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Παρασκευή 2 Μαρτίου 2018

Asthma phenotypes defined from parameters obtained during recovery from a hospital-treated exacerbation

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Rihuang Qiu, Jiaxing Xie, Kian Fan Chung, Naijian Li, Zhaowei Yang, Mengzhang He, Jing Li, Rongchang Chen, Nanshan Zhong, Qingling Zhang
BackgroundAsthma is a heterogeneous disease with diverse clinical manifestations and inflammatory pathologies that is punctuated by exacerbations.ObjectivesTo describe the clinical and inflammatory characteristics of asthma patients treated in hospital for an acute exacerbation.MethodsData from 320 adult patients receiving treatment for an acute exacerbation of asthma were obtained. In 218 with complete data , we used Ward's hierarchical clustering to obtain clusters. Pulmonary function, blood counts, sputum cell counts, serum IgE levels, and fractional exhaled nitric oxide were measured during the hospital admission. We selected 13 variables with which we performed Ward's minimum variance hierarchical clustering.ResultsFour clusters were defined. Clusters 1(24.5%) and 3(36.7%) were characterized by predominantly-female asthmatics with sputum neutrophilia, with Cluster 1 associated with small degree of airflow obstruction and early onset of asthma while Cluster 3 had a moderate degree of reduction in FEV1. Clusters 2(22.0%) and 4(16.5%) were associated with high sputum eosinophilia and severe airflow obstruction, but Cluster 4 was made up exclusively of male smoking subjects while Cluster 2 of predominantly female non-smoking subjects with the worst FEV1, FEF25-75 (% predicted) and arterial partial pressure of oxygen (PaO2) on admission. There were no differences between clusters in terms of atopy, serum IgE, prevalence of nasal disease, maintenance inhaled corticosteroids, or oral/systemic corticosteroid use and asthma exacerbations.ConclusionThe clusters during recovery from an exacerbation of asthma were distinguished by airflow obstruction and a neutrophilic, eosinophilic or mixed inflammation. Eosinophilic inflammation was found in smoking and non-smoking asthmatics during an exacerbation.



A multicenter evaluation of diagnosis and management of omega-5 gliadin allergy (also known as wheat-dependent exercise induced anaphylaxis) in 132 adults

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Lucinda Kennard, Iason Thomas, Krzysztof Rutkowski, Vian Azzu, Patrick FK. Yong, Bogusia Kasternow, Hannah Hunter, Naeema MO. Cabdi, Alla Nakonechna, Annette Wagner
BackgroundOmega-5 gliadin allergy (also known as wheat-dependent exercise induced anaphylaxis) is a rare allergy to wheat which often presents with intermittent severe anaphylaxis in the context of a co-factor, such as exercise.ObjectivesTo undertake a detailed clinical characterisation of the largest cohort of omega 5-gliadin allergic patients to date.MethodsWe retrospectively analysed the demographics, presentation, investigation and management of 132 patients presenting to 4 UK centres with omega-5 gliadin allergy.ResultsThere are significant delays to diagnosis of 1-5 years (40% of patients) and over 5 years (29% of patients). The most common cofactors were exercise (80%), alcohol (25%) and NSAIDs (9%). A minority of patients (11%) present without an identifiable cofactor. The level of specific IgE to omega-5 gliadin does not predict the severity of allergic reactions. Patients adhering to either a gluten-free diet or who avoid wheat in combination with exercise achieve the largest reductions in subsequent allergic reactions by 67% and 69%, respectively.ConclusionsOmega-5 gliadin allergy is a rare wheat allergy that presents with severe anaphylaxis. The diagnosis is frequently delayed, therefore we recommend that all adult patients presenting with anaphylaxis of unclear cause should have omega-5 gliadin specific IgE tested. A gluten-free diet or avoidance of wheat based meals in combination with exercise (if the cofactor is exercise) helps to significantly decrease the risk of future allergic reactions. However, antihistamines and an epinephrine auto-injector must always be prescribed, as a third of patients continue to have allergic reactions despite dietary advice.



Treatment with the SQ house dust mite sublingual immunotherapy tablet may be initiated year-round

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Hendrik Nolte, David I. Bernstein, Jörg Kleine-Tebbe, Peter A. Fejerskov, Qing Li, Susan Lu, Harrold S. Nelson




Disseminated abscesses due to Mycoplasma faucium in a patient with activated PI3Kδ syndrome type 2 (APDS2)

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Nerea Dominguez-Pinilla, Luis M. Allende, Jérémie Rosain, Carmen Gallego Maria del, Fernando Chaves, Caroline Deswarte, Esther Viedma, Jaime de Inocencio Arocena, Jesús Ruiz-Contreras, Jacinta Bustamante, Luis Ignacio Gonzalez-Granado




A Survey of Caregiver Perspectives on Emergency Epinephrine Autoinjector Sharing

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Marcus Shaker, Tsuzumi Kanaoka, Robert GP. Murray, Dana Toy, Susan Shaker, Aurora Drew




Comparison of gold nanoparticles biosynthesized by cell-free extracts of Labrys , Trichosporon montevideense , and Aspergillus

Abstract

Biosynthesis of gold nanoparticles (AuNPs) by microbes has received much attention as an efficient and eco-friendly process. However, the characteristics of AuNPs biosynthesized by different microbial cell-free extracts are rarely comparatively studied. In this study, three locally isolated strains, i.e., bacteria Labrys sp. WJW, yeast Trichosporon montevideense WIN, and filamentous fungus Aspergillus sp. WL-Au, were selected for AuNPs biosynthesis. UV-Vis absorption bands at 538, 539, and 543 nm confirmed the formation of AuNPs by these strains. Transmission electron microscopy and selected area electron diffraction analyses revealed that the as-synthesized AuNPs were crystalline with spherical or pseudo-spherical shapes. However, the average sizes of these AuNPs were diverse, which were 18.8, 22.2 and 9.5 nm, respectively. The biomolecules involved in nanoparticles stabilization were demonstrated by Fourier transform infrared spectroscopy analysis. Four common functional groups such as –N–H, –C=C, –N=O, and –S=O groups were detected in these AuNPs, while a distinct –C=O group was involved in WL-Au-AuNPs. The catalytic rate of WL-Au-AuNPs toward 4-nitrophenol reduction (0.37 min−1) was much higher than those of others (WJW-AuNPs 0.27 min−1 and WIN-AuNPs 0.23 min−1). This research would provide useful information for exploring efficient microbial candidates to synthesize AuNPs with excellent performances.



Activation of RhoA, Smad2, c-Src, PKC-βII/δ and JNK in atopic dermatitis

Abstract

Atopic dermatitis is a multifactorial skin disease characterised by chronic and relapsing inflammation whose pathogenesis is incompletely understood. We found that the expression of TGFβR1 and the activation of SMAD2, RhoA, JNK, PKC-βII/δ and c-Src were upregulated in the infiltrated inflammatory cells, fibroblasts and vasculatures in the dermis and epidermis. In addition, increases in the expression of TGFβR1 and phosphorylation levels of JNK and c-Src were positively correlated with the inflammatory progression of atopic dermatitis severity.



The effect of template-based sequential (TBS) coding on an NHS plastic surgical practice

Publication date: Available online 1 March 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Ruben Y. Kannan, Catriona Neville, Tamsin Gwynn, Vanessa Venables, Raman Malhotra, Charles Nduka
IntroductionClinical coding is often a mystery to us surgeons but in actuality, it has a huge bearing on the financial sustainability of our services. Given the rapid innovations in plastic surgical procedures, clinical coders often struggle to decipher the extent of surgery. Meeting midway is the way forward here.MethodsIn a prospective audit over a six-month period, we analysed data from 2586 patients' in our practice; a combination of general plastic surgery and specialist facial reanimation services. This involved comparing data from the first three months' where coding was performed by clinical coders' based on operating notes per se (phase I) and the subsequent three months' when the operating surgeon filled in the OPCS 4.7 (version 2014) codes at the time of completing the operating notes and the clinical coders' then vetted this information (phase II) as part of a sequential TBS coding system.ResultsIn terms of out-patient income, there was a 3% increase in facial palsy income and 6% increase in general plastic services but the most significant improvement was in terms procedural income per case. General plastic surgery cases saw an increase of 49% while facial palsy income increased by 58% over the same period. Greater insight into OPCS and HRG codes also allowed for the calculation of the actual tariffs for specific procedures.ConclusionsHaving the operating surgeon as the primary coder, using a template, with subsequent vetting by the clinical coders, improves data capture which in turn, increases income. Future recommendations includes the use of proforma-based operating notes for workhorse procedures.



Cost analysis of enhanced recovery after surgery in microvascular breast reconstruction

Publication date: Available online 2 March 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Christine Oh, James Moriarty, Bijan J. Borah, Kristin C. Mara, William S. Harmsen, Michel Saint-Cyr, Valerie Lemaine
BackgroundEnhanced recovery after surgery (ERAS) pathways has been shown in multiple surgical speciaalties to decrease hospital length of stay (LOS) after surgery. ERAS in breast reconstruction has been found to decrease hospital length of stay and inpatient opioid use. ERAS protocols can facilitate a patient's recovery and is a systemwide improvement that can potentially increase the quality of care while decreasing costs.MethodsA standardized ERAS pathway was developed through multidisciplinary collaboration. It addressed all phases of surgical care for patients undergoing free-flap breast reconstruction utilizing an abdominal donor site. In this retrospective cohort study, clinical variables associated with hospitalization costs for patients who underwent free-flap breast reconstruction with the ERAS pathway were compared with those of historical controls, termed traditional recovery after surgery (TRAS). All patients included in the study underwent surgery between September 2010 and September 2014. Predicted costs of the study groups were compared using generalized linear modeling.ResultsA total of 200 patients were analyzed: 82 in the ERAS cohort and 118 in the TRAS cohort. Clinical variables found to have a statistically significant difference between groups that affected costs included unilateral versus bilateral procedure (p=0.04) and need for postoperative blood transfusion (p=0.03). The cost regression analysis on the two cohorts adjusted for these significant variables. Adjusted mean costs of ERAS patients were found to be $4,576 less than the TRAS control group ($38,688 versus $43,264).ConclusionsImplementation of the ERAS pathway was associated with significantly decreased costs when compared to historical controls. There has been a healthcare focus towards prudent resource allocation that dictates the need for plastic surgeons to recognize economic evaluation of clinical practice. The ERAS pathway can increase health care accountability by improving quality of care while simultaneously decreasing the costs associated with autologous breast reconstruction.



