Ιατρικά Άρθρα

Τρίτη 29 Ιανουαρίου 2019

Patient Satisfaction with the Veteran’s Administration Teledermatology Service

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Marissa L.H. Baranowski, Vijay Balakrishnan, Suephy C. Chen

Abstract

Background

Teledermatology is comparable to face-to-face visits in providing accurate diagnoses and effective treatments. However, there are limited data regarding patient satisfaction with teledermatology models that more directly convey provider recommendations to patients.

Objective

To assess patient satisfaction with the teledermatology service at the Atlanta Veterans Affairs Medical Center (AVAMC).

Methods

A cross-sectional, phone-based questionnaire study of 175 AVAMC teledermatology patients was performed to investigate patient satisfaction. Phase One (n=100) compared teleconsultative and models. Phase Two (n=75) compared patients who received one of three possible consult outcomes: (1) reassurance, (2) appointment for biopsy, or (3) appointment for face-to-face evaluation.

Results

There were no statistically significant differences in satisfaction between patients who were seen with the telemedicine and teleconsultative models. Patients who received appointments for face-to-face evaluation or biopsy were more satisfied than patients who received reassurance only. Both phases were remarkable for high patient satisfaction among all cohorts.

Limitations

This study was performed at a single VA medical center and is vulnerable to both non-response bias and recall bias.

Conclusion

Overall, patients are satisfied with teledermatology services at the AVAMC. Strong partnership with referring primary care providers and clear delineation of responsibilities is vital to the teledermatology process.

http://bit.ly/2WqSyAA

Age as key factor for pattern, timing and extent of distant metastasis in patients with cutaneous melanoma. A study of the German Central Malignant Melanoma Registry

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Maximilian Gassenmaier, Ulrike Keim, Ulrike Leiter, Thomas K. Eigentler, Martin Röcken, Anja Gesierich, Rose K.C. Moritz, Lucie Heinzerling, Thomas Tüting, Uwe Wollina, Claus Garbe

Abstract

Background

Melanoma incidence rates rise as people age but the impact of aging on distant metastasis is unclear.

Objective

To investigate how timing, pattern and extent of distant metastasis is influenced by age.

Methods

Analysis of a single-center cohort of 1.457 patients of the German Central Malignant Melanoma Registry with prospectively documented follow-up. Findings were compared with those of 1.682 patients from five different institutions. All patients presented initially with stage IA – IIC and developed distant metastasis in their further course.

Results

The number of metastatic sites decreased with increasing age at melanoma diagnosis (p < 0.001). The rate of stage M1d decreased from 50.2% in patients ≤ 50 years to 30.1% in patients > 70 years and the rate of stage M1b increased from 5.8% to 21.5%. The rate of lung metastases remained stable in all investigated age groups (p = 0.54). Distant metastases occurred earlier and more synchronized in patients > 70 years compared with patients ≤ 50 years. The age-dependent decrease of metastatic sites and stable rate of lung metastasis were confirmed by the multi-institutional cohort.

Limitations

The study was not population-based.

Conclusion

Pattern, timing and extent of distant metastasis changes as people age. These findings may be considered when treating melanoma patients of different age.

http://bit.ly/2Rl7mN7

Patient-Reported Outcomes are Important Elements of Psoriasis Treatment Decision Making: A Discrete Choice Experiment Survey of Dermatologists in the United States

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Steven R. Feldman, Stephane A. Regnier, Alexandra Chirilov, Felix Hey, Isabelle Gilloteau, David Cella

Abstract

Background

Psoriasis Area and Severity Index (PASI) response rates have been the benchmark for evaluating treatment efficacy in moderate-to-severe psoriasis trials.

Objective

Understand how dermatologists assess biologics and what trade-off rules they apply when planning psoriasis treatment.

Methods

Two online surveys of 130 and 129 U.S. dermatologists (Survey 1 and 2, respectively) were conducted using direct and indirect elicitation via discrete-choice experiment. Respondents were asked to choose hypothetical biologics based on six attributes (PASI 75 or 90 response rate, infection risk, dosing frequency, and three patient-reported outcomes [PROs] [relief of depression and itching, impact on usual activities]).

Results

Most dermatologists (Survey 1: 74%, Survey 2: 76%) reported using both PASI and PROs when selecting a biologic. PASI response rate was the most important attribute (35–38% of overall decision weight), while combined PRO attributes had similar importance (36% of decision weight). Infection risk and dosing frequency influenced the decision to a lesser extent.

Limitations

Potential bias in considering three PROs versus one PASI rate and one safety attribute.

Conclusion

PASI is most important for dermatologists selecting biologics, but PROs are also considered, especially when PASI response rate is similar between treatments. PRO data should be collected in moderate-to severe-psoriasis trials.

http://bit.ly/2WrNCLB

Fractionated de-volumizing Keloid tissue - The ‘pop’ method- A novel technique to facilitate administration of intralesional corticosteroid in difficult keloids

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Rachita Dhurat, Sanober B. Daruwalla, Aseem Sharma

http://bit.ly/2RsdpQk

Treatment and survival of Merkel cell carcinoma since 1993: a population-based cohort study in the Netherlands

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Sanne E. Uitentuis, Marieke W.J. Louwman, Alexander C.J. van Akkooi, Marcel Bekkenk

Abstract

Background

Merkel cell carcinoma (MCC) is a rare and potentially lethal skin-cancer. MCC is known for its potential rapid growth and its propensity to metastasise.

Objective

To describe the incidence, treatment and survival of MCC in a population-based setting.

Methods

All MCC's diagnosed in the Netherlands between 1993 and 2016 were selected from the Netherlands Cancer Registry. Patient and tumour characteristics, therapy and vital status were obtained. Cox' proportional hazards were computed and relative survival analyses were performed.

Results

Our cohort included 1977 patients with MCC. Incidence increased from 0.17/100,000 personyears in 1993 to 0.59/100,000 in 2016. The mean age at diagnosis was 75.5. Most MCC's (59.8%), were treated with surgery alone. Relative five-year survival was low (63.0%) and did not improve. Mortality was higher among males (HR: 1.24, 95%CI: 1.11-1.39), higher age (HR 1.07, 95%CI: 1.06-1.07) and nodal (HR1.26, 95%CI: 1.08-1.48) and distant spread of disease (HR2.44, 95%CI: 1.99-2.99).

Limitations

We lacked data on cause of death, comorbidity and pathological margins, which may have led to misinterpretation of the data.

Conclusion

This study shows continuously increasing incidence rates of MCC in the Netherlands. Survival after MCC diagnosis remained low. Our results emphasise the need for implementation of new therapies.

http://bit.ly/2WtJmLt

Corrigendum to 'Injection technique in neurotoxins and fillers: Indications, products, and outcomes' [J Am Acad Dermatol 79 (2018) 423–435]

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s):

http://bit.ly/2RscRtK

“A Reliability Study Using Network-Oriented Research Assistant (NORA®) to Evaluate the Use of Digital Photographs in the Assessment of Atopic Dermatitis”

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Meagan E. Hughes, Hilary Aralis, Kevin W. Bruhn, Jonathan Cotliar, Noah Craft, Ilana J. DeLuca, Reyhaneh Hamidi, Kathy Nguyen, Mayha Patel, Vishal A. Patel, Howard Sofen, Belinda H. Tan, Consuelo V. David

http://bit.ly/2Wo2nzf

Treatment of Morphea With Hydroxychloroquine: A Retrospective Review of 84 Patients at Mayo Clinic, 1996-2013

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Anagha Bangalore Kumar, Elizabeth K. Blixt, Lisa A. Drage, Rokea A. el-Azhary, David A. Wetter

Abstract

Background

Few studies support treating morphea (localized scleroderma) with hydroxychloroquine.

Objective

To assess the efficacy of hydroxychloroquine treatment of morphea.

Methods

We conducted a retrospective study of 84 patients who had morphea and were treated with hydroxychloroquine monotherapy for at least 6 months at our institution from 1996 through 2013. The median times to initial and maximal responses were assessed.

Results

Of 84 patients (median age at diagnosis, 29.5 years), 65 (77.4%) were female; 36 (42.9%) had a complete response to hydroxychloroquine; 32 (38.1%) had a partial response greater than 50%; 10 (11.9%) had a partial response less than or equal to 50%; and 6 (7.1%) had no response. The median time to initial response was 4 months; the median time to maximal response was 12 months. Ten patients (11.9%) experienced adverse effects from hydroxychloroquine; the most common was nausea (6 patients).

Limitations

Retrospective study.

Conclusions

Hydroxychloroquine is a valuable treatment for morphea because of its high response rate and low rate of adverse effects; however, prospective studies are needed to determine its true efficacy.

http://bit.ly/2Rscmjm

Risk Factors for Keratinocyte Carcinoma Skin Cancer In Nonwhite Individuals: A Retrospective Analysis

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Kumar S. Nadhan, Christina L. Chung, Erin M. Buchanan, Christine Shaver, Scott Shipman, Rina M. Allawh, Melissa L. Hoffman, Geoffrey Lim, Mark Abdelmalek, Carrie Ann Cusack

Abstract

Background

As the majority of the U.S. population will consist of nonwhite individuals by the year 2043, it is essential that both physicians and patients are educated about skin cancer in nonwhite individuals.

Objective

To update the epidemiology, investigate specific risk factors, and facilitate earlier diagnosis and intervention of KC in nonwhite individuals

Methods

IRB-approved retrospective chart review of all non-white individuals who had received a biopsy-proven diagnosis of skin cancer at Drexel Dermatology from June 2008 to June 2015.

Results

Squamous cell carcinoma (SCC) was the most commonly diagnosed skin cancer in Black and Asian populations, while basal cell carcinoma (BCC) was the most common skin cancer in Hispanics. Blacks exhibited the majority of their SCC lesions in sun-protected areas, particularly the anogenital area. On average, current smokers were diagnosed with skin cancer 12.27 years earlier than former smokers and 9.36 years earlier than nonsmokers.

Limitations

Single-center design and inter-practitioner variability of skin examination

Conclusions

The importance of photoprotection in nonwhite individuals should not go overlooked. However, emphasis should also be placed on active examination of sun-protected areas in nonwhites and recognition of the relationship between HPV and genital SCC lesions. Smoking cessation should be integrated in dermatologic counseling of all patients. Interventions tailored to each of these ethnic groups are needed.

http://bit.ly/2WrNI64

Telementoring and Smart-Phone-Based Answering Systems to Optimize Dermatology Resident Dermoscopy Education

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Kelly C. Nelson, Jeffrey E. Gershenwald, Stephanie A. Savory, Janice M. Wilson, Julie M. Simon, Elizabeth M. Burton, Lauren E. Haydu

http://bit.ly/2RkuEms

Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An eight-year multicenter study

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Hsien-Yi Chiu, Rosaline Chung-yee Hui, Tsen-Fang Tsai, Yang-Ching Chen, Nien-Feng Chang Liao, Po-Hua Chen, Po-Ju Lai, Ting-Shun Wang, Yu-Huei Huang

Abstract

Background

Data on predictors and time to relapse in psoriasis patients discontinuing therapy in a real world setting are scarce.

