Primary radiotherapy in progressive optic nerve sheath meningiomas: a long-term follow-up study

Background/aims: To report the outcome of primary radiotherapy in patients with progressive optic nerve sheath meningioma (ONSM). Methods: The clinical records of all patients were reviewed in a retrospective, observational, multicentre study. Results: Thirty-four consecutive patients were included. Twenty-six women and eight men received conventional or stereotactic fractionated radiotherapy, and were followed for a median 58 (range 51–156) months. Fourteen eyes (41%) showed improved visual acuity of at least two lines on the Snellen chart. In 17 (50%) eyes, the vision stabilised, while deterioration was noted in three eyes (9%). The visual outcome was not associated with age at the time of radiotherapy (p=0.83), sex (p=0.43), visual acuity at the time of presentation (p=0.22) or type of radiotherapy (p=0.35). Optic disc swelling was associated with improved visual acuity (p<0.01) and 4/11 patients with optic atrophy also showed improvement. Long-term complications were dry eyes in five patients, cataracts in three, and mild radiation retinopathy in four. Conclusion: Primary radiotherapy for patients with ONSM is associated with long-term improvement of visual acuity and few adverse effects.Peerooz Saeed, Leo Blank, Dinesh Selva, John G. Wolbers, Peter J.C.M. Nowak, Ronald B. Geskus, Ezekiel Weis, Maarten P. Mourits, Jack Rootma

Does serous tubal intraepithelial carcinoma (STIC) metastasize?:The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy

Objective: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. Methods: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. Results: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24–118 months). Conclusion: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.</p

Does serous tubal intraepithelial carcinoma (STIC) metastasize?:The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy

Objective: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. Methods: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. Results: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24–118 months). Conclusion: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.</p

Dutch dairy farmers' perspectives on culling reasons and strategies

Since the abolishment of the milk quota system in Europe in 2014 and the introduction of environmental policies such as the phosphate rights system in the Netherlands, the reasons for culling dairy cows might have changed. The aim of this study was to determine the culling reasons for dairy cattle and to identify farmers' culling strategies and their intentions regarding the alteration of indicated culling strategies. To this end, an online questionnaire was distributed among dairy farmers nationally that resulted in 207 responses. Results showed that the most frequent culling reasons were related to problems with reproduction, udder, and hoof health. Primiparous cows were primarily culled for miscellaneous reasons such as injury, reproduction failure, and low milk yield. Multiparous cows were culled predominantly for reproduction failure, udder health and hoof health reasons. Most respondents indicated that they consider formulating a culling strategy, based on certain rules of thumb regarding the most common reasons for culling. Most farmers also reported that culling decisions on their farms were perceived to be unavoidable, though reproductive culling decisions are primarily voluntary. Most respondents stated that they intended to reduce the culling rate for better economic gain did not intend to alter the amount of replacement stock reared. The applied rules of thumb regarding culling strategies do not seem to have changed since the policy changes in dairy farming. The question remains whether farmers' rules of thumb might have made them unaware of the actual economic consequences of their culling strategies under the altered situation

Exploring patients' experience using PROMs within routine post-discharge follow-up assessment after stroke: a mixed methods approach

BACKGROUND: Patient Reported Outcomes Measures (PROMs) are being used increasingly to measure health problems in stroke clinical practice. However, the implementation of these PROMs in routine stroke care is still in its infancy. To understand the value of PROMs used in ischemic stroke care, we explored the patients' experience with PROMs and with the consultation at routine post-discharge follow-up after stroke. METHODS: In this prospective mixed methods study, patients with ischemic stroke completed an evaluation questionnaire about the use of PROMs and about their consultation in two Dutch hospitals. Additionally, telephone interviews were held to gain in-depth information about their experience with PROMs. RESULTS: In total, 63 patients completed the evaluation questionnaire of which 10 patients were also interviewed. Most patients (82.2-96.6%) found completing the PROMs to be feasible and relevant. Half the patients (49.2-51.6%) considered the PROMs useful for the consultation and most patients (87.3-96.8%) reported the consultation as a positive experience. Completing the PROMs provided 51.6% of the patients with insight into their stroke-related problems. Almost 75% of the patients found the PROMs useful in giving the healthcare provider greater insight, and 60% reported discussing the PROM results during the consultation. Interviewed patients reported the added value of PROMs, particularly when arranging further care, in gaining a broader insight into the problems, and in ensuring all important topics were discussed during the consultation. CONCLUSIONS: Completing PROMs appears to be feasible for patients with stroke attending post-discharge consultation; the vast majority of patients experienced added value for themselves or the healthcare provider. We recommend that healthcare providers discuss the PROM results with their patients to improve the value of PROMs for the patient. This could also improve the willingness to complete PROMs in the future

Natural history of spheno-orbital meningiomas

To investigate the natural history and the growth rate of spheno-orbital meningiomas (SOMs). Ninety patients with a diagnosis of SOM were included, and patient charts and imaging were evaluated. In a subset of 32 patients, volumetric studies were performed. The median follow-up for the entire group was 4 years (range, 1-15); the mean age was 47.8 (range, 26-93) years; 94% of the patients were female. The most common clinical signs and symptoms were proptosis (93%), visual deterioration (65%), retro-bulbar pain (23%) and diplopia (6%). In 35% of patients in this series, no visual deterioration occurred, and in 30% only mild proptosis was present. The median annual growth rate of the SOMs in the subset of 32 patients was 0.3 cm³/year (range, 0.03-1.8 cm³/year). We assessed a trend for more rapid tumour growth in younger patients and found the initial volume of the tumour (rho = 0.63) and of the soft tissue component (rho = 074) to be significantly related to the growth rate. SOMs are slow-growing tumours that cause primarily proptosis and visual deterioration. In a significant number of patients, these tumours cause minimal discomfort and symptomatology. Therefore, in the absence of risk factors, we advocate a "wait and see" policy. For patients with large SOMs or with a large soft tissue component at first visit or with fast growing SOMs (>1cm³/year), a follow-up examination every 6 months is indicate

Thyrotrophin and thyroxine support immune homeostasis in humans

The endocrine and the immune systems interact by sharing receptors for hormones and cytokines, cross-control and feedback mechanisms. To date, no comprehensive study has assessed the impact of thyroid hormones on immune homeostasis. By studying immune phenotype (cell populations, antibody concentrations, circulating cytokines, adipokines and acute-phase proteins, monocyte-platelet interactions and cytokine production capacity) in two large independent cohorts of healthy volunteers of Western European descent from the Human Functional Genomics Project (500FG and 300BCG cohorts), we identified a crucial role of the thyroid hormone thyroxin (T4) and thyroid-stimulating hormone (TSH) on the homeostasis of lymphocyte populations. TSH concentrations were strongly associated with multiple populations of both effector and regulatory T cells, whereas B-cell populations were significantly associated with free T4 (fT4). In contrast, fT4 and TSH had little impact on myeloid cell populations and cytokine production capacity. Mendelian randomization further supported the role of fT4 for lymphocyte homeostasis. Subsequently, using a genomics approach, we identified genetic variants that influence both fT4 and TSH concentrations and immune responses, and gene set enrichment pathway analysis showed enrichment of fT4-affected gene expression in B-cell function pathways, including the CD40 pathway, further supporting the importance of fT4 in the regulation of B-cell function. In conclusion, we show that thyroid function controls the homeostasis of the lymphoid cell compartment. These findings improve our understanding of the immune responses and open the door for exploring and understanding the role of thyroid hormones in the lymphocyte function during disease