Imaging in Primary Sjogren's Syndrome

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by dysfunction and lymphocytic infiltration of the salivary and lacrimal glands. Besides the characteristic sicca complaints, pSS patients can present a spectrum of signs and symptoms, which challenges the diagnostic process. Various imaging techniques can be used to assist in the diagnostic work-up and follow-up of pSS patients. Developments in imaging techniques provide new opportunities and perspectives. In this descriptive review, we discuss imaging techniques that are used in pSS with a focus on the salivary glands. The emphasis is on the contribution of these techniques to the diagnosis of pSS, their potential in assessing disease activity and disease progression in pSS, and their contribution to diagnosing and staging of pSS-associated lymphomas. Imaging findings of the salivary glands will be linked to histopathological changes in the salivary glands of pSS patients

Folate Receptor-Beta Has Limited Value for Fluorescent Imaging in Ovarian, Breast and Colorectal Cancer

Aims Tumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-alpha) has already been identified as a suitable target for cancer therapy and imaging. FR-alpha is present on similar to 40% of human cancers. FR-beta is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-beta expression in solid tumors. Additional or simultaneous expression of FR-beta could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-beta is evaluated in ovarian, breast and colorectal cancer. Methods FR-beta expression was analyzed by semi-quantitative scoring of immunohistochemical staining on tissue microarrays (TMAs) of 339 ovarian cancer patients, 418 breast cancer patients, on 20 slides of colorectal cancer samples and on 25 samples of diverticulitis. Results FR-beta expression was seen in 21% of ovarian cancer samples, 9% of breast cancer samples, and 55% of colorectal cancer samples. Expression was weak or moderate. Of the diverticulitis samples, 80% were positive for FR-beta expression in macrophages. FR-beta status neither correlated to known disease-related variables, nor showed association with overall survival and progression free survival in ovarian and breast cancer. In breast cancer, negative axillary status was significantly correlated to FR-beta expression (p=0.022). Conclusions FR-beta expression was low or absent in the majority of ovarian, breast and colorectal tumor samples. From the present study we conclude that the low FR-beta expression in ovarian and breast tumor tissue indicates limited practical use of this receptor in diagnostic imaging and therapeutic purposes. Due to weak expression, FR-beta is not regarded as a suitable target in colorectal cancer

Histopathology, salivary flow and ultrasonography of the parotid gland:three complementary measurements in primary Sjögren's syndrome

OBJECTIVE: The involvement of salivary glands in primary Sjögren's syndrome (pSS) can be assessed in different ways: histopathology, salivary flow and ultrasonography. To understand the relative value of these different approaches, it is crucial to understand the relationship between them. As we routinely perform these three modalities in the parotid gland for disease evaluation, our aim was to investigate the construct validity between these modalities in one and the same gland. METHODS: Consecutive sicca patients underwent a multidisciplinary diagnostic work-up including parotid gland biopsy, collection of parotid gland-specific saliva and parotid gland ultrasonography. Patients who were classified as pSS according to the ACR-EULAR criteria were included. Construct validity was assessed using Spearman's correlation coefficients. RESULTS: The 41 included pSS patients completed a full work-up within mean time interval of 2.6 months. Correlations between histopathological features and stimulated parotid salivary flow were fair (ρ=-0.123 for focus score, and ρ=-0.259 for percentage of CD45+ infiltrate). Likewise, poor correlations were observed between stimulated parotid salivary flow and parotid ultrasonography (ρ=-0.196). Moderate to good associations were found between the histopathological items focus score and percentage of CD45+ infiltrate, with parotid ultrasound scores (total ultrasound score: ρ = 0.510 and ρ = 0.560; highest for homogeneity: ρ = 0.574 and ρ = 0.633). CONCLUSION: Although pSS associated ultrasonographic findings did correlate with histopathological features, the three modalities that evaluate salivary gland involvement assess different (or at best partly related) constructs. Therefore, histopathology, salivary flow and ultrasonography are complementary measurements and cannot directly replace each other in the work-up of pSS

Abatacept treatment for patients with early active primary Sjogren's syndrome:a single-centre, randomised, double-blind, placebo-controlled, phase 3 trial (ASAP-III study)