Objective

To investigate predictors of relapse after withdrawal of ustekinumab in psoriasis patients.

Method

This study screened 500 psoriasis patients who received ustekinumab (669 treatment episodes (TEs)) between 2011 and 2018. Overall, 202 patients (304 TEs), who had responded to therapy and were withdrawn from ustekinumab treatment, were included.

Results

The cumulative probabilities of relapse-free at 6 months, 12 months, 18 months, 24 months and 36 months of withdrawal from ustekinumab treatment was 49.3%, 12.6%, 5.3%, 4.7% and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologics-naive, the maximum Psoriasis Area and Severity Index (PASI) improvement on ustekinumab, time to achieve PASI-50 after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressants use while off ustekinumab were significant predictors of time to relapse following ustekinumab discontinuation.

Limitation

Non-randomized allocation of duration of treatment and follow-up.

Conclusion

Given high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.

http://bit.ly/2WsZTPP

Role of imaging in low grade cutaneous B-cell lymphoma presenting in the skin

Publication date: Available online 29 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): M.K. Kheterpal, J. Dai, S. Geller, M. Pulitzer, Andy Ni, P.L. Myskowski, A. Moskowitz, J. Kim, E.K. Hong, S. Fong, R.T. Hoppe, Y.H. Kim, S.M. Horwitz

Abstract

Background

Whole body imaging is current standard of care for staging all patients presenting with skin lesion(s) of B-cell lymphomas (BCL), regardless of skin disease extent, however supporting data are lacking.

Objective

To determine the clinical utility of imaging in detection of systemic involvement in low grade cutaneous B-cell lymphoma presenting in the skin.

Methods

Retrospective cohort analysis of patients presenting with cutaneous lesions of BCLs at Memorial Sloan Kettering Cancer Center (MSKCC) and Stanford University (SU) from 1997-2016.

Results

At initial staging, of the 522 patients (306 marginal zone and 216 follicle-center cell histology), extracutaneous disease was noted in 3.6% and 8.8% of patients with MZL and FCL histology respectively. In patients with systemic involvement, imaging alone identified 81.8% (9/11) of MZL and 89.4% of follicular lymphoma (FL) cases. In primary cutaneous MZL (pc-MZL) and primary cutaneous follicle center lymphoma (pc-FCL), 1.7% and 3.0% subsequently developed extracutaneous involvement (median follow-up of 45 and 47 months respectively).

Limitations

Retrospective nature of this study.

Conclusions

Imaging is effective in identifying the patients with systemic involvement in indolent BCLs presenting in the skin, however incidence is low. After negative initial staging, pc-MZL patients may be followed clinically without routine imaging.

http://bit.ly/2ME9gI5

Investigation of the Skin Microbiome: Swabs vs Biopsies

Abstract

Background

Human skin is populated by diverse bacteria and there is increasing evidence that resident bacteria play a key role initiating immune responses in cutaneous diseases such as atopic dermatitis, psoriasis and hidradenitis suppurativa. Bacteria are present at all layers of the skin but many studies have relied on swabs to profile the skin microbiota. As the pathogenesis of many skin conditions is dermal, we wished to compare the microbiota obtained in swabs (surface) and biopsies (dermis).

Using 16S rRNA gene sequencing we established the microbial profiles of skin swabs and skin biopsies in sixteen subjects. We found differences in both diversity and taxonomic composition of the microbiome obtained from swabs and biopsies of the same individual. Several taxa were found to be more abundant in the swabs, which displayed significantly higher community richness, but Clostridiales and Bacteroidetes were significantly enriched in the biopsies.

The majority of published research on cutaneous microbiota has been based on skin swabs, which represent the surface of the skin. Our study demonstrated a clear difference between the microbiome observed in skin swabs and skin biopsies. These findings may be highly relevant in disorders such as psoriasis where pathogenesis arises in the dermis.

http://bit.ly/2CNq4I6

Inter‐Relater Reliability of Phenotypes, and Exploratory Genotype‐ Phenotype Analysis in Inherited Hidradenitis Suppurativa

Abstract

Background

Genotype‐phenotype correlation is a statistical relationship that measures correlation between the presence of a physical trait with a group of similar mutations but is dependent upon reliable phenotyping. It can provide information regarding disease pathogenesis, future disease progression, severity or activity. Such indicators would be valuable in Hidradenitis Suppurativa.

Aims and Methods

This study aimed to assess the inter‐rater reliability of hidradenitis suppurativa clinical phenotypes and perform exploratory genotype‐phenotype correlation in cases of hidradenitis suppurativa with identified sequence variants. Linkage disequilibrium between variants was assessed. Genotype‐Phenotype correlations were explored using Spearman correlation coefficients. Inter‐rater reliability was calculated using Cohen's kappa. Correlation between phenotype classifications was assessed using χ² statistic.

Results

43 sequence variants with clinical information were identified. Clinical phenotypes were classified as LC2 (n=29, 67.4%), Scarring Folliculitis (n=18, 41.8%), atypical (n=38, 88.3%) and nodular (n=26, 60.5%). LC1 phenotype was associated with Regular (χ2=41.289, p<0.0001) and Typical (χ2=29.013, p<0.0001) phenotypes. Cohen's kappa was highest for Van der Zee (0.815), followed by Martorell (0.813), Naasan (0.774) and Canoui (0.435) classifications. High linkage disequilibrium was seen between variants of Han Chinese pedigrees. No significant genotype‐phenotype correlations were identified.

Conclusions

These findings may be influenced by selection, publication bias and the assumption that HS is a monogenic disorder. The poor inter‐rater reliability of existing phenotype measures suggests limited utility of existing measures. Further investigations into the correlation of clinical phenotypes with inflammatory biomarkers may aid in prognostic efforts for this disease.

http://bit.ly/2RV6eoS

Understanding economic evidence for the prevention and treatment of atopic eczema

Abstract

Background

Atopic eczema is an inflammatory skin condition, with a similar impact on health‐related quality‐of‐life as other chronic diseases. Increasing pressures on resources within the NHS increase the importance of having good economic evidence to inform their allocation. This paper aims to educate dermatologists about economic methods with illustration to currently available economic evidence on eczema.

Methods/design

The type and role of different types of economic evidence is illustrated by evidence found in a systematic literature search conducted across 12 online databases published until 22^nd May 2017. Primary empirical studies either reporting the results of a cost of illness study or evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema were included. Two reviewers independently assessed studies for eligibility and performed data abstraction, with disagreements resolved by a third reviewer. Evidence tables of results were produced for narrative discussion. The reporting quality of economic evaluations was assessed.

Results

78 studies (described in 80 papers) were deemed eligible. 33 (42%) were judged to be economic evaluations, 12 (15%) cost analyses, 6 (8%) utility analyses, 26 (34%) cost‐of‐illness studies and 1 feasibility study (1%). The calcineurin inhibitors: tacrolimus and pimecrolimus, as well as barrier creams had most economic evidence available. Partially hydrolysed infant formula was the most commonly evaluated prevention.

Conclusions

The current level of economic evidence for interventions aimed at preventing and treating eczema is limited compared to that available for clinical outcomes suggesting that greater collaboration between clinicians and economists might be beneficial.

http://bit.ly/2CNqoXk

Indirect immunofluorescence in mucous membrane pemphigoid: which substrate should be used?

Abstract

detection of circulating autoantibodies in mucous membrane pemphigoid (MMP) is challenging. Kamaguchi et al showed that using normal human oral mucosa (NHOM) as a substrate for indirect immunofluorescence (IIF) instead of normal human skin (NHS) or salt‐split‐skin (SSS) resulted in increased sensitivity.¹ We recently conducted a similar study in our department.

We collected serum samples from 22 patients with oral MMP. Diagnosis was made upon histopathology consistent with a subepithelial blistering process and direct immunofluorescence (DIF) showing linear IgG, IgA and/or C3 deposits at the basement membrane zone (BMZ). Serum levels of anti‐BP180 NC16A and BP230 autoantibodies were assessed by Enzyme‐Linked‐Immunosorbent‐Assay. IIF was performed on monkey oesophagus (MO), on SSS and NHOM as previously described.

http://bit.ly/2RTb99E

Fibroblasts activation and abnormal extracellular matrix remodelling as common hallmarks in three cancer‐prone genodermatoses

Summary

Background

Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and Xeroderma pigmentosum C (XPC) are three cancer‐prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders.

Objectives

To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC.

Methods

We conducted RNA‐Seq analysis that included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies.

Results

Inter‐disease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and 4 signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analysis validated the RNA‐Seq data. In addition, enzyme‐linked immunosorbent assay (ELISA) revealed increased circulating levels of periostin in RDEB patients.

Conclusions

Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury‐sensitive events. These, in turn, trigger a cascade of reactions involving the abnormal ECM deposition and under‐expression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS.

http://bit.ly/2CRMKXz

Sonic Hedgehog Pathway Inhibitors: from Clinical Trials to Clinical Practice

Abstract

Basal cell carcinoma (BCC) is the most common malignancy. It can rarely become locally advanced (laBCC) or metastasize (mBCC). For recurrent, inoperable, laBCC and/or mBCC, Sonic Hedgehog (Shh) pathway inhibitors, vismodegib and sonidegib, are treatment options. This case series evaluates limitations surrounding their use in clinical practice.

This was an IRB‐approved retrospective case series of BCC treatment with vismodegib and/or sonidegib at our institution between January 2006 and March 2017, with follow‐ up through August 2018. Patients receiving concurrent Shh inhibitors and radiotherapy were excluded. The examined outcomes included clinical response, progression free survival (PFS), drug holidays (DH), and adverse effects (AE).

http://bit.ly/2RV5XSS

Screening for hepatitis B virus and tuberculosis infection in patients with moderate‐to‐severe psoriasis recruiting for biologic therapy in China

Abstract

Biologics have greatly advanced the therapy of moderate‐to‐severe psoriasis. Screening for Hepatitis B virus (HBV) and tuberculosis (TB) infection is mandatory before biologic therapy to avoid the risk of active infection, which is more likely to be disseminated, fulminant and fatal. Testing and treatment for latent TB infection (LTBI) in at‐risk populations is strongly recommended by recent WHO's guidelines.¹ Both HBV and TB infection are endemic in China and also represent important issues for global public health. The purpose of this study was to describe the screening results of HBV and TB infection in patients with moderate‐to‐severe psoriasis in China, which has not been reported.

http://bit.ly/2CTHyCR

Experience of skin disease and relationships with healthcare providers: a qualitative study of Traveller women in Ireland

Abstract

Background

Significant health disparities exist between members of the Travelling community and that of the general population. Barriers to Traveller engagement with health services include the experience or perception of discrimination, cultural and health literacy barriers. Experience of skin disease and interactions with healthcare providers has not been widely explored among this ethnic minority. The formation of positive relationships between the Travelling community and healthcare providers is important in the promotion of treatment adherence and improving health outcomes.

