Distinguishing immune checkpoint inhibitor-related pneumonitis from radiation pneumonitis by CT radiomics features in non-small cell lung cancer.

PURPOSE: To develop a CT-based model to classify pneumonitis etiology in patients with non-small cell lung cancer(NSCLC) after radiotherapy(RT) and Immune checkpoint inhibitors(ICIs). METHODS: We retrospectively identified 130 NSCLC patients who developed pneumonitis after receipt of ICIs only (n = 50), thoracic RT only (n = 50) (ICIs only + thoracic RT only, the training cohort, n = 100), and RT + ICIs (the test cohort, n = 30). Clinical and CT radiomics features were described and compared between different groups. We constructed a random forest (RF) classifier and a linear discriminant analysis (LDA) classifier by CT radiomics to discern pneumonitis etiology. RESULTS: The patients in RT + ICIs group have more high grade (grade 3-4) pneumonitis compared to patients in ICIs only or RT only group (p < 0.05). Pneumonitis after the combined therapy was not a simple superposition mode of RT-related pneumonitis(RP) and ICI-related pneumonitis(CIP), resulting in the distinct characteristics of both RT and ICIs-related pneumonitis. The RF classifier showed favorable discrimination between RP and CIP with an area under the receiver operating curve (AUC) of 0.859 (95 %CI: 0.788-0.929) in the training cohort and 0.851 (95 % CI: 0.700-1) in the test cohort. The LDA classifier achieved an AUC of 0.881 (95 %CI: 0.815-0.947) in the training cohort and 0.842 (95 %CI: 0.686-0.997) in the test cohort. Our analysis revealed four principal CT-based features shared across both models:original_glrlm_LongRunLowGrayLevelEmphasis, wavelet-HLL_firstorder_Median, wavelet-LLL_ngtdm_Busyness， and wavelet-LLL_glcm_JointAverage. CONCLUSION: CT radiomics-based classifiers could provide a noninvasive method to identify the predominant etiology in NSCLC patients who developed pneumonitis after RT alone, ICIs alone or RT + ICIs.

Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

[Study on the current status and relationship between psychological capital and compassion fatigue with work engagement of clinical nurses].

Objective: To explore the relationship between clinical nurses' psychological capital, compassion fatigue with work engagement, and analyze the mediating effect of psychological capital between compassion fatigue and work engagement, so as to provide scientific evidence for reducing compassion fatigue and improving work engagement of clinical nurses. Methods: From December 2021 to February 2022, 494 clinical nurses from 7 general hospitals in Sichuan Province were selected for the study using convenience sampling. The General Information Questionnaire, the Compassion Fatigue Short Scale, the Work Engagement Short Scale and the Psychological Capital Questionnaire for Nurses were used to conduct the survey. Pearson correlation was used to analyze the correlation between compassion fatigue, work engagement and psychological capital. And stepwise regression analysis and Bootstrap method were used to analyze the effects of compassion fatigue and psychological capital on work engagement as well as the mediating effect of psychological capital between compassion fatigue and work engagement. Results: Of the 494 clinical nurses, 33 (6.7%) were male and 461 (93.3%) were female, with an average age of (31.47±6.89) years old and an average working years (9.87±7.61) years. The average scores of psychological capital, compassion fatigue and work engagement of clinical nurses were (5.01±0.76), (3.19±2.08) and (4.60±1.37) points, respectively. Compassion fatigue was negatively correlated with psychological capital and work engagement (r=-0.608, -0.580, P<0.001), and work engagement was positively correlated with psychological capital (r=0.771, P<0.001). Compassion fatigue and psychological capital together accounted for 61.3% of the variation in work engagement, with the direct effects on work engagement were -0.206 (95%CI: -0.283--0.138, P<0.001) and 0.677 (95%CI: 0.599-0.744, P=0.001), respectively. Psychological capital partially mediated the relationship between compassion fatigue and work engagement, with a mediating effect of -0.397 (95%CI: -0.456--0.340, P<0.001), accounting for 65.8% of the total effect. Conclusion: The work engagement of clinical nurses is at a high level. Managers should take targeted measures to alleviate the symptoms of clinical nurses' compassion fatigue, improve their psychological capital, and then stabilize and improve their level of work engagement.