Assessment of quality of life in patients who underwent breast reduction using BREAST-Q

Publication date: Available online 1 March 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): M.P.D. Corrêa, M.T. Dornelas, E.N. de Carvalho, A. Barra, E.P. Venturelli, L.D. Corrêa, A. Chaoubah




A supermicrosurgery training model using the chicken mid and lower wing

Publication date: Available online 1 March 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Kota Hayashi, Yasunori Hattori, Dawn Sinn Yii Chia, Sotetsu Sakamoto, Abdelhakim Marei, Kazuteru Doi




Protective effects of PACAP in ischemia

Pituitary adenylate cyclase activating polypeptide (PACAP) is an ubiquitous peptide involved, among others, in neurodevelopment, neuromodulation, neuroprotection, neurogenic inflammation and nociception. Prese...

Role of percutaneous cholecystostomy for acute acalculous cholecystitis: clinical outcomes of 271 patients

Abstract

Objectives

To examine the outcomes of percutaneous cholecystostomy (PC) in patients with acute acalculous cholecystitis (AAC).

Methods

The study population comprised 271 patients (mean age, 72 years; range, 22–97 years, male, n=169) with AAC treated with PC with or without subsequent cholecystectomy. Clinical data from total 271 patients were analysed, and outcomes were assessed according to whether the catheter was removed or remained indwelling. Patient survival and recurrence rates were calculated.

Results

Symptom resolution and significant improvement of laboratory test values were achieved in 235 patients (86.7%) within 4 days after PC. Complications occurred in six patients (2.2%). Interval elective cholecystectomy was performed in 127 (46.8%) patients. Among the remaining 121 patients, successful removal of the PC catheter was achieved in 88 patients (72.7%) at a mean of 30 days (range, 4–365 days). Of the catheter removal group, 86/88 (97.7%) were successfully treated with the initial PC, whereas two (2.3%) experienced recurrence of cholecystitis. Cumulative recurrence rates were 1.1%, 2.7%, and 2.7% at 1, 2, and 8 years, respectively.

Conclusions

The good therapeutic outcomes of PC and low recurrence rate suggest that PC can be a definitive treatment option in the majority of AAC patients.

Key Points

Many patients with AAC are too ill to undergo cholecystectomy.

PC in AAC patients shows low complication and recurrence rate.

PC solely can be a definitive treatment option in the majority of AAC patients



Discrepancies between coronary CT angiography and invasive coronary angiography with focus on culprit lesions which cause future cardiac events

Abstract

Objectives

To evaluate the clinical significance of discrepant lesions between coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) in a longitudinal study.

Methods

In 220 patients with suspected coronary artery disease (CAD) who underwent both 256-row CCTA and ICA, the obstructive CAD (≥ 50% stenosis) on CCTA was compared with that on ICA as the reference standard. We analysed the causes of the discrepancy between CCTA and ICA. During a 40-month follow-up period, major adverse cardiac events (MACE) were assessed.

Results

Discordance between CCTA and ICA was observed in 121 of the 3166 coronary artery segments (3.8%). Common causes were calcification (45.9%) and positive remodelling (PR) (29.6%) in 83 false positive lesions, and noise (40.0%) and motion artefact (37.8%) in 38 false negative lesions. MACE occurred in seven lesions among the discrepant lesions; six among the 29 PR lesions (20.7%) and one among the 53 calcified lesions (1.9%). With respect to the prediction power of MACE in an intermediate stenosis, the CCTA-related value including PR was higher than the ICA-related value.

Conclusions

PR was a frequent cause of MACE among the false positive lesions on CCTA. Therefore, the presence of PR on CCTA may suggest clinical significance, although it can be missed by ICA.

Key Points

• Compared to ICA, PR in CCTA may be cause of false positive lesion.

• CCTA-related value including PR shows higher prediction power of MACE than ICA-related value.

• PR reflects atherosclerotic burden that can be related to cardiac events.

• PR in CCTA should be observed carefully, even if it is false positive.



Image quality and radiation dose of coronary CT angiography performed with whole-heart coverage CT scanner with intra-cycle motion correction algorithm in patients with atrial fibrillation

Abstract

Objectives

To evaluate image quality, coronary evaluability and radiation exposure of coronary CT angiography (CCTA) performed with whole-heart coverage cardiac-CT in patients with atrial fibrillation (AF).

Materials and methods

We prospectively enrolled 164 patients with AF who underwent a clinically indicated CCTA with a 16-cm z-axis coverage scanner. In all patients CCTA was performed using prospective ECG-triggering with targeted RR interval. We evaluated image quality, coronary evaluability and effective dose (ED). Patients were divided in two subgroups based on heart rate (HR) during imaging. Group 1: 64 patients with low HR (<75 bpm), group 2: 100 patients with high HR (≥75 bpm). Written informed consent was obtained from all patients and the institutional ethics committee approved the study protocol.

Results

In a segment-based analysis, coronary evaluability was 98.4 % (2,577/2,620 segments) in the whole population, without significant differences between groups (1,013/1,024 (98.9 %) and 1,565/1,596 (98.1 %), for groups 1 and 2, respectively, p=0.15). Mean ED was similar in both groups (3.8±1.9 mSv and 3.9±2.1 mSv in groups 1 and 2, respectively, p=0.75)

Conclusions

The whole-heart-coverage scanner could evaluate coronary arteries with high image quality and without increase in radiation exposure in AF patients, even in the high HR group.

Key points

• Last-generation CT scanner improves coronary artery assessment in AF patients.

• The new CT scanner enables low radiation exposure in AF patients.

• Diagnostic ICA maybe avoided in AF patients with suspected CAD.

• Whole-heart coverage CT scanner enables low radiation exposure in AF patients.



The impact of MRI sequence on tumour staging and gross tumour volume delineation in squamous cell carcinoma of the anal canal

Abstract

Objectives

To compare maximum tumour diameter (MTD) and gross tumour volume (GTV) measurements between T2-weighted (T2-w) and diffusion-weighted (DWI) MRI in squamous cell carcinoma of the anal canal (SCCA) and assess sequence impact on tumour (T) staging. Second, to evaluate interobserver agreement and reader delineation confidence.

Methods

The staging MRI scans of 45 SCCA patients (25 females) were assessed retrospectively by two independent radiologists (0 and 5 years' experience of anal cancer MRI). MTD and GTV were delineated on both T2-w and high-b-value DWI images and compared between sequences; T staging was derived from MTD. Interobserver agreement was assessed and delineation confidence scored (1 to 5) by each observer.

Results

GTV and MTD were significantly and systematically lower on DWI versus T2-w sequences by 14.80%/9.98% (MTD) and 29.70%/12.25% (GTV) for each reader, respectively, causing T staging discordances in approximately a quarter of cases. Bland-Altman limits of agreement were narrower and intraclass correlation coefficients higher for DWI. Delineation confidence was greater on DWI: 40/42 cases were scored confidently (4 or 5) by each reader, respectively, versus 31/36 cases based on T2-w images.

Conclusions

Sequence selection affects SCCA measurements and T stage. DWI yields higher interobserver agreement and greater tumour delineation confidence.

Key Points

MTD and GTV measurements are significantly lower on DWI than on T 2 -w MRI.

Such differences cause T staging discordances in up to a quarter of cases.

DWI results in higher agreement between inexperienced and experienced observers.

DWI offers greater tumour delineation confidence to inexperienced readers.



Apparent diffusion coefficient of vertebral haemangiomas allows differentiation from malignant focal deposits in whole-body diffusion-weighted MRI

Abstract

Objectives

The aim of this study was to identify apparent diffusion coefficient (ADC) values for typical haemangiomas in the spine and to compare them with active malignant focal deposits.

Methods

This was a retrospective single-institution study. Whole-body magnetic resonance imaging (MRI) scans of 106 successive patients with active multiple myeloma, metastatic prostate or breast cancer were analysed. ADC values of typical vertebral haemangiomas and malignant focal deposits were recorded.

Results

The ADC of haemangiomas (72 ROIs, median ADC 1,085×10-6mm2s-1, interquartile range 927–1,295×10-6mm2s-1) was significantly higher than the ADC of malignant focal deposits (97 ROIs, median ADC 682×10-6mm2s-1, interquartile range 583–781×10-6mm2s-1) with a p-value < 10-6. Receiver operating characteristic (ROC) analysis produced an area under the curve of 0.93. An ADC threshold of 872×10-6mm2s-1 separated haemangiomas from malignant focal deposits with a sensitivity of 84.7 % and specificity of 91.8 %.

Conclusions

ADC values of classical vertebral haemangiomas are significantly higher than malignant focal deposits. The high ADC of vertebral haemangiomas allows them to be distinguished visually and quantitatively from active sites of disease, which show restricted diffusion.

Key Points

• Whole-body diffusion-weighted MRI is becoming widely used in myeloma and bone metastases.

• ADC values of vertebral haemangiomas are significantly higher than malignant focal deposits.

• High ADCs of haemangiomas allows them to be distinguished from active disease.



Intraprocedural 3D perfusion measurement during chemoembolisation with doxorubicin-eluting beads in liver metastases of malignant melanoma

Abstract

Objectives

To study feasibility and validity of a new software application for intraprocedural assessment of perfusion during chemoembolisation of melanoma metastases.

Methodology

In a prospective phase-II trial, ten melanoma patients with liver-only metastases underwent chemoembolisation with doxorubicin-eluting beads (DEBDOX-TACE). Tumour perfusion was evaluated immediately before and after treatment at cone beam computer tomography (CBCT) using a new software application. For control and comparison, patients underwent perfusion measurement via contrast-enhanced multidetector CT (MDCT) before and after treatment.

Results

CBCT showed 94.7 % reduction in perfusion in metastases after DEBDOX-TACE, whereas MDCT showed 96.8 %. Reduction in perfusion after treatment was statistically significant (p < 0.01) for both methods. The additional time needed for data acquisition during treatment was 5 min per case or less; the post-processing data analysis was 10 min or less. Perfusion imaging was associated with additional contrast agent and patient exposure to radiation (dose-length product [DLP]): 18 ml and 394 mGy*cm in CBCT and 100 ml and 446 mGy*cm in MDCT, respectively.

Conclusions

Reduction in perfusion of melanoma metastases after DEBDOX-TACE can be reliably assessed during the intervention via perfusion software at CBCT. Data acquisition and analysis require additional time but can be easily performed during the treatment.

Key Points

Tumour perfusion of melanoma metastases can be assessed at cone beam CT.

The software shows a significant decrease of tumour perfusion after DEBDOX-TACE.

Data acquisition and analysis require an acceptable additional time during the procedure.

CBCT requires less radiation exposure and contrast for perfusion study than MSCT.

This software can monitor the course of DEBDOX-TACE in melanoma metastases.



Conventional and synthetic MRI in multiple sclerosis: a comparative study

Abstract

Objectives

To compare the assessment of patients with multiple sclerosis (MS) using synthetic and conventional MRI.