Objectives

We aimed to investigate Travellers' experience of skin disease and their relationships with healthcare providers.

Methods

Focus groups were conducted with a purposive sample of female members of the Irish Travelling community with experience of skin health issues, between January 2018 and April 2018. Three focus groups were conducted at three separate locations with ten participants in each group. Themes were identified from the focus group transcripts using an inductive thematic analysis framework.

Results

Emergent themes surrounding relationships between Travellers and healthcare providers included health literacy, discrimination, information inconsistency, trust and communication. Factors that were valued in the creation of positive relationships included an appreciation of varying degrees of health literacy, the provision of sufficient information tailored to an individual's needs and a demonstration of cultural competence.

Conclusion

Dermatologists are well placed to provide practical, customised, treatment guidance and engage patients while integrating their culturally based beliefs.

http://bit.ly/2RTb9qa

ERYTHEMA MULTIFORME: DIFFERENCES BETWEEN HSV‐1 AND HSV‐2 AND MANAGEMENT OF THE DISEASE ‐ A CASE REPORT AND MINI REVIEW

ABSTRACT

Erythema multiforme (EM) is an immune‐mediated reaction characterized by target lesions and with possible mucosal involvement. Its most frequent cause is HSV, with HSV‐1 more common than ‐2. It is usually self‐limited but it can show recurrences. We report a peculiar case of recurrent herpes‐associated erythema multiforme (HAEM) in a 35‐year old man. The patient was affected by both herpes labialis and genitalis, but the typical target lesions were only associated with recurrent herpes labialis. Here we hypothesize about the pathogenic differences between HSV‐1 and ‐2 and discuss the therapeutic management of HAEM.

http://bit.ly/2FVsRTK

Complete resolution of cutaneous larva migrans with topical ivermectin: A case report

Abstract

Cutaneous larva migrans (CLM) (also called creeping eruption) is a cutaneous ectoparassitosis commonly observed in tropical countries. It is characterized by an erythematous, pruritic, and raised lesion with linear or serpiginous distribution, typically localized at the lower extremities. Oral ivermectin represents the most recommended current treatment, with important adverse effects associated. We report the clinical case of a 52‐year old with CLM, successfully treated with topical ivermectin.

http://bit.ly/2FWEbP8

Clinical experiences on alopecia areata treatment with tofacitinib: A study of 63 patients

http://bit.ly/2Gcm5bc

THE ANALYSIS OF THE THERAPEUTIC POTENTIAL OF USTEKINUMAB IN PSORIASIS VULGARIS TREATMENT

Abstract

The molecular mechanism of ustekinumab action involves an interruption of signaling pathways activated by IL‐12/23.

The aim of this paper was to evaluate the efficacy of the anti‐IL12/23 therapy in 7 psoriatic patients by assessing changes in the values of PASI, DLQI, BSA indexes, and an analysis of changes in the mRNA expression profile of genes IL12A, IL12B, IL23A during three 40‐week long observation periods.

The clinical (PASI, DLQI, BSA indexes) and molecular (RTqPCR for IL12A, IL12B, IL23A) analyses were performed on the day of ustekinumab therapy initiation, 4 weeks post first administration, and every 12 weeks thereafter. The statistically significant differences were observed only during stage I for values of PASI (p=0.0134), DLQI (p=0.01299), BSA (p=0.0355). During the subsequent stages, we observed lower values of PASI, BSA indexes, which suggests that the lesions are less intensified than at the moment of the therapy commencing. The relationship between the selected genes was observed: IL23A>IL12A>IL12B.

In conclusion, the aforementioned clinical and molecular analysis suggests the efficacy of ustekinumab therapy in patients with psoriasis vulgaris can be analyzed with the PASI, BSA, DLQI indexes, and changes in the expression of selected genes. The analysis of IL12A, IL12B, IL23A expression may serve as a valuable supplementation for the therapeutic methods currently used to evaluate the degree of disease progression and treatment efficacy.

http://bit.ly/2FVnfsn

Treatment of Telogen Effluvium using a dietary supplement containing Boswellia serrata, Curcuma longa and Vitis Vinifera: results of an observational study

Abstract

Telogen effluvium (TE) is a diffuse hair loss characterized by shortening of the anagen phase and precipitation of the telogen phase, with consequent reduction of the total hair volume. Many supplements are used in order to counteract TE but a definitive therapy is still unavailable.

27 patients, 4 males and 23 females, aged between 19 and 76 have been enrolled in this open study. All were diagnosed with telogen effluvium hair loss pattern. They were asked to take a supplement containing Boswellia Serrata, Curcuma Longa and Vitis Vinifera for a period of 3 months. The aim of the study was to evaluate the synergistic effect of these plant extracts in the treatment of TE.

The results obtained, although non statistically significant, show an overall improvement of clinical and subjective evaluations of the disease, although a larger study with a bigger sample may be required to better understand the real effects of this plant extracts in TE

The results obtained in this study suggest that the products tested have an eutrophic effect on scalp hair, and we believe that this supplement may determine anti‐oxydant, angiogenic and hair stimulating properties.

http://bit.ly/2G4ZHAK

Hidradenitis Suppurativa and Botulinum Toxin Type a Therapy: Two Cases

Abstract

Hidradenitis suppurativa is a chronic skin disease with an intense inflammatory activation. It typically affects the intertriginous areas with cysts, fistulae and scarring extremely painful. Patients suffer from severe psychological impact. HS still results in a high unmet medical need with several underdiagnosed cases, probably due to the incomplete knowledge of the pathogenesis of HS. The use of botulinum toxin a has recently been proposed as an effective therapy for HS.

http://bit.ly/2FVUDz9

Current and Emerging Therapies for Hand Eczema

Abstract

Purpose

Though hand eczema (HE) and chronic hand eczema (CHE) are common conditions with significant disease burden, they traditionally have had limited treatment options beyond topical and short‐term systemic corticosteroids. We reviewed published and preliminary evidence on the current and emerging topical and systemic therapeutic agents for HE and CHE. The etiologies of various HE subtypes are discussed, and remaining knowledge and practice gaps are highlighted to encourage further investigations.

Material and Methods

A comprehensive search of ClinicalTrials.gov and PubMed was completed for clinical trials that utilized known and emerging treatment options for HE and CHE.

Results

Several agents that target IL‐4 and IL‐13 signaling, keratinocyte proliferation, inflammatory cytokine production, bacterial protein synthesis, and inflammatory mediator (TNF‐ α, JAK1, JAK2, JAK3) proliferation are shown to be involved in the pathogenesis of CHE. Systemic agents include dupilumab, alitretinoin, acitretin, cyclosporine, azathioprine, and probiotics. Topical agents include delgocitinib, retapamulin, halometasone/triclosan, calcipotriol/betamethasone, tacrolimus, and pimecrolimus. These modalities have demonstrated varying degrees of clinical efficacy, evaluated by subjective assessments and scoring indexes.

Conclusions

Targeted therapies are emerging for HE, but options are still limited, partially due to our narrow understanding of this heterogeneous condition. Additional and targeted therapeutic options are needed to match the rising prevalence and burden of HE.

http://bit.ly/2Gdg2DF

Treatment resistant impetigo herpetiformis treated with infliximab

Abstract

Impetigo herpetiformis is a rare disease of pregnancy with the onset being in the second half of pregnancy and resolution after delivery. It is associated with a high rate of perinatal mortality and fetal abnormalities. Clinical and histological features of the disease are consistent with pustuler psoriasis. We reported a case of 25‐year‐old female gravida 1 para 0, who responded poorly to consecutively treatments with systemic steroids, cyclosporine, intravenous immunoglobulin, and acitretin. Good response was obtained with adding infliximab to the treatment.

http://bit.ly/2FUQsng

Angiolymphoid hyperplasia with eosinophilia: Two case reports

http://bit.ly/2HE57VA

Periungual thumb papule on a 62‐year‐old man

http://bit.ly/2RWjNEf

Linear immunoglobulin A/immunoglobulin G bullous dermatosis with autoantibodies to LAD‐1 and laminin‐γ1

http://bit.ly/2CMfS2o

Δευτέρα 28 Ιανουαρίου 2019

Left or right? An Australian study of the laterality of skin cancers

http://bit.ly/2G9we8H

Transarterial radioembolization in patients with hepatocellular carcinoma of intermediate B2 substage

Abstract

Purpose

Patients with hepatocellular carcinoma (HCC) of intermediate stage (BCLC-B according to the Barcelona Clinic Liver Cancer classification) are a heterogeneous group with different degrees of liver function impairment and tumour burden. The recommended treatment is transarterial chemoembolization (TACE). However, patients in this group may be judged as poor candidates for TACE because the risk-benefit ratio is low. Such patients may receive transarterial radioembolization (TARE) only by entering a clinical trial. Experts have proposed that the stage could be further divided into four substages based on available evidence of treatment benefit. We report here, for the first time, the outcome in patients with BCLC-B2 substage HCC treated with TARE.

Methods

A retrospective analysis of the survival of 126 patients with BCLC-B2 substage HCC treated with TARE in three European hospitals was performed.

Results

Overall median survival in patients with BCLC-B2 substage was not significantly different in relation to tumour characteristics; 19.35 months (95% CI 8.27–30.42 months) in patients with a single large (>7 cm) HCC, and 18.43 months (95% CI 15.08–21.77 months) in patients with multinodular HCC (p = 0.27). However, there was a higher proportion of long-term survivors at 36 months among those with a single large tumour (29%) than among those with multiple tumours (16.8%).

Conclusion

Given the poor efficacy of TACE in treating patients with BCLC-B2 substage HCC, TARE treatment could be a better choice, especially in those with a large tumour.

http://bit.ly/2MCfx6X

Comparison of 18 F-GE-180 and dynamic 18 F-FET PET in high grade glioma: a double-tracer pilot study

Abstract

Background

PET represents a valuable tool for glioma imaging. In addition to amino acid tracers such as ¹⁸F-FET, PET targeting the 18-kDa mitochondrial translocator-protein (TSPO) is of high interest for high-grade glioma (HGG) imaging due to its upregulation in HGG cells. ¹⁸F-GE-180, a novel TSPO ligand, has shown a high target-to-background contrast in HGG. Therefore, we intra-individually compared its uptake characteristics to dynamic ¹⁸F-FET PET and contrast-enhanced MRI in patients with HGG.