[Intermittent catheterization: What are the environmental impacts and how can they be reduced?] / Sondage intermittent : quels sont les impacts environnementaux et comment les réduire ?

INTRODUCTION: If the use of intermittent catheterization has revolutionized the prognosis of neuro-urology patients, it seems necessary to question the ecological cost of single-use catheters, in a process of decarbonization of the health sector. The aim of this work is to identify the environmental impact of intermittent catheterization and potential solutions to reduce it. METHODS: A review of the literature on the environmental impact of intermittent catheterizations was conducted. Potential solutions to reduce this impact and possible alternatives were then studied based on data from the literature. RESULTS: Only two studies were identified. The first estimated the amount of waste generated by intermittent catheterization in the USA to be between 4400 and 38,964 tons per year. The second study showed a higher overall environmental impact of thermoplastic polyurethane (TPU) catheters than polyvinyl chloride (PVC) catheters and catheters made from polyolefin material. Reuse of catheters would reduce the amount of waste, but the paucity of data does not allow us to determine if the incidence of urinary tract infection would be affected. Alternative micturition methods, in addition to the complications they may cause, require the use of collection bags or pads, which also have an environmental impact. Other treatments for dysuria exist, but the evidence is limited and does not cover all patient populations. CONCLUSION: With limited alternatives, it appears essential to develop more environmentally friendly catheters.

Rapid screening of monoclonal antibodies against porcine circovirus type 2 using colloidal gold-based paper test.

A proof of concept for using paper test as a suitable method in the production of monoclonal antibodies (MAbs) is reported. The paper test which detects antibodies against porcine circovirus type 2 (PCV2) using colloidal gold-labelled capsid protein as the antigen probe was applied exclusively in the screening of anti-PCV2 MAbs. It allowed the detection of 118 single cell clones within 30 min using naked eyes. MAbs with specific binding to authentic epitopes on the virus were selected using a blocking strategy in which the antibody was pre-incubated with PCV2 viral sample before applying to the test paper. Five hybridomas secreting MAbs against the capsid protein were obtained, with only three of them capable of binding to PCV2. The results were validated and confirmed using enzyme-linked immunosorbent assay and immunofluorescence assay. The paper test is simple, rapid, and independent on professional technicians and proves to be an excellent approach for the screening of MAbs against specific targets.

Practice of tracheostomy in patients with acute respiratory failure related to COVID-19 - Insights from the PRoVENT-COVID study.

OBJECTIVE: Invasively ventilated patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) potentially benefit from tracheostomy. The aim of this study was to determine the practice of tracheostomy during the first wave of the pandemic in 2020 in the Netherlands, to ascertain whether timing of tracheostomy had an association with outcome, and to identify factors that had an association with timing. METHODS: Secondary analysis of the 'PRactice of VENTilation in COVID-19' (PRoVENT-COVID) study, a multicenter observational study, conducted from March 1, 2020 through June 1, 2020 in 22 Dutch intensive care units (ICU) in the Netherlands. The primary endpoint was the proportion of patients receiving tracheostomy; secondary endpoints were timing of tracheostomy, duration of ventilation, length of stay in ICU and hospital, mortality, and factors associated with timing. RESULTS: Of 1023 patients, 189 patients (18.5%) received a tracheostomy at median 21 [17 to 28] days from start of ventilation. Timing was similar before and after online publication of an amendment to the Dutch national guidelines on tracheostomy focusing on COVID-19 patients (21 [17-28] vs. 21 [17-26] days). Tracheostomy performed ≤ 21 days was independently associated with shorter duration of ventilation (median 26 [21 to 32] vs. 40 [34 to 47] days) and higher mortality in ICU (22.1% vs. 10.2%), hospital (26.1% vs. 11.9%) and at day 90 (27.6% vs. 14.6%). There were no patient demographics or ventilation characteristics that had an association with timing of tracheostomy. CONCLUSIONS: Tracheostomy was performed late in COVID-19 patients during the first wave of the pandemic in the Netherlands and timing of tracheostomy possibly had an association with outcome. However, prospective studies are needed to further explore these associations. It remains unknown which factors influenced timing of tracheostomy in COVID-19 patients.