Materials and methods

Synthetic and conventional axial images were prospectively acquired for 52 patients with diagnosed MS. Quantitative MRI (qMRI) was used for measuring proton density and relaxation times (T1, T2) and then, based on these parameters, synthetic T1W, T2W and FLAIR images were calculated. Image stacks were reviewed blindly, independently and in random order by two radiologists. The number and location for all lesions were documented and categorised. A combined report of lesion load and presence of contrast-enhancing lesions was compiled for each patient. Agreement was evaluated using kappa statistic.

Results

There was no significant difference in lesion detection using synthetic and conventional MRI in any anatomical region or for any of the three image types. Inter- and intra-observer agreements were mainly higher (p < 0.05) using conventional images but there was no significant difference in any specific region or for any image type. There was no significant difference in the outcome of the combined reports.

Conclusion

Synthetic MR images show potential to be used in the assessment of MS dissemination in space (DIS) despite a slightly lower inter- and intra-observer agreement compared to conventional MRI.

Key Points

• Synthetic MR images may potentially be useful in the assessment of MS.

• Examination times may be shortened.

• Inter- and intra-observer agreement is generally higher using conventional MRI.



Extracellular contrast agent-enhanced MRI: 15-min delayed phase may improve the diagnostic performance for hepatocellular carcinoma in patients with chronic liver disease

Abstract

Objectives

To determine the value of a 15-min delayed phase in extracellular contrast agent (ECA)-enhanced magnetic resonance imaging (MRI) for evaluation of hepatocellular carcinoma (HCC) in patients with chronic liver disease.

Methods

Between 2014 and 2015, 103 patients with chronic liver disease underwent ECA-enhanced MRI; 133 lesions consisting of 107 HCCs, 23 benign lesions and three non-HCC malignancies were identified with pathological or clinical diagnosis. MRI images were reviewed by two abdominal radiologists independently using the European Association for the Study of the Liver (EASL) and Liver Imaging Reporting and Data System (LI-RADS) criteria. Imaging features observed in the 15-min delayed phase were recorded.

Results

Of 107 HCCs, three or four additional HCCs were diagnosed according to the EASL criteria by adding the 15-min delayed phase, increasing sensitivity (Reviewer 1, from 69.2–72.0 % [P = 0.072]; Reviewer 2, from 75.7–79.4 % [P = 0.041]). Reviewers 1 and 2 upgraded one and four HCCs from LR-4 to LR-5 based on the LI-RADS, respectively. Among 23 benign lesions, no additional findings were observed in the 15-min delayed phase.

Conclusions

Including the 15-min delayed phase in ECA-enhanced MRI may improve the diagnostic performance for HCC in patients with chronic liver disease.

Key Points

• Additional acquisition of 15-min delayed phase (FDP) requires approximately 20 s.

• About 5 % of HCCs show washout or capsule appearance only in FDP.

• Including FDP improves the sensitivity of extracellular contrast agent-enhanced MRI for HCC.

• These results are applicable only to patients with chronic liver disease.



Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort: gender-corrected and education-corrected normative data

Abstract

Objectives

To find cut-off values for different medial temporal lobe atrophy (MTA) measures (right, left, average, and highest), accounting for gender and education, investigate the association with cognitive performance, and to compare with decline of cognitive function over 5 years in a large population-based cohort.

Methods

Three hundred and ninety 75-year-old individuals were examined with magnetic resonance imaging of the brain and cognitive testing. The Scheltens's scale was used to assess visually MTA scores (0–4) in all subjects. Cognitive tests were repeated in 278 of them after 5 years. Normal MTA cut-off values were calculated based on the 10th percentile.

Results

Most 75-year-old individuals had MTA score ≤2. Men had significantly higher MTA scores than women. Scores for left and average MTA were significantly higher in highly educated individuals. Abnormal MTA was associated with worse results in cognitive test and individuals with abnormal right MTA had faster cognitive decline.

Conclusion

At age 75, gender and education are confounders for MTA grading. A score of ≥2 is abnormal for low-educated women and a score of ≥2.5 is abnormal for men and high-educated women. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later.

Key Points

Gender and education are confounders for MTA grading.

We suggest cut-off values for 75-year-olds, taking gender and education into account.

Males have higher MTA scores than women.

Higher MTA scores are associated with worse cognitive performance.



In memoriam Prof. Erik Boijsen



Detection of lung carcinoma with predominant ground-glass opacity on CT using temporal subtraction method

Abstract

Purpose

To evaluate the usefulness of the CT temporal subtraction (TS) method for the detection of the lung cancer with predominant ground-glass opacity (LC-pGGO).

Materials and methods

Twenty-five pairs of CT and their TS images in patients with LC-pGGO (31 lesions) and 25 pairs of those in patients without nodules were used for an observer performance study. Eight radiologists participated and the statistical significance of differences with and without the CT-TS was assessed by JAFROC analysis.

Results

The average figure-of-merit (FOM) values for all radiologists increased to a statistically significant degree, from 0.861 without CT-TS to 0.912 with CT-TS (p < .001). The average sensitivity for detecting the actionable lesions improved from 73.4 % to 85.9 % using CT-TS. The reading time with CT-TS was not significantly different from that without.

Conclusion

The use of CT-TS improves the observer performance for the detection of LC-pGGO.

Key Points

CT temporal subtraction can improve the detection accuracy of lung cancer.

Reading time with temporal subtraction is not different from that without.

CT temporal subtraction improves observer performance for ground-glass/subsolid nodule detection.



Management of subcentimetre arterially enhancing and hepatobiliary hypointense lesions on gadoxetic acid-enhanced MRI in patients at risk for HCC

Abstract

Objectives

To investigate the significance of subcentimetre (≤1 cm) arterially enhancing and hepatobiliary hypointense lesions (SAELs) observed on gadoxetic acid-enhanced magnetic resonance imaging (MRI) of patients at risk of hepatocellular carcinoma (HCC).

Methods

A SAEL was defined as a subcentimetre hypervascular nodule exhibiting a hepatobiliary phase defect on gadoxetic acid-enhanced MRI. We included 52 SAELs from 46 patients in a HCC surveillance population. The HCC reference standard was pathologic confirmation or a nodule >1 cm with typical imaging features of HCC at follow-up imaging. The malignancy rate and HCC-favourable imaging findings of SAELs were evaluated.

Results

The malignancy rate among SAELs was 57.7% (30/52). At diagnosis, all SAELs that progressed to overt HCC were treatable with curative intention. Venous or late dynamic phase washout was more frequently observed with malignant SAELs than with benign SAELs (57.7% vs. 30.6%; P = 0.01). If SAELs exhibiting washout were considered as HCC, sensitivity, specificity, and positive predictive value was 83.3%, 50%, and 69.4%, respectively.

Conclusion

Among patients at risk of HCC, SAELs on gadoxetic acid-enhanced MRI exhibited high malignant potential. However, close observation may be an appropriate strategy for isolated SAELs. A washout appearance may be helpful for predicting malignancy.

Key Points

Gadoxetic acid-enhanced MRI provides hepatobiliary phase (HBP) images.

Screening frequently detects subcentimetre arterially enhancing and hepatobiliary hypointense lesions (SAELs).

A majority of SAELs progressed to overt HCC within 2 years.

A venous-phase washout appearance correlated significantly with malignancy in SAELs.



CAD-RADS – a new clinical decision support tool for coronary computed tomography angiography

Abstract

Coronary computed tomography angiography (CTA) has been established as an accurate method to non-invasively assess coronary artery disease (CAD). The proposed 'Coronary Artery Disease Reporting and Data System' (CAD-RADS) may enable standardised reporting of the broad spectrum of coronary CTA findings related to the presence, extent and composition of coronary atherosclerosis. The CAD-RADS classification is a comprehensive tool for summarising findings on a per-patient-basis dependent on the highest-grade coronary artery lesion, ranging from CAD-RADS 0 (absence of CAD) to CAD-RADS 5 (total occlusion of a coronary artery). In addition, it provides suggestions for clinical management for each classification, including further testing and therapeutic options. Despite some limitations, CAD-RADS may facilitate improved communication between imagers and patient caregivers. As such, CAD-RADS may enable a more efficient use of coronary CTA leading to more accurate utilisation of invasive coronary angiograms. Furthermore, widespread use of CAD-RADS may facilitate registry-based research of diagnostic and prognostic aspects of CTA.

Key points

• CAD-RADS is a tool for standardising coronary CTA reports.

• CAD-RADS includes clinical treatment recommendations based on CTA findings.

• CAD-RADS has the potential to reduce variability of CTA reports.



Histogram analysis of diffusion kurtosis imaging derived maps may distinguish between low and high grade gliomas before surgery

Abstract

Objective

To investigate the value of histogram analysis of diffusion kurtosis imaging (DKI) maps in the evaluation of glioma grading.

Methods

A total of 39 glioma patients who underwent preoperative magnetic resonance imaging (MRI) were classified into low-grade (13 cases) and high-grade (26 cases) glioma groups. Parametric DKI maps were derived, and histogram metrics between low- and high-grade gliomas were analysed. The optimum diagnostic thresholds of the parameters, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were achieved using a receiver operating characteristic (ROC).

Result

Significant differences were observed not only in 12 metrics of histogram DKI parameters (P<0.05), but also in mean diffusivity (MD) and mean kurtosis (MK) values, including age as a covariate (F=19.127, P<0.001 and F=20.894, P<0.001, respectively), between low- and high-grade gliomas. Mean MK was the best independent predictor of differentiating glioma grades (B=18.934, 22.237 adjusted for age, P<0.05). The partial correlation coefficient between fractional anisotropy (FA) and kurtosis fractional anisotropy (KFA) was 0.675 (P<0.001). The AUC of the mean MK, sensitivity, and specificity were 0.925, 88.5% and 84.6%, respectively.

Conclusions

DKI parameters can effectively distinguish between low- and high-grade gliomas. Mean MK is the best independent predictor of differentiating glioma grades.

Key points

DKI is a new and important method.

DKI can provide additional information on microstructural architecture.

Histogram analysis of DKI may be more effective in glioma grading.



Subtraction multiphase CT angiography: A new technique for faster detection of intracranial arterial occlusions

Abstract

Objective

To describe and evaluate a novel technical development to improve detection of intracranial vessel occlusions using multiphase CT angiography (MPCTA).

Materials and methods

The institutional ethics committee approved the study. Fifty patients (30 consecutive distal (M2 or smaller) anterior circulation occlusions, ten M1 occlusions, ten cases without occlusion) presenting with suspected AIS who underwent MPCTA were included. Post-processing of MPCTA studies created "subtraction" and "delayed enhancement" (DE) datasets. Initially, non-contrast CT and MPCTA studies for each patient were evaluated. Readers' confidence, speed and sensitivity of detection of intracranial vessel occlusions were recorded. After an interval of at least 4 weeks, readers were provided with post-processed images and studies were re-evaluated.

