadenopathy (19%) and pleural effusion (11%) were common. On multivariate analysis, inferior vena caval area, the presence of pleural effusion and septal lines predicted outcome. In PAH, CTPA provides diagnostic and prognostic information. In addition, the presence of GGO on a CT performed for unexplained breathlessness should alert the physician to the possibility of PAH.

FESS, fingers and other things--you are not alone!

BACKGROUND: The objectives of the study were: firstly, to determine the prevalence and severity of musculoskeletal symptoms attributed to the use of endoscope or body posture during endoscopic sinus surgery (ESS) among members of the British Rhinological Society (BRS); and secondly, to review the available literature and highlight posture recommendations during ESS. METHODOLOGY: The study design consisted of a cross-sectional survey carried out among members of the BRS. The survey was distributed electronically and data was collected for statistical analysis. RESULTS: A total of 82 members responded to the questionnaire (22.4%); 78 respondents (94%) answered the main questions in the survey regarding the symptoms attributed to the use of endoscope or body posture during ESS. Fifty-three respondents (64%) completed all 19 questions. 58% and 59% of the 78 respondents reported suffering from pain and stiffness respectively. We found positive correlations between musculoskeletal symptoms and operating in the standing position and musculoskeletal symptoms and age. CONCLUSION: This survey reveals a high prevalence of musculoskeletal symptoms, attributed to ESS and body posture during surgery, among the British rhinologists who responded to the survey. ESS is evidently physically demanding on the surgeon with potential personal health hazards. This emphasizes the need to increase awareness among surgeons, familiarize ourselves with good operating posture habits and new ergonomic instruments and to create a drive to change operating theatre culture in an attempt to reduce these health risks.

Single centre prospective study of the efficacy of percutaneous cement augmentation in the treatment of vertebral compression fractures.

INTRODUCTION: Despite controversial outcomes of recent published trials, percutaneous cement augmentation remains widely used in managing painful vertebral compression fractures. We prospectively assessed patients with such fractures using an eleven-point visual analogue scale for pain and the Qualeffo 41 questionnaire for quality of life. METHODS: Consecutive patients undergoing percutaneous cement augmentation for painful vertebral compression fractures were recruited. Patients were assessed pre-procedure by completing a visual analogue scale for pain, on a scale of 0 to 10. A Qualeffo 41 questionnaire was also completed. Patients were followed up at 1 week and 3 months. RESULTS: Fifty six patients were prospectively recruited (111 vertebroplasty and 5 kyphoplasty). Visual analogue scores dropped from 6.4 ± 2.3 pre-procedure to 4.0 ± 2.7 at 1 week (p < 0.0001) and 4.3 ± 2.7 (p < 0.0001) at 3 months. Three subgroups were identified; osteoporotic patients (n = 28), a second non-osteoporotic group (n = 20) who had acute fracture following fall and a third group with compression fractures secondary to metastatic disease (n = 8). At 3-month follow-up, patients with osteoporotic fractures had reduction in pain score from 6.3 ± 2.1 to 4.8 ± 2.7 (p = 0.02). Patients who had traumatic fractures experienced more significant pain relief, 6.4 ± 2.6 to 3.8 ± 2.7 (p = 0.0009) but patients with malignant fracture had most benefit, 6.0 ± 3.0 to 1.8 ± 0.8 (p = 0.01). Total Qualeffo scores improved from 63 ± 15 to 49 ± 22 (p < 0.0001). Within the domains of the Qualeffo questionnaire, most improvement was seen in pain and physical function. Median in-patient stay post procedure was one day. CONCLUSION: In our experience percutaneous cement augmentation is safe and efficacious in the management of painful VCF related to osteoporosis, trauma and cancer, achieving rapid and significant pain reduction and improvement in physical function as measured with a visual analogue scale and the Qualeffo 41 questionnaire.

A role for coding functional variants in HNF4A in type 2 diabetes susceptibility.