Background: Several small open-label studies have suggested efficacy of abatacept—a co-stimulation inhibitor—in patients with primary Sjögren's syndrome. These promising results warranted further evaluation. We therefore aimed to further assess the safety and efficacy of abatacept compared with placebo in patients with primary Sjögren's syndrome. Methods: We did a single-centre, randomised, double-blind, placebo-controlled, phase 3 trial at the University Medical Center Groningen (Groningen, Netherlands). We included patients with primary Sjögren's syndrome fulfilling the American–European Consensus Group criteria, aged 18 years or older, with positive salivary gland biopsies, time from diagnosis of 7 years or less, and a European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) score of 5 or more. Independent pharmacists randomly allocated patients (1:1) to either the abatacept group or placebo group using a computer-generated sequence stratified by previous use of disease-modifying anti-rheumatic drugs. Patients received at-home subcutaneous injections of abatacept (125 mg) or placebo once a week for 24 weeks. The primary outcome was the between-group difference in ESSDAI score at week 24. Efficacy was analysed in patients who received at least one drug dose and for whom post-baseline data were collected. Safety was analysed in all patients who received at least one drug dose. Findings: Between Aug 14, 2014, and Aug 23, 2018, 580 patients were reviewed for eligibility, of which 80 patients were randomly assigned to receive study treatment. Efficacy was analysed in 40 patients receiving abatacept and 39 patients receiving placebo (one patient in this group was lost to follow-up). The primary outcome did not significantly differ between the treatment groups. The adjusted mean difference in ESSDAI score at week 24 between the abatacept group and placebo group was −1·3 (95% CI −4·1 to 1·6). No deaths or treatment-related serious adverse events occurred. In 38 (95%) of 40 patients in the abatacept group, 103 adverse events occurred, including one serious adverse event and 46 infections. In 38 (95%) of 40 patients in the placebo group, 87 adverse events occurred, including four serious adverse events and 49 infections. Interpretation: On the basis of this trial, we cannot recommend abatacept treatment as standard of care to reduce systemic disease activity in patients with primary Sjögren's syndrome. Further studies should evaluate whether patients with specific clinical manifestations and biological characteristics might benefit from abatacept treatment. Funding: Bristol-Myers Squibb

Early childhood adversities and trajectories of psychiatric problems in adoptees: Evidence for long lasting effects

The aim of the present study is to investigate whether early childhood adversities determine the longitudinal course of psychiatric problems from childhood to adulthood; in particular if the impact of early maltreatment on psychopathology decreases as time passes. A sample of 1,984 international adoptees was followed (955 males and 1029 females; adopted at the mean age of 29 months). Parents provided information about abuse, neglect and numbe

Vuurwerkletsel in Zuidwest-Nederland rond de jaarwisseling 2017-2018

OBJECTIVE: To report the number of patients with firework-related injuries treated in December 2017 and January 2018 in a hospital in the south-west Netherlands trauma region, and to provide details about the types of firework used and the specific injuries. DESIGN: A prospective multicentre cohort study (NTR6793). METHODS: Patients of all ages with firework-related injuries were eligible for inclusion. The injury had to have been sustained between 1 December 2017 and 31 January 2018, and treated at a hospital in the south-west Netherlands trauma region (approximately 2.5 million inhabitants). Data were extracted from patients' medical files and additional information was obtained from patient interviews. RESULTS: Fifty-four patients were included. The majority were male (93%) and the median age was 15 years. Twenty-five (46%) patients were bystanders and 12 (22%) were injured by illegal fireworks. Fifty patients were injured by bangers (n=22) or decorative fireworks (n=28). The patients had a total of 79 injuries, of which 29 (37%) were localised to the upper extremity and 19 (24%) to the eyes. Most upper extremity injuries were burns (69%), primarily partial thickness. Of the eye injuries, 14 were caused by blunt trauma, seven by chemical trauma, and one by penetrating trauma. Three patients sustained indirect firework-related injuries. CONCLUSION: Between 1 December 2017 and 31 January 2018 in the south-west Netherlands trauma region mainly teenage males and bystanders sustained firework-related injuries. Most injuries were upper extremity burns and eye injuries, mainly due to legal fireworks and bangers or decorative fireworks. The extent of the sample indicatDoel Een volledig overzicht geven van het aantal vuurwerkslachtoffers dat in december 2017 en januari 2018 behandeld werd in een ziekenhuis in de traumaregio Zuidwest-Nederland, het gebruikte soort vuurwerk en de specifieke letsels. Opzet Een prospectieve, multicentrische cohortstudie (NTR6793). Methode Patiënten van alle leeftijden met vuurwerkletsel kwamen in aanmerking voor inclusie. Het letsel moest zijn ontstaan in de periode 1 december 2017-31 januari 2018 en zijn behandeld in een ziekenhuis in de traumaregio Zuidwest-Nederland (circa 2,5 miljoen inwoners). Gegevens werden verzameld vanuit het patiëntendossier en aanvullende gegevens werden verkregen tijdens een interview. Resultaten Er werden 54 patiënten geïncludeerd. Het overgrote deel betrof mannen (93%) en de mediane leeftijd was 15 jaar. 25 gewonden (46%) waren omstander en 12 mensen (22%) raakten gewond door illegaal vuurwerk. Van de 54 patiënten raakten er 50 gewond door knalvuurwerk (n = 22) of siervuurwerk (n = 28). De 54 geïncludeerde patiënten hadden 79 letsels; het letsel was 29 keer (37%) gelokaliseerd aan armen of handen en 19 keer (24%) aan de ogen. Letsel aan de arm of hand bestond voornamelijk uit brandwonden (69%), met name tweedegraads. Oogletsel werd 14 keer door stomp inwerkend geweld veroorzaakt, 7 keer door chemisch letsel en 1 keer werd het oog gepenetreerd. Er raakten 3 patiënten indirect gewond door vuurwerk. Conclusie In de traumaregio Zuidwest-Nederland raakten in de 2 maanden rond de jaarwisseling 2017-2018 vooral minderjarige mannen en omstanders gewond. Slachtoffers liepen met name brandwonden aan armen of handen of oogletsel op. De verwondingen waren met name het gevolg van legaal knal- en siervuurwerk. Door de omvang van de steekproef lijken de studiebevindingen goed te extrapoleren naar het gehele land