Results

While the sensitivity of detection of intracranial vessel occlusions was equal for both conventional MPCTA and subMPCTA, the mean time taken to identify a vessel occlusion decreased by 64 % using subMPCTA (16 s vs. 45 s with conventional MPCTA) (p<0.001). In addition, confidence in interpretation improved (from 4.4 to 4.9) using subMPCTA (p<0.001).

Conclusion

SubMPCTA is a novel technique that aids in identifying small intracranial vessel occlusions in the suspected AIS patient. SubMPCTA increases confidence in interpretation and reduces the time taken to detect intracranial vessel occlusions.

Key Points

• SubMPCTA processes MPCTA data to better demonstrate intracranial arterial occlusions.

• SubMPCTA increases confidence and speed of interpretation of MPCTA studies.

• SubMPCTA may aid in rapidly differentiating acute ischaemic stroke from stroke mimics.



Secretin-stimulated ultrasound estimation of pancreatic secretion in cystic fibrosis validated by magnetic resonance imaging

Abstract

Objectives

Secretin-stimulated magnetic resonance imaging (s-MRI) is the best validated radiological modality assessing pancreatic secretion. The purpose of this study was to compare volume output measures from secretin-stimulated transabdominal ultrasonography (s-US) to s-MRI for the diagnosis of exocrine pancreatic failure in cystic fibrosis (CF).

Methods

We performed transabdominal ultrasonography and MRI before and at timed intervals during 15 minutes after secretin stimulation in 21 CF patients and 13 healthy controls. To clearly identify the subjects with reduced exocrine pancreatic function, we classified CF patients as pancreas-sufficient or -insufficient by secretin-stimulated endoscopic short test and faecal elastase.

Results

Pancreas-insufficient CF patients had reduced pancreatic secretions compared to pancreas-sufficient subjects based on both imaging modalities (p < 0.001). Volume output estimates assessed by s-US correlated to that of s-MRI (r = 0.56–0.62; p < 0.001). Both s-US (AUC: 0.88) and s-MRI (AUC: 0.99) demonstrated good diagnostic accuracy for exocrine pancreatic failure.

Conclusions

Pancreatic volume-output estimated by s-US corresponds well to exocrine pancreatic function in CF patients and yields comparable results to that of s-MRI. s-US provides a simple and feasible tool in the assessment of pancreatic secretion.

Key points

• Cystic fibrosis patients with affected pancreas have reduced pancreatic secretions.

Secretin-stimulated sonography is a simple and feasible method to assess pancreatic output.

Secretin-simulated MRI is a more precise method to assess pancreatic secretions.

The sonographic and MRI methods yielded comparable pancreatic secretory output estimates.



Early US findings of biliary atresia in infants younger than 30 days

Abstract

Purpose

To investigate and compare ultrasound (US) findings for the diagnosis of biliary atresia (BA) in infants younger than 30 days with those of infants older than 30 days.

Materials and Methods

From 2000 to 2015, we reviewed hepatobiliary US images in 12 BA infants younger than 30 days (younger BA group) and 62 BA infants older than 30 days (older BA group) before Kasai procedure. Eight (67%) of younger BA group underwent follow-up US examinations before Kasai procedure. Our review of the images focused on triangular cord sign, gallbladder (GB) abnormalities, vascular changes, and signs of portal hypertension.

Results

The triangular cord sign was present in 17% of younger BA group and in 56% of older BA group (P=.024). GB abnormalities were commonly identified in both groups. The hepatic artery diameter was significantly smaller in younger BA group than in older BA group (P<.001). Signs of portal hypertension were less common in younger BA group (17%) than in older BA group (84%) (P<.001). Follow-up US of two infants in younger BA group showed a new appearance of the triangular cord sign.

Conclusion

BA infants younger than 30 days showed atypical US findings compared with those older than 30 days.

Key Points

BA infants younger than 30 days show atypical US findings.

GB abnormalities were common in both younger and older BA group.

Subsequent US examination may be helpful to diagnose BA in young infants.



Accuracy of apparent diffusion coefficient in differentiating pancreatic neuroendocrine tumour from intrapancreatic accessory spleen

Abstract

Objectives

To evaluate and compare the accuracy of absolute apparent diffusion coefficient (ADC) and normalised ADC (lesion-to-spleen ADC ratio) in differentiating pancreatic neuroendocrine tumour (NET) from intrapancreatic accessory spleen (IPAS).

Methods

Study included 62 patients with the diagnosis of pancreatic NET (n=51) or IPAS (n=11). Two independent reviewers measured ADC on all lesions and spleen. Receiver operating characteristics (ROC) analysis to differentiate NET from IPAS was performed and compared for absolute and normalised ADC. Inter-reader reliability for the two methods was assessed.

Results

Pancreatic NET had significantly higher absolute ADC (1.431x10-3 vs 0.967x10-3 mm2/s; P<0.0001) and normalised ADC (1.59 vs 1.09; P<0.0001) compared to IPAS. An ADC value of ≥1.206x10-3 mm2/s was 70.6% sensitive and 90.9% specific for the diagnosis of NET vs. IPAS. Lesion to spleen ADC ratio of ≥1.25 was 80.4% sensitive, and 81.8% specific while ratio of ≥1.29 was 74.5% sensitive and 100% specific in the differentiation. The area under the curve (AUCs) for two methods were similar (88.2% vs. 88.8%; P=0.899). Both methods demonstrated excellent inter-reader reliability with ICCs for absolute ADC and ADC ratio being 0.957 and 0.927, respectively.

Conclusion

Both absolute and normalised ADC allow clinically relevant differentiation of pancreatic NET and IPAS.

Key points

• Imaging overlaps between IPASs and pancreatic-NETs lead to unnecessary procedures including pancreatectomy.

• Uniquely low ADC of spleen allows differentiating IPASs from pancreatic NETs.

• Both absolute-ADC and normalised-ADC (lesion-to-spleen ADC-ratio) demonstrate high accuracy in differentiating IPASs from NETs.

• Both methods demonstrate excellent inter-reader reliability.



Correlation between the availability of dopamine transporter and olfactory function in healthy subjects

Abstract

Objectives

Olfactory dysfunction in Parkinson's disease is usually prodromal to other symptoms. In this study, we aimed to explore the association of olfactory function with the availabilities of striatal dopamine transporter (DAT) in healthy subjects.

Methods

Data used in the preparation of this article were obtained from Parkinson's Progression Markers Initiative database (www.ppmi-info.org/data). The study population consisted of healthy controls with screening 123I-FP-CIT single photon emission tomography (SPECT). University of Pennsylvania Smell Identification Test (UPSIT) was assessed to evaluate the olfactory function. Results: Totally, 181 healthy subjects (117 male, 64 female) with 123I-FP-CIT SPECT data were included in this study. Specific binding ratios (SBRs) of the caudate nucleus (rho = -0.4217, p < 0.0001), putamen (rho = -0.2292, p = 0.0019), and striatum (rho=-0.3425, p < 0.0001) showed a reduction with ageing. SBRs of the caudate nucleus, putamen, and striatum were positively correlated with UPSIT (rho = 0.3716, p < 0.0001; rho = 0.3655, p < 0.0001; rho = 0.3880, p < 0.0001). After controlling for age by partial correlation, SBRs of the caudate nucleus, putamen, and striatum showed an influence on UPSIT (rho = 0.3288, p < 0.0001; rho = 0.3374, p < 0.0001; rho = 0.3511, p < 0.0001).

Conclusion

Olfactory function is associated with the availability of striatal DAT independent of age in healthy subjects.

Key Points

Olfactory dysfunction in Parkinson's disease is prodromal to other symptoms.

The availability of dopamine transporter showed a reduction with ageing.

Olfactory function is associated with the availability of dopamine transporter.



Political liberalism and autonomy education: Are citizenship-based arguments enough?

Abstract

Several philosophers of education argue that schooling should facilitate students' development of autonomy. Such arguments fall into two main categories: Student-centered arguments support autonomy education to help enable students to lead good lives; Public-goods-centered arguments support autonomy education to develop students into good citizens. Critics challenge the legitimacy of autonomy education—of the state imposing a schooling curriculum aimed at making children autonomous. In this paper, I offer a unified solution to the challenges of legitimacy that both arguments for autonomy education face. I first defend a particular construal of liberal legitimacy, and then consider each legitimacy challenge in light of that construal. I argue that the legitimacy challenges confronting both types of argument can be overcome. Further, I explain why we should pursue both arguments, rather than resting the entire case for autonomy education on one or the other. I conclude that each argument—if it can justify autonomy education at all—can justify autonomy education consistent with the requirements of liberal democratic legitimacy.



Editorial Board

Publication date: March 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 180





Cutaneous squamous cell carcinoma with epidermodysplasia verruciformis-like features in a patient with Schimke immune-osseous dysplasia (SIOD)

Schimke immune-osseous dysplasia1 (SIOD) is an autosomal recessive disorder caused by mutations in the SMARCAL1 gene encoding an ATP-driven annealing helicase that stabilizes stalled replication forks and facilitates DNA repair during replication2. The syndrome is characterized by spondyloepiphyseal dysplasia, steroid-resistant nephropathy and cellular immune deficiency.



Urban wastewater treatment by using Ag/ZnO and Pt/TiO 2 photocatalysts

Abstract

In this study, the treatment of wastewater coming from a river highly polluted with domestic and industrial effluents was evaluated. For this purpose, series of photocatalysts obtained by ZnO and TiO2 modification were evaluated. The effect of metal addition and Ti precursor (in the case of the titania series) over the physicochemical and photocatalytic properties of the materials obtained was also analyzed. The evaluation of the photocatalytic activity showed that semiconductor modification and precursor used in the materials synthesis are important factors influencing the physicochemical and therefore the photocatalytic properties of the materials obtained. The water samples analyzed in the present work were taken from a highly polluted river, and it was found that the effectiveness of the photocatalytic treatment increases when the reaction time increases and for both, wastewater samples and isolated Escherichia coli strain follow the next order Pt/TiO2 << ZnO. It was also observed that biochemical and chemical demand oxygen and turbidity significantly decrease after treatment, thus indicating that photocatalysis is a non-selective technology, which can lead to recover wastewater containing different pollutants.