[Effects of bio-strength electric field on the motility and CD9 expression of human epidermal cell line HaCaT and mouse epidermal cells].

Objective: To investigate the regulatory effect of bio-strength electric field (EF) on the motility and CD9 expression of human epidermal cell line HaCaT and mouse epidermal cells. Methods: The experimental research method was used. Human immortal epidermal cell line HaCaT cells in logarithmic growth phase and primary epidermal cells isolated from 16 BALB/c mice (no matter male or female) aged 1-3 days were used for experiments. HaCaT cells were divided into EF group treated for 3 h at the EF intensity of 200 mV/mm and sham EF group with simulated treatment. The cell migration (direction, displacement velocity, and trajectory velocity, with 46 samples in EF group and 34 samples in sham EF group) and arrangement were observed in the living cell workstation, and the distribution and expression of CD9 protein were detected by immunofluorescence method. Both HaCaT cells and mouse epidermal cells were divided into sham EF group (simulated treatment) and EF groups treated respectively for 3 h at the corresponding EF intensity of 50, 100, 200, and 400 mV/mm. Both HaCaT cells and mouse epidermal cells were divided into blank control group without any treatment, and 1 h group, 3 h group, and 6 h group treated with EF at the intensity of 200 mV/mm for corresponding time respectively. The expression of CD9 protein was detected by Western blotting (n=3). Data were statistically analyzed with Mann-Whitney U test, one-way analysis of variance, independent sample t test and least significant difference test. Results: Within 3 hours of treatment, HaCaT cells in EF group tended to move towards the negative electrode obviously, while HaCaT cells in sham EF group moved randomly around the origin; compared with those of sham EF group, the directivity of HaCaT cells in EF group was significantly enhanced, and the displacement velocity and trajectory velocity were significantly increased (Z=-3.975, -6.052, -6.299, P<0.01). After 3 hours of treatment, the long axis of HaCaT cells in EF group was perpendicular to the direction of EF, while HaCaT cells in sham EF group arranged randomly. After 3 hours of treatment, the expression of CD9 protein in HaCaT cells in EF group was significantly down-regulated compared with that of sham EF group (t=4.527, P<0.01), although both expressed on cytomembrane. After 3 hours of treatment, the expression of CD9 protein in HaCaT cells and mouse epidermal cells in sham EF group, 50 mV/mm group, 100 mV/mm group, 200 mV/mm group, and 400 mV/mm group were 0.332±0.021, 0.283±0.032, 0.254±0.020, 0.231±0.041, 0.212±0.031 and 0.565±0.021, 0.453±0.022, 0.389±0.020, 0.338±0.021, 0.233±0.011, respectively. For both types of cells, compared with that of sham EF group, the expression of CD9 protein in cells was significantly decreased in the four groups of EF treatment (P<0.01); compared with that of 50 mV/mm group, the expression of CD9 protein in cells was significantly decreased in the other three groups of EF treatment (P<0.01); compared with that of 100 mV/mm group, the expression of CD9 protein in cells was significantly decreased in 200 mV/mm group and 400 mV/mm group (P<0.01); compared with that of 200 mV/mm group, the expression of CD9 protein in cells was significantly decreased in 400 mV/mm group (P<0.01). The expression levels of CD9 protein in HaCaT cells and mouse epidermal cells in blank control group, 1 h group, 3 h group, and 6 h group were 0.962±0.031, 0.784±0.020, 0.531±0.021, 0.409±0.011 and 0.963±0.031, 0.872±0.031, 0.778±0.040, 0.591±0.041, respectively. For both types of cells, compared with that of blank control group, the expression of CD9 protein in cells was significantly decreased in 1 h group, 3 h group, and 6 h group (P<0.01); compared with that of 1 h group, the expression of CD9 protein in cells was significantly decreased in 3 h group and 6 h group (P<0.05 or P<0.01); compared with that of 3 h group, the expression of CD9 protein in cells was significantly decreased in 6 h group (P<0.01). Conclusions: The bio-strength intensity EF can induce the directional migration and arrangement of HaCaT cells and down-regulate the expression of CD9 in HaCaT cells and mouse epidermal cells in a time-dependent and intensity-dependent manner.