Methods

Twenty HGG patients (nine IDH-wildtype, 11 IDH-mutant) at initial diagnosis (n = 8) or recurrence (n = 12) were consecutively included and underwent ¹⁸F-GE-180 PET, dynamic ¹⁸F-FET PET, and MRI. The maximal tumour-to-background ratios (TBR_max) and biological tumour volumes (BTV) were evaluated in ¹⁸F-GE-180 and ¹⁸F-FET PET. Dynamic ¹⁸F-FET PET analysis included the evaluation of minimal time-to-peak (TTP_min). In MRI, the volume of contrast-enhancement was delineated (VOL_CE). Volumes were spatially correlated using the Sørensen–Dice coefficient.

Results

The median TBR_max tended to be higher in ¹⁸F-GE-180 PET compared to ¹⁸F-FET PET [4.58 (2.33–8.95) vs 3.89 (1.56–7.15); p = 0.062] in the overall group. In subgroup analyses, IDH-wildtype gliomas showed a significantly higher median TBR_max in ¹⁸F-GE-180 PET compared to ¹⁸F-FET PET [5.45 (2.56–8.95) vs 4.06 (1.56–4.48); p = 0.008]; by contrast, no significant difference was observed in IDH-mutant gliomas [3.97 (2.33–6.81) vs 3.79 (2.01–7.15) p = 1.000]. Only 5/20 cases showed higher TBR_max in ¹⁸F-FET PET compared to ¹⁸F-GE-180 PET, all of them being IDH-mutant gliomas. No parameter in ¹⁸F-GE-180 PET correlated with TTP_min (p > 0.05 each). There was a tendency towards higher median BTV_GE-180 [32.1 (0.4–236.0) ml] compared to BTV_FET [19.3 (0.7–150.2) ml; p = 0.062] with a moderate spatial overlap [median Sørensen–Dice coefficient 0.55 (0.07–0.85)]. In MRI, median VOL_CE [9.7 (0.1–72.5) ml] was significantly smaller than both BTV_FET and BTV_GE180 (p < 0.001 each), leading to a poor spatial correlation with BTV_GE-180 [0.29 (0.01–0.48)] and BTV_FET [0.38 (0.01–0.68)].

Conclusion

PET with ¹⁸F-GE-180 and ¹⁸F-FET provides differing imaging information in HGG dependent on the IDH-mutational status, with diverging spatial overlap and vast exceedance of contrast-enhancement in MRI. Combined PET imaging might reveal new insights regarding non-invasive characterization of tumour heterogeneity and might influence patients' management.

http://bit.ly/2sVhWR6

Christopher E. Comstock, Christiane Kuhl (Eds.): Abbreviated MRI of the Breast: A Practical Guide

http://bit.ly/2MCVQw2

Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis

Abstract

Purpose

Hyperparathyroidism (HPT) is a common endocrine disorder caused by hyperfunctioning parathyroid glands (HP). The correct detection and localization of HP is challenging but crucial, as it may guide surgical treatment, particularly in patients with primary HPT. There is a growing body of data regarding the role of radiolabelled choline positron emission tomography (PET) in this setting. Therefore, we performed a systematic review and meta-analysis of the diagnostic performance of this method in detecting HP in patients with HPT.

Methods

This systematic review and meta-analysis was carried out according to PRISMA guidelines. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE and Cochrane Library databases for studies published through May 2018 was performed using the following search algorithm: (a) "choline" or "fluorocholine" or "F-choline" or "C-choline" or "FCH" or "CH" or "FECH" or "FMCH" and (b) "PET" or "positron emission tomography" and (c) "parathyroid" or "hyperparathyroidism". The diagnostic performance of radiolabelled choline PET was expressed as sensitivity and positive predictive value (PPV) on a per-patient and per-lesion basis and as detection rate (DR) on a per-patient basis, with pooled proportion and 95% confidence interval (95% CI) obtained using a random-effects model.

Results

Eighteen studies were included in the systematic review. Fourteen articles (517 patients) were selected for the meta-analysis. The meta-analysis provided the following results on a per-patient analysis analysis: sensitivity 95% (95% CI: 92–97%), PPV 97% (95% CI: 95–98%) and DR 91% (95% CI: 87–94%). On a per-lesion analysis, pooled sensitivity and PPV were 92% (95% CI: 88–96) and 92% (95% CI: 89–95%), respectively. No significant heterogeneity was found among the selected studies.

Conclusions

Radiolabelled choline PET demonstrated excellent diagnostic performance in detecting HP in patients with HPT. Large multicentre studies and cost-effectiveness analyses are needed to better define the role of this imaging method in this setting.

http://bit.ly/2sRLgIl

Regulation of human brown adipose tissue by adenosine and A 2A receptors – studies with [ 15 O]H 2 O and [ 11 C]TMSX PET/CT

Abstract

Purpose

Brown adipose tissue (BAT) has emerged as a potential target to combat obesity and diabetes, but novel strategies to activate BAT are needed. Adenosine and A_2A receptor (A2AR) agonism activate BAT in rodents, and endogenous adenosine is released locally in BAT as a by-product of noradrenaline, but physiological data from humans is lacking. The purpose of this pilot study was to investigate the effects of exogenous adenosine on human BAT perfusion, and to determine the density of A2ARs in human BAT in vivo for the first time, using PET/CT imaging.

Methods

Healthy, lean men (n = 10) participated in PET/CT imaging with two radioligands. Perfusion of BAT, white adipose tissue (WAT) and muscle was quantified with [¹⁵O]H₂O at baseline, during cold exposure and during intravenous administration of adenosine. A2AR density of the tissues was quantified with [¹¹C]TMSX at baseline and during cold exposure.

Results

Adenosine increased the perfusion of BAT even more than cold exposure (baseline 8.3 ± 4.5, cold 19.6 ± 9.3, adenosine 28.6 ± 7.9 ml/100 g/min, p < 0.01). Distribution volume of [¹¹C]TMSX in BAT was significantly lower during cold exposure compared to baseline. In cold, low [¹¹C]TMSX binding coincided with high concentrations of noradrenaline.

Conclusions

Adenosine administration caused a maximal perfusion effect in human supraclavicular BAT, indicating increased oxidative metabolism. Cold exposure increased noradrenaline concentrations and decreased the density of A2AR available for radioligand binding in BAT, suggesting augmented release of endogenous adenosine. Our results show that adenosine and A2AR are relevant for activation of human BAT, and A2AR provides a future target for enhancing BAT metabolism.

http://bit.ly/2MIabaA

Ectopic corticotropin-releasing hormone syndrome caused by pancreatic neuroendocrine tumor localized by 68 Ga-DOTATATE PET/CT

http://bit.ly/2sS3rxF

Highly favourable outcomes with peptide receptor radionuclide therapy (PRRT) for metastatic rectal neuroendocrine neoplasia (NEN)

Abstract

Purpose

Rectal neuroendocrine neoplasia (NEN) is more common than other NEN origins, but is less commonly metastatic. However, when present, distant disease carries a particularly poor prognosis. Evidence guiding optimal treatment of such patients is lacking. We assessed PRRT outcomes in patients with somatostatin receptor (SSTR) positive metastatic rectal NEN from two referral centres.

Methods

Patients treated with PRRT were retrospectively reviewed. Morphologic (RECIST 1.1), SSTR imaging responses and toxicity were assessed 3 months post-PRRT. Kaplan-Meier estimate was used to determine progression-free survival (PFS) and overall survival (OS) from start of PRRT.

Results

Twenty-seven consecutive patients (M = 20, age 31-81 years) were reviewed. The majority (70%) had ENETs grade 2 disease (19 patients), three had Grade 3, one Grade 1, and four not documented. Overall, 63% (10/16 patients with available FDG PET/CT) had FDG avid disease. Twenty-six patients were treated for disease progression. Most had ¹⁷⁷Lu-DOTA-octreotate with median cumulative activity of 30 GBq, median four cycles. 14 patients had radiosensitising chemotherapy (5FU or capecitabine). At 3 months post-PRRT, CT disease control rate (DCR) was 96%: partial response was observed in 70% (19/27) and stable disease in 26%. All but one had partial SSTR imaging response. The median PFS was 29 months. Ten patients died, with median overall survival 81 months with a median follow-up of 67 months. Seventeen patients had further treatments after initial PRRT (10 had further cycles of PRRT). Three patients had grade 3 lymphopenia, without significant renal toxicity, MDS or leukaemia.

Conclusion

Our results indicate high efficacy and morphologic responses with minimal toxicity and very encouraging survival from PRRT in patients with metastatic rectal NEN despite the adverse prognostic features of this cohort. Further prospective PRRT trials are warranted in this subgroup.

http://bit.ly/2MIa272

Treatment of aggressive recurrent meningiomas: spinning towards peptide receptor radionuclide therapy

http://bit.ly/2sOSPj2

Bombardieri E, Seregni E, Evangelista L, Chiesa C, Chiti A (Eds.) Clinical Applications of Nuclear Medicine Targeted Therapy. Springer International Publishing Switzerland 2018. ISBN 978-3-319-63067-0

http://bit.ly/2FW4cyj

Influence of lanreotide on uptake of 68 Ga-DOTATATE in patients with neuroendocrine tumours: a prospective intra-patient evaluation

Abstract

Introduction

Somatostatin receptor imaging with PET is the standard of care for patients with a neuroendocrine tumour (NET). Since therapy and imaging with somatostatin analogues utilize the same receptor, current guidelines recommend withdrawing long-acting somatostatin analogues for 3-4 weeks prior to somatostatin receptor PET imaging. The aim of this study is to prospectively assess the effect of lanreotide use on the uptake of ⁶⁸Ga-DOTATATE intra-individually 1 day prior to and 1 day post injection of lanreotide.

Methods

Thirty-four patients with metastatic and/or unresectable NET and currently on lanreotide therapy for at least 4 months were included in the study. A ⁶⁸Ga-DOTATATE PET/CT scan was performed on the day before and the day after lanreotide injection. In each patient ⁶⁸Ga-DOTATATE uptake (SUV_max, _mean, _peak) was assessed in both tumour lesions and normal tissue. All scans were assessed by two blinded nuclear medicine physicians for visual analysis. Paired T-tests were performed to determine the differences between the scans.

Results

Of the 34 patients included, 31 were available for analyses in which 190 tumour lesions were measured. Uptake of ⁶⁸Ga-DOTATATE in tumour lesions was increased significantly after lanreotide, but decreased significantly in the liver, spleen, and thyroid gland resulting in a higher tumour-to-liver ratio.