Enhanced electro-reduction of NO to NH 3 on Pt cathode at electro-scrubber

Abstract

Besides cheaper electrodes used in NH3 product formation during NO degradation by mediated electrochemical reduction (MER), a specific electrode that can perform direct electrochemical reduction (DER) and MER of NO is an added advantage. In the present study, a Pt electrode was used to examine NO degradation through NH3 formation during the electro-scrubbing process. Initially, the DER of NO was tested on a Pt electrode to determine if the DER of NO is possible. The NO degradation by only absorption, DER on Pt, and MER using electrogenerated [Ni(I)(CN)4]3− showed that a combination of DER and MER increased the NO degradation efficiency. In addition, the online FTIR spectra obtained under different conditions showed that the product formed was NH3, either from the DER or MER during electro-scrubbing. The feed gas flow rate and feed concentration results of NH3 formation revealed an additional chemical reaction that was influenced by the Pt electrode in addition to the DER and MER processes. Furthermore, the degradation efficiency of NO when using the Pt electrode increased to 90% compared to that of the Cu electrode (65%), which showed that Pt follows a combination of DER and MER processes. Based on the gas-phase FTIR results of NH3 formation during NO degradation, higher NH3 production (0.32 mg/h) was obtained when using a Pt electrode than that using a Cu electrode (0.21 mg/h), highlighting the specificity of the Pt electrode in NH3 formation during the degradation of NO gas.



MSR1 repeats modulate gene expression and affect risk of breast and prostate cancer

Abstract
Background
MSR1 repeats are a 36-38bp minisatellite element that have recently been implicated in the regulation of gene expression, through copy number variation (CNV).
Patients and methods
Bioinformatic and experimental methods were used to assess the distribution of MSR1 across the genome, evaluate the regulatory potential of such elements and explore the role of MSR1 elements in cancer, particularly non-familial breast cancer and prostate cancer.
Results
MSR1s are predominately located at chromosome 19 and are functionally enriched in regulatory regions of the genome, particularly regions implicated in short-range regulatory activities (H3K27ac, H3K4me1, and H3K4me3). MSR1-regulated genes were found to have specific molecular roles, such as serine-protease activity (P=4.80x10−7) and ion channel activity (P=2.7x10−4). The kallikrein locus was found to contain a large number of MSR1 clusters, and at least six of these showed CNV. An MSR1 cluster was identified within KLK14, with 9-copies and 11-copies being normal variants. A significant association with the 9-copy allele and non-familial breast cancer was found in two independent populations (P=0.004; P=0.03). In the white British population, the minor allele conferred an increased risk of 1.21 to 3.51-times for all non-familial disease, or 1.7 to 5.3-times in early-onset disease. The 9-copy allele was also found to be associated with increased risk of prostate cancer in an independent population (odds ratio = 1.27-1.56; P =0.009).
Conclusions
MSR1 repeats act as molecular switches that modulate gene expression. It is likely that CNV of MSR1 will affect risk of development of various forms of cancer, including that of breast and prostate. The MSR1 cluster at KLK14 represents the strongest risk factor identified to date in non-familial breast cancer and a significant risk factor for prostate cancer. Analysis of MSR1 genotype will allow development of precise stratification of disease risk and provide a novel target for therapeutic agents.

Genetic profiling using plasma-derived cell-free DNA in therapy-naïve hepatocellular carcinoma patients: a pilot study.

Abstract
Background
Hepatocellular carcinomas (HCCs) are not routinely biopsied, resulting in a lack of tumor materials for molecular profiling. Here we sought to determine if plasma-derived cell-free DNA (cfDNA) captures the genetic alterations of HCC in patients who have not undergone systemic therapy.
Patients and methods
Frozen biopsies from the primary tumor and plasma were synchronously collected from 30 prospectively recruited, systemic treatment-naïve HCC patients. Deep sequencing of the DNA from the biopsies, plasma-derived cfDNA and matched germline was performed using a panel targeting 46 coding and non-coding genes frequently altered in HCCs.
Results
In 26/30 patients, at least one somatic mutation was detected in biopsy and/or cfDNA. Somatic mutations in HCC-associated genes were present in the cfDNA of 63% (19/30) patients and could be detected 'de novo' without prior knowledge of the mutations present in the biopsy in 27% (8/30) patients. Mutational load and the variant allele fraction of the mutations detected in the cfDNA positively correlated with tumor size and Edmondson grade. Crucially, among the seven patients in whom the largest tumor was ≥5cm or was associated with metastasis, at least one mutation was detected 'de novo' in the cfDNA of 86% (6/7) cases. In these patients, cfDNA and tumor DNA captured 87% (80/92) and 95% (87/92) of the mutations, suggesting that cfDNA and tumor DNA captured similar proportions of somatic mutations.
Conclusion
In patients with high disease burden, the use of cfDNA for genetic profiling when biopsy is unavailable may be feasible. Our results support further investigations into the clinical utility of cfDNA in a larger cohort of patients.

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol

Abstract
Background
Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in STAMPEDE: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP vs SOC+DocP.
Method
Recruitment to SOC+DocP and SOC+AAP overlapped Nov-2011─Mar-2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2yrs and RT to the primary tumour. Stratified randomisation allocated pts 2:1:2 to SOC; SOC+docetaxel 75mg/m2 3-weekly x6 + prednisolone 10mg daily; or SOC+abiraterone acetate 1000mg + prednisolone 5mg daily. AAP duration depended on stage & intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards & flexible parametric models, adjusted for stratification factors. This was not a formally-powered comparison. A hazard ratio (HR)<1 favours SOC+AAP, HR > 1 favours SOC+DocP.
Results
566 consenting patients were contemporaneously randomised: 189 SOC+DocP, 377 SOC+AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66yr & median PSA 56ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1·16 (95%CI 0·82-1·65); failure-free survival HR = 0·51 (95%CI 0·39-0·67); progression-free survival HR = 0·65 (95%CI 0·48-0·88); metastasis-free survival HR = 0·77 (95%CI 0·57-1·03); prostate cancer-specific survival HR = 1·02 (0·70-1·49); and symptomatic skeletal events HR = 0·83 (95%CI 0·55-1·25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC+DocP, & 40%, 7% and 1% SOC+AAP; prevalence 11% at 1 and 2yrs on both arms. Relapse treatment patterns varied by arm.
Conclusions
This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer (HNPC) showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events, suggesting that Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs.
Trial registration
Clinicaltrials.gov: NCT00268476

Πέμπτη 1 Μαρτίου 2018

Issue Information



A new technique for evaluating heel xerosis grade and the effects of moisturizer on heel skin dryness

Abstract

Background

Dryness-related heel skin problems are common; however, there are very few studies about heel skin dryness. The objective of this study was to develop new assessment methods for evaluating heel skin dryness, to clarify the characteristics associated with heal skin dryness, and assess the effectiveness of moisturizer use according to dryness severity.

Materials and methods

We investigated the heel skin of 150 Korean women (aged 20-78 years). Heel skin images were taken using a DSLR camera and the distribution or severity of flakes, scaling, cracking, and fissures were visually assessed. Skin properties such as hydration, transepidermal water loss (TEWL), amount of dead skin cells, and efficacy of moisturizer were evaluated according to heel xerosis grade. Furthermore, as conventional evaluation methods for desquamation are not appropriate for heel skin, we developed new techniques using binarization of magnified images.

Results

Skin hydration tended to decrease and TEWL tended to increase as heel dryness grade increased. The amount of dead skin cells increased with increasing dryness grade using the new technique. Subjects in the severe dryness group achieved similar hydration levels as normal subjects at baseline after 3 hours of moisturizer application.

Conclusion

Our new methods of visually classifying heel dryness and quantifying dead skin cells using magnified images effectively evaluated heel skin properties. As heel skin is prone to dryness, daily repetitive application of moisturizer might be helpful for hydrating dry heel skin, and ultimately preventing complications.



Poor inter-rater reliability of hidradenitis suppurativa phenotypes

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): K.R. van Straalen, T. Verhagen, B. Horváth, C. Ardon, A.R.J.V. Vossen, R. Driessen, J. Boer, A. Rondags, E.P. Prens, H.H. van der Zee




T-cell–mediated immune response to pneumococcal conjugate vaccine (PCV-13) and tetanus toxoid vaccine in patients with moderate-to-severe psoriasis during tofacitinib treatment

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Kevin L. Winthrop, Neil Korman, William Abramovits, Scott T. Rottinghaus, Huaming Tan, Annie Gardner, Geoffrey Mukwaya, Mandeep Kaur, Hernan Valdez
BackgroundPsoriasis is often treated with immunomodulatory therapies that can affect the immune response to common antigens. Tofacitinib is an oral Janus kinase inhibitor.ObjectiveTo characterize the effect of long-term exposure to tofacitinib 10 mg twice daily on T-cell function in psoriasis patients.MethodsPatients completing at least 3 months' continuous treatment with tofacitinib 10 mg twice daily were vaccinated with T-cell–dependent vaccines (monovalent tetanus toxoid and 13-valent pneumococcal conjugate [PCV-13]). Patients were assessed at baseline (before vaccination) and then again 4 weeks after vaccination. For PCV-13, we evaluated serotype-specific, opsonophagocytic antibody responses, and for tetanus toxoid, we evaluated humoral responses.ResultsAmong 60 patients who completed the study, the geometric mean fold rise from baseline for the 13 PCV serotypes at 4 weeks postvaccination varied from 8.3 (serotype 3) to 101.9 (serotype 6A). Similar results were observed for patients with and without lymphopenia at baseline. For tetanus toxoid, 51 (88%) patients had ≥2-fold and 35 (60%) patients had ≥4-fold rise in antibody concentration.LimitationsThere was no placebo control.ConclusionMost psoriasis patients who receive tofacitinib can mount satisfactory T-cell–dependent responses to PCV-13 and tetanus vaccines.



Book Review: Dermatology: Visual Recognition and Case Reviews by Christine J. Ko

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Dirk M. Elston




Interleukin-17, Inflammation, and Cardiovascular Risk in Patients With Psoriasis

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Benjamin Lockshin, Yevgeniy Balagula, Joseph F. Merola
In addition to being recognized as a chronic inflammatory disease that manifests in the skin, psoriasis is increasingly understood to be a systemic disease that causes immune dysregulation throughout the body. The systemic nature of psoriasis is evidenced by the higher burden of comorbidities and shorter life expectancies of patients with psoriasis, particularly those with early onset and severe disease. Notably, psoriasis is associated with an increased risk for cardiovascular disease, which is the most common cause of morbidity and mortality in patients with psoriasis. In this review, we examine the association between psoriasis and cardiovascular disease and specifically focus on the role of interleukin-17–mediated inflammation as a potential mechanistic link between psoriasis and cardiovascular disease. Moreover, we describe potential treatment approaches to reduce the burden of cardiovascular disease in patients with psoriasis, and discuss the clinical importance of the association of these 2 diseases with respect to patient management and education.



Issue Information



Large number of cutaneous neurofibromas beyond age-appropriate incidence in a patient with a large deletion of NF1



Preface to Journal of Dermatology special issue: Psoriasis



Issue Information



Correlating the Dermatology Life Quality Index and Skin Discoloration Impact Evaluation Questionnaire tools in disorders of hyperpigmentation



Collagen type III and elastin genes polymorphism and the risk of nonsyndromic striae

Summary

Background

Striae have been reported to be one of the most common skin lesions and a commonly encountered esthetic problem.