Morphologic Change of Flow-Related Aneurysms in Brain Arteriovenous Malformations after Stereotactic Radiosurgery.

BACKGROUND AND PURPOSE: The natural history of flow-related aneurysms after obliteration of brain arteriovenous malformations is poorly understood. The purpose of this study was to evaluate the angioarchitecture and morphologic change in flow-related aneurysms after gamma knife surgery of brain arteriovenous malformations. MATERIALS AND METHODS: During a 12-year period, 823 patients with brain arteriovenous malformations underwent gamma knife surgery at our institution with complete peritherapeutic angiographic evaluation. From this population, a series of 72 patients (8.8%) with 111 flow-related aneurysms were enrolled (1.5 aneurysms per patient). There were 43 men and 29 women; ages ranged from 18 to 72 years (mean, 43 years). The morphologic change of flow-related aneurysms was longitudinally evaluated before and after obliteration of brain arteriovenous malformations. After gamma knife surgery, angiographic follow-up varied from 26 to 130 months (mean, 58 months). RESULTS: All flow-related aneurysms were small (mean, 4.1 mm; range, 2-9 mm). There were 72 proximal flow-related aneurysms (mean size, 4.3 mm) and 39 distal flow-related aneurysms (mean size, 3.7 mm). Spontaneous thrombosis occurred more frequently in distal flow-related aneurysms than in proximal flow-related aneurysms (P < .001). Smaller flow-related aneurysms (<5 mm) tended to spontaneously occlude after obliteration of brain arteriovenous malformations (P = .036). Two patients had ruptures of proximal flow-related aneurysms at 27- and 54-month follow-ups, respectively. CONCLUSIONS: Spontaneous thrombosis occurred more frequently in distal flow-related aneurysms due to occlusion or normalization of distal feeders. Smaller flow-related aneurysms also tended to spontaneously thrombose after obliteration of brain arteriovenous malformations. The rate of flow-related aneurysm rupture in our series was similar to that of natural intradural aneurysms.

[Absorbent products for urinary incontinence management]. / Place des protections dans la prise en charge de l'incontinence urinaire.

INTRODUCTION: Despite therapeutic strategies of female and male urinary incontinence (UI) are currently well defined, there is no precise indication of the real place or strategy use of absorbent products regardless of the etiology of the incontinence or the clinical context. METHODS: We performed a research from the PubMed database using the following keywords: (urinary incontinence [MESH Terms]) AND absorbent pad [MeSH Terms]; allowing us to isolate 362 articles. RESULTS: Many protections designs are available over-the-counter without prescription and without reimbursement in France. For "light UI", disposable insert pads are the design that seems to be the most suitable for women, compared to disposable menstrual pads, OR=0.27 [0.14, 0.52], washable pants with integral pad OR=0.12 [0.06, 0.26] or washable insert pads OR=0.05 [0.02, 0.26]. For moderate to severe UI, there is no "best universal product". There are differences between the gender and the use of a panel of protections seems the most appropriate. Both women and men prefer pull-ups to disposable insert pads, OR=0.41 [0.20, 0.87] and OR=0.39 [0.22, 0.68] respectively. In men, a preference in 70 % of subjects for urisheats is observed compared to the protections they usually use (P=0.02). The use of protections improves independence in daily OR activities=0.102 [0.046, 0.158] and quality of life related to UI OR=4.40 [1.74, 7.07] compared to patients not using protections. Despite this, their use must remain cautious because of the potential infectious urinary complications, more frequent in particular in institutional people, with 41 % of users developing at least one urinary infection over an evaluation period of 12 months vs. 11 % of non-users (P=0.001), or immuno-allergic with the "dermatitis associated incontinence" whose prevalence can reach a rate of 50 %. CONCLUSION: Comparative analyzes of risk-benefit, economic costs, patient satisfaction, protections vs. other measures are lacking. It is necessary to continue the development of these products and to compare more precisely their intrinsic characteristics, to best support patients choices.