Conclusion

Lanreotide injection prior to ⁶⁸Ga-DOTATATE PET/CT does not result in decreased tumour uptake. In contrast, tumour uptake was increased, whereas the uptake in normal organs is decreased, leading to an increased tumour-to-liver ratio. However, these differences were small and not deemed clinically relevant. These results strongly suggest that discontinuation of lanreotide injections in the weeks prior to ⁶⁸Ga-DOTATATE PET examinations is unnecessary and does not compromise nuclear medicine imaging results.

http://bit.ly/2MI9VIE

Safety and efficacy of targeted alpha therapy with 213 Bi-DOTA-substance P in recurrent glioblastoma

Abstract

Treatment options for recurrent glioblastoma multiforme (GBM) are very limited. GBM cells express high levels of the GPCR neurokinin type 1 receptor (NK-1R), and a modified substance P can be used as its ligand for the tumor cell targeting. Targeted alpha therapy with DOTA-Substance P labeled with the short range alpha emitter ²¹³Bi allows for selective irradiation and killing of tumor cells.

Material and methods

Twenty patients with recurrent GBM were included into the study following a standard therapy. 1–2 intracavitary or intratumoral port-a-cath systems were stereotactically inserted. Patients were treated with 1–7 doses of ²¹³Bi-DOTA-Substance P (²¹³Bi-DOTA-SP) in 2-month intervals. ⁶⁸Ga-DOTA-Substance P (⁶⁸Ga-DOTA-SP) was co-injected with ²¹³Bi-DOTA-SP to assess the biodistribution using PET/CT. Therapeutic response was monitored with performance status and MRI imaging.

Results

Treatment with activity up to 11.2 GBq ²¹³Bi-DOTA-SP was well tolerated with only mild and transient adverse reactions. The median progression free survival was 2.7 months. The median overall survival from the first diagnosis was 23.6 months and median survival after recurrence was 10.9 months. The median survival time from the start of ²¹³Bi-DOTA-SP was 7.5 months.

Conclusions

Treatment of recurrent GBM with ²¹³Bi-DOTA-SP is safe and well tolerated. The median overall survival after recurrence of 10.9 months compares favorably to the available alternative treatment options. Once the supply of high activity ²²⁵Ac/²¹³Bi radionuclide generators is secured, targeted alpha therapy with ²¹³Bi-DOTA-SP may evolve as a promising novel option to treat recurrent GBM.

http://bit.ly/2sPRGrs

FET PET reveals considerable spatial differences in tumour burden compared to conventional MRI in newly diagnosed glioblastoma

Abstract

Purpose

Areas of contrast enhancement (CE) on MRI are usually the target for resection or radiotherapy target volume definition in glioblastomas. However, the solid tumour mass may extend beyond areas of CE. Amino acid PET can detect parts of the tumour that show no CE. We systematically investigated tumour volumes delineated by amino acid PET and MRI in patients with newly diagnosed, untreated glioblastoma.

Methods

Preoperatively, 50 patients with neuropathologically confirmed glioblastoma underwent O-(2-[¹⁸F]-fluoroethyl)-l-tyrosine (FET) PET, and fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced MRI. Areas of CE were manually segmented. FET PET tumour volumes were segmented using a tumour-to-brain ratio of ≥1.6. The percentage overlap volumes, and Dice and Jaccard spatial similarity coefficients (DSC, JSC) were calculated. FLAIR images were evaluated visually.

Results

In 43 patients (86%), the FET tumour volume was significantly larger than the CE volume (21.5 ± 14.3 mL vs. 9.4 ± 11.3 mL; P < 0.001). Forty patients (80%) showed both increased uptake of FET and CE. In these 40 patients, the spatial similarity between FET uptake and CE was low (mean DSC 0.39 ± 0.21, mean JSC 0.26 ± 0.16). Ten patients (20%) showed no CE, and one of these patients showed no FET uptake. In five patients (10%), increased FET uptake was present outside areas of FLAIR hyperintensity.

Conclusion

Our results show that the metabolically active tumour volume delineated by FET PET is significantly larger than tumour volume delineated by CE. Furthermore, the results strongly suggest that the information derived from both imaging modalities should be integrated into the management of patients with newly diagnosed glioblastoma.

http://bit.ly/2MI9RIU

Personalized 177 Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial

Abstract

Purpose

Peptide receptor radionuclide therapy (PRRT) is mostly administered using a fixed injected activity (IA) per cycle. This empiric regime results in highly variable absorbed doses to the critical organs and undertreatment of the majority of patients. We conceived a personalized PRRT protocol in which the IA is adjusted to deliver a prescribed absorbed dose to the kidney, with the aim to safely increase tumour irradiation. We herein report on the initial results of our prospective study of personalized PRRT, the P-PRRT Trial (NCT02754297).

Methods

PRRT-naïve patients with progressive and/or symptomatic neuroendocrine tumour (NET) were scheduled to receive a four-cycle induction course of ¹⁷⁷Lu-octreotate with quantitative SPECT/CT-based dosimetry. The IA was personalized according to the glomerular filtration rate and the body surface area for the first cycle, and according to the prior renal Gy/GBq for the subsequent cycles. The prescribed renal absorbed dose of 23 Gy was reduced by 25–50% in case of significant renal or haematological impairment. Responders were allowed to receive consolidation or maintenance cycles, for each of which 6 Gy to the kidney were prescribed. We simulated the empiric PRRT regime by fixing the IA at 7.4 GBq per cycle, with the same percentage reductions as above. Radiological, molecular imaging, biochemical, and quality of life responses, as well as safety, were assessed.

Results

Fifty-two patients underwent 171 cycles. In 34 patients who completed the induction course, a median cumulative IA of 36.1 (range, 6.3–78.6) GBq was administered, and the median cumulative kidney and maximum tumour absorbed doses were 22.1 (range, 8.3–24.3) Gy and 185.7 (range: 15.2–443.1) Gy respectively. Compared with the simulated fixed-IA induction regime, there was a median 1.26-fold increase (range, 0.47–2.12 fold) in the cumulative maximum tumour absorbed dose, which was higher in 85.3% of patients. In 39 assessable patients, the best objective response was partial response in nine (23.1%), minor response in 14 (35.9%), stable disease in 13 (33.3%) and progressive disease in three patients (7.7%). In particular, 11 of 13 patients (84.6%) with pancreatic NET had partial or minor response. The global health status/quality of life score significantly increased in 50% of patients. Acute and subacute side-effects were all of grade 1 or 2, and the most common were nausea (in 32.7% of patients) and fatigue (in 30.8% of patients) respectively. Subacute grade 3 or 4 toxicities occurred in less than 10% of patients, with the exception of lymphocytopenia in 51.9% of patients, without any clinical consequences however. No patient experienced severe renal toxicity.

Conclusions

Personalized PRRT makes it possible to safely increase tumour irradiation in the majority of patients. Our first results indicate a favourable tolerance profile, which appears similar to that of the empiric regime. The response rates are promising, in particular in patients with NET of pancreatic origin.

http://bit.ly/2sUMqD3

Comprehensive anatomical and functional imaging in patients with type I neurofibromatosis using simultaneous FDG-PET/MRI

Abstract

Purpose

To demonstrate the clinical use of FDG-PET/MRI for monitoring enlargement and metabolism of plexiform neurofibromas (PNF) in patients with neurofibromatosis type 1 (NF1), in whom the development of a malignant peripheral nerve sheath tumor (MPNST) is often a life limiting event.

Methods

NF1 patients who underwent a simultaneous FDG-PET/MRI examination in our institution from September 2012 to February 2018 were included. Indication was suspicion of malignant transformation of a PNF to MPNST. A maximum of six peripheral nerve lesions per patient were defined as targets. Standardized uptake values (SUV) and apparent diffusion coefficients (ADC) were measured. The presence of target sign and contrast-medium enhancement was visually recorded. Growth rates were estimated comparing prior or follow-up examinations and correlated with FDG uptake and ADC values. The presence of CNS lesions in cerebral T2 weighted images was recorded.

Results

In 28 NF1 patients a total number of 83 peripheral nerve tumors, 75 benign PNFs and eight MPNSTs, were selected as target lesions. The SUVs of MPNSTs were significantly higher than the SUVs of PNF (3.84 ± 3.98 [SUV_mean MPNSTs] vs. 1.85 ± 1.03 [SUV_mean PNF], P < .01). Similarly, lesion SUV_mean-to-liver SUV_mean ratios significantly differed between MPNSTs and PNF (3.20 ± 2.70 [MPNSTs] vs. 1.23 ± 0.61 [PNF]; P < .01). For differentiation between still benign PNF and MPNSTs, we defined SUV_max ≥ 2.78 as a significant cut-off value. Growth rate of PNF correlated significantly positively with SUV_mean (r_s = .41; P = .003). MRI parameters like ADC_mean (1.87 ± 0.24 × 10⁻³ mm²/s [PNF] vs. 1.76 ± 0.11 × 10⁻³ mm²/s [MPNSTs]; P > .05], contrast medium enhancement (P = .50) and target sign (P = .86) did not differ between groups.

Conclusion

Simultaneous FDG-PET/MRI is a comprehensive imaging modality for monitoring PNF in NF1 patients. The combined acquisition of both morphologic information in MRI and metabolic information in PET enables the correlation of lesion growth rates with metabolic activity and to define SUV thresholds of significance to identify malignant transformation, which is of utmost clinical significance.

http://bit.ly/2MFfMhA

The EANM practical guidelines for sentinel lymph node localisation in oral cavity squamous cell carcinoma

Abstract

Purpose

Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized oral cavity squamous cell carcinoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery, and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with early N0 oral cavity squamous cell carcinoma.

Methods

These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) and the International Atomic Energy Agency (IAEA) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, and national nuclear medicine societies. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI).

These guidelines, together with another two focused on Surgery and Pathology (and published in specialised journals), are part of the synergistic efforts developed in preparation for the "2018 Sentinel Node Biopsy in Head and Neck Consensus Conference".

Conclusion

The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of early N0 oral cavity squamous cell carcinoma patients.

http://bit.ly/2FTTLLz

Additional value of integrated 18 F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile

Abstract

Purpose

The localization of hyperfunctioning parathyroid gland(s) (HPTG) in patients with primary hyperparathyroidism (PHPT) with negative or inconclusive first-line imaging is a significant challenge. This study aimed to evaluate the role of integrated ¹⁸F-choline PET/4D contrast-enhanced computed tomography (4DCeCT) in these patients, compare its detection rate and sensitivity with those of ¹⁸F-choline PET/CT and (4DCeCT), and analyse the association between choline metabolism and morphological, biochemical and molecular parameters of HPTG.

Methods

We prospectively enrolled 44 PHPT patients with negative or inconclusive first-line imaging. ¹⁸F-Choline PET/CT and 4DCeCT were performed at the same time, and integrated ¹⁸F-choline PET/4DCeCT images were obtained after coregistration. Experienced physicians examined the images. The SUVratio and degree of contrast enhancement were recorded for each positive finding. Histopathology, laboratory and multidisciplinary follow-up were used as the standard of reference. Both the detection rates and sensitivities of the three imaging modalities were calculated retrospectively. Immunohistochemistry was performed to evaluate the molecular profile of HPTGs.