Objectives

The aim of this research was to examine elastin gene polymorphism (rs7787362, ELN) and collagen type III alpha 1 polymorphism (rs1800255, COL3A1) among polish woman population with SD in comparison with women without the lesions and to verify these polymorphisms as risk factors for SD.

Methods

Seventy female students (35 with striae (the mean age 23.9 years, SD 1.2 years) and 35 without these lesions (22.9 years, SD 1.7 years)) were included in the study. The subjects were asked to fill out a questionnaire including questions concerning risk factors for SD and had a cheek swabbed for cells for DNA isolation.

Results

Analysis of polymorphisms of elastin gene (rs7787362) and COL3A1 gene (rs1800255) showed that women with SD and without these lesions did not differ in these aspects. Polymorphism rs7787362 was also analyzed in relation to SD in different locations, and showed no differences.

Conclusion

In conclusion, we found that there are some clinical factors that reduced the risk of SD: history of intended weight loss, negative family history of SD, and lower BMI. Gene polymorphisms analysis in patients with SD may help to establish the etiology of these lesions and to target the therapy. Analysis of polymorphisms of elastin gene (rs7787362) did not show differences in allele distribution between women with and without SD. Polymorphisms of COL3A1 gene (rs1800255) also did not differ between the examined groups.



IL1A (-889) gene polymorphism is associated with the effect of diet as a risk factor in Acne Vulgaris

Summary

Background

Despite the several studies suggesting the genetic basis of acne vulgaris, the exact genetic architecture of this very common condition is not yet clear.

Aim of the work

This study aimed to investigate the association between IL-1A (−889) gene polymorphism and acne vulgaris in a sample of patients.

Subjects and Method

Blood samples from 100 patients with acne vulgaris and 100 healthy age, sex, and BMI matched controls were obtained. DNA samples were isolated from blood cells, and the PCR-RFLP method was used for genotyping.

Results

The genotype distributions of IL-1A (−889) polymorphism were as expected under Hardy-Weinberg equilibrium. T allele was predominant in the patients, while C allele predominated in the control subjects (P value < .001). The frequency of TT genotype in patients was significantly higher than in the control subjects (P value < .001). CT genotype was significantly more frequent in the control subjects compared to patients (P value < .001). Among the 47 patients who reported diet as a risk factor for triggering or exacerbating their lesions, 62.5% had TT genotype (P value = .038).

Conclusion

IL-1A (−889) gene polymorphism has a role in the pathogenesis of acne vulgaris. We suggest that the triggering or exacerbating effect of diet on acne may be related to IL-1A (−889) gene polymorphism.



Pacemakers in MRI for the Neuroradiologist: Revisited [LETTERS]



Reply: [LETTERS]



Radiation Dosimetry of 3D Rotational Neuroangiography and 2D-DSA in Children [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

The benefit-risk assessment concerning radiation use in pediatric neuroangiography requires an extensive understanding of the doses delivered. This work evaluated the effective dose of 3D rotational angiography in a cohort of pediatric patients with complex neurovascular lesions and directly compared it with conventional 2D-biplane DSA.

MATERIALS AND METHODS:

Thirty-three 3D rotational angiography acquisitions were acquired in 24 pediatric patients (mean age, 10.4 years). When clinically indicated, following 2D-biplane DSA, 3D rotational angiography was performed with 1 of 3 technical protocols (2 subtracted, 1 unsubtracted). The protocols consisted of 1 factory and 2 customized techniques, with images subsequently reconstructed into CT volumes for clinical management. Raw projections and quantitative dose metrics were evaluated, and the effective dose was calculated.

RESULTS:

All 3D rotational angiography acquisitions were of diagnostic quality and assisted in patient management. The mean effective doses were 0.5, 0.12, and 0.06 mSv for the factory-subtracted, customized-subtracted, and customized-unsubtracted protocols, respectively. The mean effective dose for 2D-biplane DSA was 0.9 mSv. A direct intraprocedural comparison between 3D and 2D acquisitions indicated that customized 3D rotational angiography protocols delivered mean relative doses of 9% and 15% in unsubtracted and subtracted acquisitions, respectively, compared with biplane DSA, whereas the factory subtracted protocol delivered 68%.

CONCLUSIONS:

In pediatric neuroangiography, the effective dose for 3D rotational angiography can be significantly lower than for 2D-biplane DSA and can be an essential adjunct in the evaluation of neurovascular lesions. Additionally, available 3D rotational angiography protocols have significant room to be tailored for effectiveness and dose optimization, depending on the clinical question.



Utility of Repeat Head CT in Patients with Blunt Traumatic Brain Injury Presenting with Small Isolated Falcine or Tentorial Subdural Hematomas [ADULT BRAIN]

BACKGROUND AND PURPOSE:

In blunt traumatic brain injury with isolated falcotentorial subdural hematoma not amenable to neurosurgical intervention, the routinely performed, nonvalidated practice of serial head CT scans frequently necessitates increased hospital resources and exposure to ionizing radiation. The study goal was to evaluate clinical and imaging features of isolated falcotentorial subdural hematoma at presentation and short-term follow-up.

MATERIALS AND METHODS:

We performed a retrospective analysis of patients presenting to a level 1 trauma center from January 2013 to March 2015 undergoing initial and short-term follow-up CT with initial findings positive for isolated subdural hematoma along the falx and/or tentorium. Patients with penetrating trauma, other sites of intracranial hemorrhage, or depressed skull fractures were excluded. Patient sex, age, Glasgow Coma Scale score, and anticoagulation history were obtained through review of the electronic medical records.

RESULTS:

Eighty patients met the inclusion criteria (53 males; 27 females; median age, 61 years). Of subdural hematomas, 57.1% were falcine, 33.8% were tentorial, and 9.1% were mixed. The mean initial Glasgow Coma Scale score was 14.2 (range, 6–15). Isolated falcotentorial subdural hematomas were small (mean, 2.8 mm; range, 1–8 mm) without mass effect and significant change on follow-up CT (mean, 2.7 mm; range, 0–8 mm; P = .06), with an average follow-up time of 10.3 hours (range, 3.9–192 hours). All repeat CTs demonstrated no change or decreased size of the initial subdural hematoma. No new intracranial hemorrhages were seen on follow-up CT.

CONCLUSIONS:

Isolated falcotentorial subdural hematomas in blunt traumatic brain injury average 2.8 mm in thickness and do not increase in size on short-term follow-up CT. Present data suggest that repeat CT in patients with mild traumatic brain injury with isolated falcotentorial subdural hematoma may not be necessary.



Normal Values of Magnetic Relaxation Parameters of Spine Components with the Synthetic MRI Sequence [SPINE]

BACKGROUND AND PURPOSE:

SyMRI is a technique developed to perform quantitative MR imaging. Our aim was to analyze its potential use for measuring relaxation times of normal components of the spine and to compare them with values found in the literature using relaxometry and other techniques.

MATERIALS AND METHODS:

Thirty-two spine MR imaging studies (10 cervical, 5 dorsal, 17 lumbosacral) were included. A modified multiple-dynamic multiple-echo sequence was added and processed to obtain quantitative T1 (millisecond), T2 (millisecond), and proton density (percentage units [pu]) maps for each patient. An ROI was placed on representative areas for CSF, spinal cord, intervertebral discs, and vertebral bodies, to measure their relaxation.

RESULTS:

Relaxation time means are reported for CSF (T1 = 4273.4 ms; T2 = 1577.6 ms; proton density = 107.5 pu), spinal cord (T1 = 780.2 ms; T2 = 101.6 ms; proton density = 58.7 pu), normal disc (T1 = 1164.9 ms; T2 = 101.9 ms; proton density = 78.9 pu), intermediately hydrated disc (T1 = 723 ms; T2 = 66.8 ms; proton density = 60.8 pu), desiccated disc (T1 = 554.4 ms; T2 = 55.6 ms; proton density = 47.6 ms), and vertebral body (T1 = 515.3 ms; T2 = 100.8 ms; proton density = 91.1 pu). Comparisons among the mean T1, T2, and proton density values showed significant differences between different spinal levels (cervical, dorsal, lumbar, and sacral) for CSF (proton density), spinal cord (T2 and proton density), normal disc (T1, T2, and proton density), and vertebral bodies (T1 and proton density). Significant differences were found among mean T1, T2, and proton density values of normal, intermediately hydrated, and desiccated discs.

CONCLUSIONS:

Measurements can be easily obtained on SyMRI and correlated with previously published values obtained using conventional relaxometry techniques.



Altered Regional Homogeneity in Chronic Insomnia Disorder with or without Cognitive Impairment [FUNCTIONAL]

BACKGROUND AND PURPOSE:

Many studies have shown that insomnia is an independent factor in cognitive impairment, but the involved neurobiological mechanisms remain unclear. We used regional homogeneity to explore the specific neurobiologic indicators of chronic insomnia disorder with mild cognitive impairment.

MATERIALS AND METHODS:

Thirty-nine patients with insomnia were divided into a group with and without cognitive impairment; we also included a control group (n = 28). Abnormalities in brain functional activity were identified by comparing the regional homogeneity values for each brain region among the groups.

RESULTS:

Subjective insomnia scores were negatively correlated with cognitive impairment after controlling for age, sex, and educational effects. Regions with significant differences in regional homogeneity values in the 3 groups were concentrated in the right medial prefrontal cortex, the right superior frontal gyrus, and the left superior occipital gyrus. Meanwhile, subjective insomnia scores were negatively correlated with the strength of the decreased regional homogeneity in the right medial prefrontal cortex. The increased regional homogeneity value in the right superior frontal gyrus was positively correlated with the Montreal Cognitive Assessment score in patients.

CONCLUSIONS:

Our results indicate that decreased regional homogeneity values in the medial prefrontal cortex and increased regional homogeneity values in the cuneus may be important neurobiologic indicators of chronic insomnia disorder and accompanying cognitive impairment. Overall, our study described the regional homogeneity of the whole brain in chronic insomnia disorder with mild cognitive impairment and could be the basis for future studies.



Book Review: Dermatology: Visual Recognition and Case Reviews by Christine J. Ko



Assessment of quality of life in patients who underwent breast reduction using BREAST-Q

Dear Sir,

The effect of template-based sequential (TBS) coding on an NHS plastic surgical practice

Clinical coding is often a mystery to us surgeons but in actuality, it has a huge bearing on the financial sustainability of our services. Given the rapid innovations in plastic surgical procedures, clinical coders often struggle to decipher the extent of surgery. Meeting midway is the way forward here.

A supermicrosurgery training model using the chicken mid and lower wing

Supermicrosurgery is considered the pinnacle of microsurgery with its challenging nature of dissection and anastomosis of very small diameter vessels in the 0.3 to 0.8 mm range.