[Menthol in the control of bladder activity: A review]. / Le menthol dans le contrôle de l'activité de la vessie : revue de littérature.

INTRODUCTION: Menthol is a natural compound, of which the known effects on human physiology are manifold (a feeling of freshness, decongestant, bowel antispasmodic). Its implication in vesico-sphincteral physiopathology has been studied since the nineties. METHOD: Literature review of the previous studies having implied menthol in pelvi-perineal physiology through the articles indexed on the Pubmed database, with keywords menthol, menthol and bladder, menthol and toxicity, and TRPM8. Only articles in English were selected. RESULTS: Of the 30 articles that were included, most demonstrated the existence of a micturition reflex to menthol and cold, mediated by the C-type nerve to the spine through activation of TRPM8 urothelial receptors. More recent experiments paradoxically showed an inhibitory effect of menthol on detrusor contractility, independently of TRPM8, when muscle tissue is directly exposed to the compound. However, similar effects of targeted cutaneous exposure or urothelial exposure on detrusorian function have also been demonstrated through TRPM8. This receptor also appears to be involved in interstitial cystitis and idiopathic detrusor overactivity. Lastly, the potential toxicity of menthol appears negligible. Most of the referenced studies are related to animal experiments. Of the three studies that implied humans, only one elucidates some therapeutic applications. CONCLUSION: It seems that menthol and its receptors are involved in vesico-sphincteral physiopathology and could provide therapeutic potential in detrusorian overactivity and interstitial cystitis with reduced toxicity.

[Coital incontinence]. / L'incontinence coïtale.

INTRODUCTION: Urinary incontinence may seriously impact quality of life, self-image and subsequently the sexual life. Beside this fact, urinary leakage can specifically occur during sexual intercourse, formally named coital incontinence, and thus lead to specific alteration of the sexual life. AIM: To analyse the prevalence, pathophysiological mechanisms and possible therapeutic options for coital urinary incontinence. METHODS: Related terms to urinary incontinence and sexual dysfunction were search on PubMed database. RESULTS: Whereas at least a quarter of incontinent women have a coital incontinence, this symptom was rarely spontaneously reported. Some women had only coital incontinence (7.6 to 20% of cases). In men, urinary incontinence during sexual intercourse was mainly observed after prostatectomy in 20 to 64% of cases. Coital incontinence requires precise assessment. Indeed, it can occur whatever the phase of coitus: local stimulation (20-30%), excitement (13-18%), penetration (62.9-68%), movements back and forth, orgasm (27-37.1%). Cervico-urethral hypermobility, sphincter incompetence, urethral instability, detrusor overactivity could be the principal physiopathological mechanisms. In men, the main cause was a stress incontinence secondary to sphincter deficiency. Specific therapeutic strategies have proved their effectiveness. The rehabilitative approach (RR=0.25, CI [0.06-1.01]), medicinal (anticholinergic were effective in 59% of cases) or surgical therapeutic (slings with an efficiency of 87%) was proposed to patients. CONCLUSION: Coital incontinence is a common and troublesome symptom. Its precise assessment may suggest a specific mechanism and thus a specific treatment.

Peritherapeutic Hemodynamic Changes of Carotid Stenting Evaluated with Quantitative DSA in Patients with Carotid Stenosis.