AIMS/HYPOTHESIS: Rare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4α (HNF-4A), account for ~5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes. Two low-frequency, non-synonymous variants in HNF4A (V255M, minor allele frequency [MAF] ~0.1%; T130I, MAF ~3.0%)-known to influence downstream HNF-4A target gene expression-are of interest, but previous type 2 diabetes association reports were inconclusive. We aimed to evaluate the contribution of these variants to type 2 diabetes susceptibility through large-scale association analysis. METHODS: We genotyped both variants in at least 5,745 cases and 14,756 population controls from the UK and Denmark. We also undertook an expanded association analysis that included previously reported and novel genotype data obtained in Danish, Finnish, Canadian and Swedish samples. A meta-analysis incorporating all published association studies of the T130I variant was subsequently carried out in a maximum sample size of 14,279 cases and 26,835 controls. RESULTS: We found no association between V255M and type 2 diabetes in either the initial (p = 0.28) or the expanded analysis (p = 0.44). However, T130I demonstrated a modest association with type 2 diabetes in the UK and Danish samples (additive per allele OR 1.17 [95% CI 1.08-1.28]; p = 1.5 × 10⁻4), which was strengthened in the meta-analysis (OR 1.20 [95% CI 1.10-1.30]; p = 2.1 × 10⁻5). CONCLUSIONS/INTERPRETATION: Our data are consistent with T130I as a low-frequency variant influencing type 2 diabetes risk, but are not conclusive when judged against stringent standards for genome-wide significance. This study exemplifies the difficulties encountered in association testing of low-frequency variants.

Self-Rated Frailty and Mortality in Old Men: The Manitoba Follow-up Study.

BACKGROUND: While a multitude of definitions and operationalizations of frailty have been developed, rarely have these considered the perspective of the older adult themselves. This knowledge gap was addressed by examining older adults' self-rating of frailty. OBJECTIVES: To assess the validity of self-rated frailty and to determine whether self-rated frailty relates to mortality. DESIGN: The Manitoba Follow-up Study was initiated in 1948 as a prospective cohort study of 3,983 men. SETTING: Community dwelling older adult men. PARTICIPANTS: Survivors of the original cohort (231 men) were sent a quality of life survey in 2015. A response was received from 186 men, including 146 surveys completed by the participant himself and thus were eligible to include (completion rate of 78.4%). MEASUREMENTS: The quality of life survey is sent out annually to the study participants to ascertain information about mental, physical, and social functioning. In 2015, the Clinical Frailty Scale was adapted and added to the survey as a simple self-rating of frailty. RESULTS: The mean age of the 146 respondents in 2015 was 93.7 years (SD 2.7) Self-ratings of "moderate-severe" frailty, received from 132 men, were associated with worse measures of physical health and functional impairment, thus supporting the significance of self-rated frailty. Adjusted for age, the Hazard Ratio for mortality over the next 3 years was 3.3 (95% CI: 1.5, 7.1) for those who rated themselves as "mildly to severely frail" vs. "very fit or well, with no disease". CONCLUSION: The present study has illustrated that self-rated frailty is associated with other measures of health and that self-rated frailty predicts mortality over a three-year period. These findings support the utilization of older adult's self-ratings of frailty for new avenues of operationalizing frailty.

A Golgi retention signal in a membrane-spanning domain of coronavirus E1 protein.

The E1 glycoprotein from an avian coronavirus is a model protein for studying retention in the Golgi complex. In animal cells expressing the protein from cDNA, the E1 protein is targeted to cis Golgi cisternae (Machamer, C. E., S. A. Mentone, J. K. Rose, and M. G. Farquhar. 1990. Proc. Natl. Acad. Sci. USA. 87:6944-6948). We show that the first of the three membrane-spanning domains of the E1 protein can retain two different plasma membrane proteins in the Golgi region of transfected cells. Both the vesicular stomatitis virus G protein and the alpha-subunit of human chorionic gonadotropin (anchored to the membrane by fusion with the G protein membrane-spanning domain and cytoplasmic tail) were retained in the Golgi region of transfected cells when their single membrane-spanning domains were replaced with the first membrane-spanning domain from E1. Single amino acid substitutions in this sequence released retention of the chimeric G protein, as well as a mutant E1 protein which lacks the second and third membrane-spanning domains. The important feature of the retention sequence appears to be the uncharged polar residues which line one face of a predicted alpha helix. This is the first retention signal to be defined for a resident Golgi protein. The fact that it is present in a membrane-spanning domain suggests a novel mechanism of retention in which the membrane composition of the Golgi complex plays an instrumental role in retaining its resident proteins.

Oligomerization of a membrane protein correlates with its retention in the Golgi complex.