Results

¹⁸F-Choline PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%), and 31 of 31 surgically treated patients (sensitivity 100%). These results were significantly (p < 0.05) better than those of ¹⁸F-choline PET/CT (56.8% and 80%, respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant correlation between SUV and calcium level was found. In a multivariate analysis, only calcium level was significantly associated with ¹⁸F-choline PET/4DCeCT findings. SUVratio and Ki67 expression were significantly correlated.

Conclusion

Integrated ¹⁸F-choline PET/4DCeCT should be considered as an effective tool to detect PHPT in patients with negative or inconclusive first-line imaging. Choline metabolism is correlated with both calcium level and Ki67 expression in HPTG.

http://bit.ly/2sUMqmx

Yttrium-90 glass microspheres radioembolization (RE) for biliary tract cancer: a large single-center experience

Abstract

Purpose

Radioembolization (RE) is a promising treatment option for biliary tract cancers (BTC). We report here the largest series to date using this treatment modality.

Methods

We retrospectively studied data from 64 patients treated outside prospective clinical trial at our institution. We studied baseline characteristics as potential prognostic factors. We studied dose delivered to the tumor as predictive factors of outcomes in patients not receiving concomitant chemotherapy.

Results

The Progression-Free Survival and Overall Survival (OS) were 7.6 months [95% Confidence Interval (CI): 4.6–10.6] and 16.4 months [95% CI: 7.8–25.0] in the whole cohort. The factors independently associated with OS in multivariable analysis were the primary localization of ICC (HR = 0.27, 95% CI: 0.11–0.68, p = 0.005) and a PS > 0 (HR = 2.21, 95% CI: 1.11–4.38, p = 0.024). During follow-up, 12 patients (19%) underwent surgery following downstaging, with a median OS of 51.9 months. In patients not treated with concomitant chemotherapy (n = 31), OS was significantly higher in patients with a dose delivered to the tumor 260Gy or higher than in patients with a dose delivered to the tumor lower than 260Gy (median 28.2 vs 11.4 months, log-rank p = 0.019).

Conclusion

Our results confirm that RE is a promising treatment modality in BTC. A high proportion of patients could be downstaged to surgery, with promising long-term survival. Dose delivered to the tumor correlated with clinical outcomes when chemotherapy was not used concomitantly.

http://bit.ly/2FUloUL

Platelet‐rich plasma and microneedling improves hair growth in patients ofandrogenetic alopecia when used as an adjuvant to minoxidil

Summary

Background

Platelet‐rich plasma (PRP) is a popular procedure for the treatment of androgenetic alopecia (AGA).

Aim

To ascertain the role of minoxidil 5% lotion alone versus minoxidil 5% lotion and PRP versus minoxidil 5% lotion, PRP with microneedling in AGA.

Material and methods

Ninety‐three AGA patients with Hamilton‐Norwood score 1‐5 were grouped into three groups A, B, and C. Patients in group A (control group) were treated with minoxidil 5% lotion twice daily (n = 31), whereas patients in group B underwent treatment with minoxidil 5% lotion twice daily and PRP (n = 31), and group C patients received minoxidil 5% lotion twice daily, PRP, and microneedling (n = 31). Baseline and post‐treatment photographs were taken along with dermoscopic evaluation. Selection of the dermoscopic variables included in the evaluation process was based on the published literature and dermoscopists' expertise and experience. Hair pull test was performed before and during follow‐up.

Results

Post‐treatment, hair pull test was negative in 27 patients (87.1%, P < 0.01) of group C, 20 patients (64.5%, P < 0.05) of group B, and 15 patients (48.4%) of group A. Hair growth was better appreciated in group C (26/31) compared to groups B (17/31)and A (10/31).The patients' self‐satisfaction score on a Likert scale was more than seven (high satisfaction) in 24/31 patients in group C. There was a statistically significant difference between three groups in terms of hair pull test, terminal‐to‐vellus hair ratio, and patient satisfaction score as determined by one‐way ANOVA.

Conclusion

PRP with microneedling is better in comparison with PRP alone or minoxidil monotherapy in patients with AGA.

http://bit.ly/2HDJ3KL

Comment on: ‘Treatment of psoriasis with ustekinumab in a patient with HIV‐related Kaposi sarcoma’

Abstract

We read with great interest the recent article by Wang et al.¹ reporting on a psoriatic patient co‐affected by HIV‐related Kaposi's sarcoma (KS), whose poorly controlled psoriasis was successfully treated with ustekinumab, a fully monoclonal antibody that targets the common p40 subunit shared by interleukins (IL)‐12 and IL‐23. Interestingly, despite the evidences supporting the role of IL‐12 in inhibiting tumorigenesis,² the authors reported no KS progression after a 16‐month follow‐up.

http://bit.ly/2TltEjC

Vulvar squamous cell carcinoma: a clinico‐dermoscopic correlation

Abstract

Squamous cell carcinoma (SCC) is the most common malignant vulvar tumor.1 It primarily affects post‐menopausal women; its precursor lesions are vulvar intraepithelial neoplasia (VIN), in particular the "differentiated" subtype, and/or human papillomavirus (HPV) infection.1 The final diagnosis of vulvar SCC is made by histopathology, which is similar to that of SCC affecting other body areas, distinguishing between well differentiated forms and poorly differentiated tumors.

http://bit.ly/2BaxOEa

Liquid chromatography–mass spectrometry is effective for Analysis of Ergosterol in Fungus Infected Nails

Abstract

Background

The identification of onychomycosis is mainly based on clinical diagnosis with auxiliary diagnostic methods such as KOH microscopy, PAS staining, or mold culture. However, they are limited by the sensitivity and specificity of each type of method. Therefore, our aim is to develop a new test method using the common end product – ergosterol – test to see if it can be used as a new diagnostic tool.

Materials and Methods

We collected consecutive data from 20 subjects with nail problems. After the clinical diagnosis, the subjects received a KOH microscopy test and the extraction of specimens for the mass spectrometer test to check for the presence of ergosterol.

Results

Among the 20 cases collected, seven came out positive by the mass spectrometry test. Four of them were suspected as onychomycosis, whereas one of the remaining three subjects was presumed to be dry nail and the other two as onycholysis. It is obvious that it is easier for the mass spectrometer test to find composites.

Conversely, among the five clinically diagnosed onychomycosis, four came out positive by mass spectrometer whereas the other one was detected negative by KOH and mass spectrometer. Three other subjects were positive with KOH test with mass spectrometer test also resulting to be positive.

Conclusion

The detection of the presence of ergosterol by a mass spectrometer is one of the good tools for confirming onychomycosis. However, there is a need to conduct studies to verify the sensitivity and specificity of the mass spectrometer method.

http://bit.ly/2Tird1p

Eccrine Porocarcinoma in a patient with Schöpf–Schulz–Passarge syndrome

Abstract

Histological analysis of the lesion proved to be challenging. An initial punch biopsy showed an ulcerated tumour comprised of islands of monomorphic cells with duct formation pushed deep into the dermis, and a lace‐like pattern of infiltration. At this point a diagnosis of eccrine porocarcinoma was favoured over poroma due to the presence of desmoplastic response and focal infiltrative growth pattern.

http://bit.ly/2B8bmLD

A retrospective review of twelve patients with trichotillomania treated in a psychodermatology service

Summary

Trichotillomania is a condition characterised by the pulling of hair from anywhere on the body and is classified as an obsessive‐compulsive and related disorder. Patients with hair disorders are commonly referred to psychodermatology services, and can represent a management challenge. Few publications exist that report outcomes for patients with trichotillomania in real clinical practice. We report twelve such patients seen within our own psychodermatology service, who were managed using a variety of treatment strategies. The rate of defaulting of appointments was high, but improvements were seen in patients engaging with services.

http://bit.ly/2Tpc8vb

Lower limb cellulitis: low diagnostic accuracy and underdiagnosis of risk factors

Abstract

Accurate diagnosis and recognition of predisposing factors has been shown to be challenging in lower limb cellulitis. Assessment of 1746 consecutive cellulitis patients presenting to a UK university hospital showed increasing overdiagnosis with only 31.9% of referred patients with confirmed lower‐limb cellulitis between 2015‐2018. Recognition of at least one predisposing factor increased from 61% to 89% following introduction of more specific screening questions. This identified a need for better primary care dermatology education and the benefit of a proforma with specific screening questions for reversible predisposing factors for lower limb cellulitis.

http://bit.ly/2Bal1Bq

Modeling the relationship between gross capital formation and CO 2 (a)symmetrically in the case of Pakistan: an empirical analysis through NARDL approach

Abstract

This paper tries to ensure the relationship between gross capital formation (GCF) and carbon dioxide (CO₂) emissions in the case of Pakistan for the period 1980–2016 by employing Non-Linear Auto Regressive Distribution Lag (NARDL) model under the expansion of Environmental Kuznets hypothesis (EKC) while controlling for coal and oil consumption variables as a potential factors of CO₂ emissions. Our main objective is to check whether or not the effect of changes in GCF on CO₂ emissions is asymmetric or symmetric for Pakistan that is among one of the main contributors to CO₂ emissions in Asia, as the emissions were grown by 15.6 million tonnes or 8.5% increase in percentage terms in 2016. Our result confirms the existence of an asymmetric effect of GCF shocks on CO₂ emissions both in the short and long-terms. Moreover, our empirical finding also suggests that coal and oil consumptions have a significant contribution to CO₂ emissions both in the short and long-terms. Further, our results also significantly support the existence of the EKC hypothesis both in the long and short-terms. That confirms the inverted U-shaped connection among per capita growth and CO₂ emissions in Pakistan. In the last, our study suggests that the implementation and use of clean energies and technologies are vital for controlling pollution in Pakistan.

http://bit.ly/2Rn4TSt

Phytoremediation potential and control of Phragmites australis as a green phytomass: an overview

Abstract

Phragmites australis (common reed) is one of the most extensively distributed emergent plant species in the world. This plant has been used for phytoremediation of different types of wastewater, soil, and sediments since the 1970s. Published research confirms that P. australis is a great accumulator for different types of nutrients and heavy metals than other aquatic plants. Therefore, a comprehensive review is needed to have a better understanding of the suitability of this plant for removal of different types of nutrients and heavy metals. This review investigates the existing literature on the removal of nutrients and heavy metals from wastewater, soil, and sediment using P. australis. In addition, after phytoremediation, P. australis has the potential to be used for additional benefits such as the production of bioenergy and animal feedstock due to its specific characteristics. Determination of adaptive strategies is vital to reduce the invasive growth of P. australis in the environment and its economic effects. Future research is suggested to better understand the plant's physiology and biochemistry for increasing its pollutant removal efficiency.

http://bit.ly/2G43wWR

The impact of sustainability performance indicators on financial stability: evidence from the Russian oil and gas industry