BACKGROUND AND PURPOSE: Quantitative data from DSA have become important tools for understanding hemodynamic changes of intracranial lesions. In this study, we evaluated 8 hemodynamic parameters in patients before and after carotid artery angioplasty. MATERIALS AND METHODS: DSA images of 34 patients with carotid stenosis who underwent angioplasty and stent placement were retrospectively analyzed. Eleven ROIs (M1, M2, A1, A2, the parietal vein, superior sagittal sinus, internal jugular vein, and 4 in the ICA) were selected on color-coded DSA. Eight hemodynamic parameters (bolus arrival time, TTP, relative TTP, full width at half maximum, wash-in slope, washout slope, maximum enhancement, and area under the curve) were measured from the time-concentration curves of these ROIs. The dependent t test for paired samples was applied to these parameters before and after stent placement. RESULTS: We found that the treatment significantly reduced TTP, relative TTP, bolus arrival time, and washout slope at all arterial ROIs and full width at half maximum and area under the curve at some arterial ROIs. Bolus arrival time was significantly reduced after treatment for all arterial ROIs, the parietal vein, and the superior sagittal sinus. The maximum enhancement and wash-in slope did not show significant changes after treatment. After treatment, the relative TTP from the ICA to M1, M2, and the parietal vein returned to normal values. CONCLUSIONS: In addition to TTP and relative TTP, other parameters can be used to evaluate peritherapeutic cerebral hemodynamic changes. Bolus arrival time has the potential to evaluate brain circulation at arterial and venous sites, especially when TTP cannot be measured because of an incomplete time-concentration curve.

Meta-analysis of the effectiveness of esomeprazole in gastroesophageal reflux disease and Helicobacter pylori infection.

WHAT IS KNOWN AND OBJECTIVE: Proton pump inhibitors (PPIs) are one of the most widely used classes of drugs. However, the quantum clinical benefit of newer and more expensive PPIs over the older generation PPIs remains uncertain. This meta-analysis sought to assess the clinical and safety profiles of esomeprazole versus omeprazole at pharmacologically equivalent doses in healing gastroesophageal reflux disease (GERD), peptic ulcer disease and eradicating Helicobacter pylori (H. pylori) infection. METHODS: PubMed and the Cochrane Library were searched for randomized controlled trials comparing esomeprazole with omeprazole at all doses up to February 2015. Trials were assessed by two reviewers for eligibility according to predefined study inclusion criteria. Meta-analysis was conducted using a random effects model, and heterogeneity in the estimated effects was investigated using meta-regression. Sensitivity analysis was performed to test the robustness of the findings. RESULTS AND DISCUSSION: Fifteen trials were included and none of which compared esomeprazole with omeprazole in peptic ulcer disease. The included studies had not evaluated esomeprazole 20 mg versus omeprazole 40 mg. In GERD, esomeprazole 40 mg (relative risk (RR) = 1·07; 95% confidence interval (CI) 1·02 to 1·12) and 20 mg (RR=1·04; 95% CI 1·01 to 1·08) significantly improved esophagitis healing when compared with omeprazole 20 mg at week 8. The corresponding numbers needed to treat were 17 and 30, respectively. No significant difference was observed between esomeprazole 20 mg and omeprazole 20 mg at week 4. In H. pylori eradication, there was no difference in the treatment effects between esomeprazole 20 mg and omeprazole 20 mg (RR = 1·01;95% CI 0·96 to 1·05). Their safety profiles were comparable. WHAT IS NEW AND CONCLUSION: Esomeprazole demonstrated better esophagitis healing rate in patients with GERD than omeprazole at week 8. However, this clinical advantage diminished when both drugs were given at the same doses at week 4. Superiority of esomeprazole was not observed in the H. pylori eradication rates.

Role of IL-17 and IL-22 in autoimmunity and cancer.

The dysregulation of inflammatory cytokines can cause a variety of diseases, such as autoimmunity and cancer. Since their identification in 2005, Th17 cells and its signature cytokine IL-17, have been implicated in the pathogenesis of autoimmune diseases such as psoriasis and rheumatoid arthritis (RA), and inflammatory associated cancers such as colorectal carcinoma (CRC). Recently, IL-22 a Th17 related cytokine has been shown to be pathogenic in psoriasis and RA. In this review, we will summarize the biological functions of IL-17 and IL-22, their role in autoimmune diseases and briefly review results from clinical trials targeting IL-17 or its receptor for the treatment of autoimmune diseases. Next, we will discuss pre-clinical and clinical data supporting the rationale of targeting other cytokines implicated in the Th17/IL-17 pathway, such as IL-22 and IL-23. Finally, we discuss the role of IL-17, and in particularly IL-22 in tumour immunity and possible therapeutic interventions.

Biomarker-based prognosis in hepatocellular carcinoma: validation and extension of the BALAD model.