The C-MAC® Video-assisted Nasoendoscopy vs Traditional Direct Flexible Nasoendoscopy: A Pilot Randomised controlled study

Abstract

The C-MAC® video monitor attachment is suitable for all otolaryngological scenarios, including post-operative follow up and difficult airway examination.

Currently, there are no studies looking at the effectiveness of C-MAC® portable monitor with portable flexible nasoendoscopy.

Our study demonstrates that the C-MAC® monitor with portable flexible nasoendoscopy is an excellent tool in terms of medical education, improving patient-doctor communication, efficiency of ward rounds and for medico-legal documentation, with distinct advantages over traditional direct flexible nasoendoscopy.

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Does otitis media in early childhood affect later behavioural development? Results from the Western Australian Pregnancy Cohort (Raine) Study

Abstract

Objectives

To examine the relationship between early life episodes of otitis media and later behavioural development with adjustment for confounders.

Design

Longitudinal cohort study.

Setting: The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnant women from King Edward Memorial Hospital (KEMH) in Perth, Western Australia, between 1989 and 1991.

Participants

Data from the children born were collected at both the Year 3 and Year 5 follow up. At Year 3, n = 611 were diagnosed with recurrent otitis media through parent-report and clinical examination. At Year 5, n = 299 were considered exposed to otitis media based upon tympanometry results.

Main Outcome Measures

Performance in the Child Behaviour Checklist (CBCL), a questionnaire completed by the primary caregiver at Year 10.

Results

Significant associations were found between recurrent otitis media at Year 3 and internalising behaviours (P = 0.011), and the somatic (P = 0.011), withdrawn (P = 0.014), attention (P = 0.003) and thought problems domains (P = 0.021), and the total CBCL score (P = 0.010). A significant association was also found between exposure to otitis media at Year 5 and externalising behaviours (P = 0.026).

Conclusions

A modest association was seen between recurrent otitis media at Year 3 and exposure to otitis media at Year 5 and a number of behaviour domains at Year 10.

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Decreasing cytokeratin 17 expression in head and neck cancer predicts nodal metastasis and poor prognosis: the first evidence

Abstract

Objectives

Cytokeratins (CKs) are mainly expressed in epithelial carcinomas and are valuable for making diagnoses and identifying metastatic status. Changes in the expression of individual CKs in certain carcinoma may be relevant to establishing a prognosis. However, the prognostic significance of CKs in head and neck squamous cell carcinoma (HNSCC) remains elusive. Herein, we investigated the diverse and unique expression patterns of Cytokeratin 13 (CK13) and Cytokeratin 17 (CK17) and assessed the role of CK17 as a predictor for HNSCC metastasis and prognosis.

Methods

CK13 and CK17 expressions were evaluated by using immunohistochemical tissue microarray (TMA) analysis with 106 patients of HNSCC. To clarify the characterization of CK17 expression with respect to its ability in predicting metastatic disease, an in-vitro study of cells migration/invasion assays was conducted. Furthermore, the correlation of CK17 expression to clinicopathologic variables and prognosis was analyzed by using a serial statistical method.

Results

CK13 was predominately expressed in noncancerous tissues and was lost in HNSCC. Decreasing expression of CK17 correlated with cancerous cell migration and invasion (P<0.0001) in an in-vitro study. CK17 expression was lower in the N1 and N2 nodal metastases category compared to the N0 stage. Moreover, Kaplan-Meier survival analyses showed that a lower CK17 expression was associated with a poorer survival connotation in HNSCC patients (P<0.05) with 10-year follow-up.

Conclusion

Our findings provide the first evidence that CK17 under-expression might be a potential predictor of nodal metastasis and adverse prognosis.

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Effects of sumatriptan nasal spray (Imigran) on human nasal mucosa

Abstract

Objectives

Sumatriptan (Imigran) is a potent and highly selective 5-HT1 receptor agonist often used in treating acute migraine. Intranasal sumatriptan is well absorbed and is generally effective in relieving headache. However, the effects of Imigran on human nasal mucosa have rarely been well explored. To verify the effect of Imigran, which act on human nasal mucosa directly in vitro.

Design and participants

We examined the effectiveness of Imigran on human nasal mucosa by testing: 1) effect on human nasal mucosa resting tension; 2) effect on contraction caused by 10-6 M methoxamine as a sympathetic mimetic; 3) effect of the drugs on electrically induced on human nasal mucosa contractions.

Results

The results indicated that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose-dependent manner. Addition of Imigran at doses of 10 −4 M elicited a significant relaxation response to 10–6 M methoxamine -induced contraction. Imigran couldn't inhibit electrical field stimulation-induced spike contraction. It also had a minimal effect on the basal tension of nasal mucosa as the concentration increased.

Conclusions

The study indicated that high concentrations of Imigran had a significant spasmolytic effect by antagonizing α-adreoceptors and nasal obstruction couldn't be released in the patient combined with acute migraine and stuffy nose by concomitant α-adrenergic agonist nasal spray plus Imigran nasal spray.

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MicroRNA-622 is a novel mediator of tumorigenicity in melanoma by targeting Kirsten rat sarcoma

Summary

The network of molecular players is similar when comparing neural crest-derived, actively migrating melanoblasts to melanoma cells. However, melanoblasts are sensitive to differentiation-initiating signals at their target site (epidermis), while melanoma cells maintain migratory and undifferentiated features.

We aimed at identifying downregulated genes in melanoma that are particularly upregulated in melanoblasts. Loss of such genes could contribute to stabilization of a dedifferentiated, malignant phenotype in melanoma.

We determined that microRNA-622 (miR-622) expression was strongly downregulated in melanoma cells and tissues compared to melanocytes and melanoblast-related cells. MiR-622 expression correlated with melanoma patient survival. MiR-622 re-expression inhibited clonogenicity, proliferation and migration in melanoma. Inhibition of miR-622 in melanocytes induced enhanced migration. Kirsten rat sarcoma (KRAS) was identified as a major functional target of miR-622 in melanoma. We conclude that miR-622 is a novel tumorsuppressor in melanoma and identify the miR-622-KRAS-axis as potential therapeutic target.

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Punctate palmoplantar keratoderma: an unusual mutation causing an unusual phenotype

Abstract

Palmoplantar keratodermas (PPKs, OMIM #144200) refers to a large phenotypically and genetically heterogeneous group of keratinization disorders characterized by marked hyperkeratosis on the surface of palms and soles. Punctate PPK (PPKP) features multiple hyperkeratotic papules that develop in early adolescence or later and are irregularly distributed on the palms and soles. The disease is clinically classified into three autosomal dominant subtypes: PPKP1 (OMIM #148600, 614936) characterized by multiple tiny punctate keratoses and caused by mutations in the AAGAB or COL14A1 genes; PPKP2 (OMIM #175860) which features tiny hyperkeratotic spinous papules and PPKP3 or acrokeratoelastoidosis (AKE, OMIM # 101850) which manifests with small hyperkeratotic papules located over the peripheral margins of the palms and soles and is typically associated with degeneration of elastic fibers on histology. The molecular etiology of PPKP2 and AKE remains unknown.

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Evaluation of treatment results in multifocal primary cutaneous anaplastic large cell lymphoma: Report of the Dutch Cutaneous Lymphoma Group

Abstract

Background

There is no consensus on the treatment of multifocal primary cutaneous anaplastic large cell lymphoma (C-ALCL). Radiotherapy (RT) and methotrexate (MTX) are the current treatment options, but their efficacy is unknown. Recently, targeted therapies showed promising results in C-ALCL, and may therefore be an attractive first choice of treatment.

Objectives

To assess the efficacy of conventional treatment strategies for patients with multifocal C-ALCL, and to define which patients may require novel targeted therapies.

Methods

In this multicenter study, treatment was evaluated in patients initially presenting (n=24) or relapsing with multifocal C-ALCL (n=17; 23 relapses). Distinction was made between cases with ≤ 5 (n=36) and >5 lesions (n=11).

Results

Treatments most commonly used were radiotherapy (n=21), systemic chemotherapy (n=9) and low-dose methotrexate (MTX; n=7) with complete response rates of 100%, 78% and 43%, respectively, and an overall response rate of 100%, 100%, and 57%, respectively. Four patients showed a complete spontaneous regression. Sixteen of 24 patients (67%) first presenting with multifocal C-ALCL relapsed, including all five patients initially treated with CHOP. Compared with patients presenting with 2-5 skin lesions, patients presenting with >5 lesions had a higher chance of developing extracutaneous relapse (56 vs 20%) and more often died of lymphoma (44% vs 7%).

Conclusion

Patients with ≤5 lesions should be treated with low-dose RT (2x4 Gy). Maintenance low-dose MTX (20 mg/week) is a suitable option in patients with >5 lesions. Targeted therapies may be considered in rare patients refractory to MTX or patients developing extracutaneous disease.

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Genome-wide association study identifies three novel susceptibility loci for systemic lupus erythematosus in Han Chinese

Abstract

Systemic lupus erythematosus (SLE) is a common prototypic autoimmune disease with substantial genetic predispositions. It is more prevalent in Asians than in Caucasians. Genome wide association studies (GWAS) have discovered more than 80 genetic loci for the risk of SLE1, which improve the understanding of SLE etiology and provide potential therapeutic targets. However, each GWAS finding only confers a relatively small effect, and they in total cannot fully explain SLE heritability, suggesting more genetic variants are yet to be discovered.

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Itch in dermatomyositis: the role of increased skin interleukin-31

Summary

Background

Interleukin-31 (IL-31) is implicated in pruritus associated with pruritic skin diseases like atopic dermatitis. Although pruritus is a prominent feature in dermatomyositis (DM), few studies have evaluated the pathogenesis of DM-associated itch.

Objectives

Our goals were to establish the prevalence of itch in DM, and to investigate the role of IL-31 in DM-related itch.

Methods

Pruritus and disease activity of DM were evaluated by a visual analog scale (VAS) and the Cutaneous Disease and Activity Severity Index (CDASI), respectively. Expression of IL-31 and IL-31 receptor alpha (IL-31RA) in lesional DM, non-lesional DM and healthy control (HC) skin was evaluated by qRT-PCR and immunofluorescence. Flow cytometry was performed on skin cells isolated from lesional DM skin to identify cellular sources of IL-31 in DM.

Results

Among 191 DM patients, 50.8% had moderate to severe itch, and itch was correlated with increased cutaneous severity (r= 0.34). In itchy DM patients, gene expression of IL-31 and IL-31RA in lesional skin was upregulated compared to non-lesional skin and HC skin. IL-31 mRNA expression positively correlated with VAS itch score (r= 0.67). On immunofluorescence, immunoreactivity for IL-31 and IL31RA was stronger in lesional skin. Flow cytometry showed lesional DM skin contained significantly more IL-31-producing cells and CD4+ cells were the most common cell type. Lenabasum, an emerging treatment for DM, significantly downregulated IL-31 from CpG-stimulated PBMCs.