Abstract

Considering the dearth of research on the impact of sustainability reporting practices on financial stability in the context of transition economies, this study aims to explore sustainability reporting practices of top oil and gas companies in Russia and investigate the effects of sustainability performance indicators on financial stability in the context of a given emerging economy. The study is based on panel data analysis of sustainability performance indicators and financial data of forty-five largest oil and gas companies listed on the Russian Trading Stock Exchange over the period 2012–2016. Data on sustainability performance were collected through analyzing sustainability reports and annual reports, while financial data were obtained from audited financial statements downloaded from company websites. The empirical results indicate that companies improve their sustainability performance indicators in order to manage risk and improve their financial stability. The results also show that firm-specific characteristics, such as financial capacity, leverage, firm size, and firm age, are important underlying factors affecting the degree of financial distress and financial stability. The findings of the study provide managers and practitioners with useful aspects of sustainability performance indicators to improve financial stability and mitigate financial distress. Additionally, investors and practitioners should consider other underlying factors, including financial capacity, leverage, firm size, and firm age, that may influence financial stability. Finally, the findings are useful for policymakers and regulators in promoting Global Reporting Initiative guidelines which will ultimately lead to sustainable development and financial stability in the context of emerging markets.

http://bit.ly/2FTEPNt

Seasonal ecotoxicological monitoring of freshwater zooplankton in Bir Mcherga dam (Tunisia)

Abstract

Dams represent large semi-closed reservoirs of pesticides and various organic and inorganic pollutants from agricultural and human activities, and their monitoring should receive special attention. This study evaluated the environmental health status of Bir Mcherga dam using zooplankton species. The dam has a capacity of 130 Mm³ and its waters are used for irrigation, water drinking supply, and fishery. Copepods and cladocerans (crustaceans) were collected in situ monthly between October and August 2012. Oxidative stress (CAT, MDA), neurotoxicity (AChE), and genotoxicity (micronucleus test) biomarkers were analyzed in two zooplankton species: Acanthocyclops robustus and Diaphanosoma mongolianum. High values of cells with a micronucleus were observed during summer. AChE activities were inhibited during early winter and summer. The high seasonal variability of CAT and MDA levels indicates that zooplankton is continuously exposed to different oxidative stresses. These results suggest that there is an obvious and continuous multi-faceted stress in Bir Mcherga reservoir and, consequently, an urgent monitoring of freshwater environments in Tunisia is needed, particularly those intended for human consumption and irrigation.

http://bit.ly/2RSlkv8

Effect of Vicia faba L. var. minor and Sulla coronaria (L.) Medik associated with plant growth-promoting bacteria on lettuce cropping system and heavy metal phytoremediation under field conditions

Abstract

Researches involving the use of association between legumes and PGPBs (plant growth-promoting bacteria) in heavy metal phytoremediation process were mainly performed for soils highly contaminated. However, even in agriculture soils, with moderate or low contamination levels, plants can accumulate high rates of heavy metals. So, food chain contamination by these metals presents a real threat to animal and human health. This work aimed to evaluate the use of two legumes/PGPB symbioses; Vicia faba var. minor and Sulla coronaria have been inoculated with specific heavy metal-resistant inocula in a crop rotation system with Lactuca sativa as a following crop, in order to assess their effects on soil fertility, lettuce yield, and heavy metal content. Our results showed that legume inoculation significantly enhanced their biomass production, nitrogen and phosphorus content. The use of our symbioses as green manure before lettuce cultivation, as a rotation cropping system, affected positively soil fertility. In fact, we recorded a higher organic matter content, with rapid decomposition in the soil of inoculated plots. Besides, results demonstrated a greater nitrogen and phosphorus content in this soil, especially in the plot cultivated with inoculated V. faba var. minor. The improvement of soil fertility enhanced lettuce yield and its nitrogen and phosphorus content. Moreover, inoculated legumes extracted and accumulated more heavy metals than non-inoculated legumes. Our symbioses play the role of organic trap for heavy metals, making them unavailable for following crops. These facts were supported by lettuce heavy metal content, showing a significant decrease in metal accumulation, mainly zinc and cadmium, in edible parts. Results showed the usefulness of the studied symbioses, as a main part of a rotation system with lettuce. Our symbioses can be suggested for agriculture soil phytoremediation, aiming to enhance non-legume crop yield and limit heavy metal translocation to food chain.

http://bit.ly/2CPGrnu

Auricular calcification in a patient with traumatic brain injury and adrenal insufficiency: clinico-radiographic correlation with 3D cinematic rendering

http://bit.ly/2RilruV

Auricular calcification in a patient with traumatic brain injury and adrenal insufficiency: clinico-radiographic correlation with 3D cinematic rendering

http://bit.ly/2RilruV

Improved Jayaweera-Mikkelsen model to quantify ammonia volatilization from rice paddy fields in China

Abstract

Current estimates of China's ammonia (NH₃) volatilization from paddy rice differ by more than twofold, mainly due to inappropriate application of chamber-based measurements and improper assumptions within process-based models. Here, we improved the Jayaweera-Mikkelsen (JM) model through multiplying the concentration of aqueous NH₃ in ponded water by an activity coefficient that was determined based on high-frequency flux observations at Jingzhou station in Central China. We found that the improved JM model could reproduce the dynamics of observed NH₃ flux (R² = 0.83, n = 228, P < 0.001), while the original JM model without the consideration of activity of aqueous NH₃ overstated NH₃ flux by 54% during the periods of fertilization and pesticide application. The validity of the improved JM model was supported by a mass-balance-based indirect estimate at Jingzhou station and the independent flux observations from the other five stations across China. The NH₃ volatilization losses that were further simulated by the improved JM model forced by actual wind speed were in general a half less than previous chamber-based estimates at six stations. Difference in wind speed between the inside and outside of the chamber and insufficient sampling frequency were identified as the primary and secondary causes for the overestimation in chamber-based estimations, respectively. Together, our findings suggest that an in-depth understanding of NH₃ transfer process and its robust representation in models are critical for developing regional emission inventories and practical mitigation strategies of NH₃.

http://bit.ly/2Biu43B

Multifunctional diesel exhaust emission soot coated sponge for water treatment

Abstract

We demonstrated that a pollutant and waste, diesel exhaust emission soot (DEES) can be used as an absorbent to remove oil and organic pollutants from wastewater. The diesel exhaust emission soot coated sponge (DEES sponge) was prepared using the dip-coating method. Prepared DEES sponge was found hydrophobic in nature as the contact angle between water drop and its surface was recorded to be 147°. The DEES sponge showed high absorption capacity with various oils, without any surface modifications and pretreatments. Highest oil absorption capacity was found to be 39 g/g for engine oil. Excellent separation efficiency was recorded (max. 98.5% for engine oil). It shows promising recyclability having 95% efficiency even after 10 cycles. DEES sponge also demonstrated the capability to be used as an adsorbent due to its ability to absorb pollutants like methylene blue (MB), ciprofloxacin, and detergent from the water. It was able to adsorb 93% of the dye MB from its aqueous solution having concentration of 15 μM.

http://bit.ly/2RkOC0s

Radiotherapy-induced dysphagia and its impact on quality of life in patients with nasopharyngeal carcinoma

Abstract

Purpose

To investigate the swallowing status and its impact on quality of life (QOL) in patients who underwent radiotherapy for nasopharyngeal carcinoma (NPC).

Methods

In this study, 334 patients with NPC who underwent radiotherapy were reviewed. Clinical characteristics, videofluoroscopic swallowing studies (VFSSs), and scores of the World Health Organization quality of life-BREF (WHOQOL-BREF) were retrospectively analyzed for all patients.

Results

In this study, 143 of 334 (42.8%) patients showed dysphagia. The nodular stage N3 of NPC, neoadjuvant and concurrent chemotherapy were clinical predictors for dysphagia. VFSS of patients with dysphagia showed a high incidence of vallecular residue (100%), apraxia (99%), premature bolus loss (98%), bolus formation (98%), pyriform sinus residue (95%), and mastication (94%). Moreover, WHOQOL-BREF scores for the physical health, psychological, and environment domains were lower of the dysphagia group than those of the control group (P < 0.01). Videofluoroscopic dysphagia scale scores showed significant negative correlations with scores for the physical health (R = −0.66, P < 0.01), psychological (R = −0.70, P < 0.01), social relationships (R = −0.56, P < 0.01), and environment (R = −0.61, P < 0.01) domains of WHOQOL-BREF.

Conclusions

Radiotherapy-induced dysphagia is common in NPC patients and is correlated with poor quality of life. Patients, caregivers, and clinical physicians should be aware of these adverse effects and provide timely treatment for radiotherapy-induced dysphagia in collaboration with cross-disciplinary colleagues.

http://bit.ly/2MEhtvG

Clinical safety and efficacy of salvage reirradiation for upper abdominal malignancies

Abstract

Purpose

Reirradiation has the potential to provide effective local control of upper abdominal malignancies. This study aimed to evaluate the safety and efficacy of reirradiation for upper abdominal malignancies.

Methods

A total of 42 patients with a history of prior radiotherapy (RT) received reirradiation for abdominal malignancies between 2005 and 2017. Each patient's medical records, contours, and dose distribution for both RT courses were reviewed. The median dose of the prior RT was 50.0 Gy (range, 30.0–60.0 Gy) and the median dose of reirradiation was 45.0 Gy (range, 15.0–75.0 Gy).

Results

With a median follow-up of 10.9 months, the median infield-failure-free survival (IFFS) rate was 9.2 months. Gross tumor volume (GTV) significantly related to IFFS in both the univariate (p = 0.009) and multivariate analyses (p = 0.024), and patients with a GTV of <60.0 mL had an improved IFFS (p = 0.001). Four patients experienced ≥grade 3 late toxicities. In the retrospective dose reconstruction analysis in these patients, the cumulative dose to the most exposed 2 cc (D2cc) of the duodenum was >60.0 Gy (range, 60.1–73.7 Gy). In the univariate analysis, the D2cc of the duodenum and a preexisting duodenal ulcer identified using endoscopy prior to reirradiation significantly correlated with late severe toxicity (p = 0.021 and 0.017, respectively).

Conclusions

Reirradiation for upper abdominal malignancies could be safely performed for patients without preexisting gastrointestinal morbidity unless the duodenum received excessive radiation doses. Reirradiation could also provide substantial IFFS, especially for patients with a GTV of <60.0 mL.

http://bit.ly/2sVjF93

Einfluss des operativen Zugangswegs auf die Prognose von Frauen mit frühem Zervixkarzinom

http://bit.ly/2MBj0CR

Risk of cardiotoxicity induced by adjuvant anthracycline-based chemotherapy and radiotherapy in young and old Asian women with breast cancer

Abstract

Purpose

The risk of cardiotoxicity induced by adjuvant anthracycline-based chemotherapy (CT) and radiotherapy (RT) is yet to be investigated in a large-scale randomized controlled trial with an adequate sample size of young and old women with breast cancer.