BACKGROUND: The Japanese 'BALAD' model offers the first objective, biomarker-based, tool for assessment of prognosis in hepatocellular carcinoma, but relies on dichotomisation of the constituent data, has not been externally validated, and cannot be applied to the individual patients. METHODS: In this Japanese/UK collaboration, we replicated the original BALAD model on a UK cohort and then built a new model, BALAD-2, on the original raw Japanese data using variables in their continuous form. Regression analyses using flexible parametric models with fractional polynomials enabled fitting of appropriate baseline hazard functions and functional form of covariates. The resulting models were validated in the respective cohorts to measure the predictive performance. RESULTS: The key prognostic features were confirmed to be Bilirubin and Albumin together with the serological cancer biomarkers, AFP-L3, AFP, and DCP. With appropriate recalibration, the model offered clinically relevant discrimination of prognosis in both the Japanese and UK data sets and accurately predicted patient-level survival. CONCLUSIONS: The original BALAD model has been validated in an international setting. The refined BALAD-2 model permits estimation of patient-level survival in UK and Japanese cohorts.

Diagnostic and mechanistic implications of serum free light chains, albumin and alpha-fetoprotein in hepatocellular carcinoma.

BACKGROUND: Mass spectroscopy analysis suggested low serum albumin and high immunoglobulin free light chain (sFLC) levels may have diagnostic value in hepatocellular carcinoma (HCC). Our aims were to apply quantitative assays to confirm these observations, determine their diagnostic utility, and investigate the mechanisms involved. METHODS: Albumin, sFLC, routine liver and renal function tests were measured in patients with chronic liver disease with (n=102) and without (n=113) HCC. The discriminant performance was compared with the current standard serological test alpha-fetoprotein (AFP) using receiver operating characteristic (ROC) and area under the curve (AUC) analyses. RESULTS: sFLC and serum albumin were each confirmed to have discriminatory utility in HCC with AUC values of 0.7 and 0.8, respectively. sFLC were strongly correlated with gammaglobulin levels and both these were inversely related to serum albumin levels. The discriminatory utility of sFLC was retained after adjusting for renal and liver function. CONCLUSIONS: Serum levels of sFLC and albumin were strongly associated with HCC as predicted by mass spectroscopy. Discrimination of HCC by AFP was improved by the addition of either albumin or sFLC. Larger prospective studies are required to determine how AFP, sFLC and albumin might be combined in a useful diagnostic approach for HCC.

The Thr205 phosphorylation site within respiratory syncytial virus matrix (M) protein modulates M oligomerization and virus production.

UNLABELLED: Human respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia in infants and the elderly worldwide; however, there is no licensed RSV vaccine or effective drug treatment available. The RSV matrix (M) protein plays key roles in virus assembly and budding, but the protein interactions that govern budding of infectious virus are not known. In this study, we focus on M protein and identify a key phosphorylation site (Thr205) in M that is critical for RSV infectious virus production. Recombinant virus with a nonphosphorylatable alanine (Ala) residue at the site was markedly attenuated, whereas virus with a phosphomimetic aspartate (Asp) resulted in a nonviable virus which could only be recovered with an additional mutation in M (serine to asparagine at position 220), strongly implying that Thr205 is critical for viral infectivity. Experiments in vitro showed that mutation of Thr205 does not affect M stability or the ability to form dimers but implicate an effect on higher-order oligomer assembly. In transfected and infected cells, Asp substitution of Thr205 appeared to impair M oligomerization; typical filamentous structures still formed at the plasma membrane, but M assembly during the ensuing elongation process seemed to be impaired, resulting in shorter and more branched filaments as observed using electron microscopy (EM). Our data thus imply for the first time that M oligomerization, regulated by a negative charge at Thr205, may be critical to production of infectious RSV. IMPORTANCE: We show here for the first time that RSV M's role in virus assembly/release is strongly dependent on threonine 205 (Thr205), a consensus site for CK2, which appears to play a key regulatory role in modulating M oligomerization and association with virus filaments. Our analysis indicates that T205 mutations do not impair M dimerization or viruslike filament formation per se but rather the ability of M to assemble in ordered fashion on the viral filaments themselves. This appears to impact in turn upon the infectivity of released virus rather than on virus production or release itself. Thus, M oligomerization would appear to be a target of interest for the development of anti-RSV agents; further, the recombinant T205-substituted mutant viruses described here would appear to be the first RSV mutants affected in viral maturation to our knowledge and hence of considerable interest for vaccine approaches in the future.