The first membrane-spanning domain (m1) of the M glycoprotein of avian coronavirus (formerly called E1) is sufficient to retain this protein in the cis-Golgi. When the membrane-spanning domain of a protein which is efficiently delivered to the plasma membrane (VSV G protein) is replaced with m1, the resulting chimera (Gm1) is retained in the Golgi (Swift, A. M., and C. E. Machamer. 1991. J. Cell Biol. 115:19-30). When assayed in sucrose gradients, we observed that Gm1 formed a large oligomer, and that much of this oligomer was SDS resistant and stayed near the top of the stacking gel of an SDS-polyacrylamide gel. The unusual stability of the oligomer allowed it to be detected easily. Gm1 mutants with single amino acid substitutions in the m1 domain that were retained in the Golgi complex formed SDS-resistant oligomers, whereas mutants that were rapidly released to the plasma membrane did not. Oligomerization was not detected immediately after synthesis of Gm1, but occurred gradually with a lag of approximately 10 min, suggesting that it is not merely aggregation of misfolded proteins. Furthermore, oligomerization did not occur under several conditions that block ER to Golgi transport. The lumenal domain was not required for oligomerization since another chimera (alpha m1G), where the lumenal domain of Gm1 was replaced by the alpha subunit of human chorionic gonadotropin, also formed an SDS-resistant oligomer, and was able to form hetero-oligomers with Gm1 as revealed by coprecipitation experiments. SDS resistance was conferred by the cytoplasmic tail of VSV G, because proteolytic digestion of the tail in microsomes containing Gm1 oligomers resulted in loss of SDS resistance, although the protease-treated material continued to migrate as a large oligomer on sucrose gradients. Interestingly, treatment of cells with cytochalasin D blocked formation of SDS-resistant (but not SDS-sensitive) oligomers. Our data suggest that SDS-resistant oligomers form as newly synthesized molecules of Gm1 arrive at the Golgi complex and may interact (directly or indirectly) with an actin-based cytoskeletal matrix. The oligomerization of Gm1 and other resident proteins could serve as a mechanism for their retention in the Golgi complex.

Reversal of the effects of clonidine using naloxone.

An 18-year-old man underwent surgery for correction of idiopathic scoliosis. Due to the requirement for intra-operative spinal cord monitoring, propofol and remifentanil total intravenous anaesthesia was chosen as the anaesthetic technique. Clonidine was given intra-operatively as part of his analgesic regimen. No long-acting opioids were administered. There was delayed emergence after switching off total intravenous anaesthesia and he remained sedated with a bispectral index of approximately 60 for 90 min. The common causes of delayed emergence were excluded. Shortly after administering naloxone, there was an increase in bispectral index and emergence from anaesthesia. We describe the successful use of naloxone to reverse the sedation effects of clonidine.

Sinonasal papilloma: what influences the decision to request a magnetic resonance imaging scan?

BACKGROUND: Computed tomography is the standard pre-operative imaging modality for sinonasal papilloma. The complementary use of magnetic resonance imaging as an additional investigation is debated. This study aimed to establish whether magnetic resonance imaging can accurately detect tumour extent and is a useful adjunct to computed tomography. METHODS: A retrospective review was conducted on 19 patients with sinonasal papilloma. The interpretation of computed tomography and magnetic resonance imaging scans, by three clinicians, was conducted by comparing prediction of tumour extent. The perceived necessity of magnetic resonance imaging was compared between clinicians. RESULTS: The addition of magnetic resonance imaging improved accuracy of pre-operative interpretation; specifically, this finding was significant in cases with frontal sinus involvement. Surgeons were more likely than a radiologist to request magnetic resonance imaging, particularly when computed tomography indicated frontal sinus disease. CONCLUSION: Pre-operative combined magnetic resonance imaging and computed tomography helped predict disease in the frontal sinus better than computed tomography alone. A close working relationship between the ENT and radiology departments is important for accurate tumour localisation.

Retention of a cis Golgi protein requires polar residues on one face of a predicted alpha-helix in the transmembrane domain.

The first membrane-spanning domain (m1) of the model cis Golgi protein M (formerly called E1) from the avian coronavirus infectious bronchitis virus is required for targeting to the Golgi complex. When inserted in place of the membrane-spanning domain of a plasma membrane protein (vesicular stomatitis virus G protein), the chimeric protein ("Gm1") is retained in the Golgi complex of transfected cells. To determine the precise features of the m1 domain responsible for Golgi targeting, we produced single amino acid substitutions in m1 and analyzed their effects on localization of Gm1. Expression at the plasma membrane was used as the criterion for loss of Golgi retention. Rates of oligosaccharide processing were used as a measure of rate and efficiency of transport through the Golgi complex. We identified four uncharged polar residues that are critical for Golgi retention of Gm1 (Asn465, Thr469, Thr476, and Gln480). These residues line one face of a predicted alpha-helix. Interestingly, when the m1 domain of the homologous M protein from mouse hepatitis virus is inserted into the G protein reporter, the chimeric protein is not efficiently retained in the Golgi complex, but transported to the cell surface. Although it possesses three of the four residues we identified as important in the avian m1 sequence, other residues in the membrane-spanning domain from the mouse protein must prevent efficient recognition of the polar face within the lipid bilayer of the cis Golgi.