Tumor-specific uptake of fluorescent bevacizumab-IRDye800CW microdosing in patients with primary breast cancer:a phase I feasibility study

PURPOSE: to provide proof of principle of safety, breast tumor-specific uptake and positive tumor margin assessment of the systemically administered near-infrared fluorescent (NIRF) tracer bevacizumab-IRDye800CW targeting vascular endothelial growth factor (VEGF)-A in breast cancer patients. EXPERIMENTAL DESIGN: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab-IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and co-registration of tumor tissue and healthy tissue. RESULTS: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared to those in the tumor margin (P < 0.05) and healthy tissue (P < 0.0001). VEGF-A tumor levels also correlated with tracer levels (r = 0.63, P < 0.0002). All but one tumor showed specific tracer uptake. Two out of 20 surgically excised lumps contained microscopic positive margins detected ex vivo by fluorescent macro- and microscopy and confirmed at the cellular level. CONCLUSIONS: Our study shows that systemic administration of the bevacizumab-IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor-margin uptake as evaluated by a systematic validation methodology. The findings are a step towards a phase II dose-finding study aimed at in vivo margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in tumor tissue

A randomized controlled trial to examine the effects of the Tackling Teenage psychosexual training program for adolescents with autism spectrum disorder

Background: Previous research underscores the importance of psychosexual guidance for adolescents with autism spectrum disorder (ASD). Such guidance is provided in the Tackling Teenage Training (TTT) program, in which adolescents with ASD receive psycho-education and practice communicative skills regarding topics related to puberty, sexuality, and intimate relationships. This randomized controlled trial investigated the effects of the TTT program on (a) cognitive outcomes (i.e. psychosexual knowledge, and insight in interpersonal boundaries) and (b) behavioral outcomes (i.e. skills needed for romantic relationships and problematic sexual behavior). Methods: A total of 189 cognitively able adolescents with ASD, aged 12–18 years old, were randomized to an intervention condition (n = 95) or a waiting-list control condition (n = 94). We assessed outcomes using self-reported as well as parent-reported questionnaires at baseline (T1), posttreatment (T2; after 6 months), and follow-up (T3; after 12 months). Results: Linear mixed model analyses showed significant treatment effects for psychosexual knowledge and adequate insight in boundaries, both posttreatment and at follow-up. All adolescents increased significantly over time in their social responsiveness and decreased their problematic sexual behavior, irrespectively of condition. The TTT program was most effective for younger adolescents with ASD; following the TTT program resulted in higher psychosexual knowledge, and higher social functioning for these adolescents. Conclusions: The results of this study indicate that the TTT program is effective as a psycho-educational program to provide adolescents with ASD with the knowledge and insight they need to prepare themselves for a healthy psychosexual development. Further research is needed to investigate how this increased knowledge and insight can subsequently ameliorate improvements in romantic skills and prevent the development of problematic sexual behavior and victimization