Evaluation of the outcomes of endovascular management for patients with head and neck cancers and associated carotid blowout syndrome of the external carotid artery.

AIM: To evaluate factors related to the technical and haemostatic outcomes of endovascular management in patients with head and neck cancers (HNC) associated with carotid blowout syndrome (CBS) of the external carotid artery (ECA). MATERIALS AND METHODS: Between 2002 and 2011, 34 patients with HNC with CBS involving branches of the ECA underwent endovascular therapy. Treatment included embolization with microparticles, microcoils, or acrylic adhesives. Fisher's exact test was used to examine demographic features, clinical and angiographic severities, and clinical and imaging findings as predictors of endovascular management outcomes. RESULTS: Technical success and immediate haemostasis were achieved in all patients. Technical complications were encountered in one patient (2.9%). Rebleeding occurred in nine patients (26.5%). Angiographic vascular disruption grading from slight (1) to severe (4) revealed that the 18 patients with acute CBS had scores of 2 (2/18, 11.1%), 3 (3/18, 16.7%), and 4 (13/18, 72.2%). The 16 patients with impending and threatened CBS had scores of 1 (1/16, 6.25%), 2 (5/16, 31.25%), and 3 (10/16, 62.5%; p = 0.0003). For the 25 patients who underwent preprocedural computed tomography (CT)/magnetic resonance imaging (MRI) examinations within 3 months of treatment, the agreement between clinical and imaging findings reached the sensitivity, specificity, and kappa values for recurrent tumours (1, 0.7143, 0.7826), soft-tissue defect (0.9091, 0.3333, 0.2424), and sinus tract/fistula (0.4737, 0, 0.4286). CONCLUSION: Endovascular management for patients with CBS of the ECA had high technical success and safety but was associated with high rebleeding rates. We suggest applying aggressive post-procedural follow-up and using preprocedural CT/MRI to enhance the periprocedural diagnosis.

Can iterative reconstruction improve imaging quality for lower radiation CT perfusion? Initial experience.

BACKGROUND AND PURPOSE: Initial results using IR for CT of the head showed satisfactory subjective and objective imaging quality with a 20-40% radiation dose reduction. The aim of our study was to compare the influence of IR and FBP algorithms on perfusion parameters at standard and lowered doses of CTP. MATERIALS AND METHODS: Forty patients with unilateral carotid stenosis post-carotid stent placement referred for follow-up CTP were divided into 2 groups (tube currents were 100 mAs in group A and 80 mAs in group B). Datasets were reconstructed with IR and FBP algorithms; and SNRs of gray matter, white matter, and arterial and venous ROIs were compared. CBF, CBV, and MTT means and SNRs were evaluated by using linear regression, and qualitative imaging scores were compared across the 2 algorithms. RESULTS: The mean effective radiation dose of group B (2.06 mSv) was approximately 20% lower than that of group A (2.56 mSv). SNRs for ROIs in the dynamic contrast-enhanced images were significantly higher than those for the FBP images. Correlations of the SNRs for CBF, CBV, and MTT across the 2 algorithms were moderate (R² = 0.46, 0.23, and 0.44, respectively). ROIs in gray matter rather than the IR algorithm predicted increasing SNRs in all CBF, CBV, and MTT maps. Two cases of significant restenosis were confirmed in both algorithms. CBV, CBF, and MTT imaging scores did not differ significantly across algorithms or groups. CONCLUSIONS: Lower dose CTP (20% below normal dose) without IR can effectively identify oligemic tissue in poststenting follow-up. IR does not alter the absolute values or increase the SNRs of perfusion parameters. Other methods should be attempted to improve SNRs in settings with low tube currents.