Patients and methods

To compare the occurrence of major heart events (heart failure and coronary artery disease) in patients with breast cancer, 3489 women who underwent surgical resection of the breast tumor were retrospectively selected from the Taiwan National Health Insurance Research Database. The patients were categorized into the following groups based on their treatment modalities: group 1 (n = 1113), no treatment; group 2 (n = 646), adjuvant RT alone; group 3 (n = 705), adjuvant anthracycline-based CT alone; and group 4 (n = 1025), combined adjuvant RT and anthracycline-based CT.

Results

The mean patient age was 50.35 years. Subsequent coronary artery disease and heart failure were identified in 244 (7.0%) and 206 (5.9%) patients, respectively. All three adjuvant therapies were significant independent prognostic factors of major heart events (adjusted hazard ratio [95% confidence interval]: 1.47 [1.24–1.73]; 1.48 [1.25–1.75], and 1.92 [1.65–2.23] in groups 2, 3, and 4, respectively). In patients aged ≥50 years with breast cancer who underwent surgery, the log-rank p values of groups 2 and 3 after adjustment were 0.537 and 0.001, respectively.

Conclusion

Adjuvant RT can increase cardiotoxicity in patients with breast cancer, particularly when used in combination with anthracycline-based CT. Therefore, it should be offered with optimal heart-sparing techniques, particularly in younger patients with good prognosis and long life expectancy.

http://bit.ly/2sRa0As

Heparin treatment mitigates radiation-induced oral mucositis in mice by interplaying with repopulation processes

Abstract

Purpose

To investigate the mechanistic background of the muco-protective effect of systemic heparin treatment on the development of radiation-induced oral mucositis in mice.

Materials and methods

Fractionated irradiation was given to the snouts of male C3H/Neu mice over 2 weeks (10 × 3 Gy), either alone or in combination with daily subcutaneous application of unfractionated or low molecular weight heparin (40 or 200 I.U./mouse, respectively). Over this course of 14 days, groups of mice (n = 3) were sacrificed every second day, their tongues excised and processed for histological analysis. The epithelial radiation response with and without heparin treatment was evaluated in terms of tissue morphology, proliferation and expression of cell contact molecules.

Results

Systemic treatment with heparins significantly reduced the cellular effects of irradiation to the oral epithelium. Heparin treated animals showed significantly higher total epithelial cell numbers and thickness throughout the study course. Bromodeoxyuridine (BrdU) incorporation analyses revealed that markedly more epithelial cells retained their proliferative capacity in the beginning of the first treatment week, but the proliferation of the mucosa was not stimulated during the rest of the study course. The expression of the adherens junction protein β‑catenin was slightly elevated in heparin treated animals, on day 2 the increase was statistically significant. The expression of e‑cadherin and occludin was mostly unaffected by the concomitant heparin treatment.

Conclusion

The findings of this study indicate an interplay of additional heparin treatment with the repopulation processes, leading to an earlier onset of this adaptive radiation response in oral mucosa. Importantly, we could demonstrate that the protective potential of heparin did not rely on stimulation of normal tissue proliferation. Since both heparin preparations are already approved for clinical use, they are considered as promising candidates for future clinical studies.

http://bit.ly/2MAlQIr

Reduzierte strahleninduzierte Hirnnekrose bei Patienten mit Nasopharynxkarzinom durch Bevacizumab-Monotherapie

http://bit.ly/2sR9XVi

Stereotactic body radiotherapy of central lung malignancies using a simultaneous integrated protection approach

Abstract

Aim

It is recognized that stereotactic body radiotherapy (SBRT) for centrally located lung metastases is affected by higher rates of severe toxicity. In the present study, we report the clinical outcomes following a novel intensity-modulated radiotherapy prescription dose, termed simultaneous integrated protection (SIP), for nearby organs at risk (OARs).

Materials and methods

The prescribed total doses of SBRT were 70 Gy in 10 fractions and 60 Gy in 8 fractions. For ultra-centrally located lesions, a dose of 60 Gy in 10 fractions was delivered. The main planning instructions were: (1) to remain within the limits of the given dose constraints for an OAR; (2) to make use of the maximum possible dose to the OARs to minimize dose inhomogeneity for the Planning Target Volume (PTV). SBRT-related toxicity was prospectively assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The primary clinical endpoint was the SBRT-related toxicity. Secondary endpoint was local control.

Results

Forty patients affected by a single central malignancy were analyzed. The median follow-up was 20 months (range, 6–58 months). Acute and late clinical pulmonary toxicity ≥grade 2 was recorded in 2 out of 40 patients (5%) and 3 out of 40 patients (7%), respectively. No patient experienced cardiac toxicity. No narrowing or stenosis of any airway or vessel was registered. One-year local control rate was 91%. The median time to local progression was 13 months (range, 6–46 months).

Conclusion

SBRT using a PTV-SIP approach for single central lung metastases achieved low SBRT-related toxicity with acceptable local control.

http://bit.ly/2MC7s2e

A possible role of biogenic silica in esophageal cancer in North China?

Abstract

Certain areas in North China have the highest incidence of esophageal squamous cell carcinoma (ESCC) in the world, which has not seen convincing explanation by any risk factor yet. Biogenic silica in millet bran was linked to ESCC in the early 1980s but the hypothesis was largely dismissed because of the lack of geographic correlation between millet consumption and ESCC. Later epidemiological studies disclosed the linkage of wheat consumption in North China to ESCC instead. Now, we hypothesize silica phytoliths (silicified bodies that have definite shapes) from wheat chaff are a major etiologic factor of ESCC in this region. This hypothesis is supported by the potentially high abundance of silica phytoliths on the bracts of wheat (Triticum aestivum) in North China due to favorable Si-accumulation genotype, arid climate, and siallitic soil with bioavailable Si. These silica phytoliths can contaminate wheat flour and cause repeated local injuries in the esophagus and stimulate proliferation by providing anchorage.

http://bit.ly/2Rpc6S2

Methodological issues in meta-analysis of the metformin effects on simple obesity

http://bit.ly/2RQWwna

Methodological issues in meta-analysis of the metformin effects on simple obesity

http://bit.ly/2RQWwna

An efficient method to determine the Hydrophile‐lipophile Balance of surfactants using the phase inversion temperature deviation of CiEj/n‐octane/water emulsions

Abstract

Objective

The aim of this study was to develop a fast and an efficient method to determine the Hydrophile‐Lipophile Balance (HLB) number of cosmetic and pharmaceutics surfactants.

Methods

This method is based on the deviation of the phase inversion temperature induced by the addition of the test compound, with respect to the phase inversion temperature of a reference system, which includes an ethoxylated surfactant. This method is called PIT‐deviation.

Results

Three calibration curves are set up with three reference ethoxylated surfactants. These calibration curves make it possible to evaluate the interfacial behavior of certain chemicals. More particularly, these curves make it possible to easily determine the surfactant HLB.

Conclusion

In this study, a fast and accurate method has been developed to determine the hydrophilic‐lipophilic balance (HLB) number of amphiphilic chemicals. This new method can be applied to establish an HLB number of all commercial amphiphilic ingredients. Compounds which have a PIT‐deviation close to zero are also discussed.

http://bit.ly/2FRAvOR

Presence of bacteroidales as a predicator of human enteric viruses in Haihe River of Tianjin City, China

Abstract

Traditional microbe indicators including total bacteria, total coliforms, fecal coliforms, Escherichia coli, enterococci, and F+ coliphage are all frequently used to characterize the microbial contamination state of water bodies for their correlation with pathogenic bacteria. However, these indicators have a poor relationship with viruses, which pose serious threat to economic and human health. Alternative indicators such as bacteroidales may be suitable complementary alternatives to traditional microbe indicators and are being increasingly reported. In the present study, water was analyzed for selected sites along Haihe River in Tianjin for traditional indicators, an alternative indicator (bacteroidales), pathogenic bacteria (Salmonella, Escherichia coli (E. coli) O157:H7, and Vibrio parahaemolyticus), viruses (enteric adenovirus, norovirus, enterovirus, poliovirus and rotavirus), and physicochemical parameters. Results indicated that traditional microbe indicators detected in this study showed good correlation with pathogenic bacteria, and the alternative indicator (bacteroidales) had a surprisingly good relationship with viral presence. We propose that bacteroidales might be a suitable complementary indicator for viral contamination in water bodies.

http://bit.ly/2WmUOZn

Outcome and molecular characteristics of non-invasive encapsulated follicular variant of papillary thyroid carcinoma with oncocytic features

Abstract

Purpose

In 2016, non-invasive encapsulated follicular variant of papillary thyroid carcinoma (NI-EFVPTC) was renamed as noninvasive thyroid follicular neoplasm with papillary-like nuclear features (NIFTP). However, as the study cohort did not mention tumors with oncocytic features, such lesions are still labeled by some as FVPTC. It is therefore crucial to evaluate the outcome and molecular profile of oncocytic NI-EFVPTC.

Methods

A multi-institutional clinico-pathologic review was conducted to select 61 patients having oncocytic NI-EFVPTC. A detailed molecular profile was carried out in 15 patients.

Results

Oncocytic NI-EFVPTCs predominantly affected women in their 50s. There was no distant metastasis, lymph node metastases, or structural recurrence in the entire cohort. Among patients with ≥5 years of FU, all 33 individuals did not recur with a median FU of 10.2 years. Oncocytic NI-EFVPTC commonly had RAS (33%) mutations, a high frequency of mitochondrial DNA mutations (67%) and multiple chromosomal gains/losses (53%). No fusion genes were detected.

Conclusions

Oncocytic NI-EFVPTC, when stringently selected for, lacks metastasis at presentation and follows an extremely indolent clinical course, even when treated conservatively with lobectomy alone without RAI therapy. These tumors share a similar mutational profile as NIFTP, FVPTC, and follicular neoplasm and are predominantly RAS-related. Like Hurthle cell neoplasms, they harbor a high frequency of mitochondrial DNA mutations, which contribute to the oncocytic cytomorphology. However, they lack the widespread chromosomal alterations observed in Hurthle cell carcinoma. Consideration should be given to include oncocytic NI-EFVPTCs as NIFTP in order to avoid overtreatment of these highly indolent tumors.

http://bit.ly/2B6RLLY

Outcome and molecular characteristics of non-invasive encapsulated follicular variant of papillary thyroid carcinoma with oncocytic features

Abstract

Purpose

Methods

A multi-institutional clinico-pathologic review was conducted to select 61 patients having oncocytic NI-EFVPTC. A detailed molecular profile was carried out in 15 patients.

Results

Conclusions

http://bit.ly/2B6RLLY

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Τρίτη 29 Ιανουαρίου 2019

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