Conclusion

Increased skin IL-31 may play a role in DM-associated itch, and ongoing trials will evaluate the effects of systemic treatment on IL-31 and itch in DM.

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A rare BRAF T599dup mutation conferring sensitivity to BRAF inhibitor in a patient with metastatic melanoma

Abstract

Treatment for patients with V600 mutation of the B-Raf protooncogene BRAF (BRAF-V600) and metastatic stage IV or unresectable stage III melanoma has greatly advanced with the introduction of selective BRAF inhibitors (BRAFi), such as vemurafenib and dabrafenib, combined with mitogen-activated protein kinase kinase inhibitors (MEKi), such as cobimetinib and trametinib, as first-line therapy [1,2]. Two mutations, V600E and V600K, are routinely searched in patients with stage IV and unresectable stage III cancer. The presence of the V600 mutation allows for prescribing BRAFi combined with MEKi according to the European Medicine Agency. Other non– BRAF-V600 mutations have been increasingly found by next-generation sequencing (NGS) and question the possible efficiency of BRAFi associated with MEKi with these mutations [3]. Here we report a case of metastatic melanoma in a patient with a non–BRAF-V600 mutation responding to combined BRAFi and MEKi treatment.

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Nasal Distortion in Short-Distance Photographs

This study presents a mathematical model to describe the distortive effects of self-photographs, prove the increased perceived nasal size, and calculate the magnitude of this effect from different camera distances.

Use of Viable Cryopreserved Placental Membrane as an Adjunct to Facial Keloid Resection

imageSummary: Keloids are the physical manifestation of an exaggerated inflammatory response resulting in excess collagen deposition. The resulting fibroproliferative mass can be distressing for patients due to appearance, pruritus, and/or pain. Despite extensive research into the pathophysiology of keloid formation and the development of numerous treatments, keloids remain a challenge to treat. Even when the initial treatment is successful, a risk of recurrence remains. Basic science research into viable cryopreserved placental membranes and viable cryopreserved umbilical tissue has demonstrated their anti-inflammatory and anti-fibrotic effects, which may decrease keloid recurrence after excision. In this article, we present the first-reported case of viable cryopreserved placental membrane, with living mesenchymal stem cells, to treat a painful preauricular keloid in conjunction with surgical resection.

Long-wave plasma radiofrequency ablation for treatment of xanthelasma palpebrarum

Summary

Xanthelasma palpebrarum is the most common type of xanthoma affecting the eyelids. It is characterized by asymptomatic soft yellowish macules, papules, or plaques over the upper and lower eyelids. Many treatments are available for management of xanthelasma palpebrarum, the most commonly used include surgical excision, ablative CO2 or erbium lasers, nonablative Q-switched Nd:YAG laser, trichloroacetic acid peeling, and radiofrequency ablation. This study aims to evaluate the effectiveness of RF ablation in the treatment of xanthelasma palpebrarum, with D.A.S. Medical portable device (Technolux, Italia), a radiofrequency tool working with long-wave plasma energy and without anesthesia. Twenty patients, 15 female and 5 male, affected by xanthelasma palpebrarum, were enrolled for long-wave plasma radiofrequency ablation treatment. The treatment consisted of 3/4 sessions that were carried out at intervals of 30 days. Treatments were well tolerated by all patients with no adverse effects and optimal aesthetic results. The procedure is very fast and can be performed without anesthesia because of the low and tolerable pain stimulation. Long-wave plasma radiofrequency ablation is an effective option for treatment of xanthelasma palpebrarum and adds an additional tool to the increasing list of medical devices for aesthetic treatments.



Use of topical therapies for pediatric psoriasis: A systematic review

Abstract

Psoriasis is one of the most common chronic skin diseases, affecting 1%-3% of the general population. It can have a significant negative impact on a patient's quality of life, and in approximately 30% of patients first symptoms can be traced back to childhood. We have performed a comprehensive literature search using the MEDLINE database in order to ascertain the efficacy and adverse reactions of topical treatments in pediatric psoriasis. A total of 13 relevant articles were identified on the following topical agents: corticosteroids, calcineurin inhibitors, vitamin D analogs, and dithranol. Corticosteroids achieved clearance in 72.7% of patients. Calcitriol lead to a 57.2%-100% mean improvement in severity, and calcipotriol to 52%-64%. Combination of calcipotriol and corticosteroids achieved an improvement in mean severity ranging between 32.1% and 80%. Treatment with tacrolimus lead to an >50% improvement. Finally, short contact dithranol lead to a variable response in clearance between different studies, ranging between 3.7% and 81%. No serious adverse reactions were documented, the most common local reaction being irritation. Pediatric psoriasis is a common and challenging condition with no easy and definitive solution. Topical agents are safe, easy to use, readily available and cheap. However, they need to be applied repeatedly, may cause skin irritation, and can be messy. Based on the results presented above, we recommend utilizing all the available topical options before escalating to systemic treatments.



Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum: A brief report

Abstract

A patient with extensive multisystem overgrowth caused by a somatic gain of function PIK3CA-mutation is described. This case is an example of the clinical diversity of the PIK3CA-Related Overgrowth Spectrum (PROS) as the patient had overlapping features of Congenital Lipomatous Overgrowth Vascular malformations Epidermal nevi and Skeletal abnormalities (CLOVES) syndrome and Megalencephaly-Capillary malformation Polymicrogyria (MCAP) syndrome and underlines the utility of this umbrella term.



First evidence of anticoagulant rodenticides in fish and suspended particulate matter: spatial and temporal distribution in German freshwater aquatic systems

Abstract

Anticoagulant rodenticides (ARs) have been used for decades for rodent control worldwide. Research on the exposure of the environment and accumulation of these active substances in biota has been focused on terrestrial food webs, but few data are available on the impact of ARs on aquatic systems and water organisms. To fill this gap, we analyzed liver samples of bream (Abramis brama) and co-located suspended particulate matter (SPM) from the German Environmental Specimen Bank (ESB). An appropriate method was developed for the determination of eight different ARs, including first- and second-generation ARs, in fish liver and SPM. Applying this method to bream liver samples from 17 and 18 sampling locations of the years 2011 and 2015, respectively, five ARs were found at levels above limits of quantifications (LOQs, 0.2 to 2 μg kg−1). For 2015, brodifacoum was detected in 88% of the samples with a maximum concentration of 12.5 μg kg−1. Moreover, difenacoum, bromadiolone, difethialone, and flocoumafen were detected in some samples above LOQ. In contrast, no first generation AR was detected in the ESB samples. In SPM, only bromadiolone could be detected in 56% of the samples at levels up to 9.24 μg kg−1. A temporal trend analysis of bream liver from two sampling locations over a period of up to 23 years revealed a significant trend for brodifacoum at one of the sampling locations.



Special issue: developments in water management technologies and systems



Ecotoxicological assessment of oil-based paint using three-dimensional multi-species bio-testing model: pre- and post-bioremediation analysis

Abstract

The present study validates the oil-based paint bioremediation potential of Bacillus subtilis NAP1 for ecotoxicological assessment using a three-dimensional multi-species bio-testing model. The model included bioassays to determine phytotoxic effect, cytotoxic effect, and antimicrobial effect of oil-based paint. Additionally, the antioxidant activity of pre- and post-bioremediation samples was also detected to confirm its detoxification. Although, the pre-bioremediation samples of oil-based paint displayed significant toxicity against all the life forms. However, post-bioremediation, the cytotoxic effect against Artemia salina revealed substantial detoxification of oil-based paint with LD50 of 121 μl ml−1 (without glucose) and > 400 μl ml−1 (with glucose). Similarly, the reduction in toxicity against Raphanus raphanistrum seeds germination (%FG = 98 to 100%) was also evident of successful detoxification under experimental conditions. Moreover, the toxicity against test bacterial strains and fungal strains was completely removed after bioremediation. In addition, the post-bioremediation samples showed reduced antioxidant activities (% scavenging = 23.5 ± 0.35 and 28.9 ± 2.7) without and with glucose, respectively. Convincingly, the present multi-species bio-testing model in addition to antioxidant studies could be suggested as a validation tool for bioremediation experiments, especially for middle and low-income countries.

Graphical abstract



Correction to: Effects-based spatial assessment of contaminated estuarine sediments from Bear Creek, Baltimore Harbor, MD, USA

Abstract

The authors of the article have informed the Journal that an author, Dr. Sacoby Wilson of the University of Maryland School of Public Health, was inadvertently omitted from the published version of their manuscript due to a miscommunication regarding authorship criteria.



Palladium-induced granulomas analysed with inductively coupled plasma mass spectrometry



Τετάρτη 28 Φεβρουαρίου 2018

Orbital Hobnail Hemangioma

A 64-year-old woman presented with a 1 year history of progressive left proptosis and "blurry vision." Imaging studies revealed a left superior orbital mass distorting the optic nerve and superior rectus muscle. Excisional biopsy established the diagnosis of hobnail hemangioma. This report describes the first case of an orbital hobnail hemangioma, a lesion that more commonly presents in the dermis. Accepted for publication January 29, 2018. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Paul D. Langer, M.D., F.A.C.S., Rutgers New Jersey Medical School, Doctors Office Center, Suite 6100, P.O. Box 1709, Newark, NJ 07101-1709. E-mail: planger@njms.rutgers.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Fibrous Histiocytoma of the Lacrimal Sac in an 11-Year-Old Male

Fibrous histiocytoma is a soft tissue tumor with cells resembling both fibroblasts and histiocytes. Occasionally in the orbit, they rarely arise in the lacrimal sac. Similar to prior cases described, the patient presented with symptoms of epiphora and a slowly enlarging mass inferior to the right medial canthus. Imaging demonstrated a circumscribed 1.2 cm × 1.1 cm × 1.1 cm mass within the lacrimal sac without surrounding bony destruction. Grossly, the tumor appeared homogenous and rubbery. Pathologic study results from the case demonstrated zones of hypercellularity and hypocellularity with a fibrous appearance, admixed with spindle cells and collections of foamy histiocytes. A diagnosis of benign fibrous histiocytoma was rendered, with the patient experiencing a complete resolution of symptoms at subsequent follow up. To the authors' knowledge, this is the first reported solitary case report of a fibrous histiocytoma of the lacrimal sac in a pediatric patient. Accepted for publication January 5, 2018. The authors have no financial or conflict of interest to disclose. Address correspondence and reprint requests to Joseph A. Santamaria, M.D., San Antonio Military Medical Center, San Antonio, TX 78234. E-mail: joesantam3@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.