Management of inverted papilloma: review.

BACKGROUND: Inverted papilloma is the most common benign tumour affecting the nose. There is a high rate of recurrence and a potential of malignant transformation. This review article aimed to identify the best available management of this pathology today. METHOD: A systematic review of the current English-language literature was performed. Only original articles with a minimum follow up of one year and an average follow up of two years were included. RESULTS: A total of 1385 patients from 16 case series were identified. The total recurrence rate for all patients was 11.5 per cent. Significantly lower recurrence rates were found for procedures using an attachment-oriented excision (recurrence of 6.9 per cent; p = 0.0001) and utilising frozen sections (recurrence of 7.0 per cent; p = 0.0001). CONCLUSION: There is a general trend towards endoscopic surgery. There may be some benefit to the use of attachment-oriented surgery and frozen sections. Multi-centred randomised controlled trials are required.

Penetrating neck trauma and the need for surgical exploration: six-year experience within a regional trauma centre.

BACKGROUND: There has been a shift towards conservative management of penetrating neck trauma in selected patients. METHODS: A retrospective case note review of the management of penetrating neck trauma (2007-2013) was undertaken at our large teaching hospital and compared against best-evidenced practice. RESULTS: Sixty-three patients were admitted over six years. The incidence of penetrating neck trauma is reducing, contrary to our belief. Most cases were knife inflicted (33 out of 63), and of these most were attempted suicide. There was a high rate of negative findings for neck explorations under general anaesthesia (18 out of 22). Only nine cases had justification for general anaesthesia exploration according to best practice. CONCLUSION: The rate of neck explorations under general anaesthesia has dramatically fallen, in line with best practice. The need for operative intervention in patients with penetration of the aerodigestive tract or a major vascular injury should be based on clinical features, and these have been shown to be reliable indicators prior to open exploration.

Nose and paranasal sinus tumours: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. With only limited high-level evidence for management of nasal and paranasal sinus cancers owing to low incidence and diverse histology, this paper provides recommendations on the work up and management based on the existing evidence base. Recommendations • Sinonasal tumours are best treated de novo and unusual polyps should be imaged and biopsied prior to definitive surgery. (G) • Treatment of sinonasal malignancy should be carefully planned and discussed at a specialist skull base multidisciplinary team meeting with all relevant expertise. (G) • Complete surgical resection is the mainstay of treatment for inverted papilloma and juvenile angiofibroma. (R) • Essential equipment is necessary and must be available prior to commencing endonasal resection of skull base malignancy. (G) • Endoscopic skull base surgery may be facilitated by two surgeons working simultaneously, utilising both sides of the nose. (G) • To ensure the optimum oncological results, the primary tumour must be completely removed and margins checked by frozen section if necessary. (G) • The most common management approach is surgery followed by post-operative radiotherapy, ideally within six weeks. (R) • Radiation is given first if a response to radiation may lead to organ preservation. (G) • Radiotherapy should be delivered within an accredited department using megavoltage photons from a linear accelerator (typical energies 4-6 MV) as an unbroken course. (R).

Comparison of polystyrene scintillator fiber array and monolithic polystyrene for neutron imaging and radiography.

The neutron imaging diagnostic at the National Ignition Facility has been operating since 2011 generating neutron images of deuterium-tritium (DT) implosions at peak compression. The current design features a scintillating fiber array, which allows for high imaging resolution to discern small-scale structure within the implosion. In recent years, it has become clear that additional neutron imaging systems need to be constructed in order to provide 3D reconstructions of the DT source and these additional views need to be on a shorter line of sight. As a result, there has been increased effort to identify new image collection techniques that improve upon imaging resolution for these next generation neutron imaging systems, such as monolithic deuterated scintillators. This work details measurements performed at the Weapons Neutron Research Facility at Los Alamos National Laboratory that compares the radiographic abilities of the fiber scintillator with a monolithic scintillator, which may be featured in a future short line of sight neutron imaging systems.