You are looking at 21 - 30 of 596 items for

Open access

Helle Døssing, Finn Noe Bennedbæk and Laszlo Hegedüs

Objective: Laser therapy (LT) is considered a safe and effective procedure for inducing thyroid nodule necrosis, fibrosis and shrinkage. Little is known about long-term efficacy of LT in benign complex thyroid nodules, which we report here.

Design and methods: One hundred and ten euthyroid outpatients [28 men and 82 women; median age 48 years (range 17-82)] with a recurrent cytologically benign cystic (≥ 2 ml cyst-volume) thyroid nodule causing local discomfort were assigned to LT. LT was performed after complete cyst aspiration and under continuous ultrasound (US)–guidance. Nineteen patients (17 within 6 months) had surgery after LT. The median follow-up for the remaining 91 patients was 45 months (range; 12-134).

Results: The overall median nodule volume in the 110 patients decreased from 9.0 ml (range; 2.0–158.0) to 1.2 ml (range; 0.0-85.0) (p<0.001) at the final evaluation, corresponding to a median reduction of 85% (range; -49% to 100%). Remission of the cystic part (volume ≤ 1 ml) was obtained in 82 of 110 (75%) patients after LT. The median cyst volume decreased from 6.3 ml (range; 2.0-158.0) to 0.0 ml (range; 0.0-85.0) (p<000.1), corresponding to a median reduction of 100% (range; -49%-100%). These results correlated with a significant decrease in pressure as well as cosmetic complaints. Side effects were restricted to mild local pain.

Conclusion: US-guided aspiration and subsequent LT of benign recurrent cystic thyroid nodules results in a satisfactory long-term clinical response in the majority of patients. LT constitutes a clinically relevant alternative to surgery in such patients.

Open access

Kris Giulia Samsom, Linde M van Veenendaal, Gerlof D. Valk, Menno R. Vriens, Margot Tesselaar and Jose G van den Berg

Background: Small intestinal neuroendocrine tumours (SI-NETs) represent a heterogeneous group of rare tumours. In recent years, basic research in SI-NETs has attempted to unravel the molecular events underlying SI- NET tumorigenesis.

Aim: We aim to provide an overview of the current literature regarding prognostic and predictive molecular factors in patients with SI-NETs.

Method: A PubMed search was conducted on (epi)genetic prognostic factors in SI-NETs from 2000 until 2019.

Results: The search yielded 1522 articles of which 18 reviews and 35 original studies were selected for further evaluation. SI-NETs are mutationally quiet tumours with a different genetic make-up compared to pancreatic NETs. Loss of heterozygosity at chromosome 18 is the most frequent genomic aberration (44-100%) followed by mutations of CDKN1B in 8%. Prognostic analyses were performed in 16 studies, of which 8 found a significant (epi)genetic association for survival or progression. Loss of heterozygosity at chromosome 18, gains of chromosome 4,5, 7, 14 and 20p, copy gain of the SRC gene and low expression of RASSF1A and P16 were associated with poorer survival. In comparison with genetic mutations, epigenetic alterations are significantly more common in SI-NETs and may represent more promising targets in the treatment of SI-NETs.

Conclusion: SI-NETs are mutationally silent tumours. No biomarkers have been identified yet that can easily be adopted into current clinical decision making. SI-NETs may represent a heterogeneous disease and larger international studies are warranted to translate molecular findings into precision oncology.

Open access

Gaëtan Prévost, Marie Picot, Marie-Anne Le Solliec, Arnaud Arabo, Hind Berrahmoune, Mouna El Mehdi, Saloua Cherifi, Alexandre Benani, Emmanuelle Nédélec, Françoise Gobet, Valéry Brunel, Jérôme Leprince, Hervé Lefebvre, Youssef Anouar and Nicolas Chartrel

Objective: Recent studies performed in mice revealed that the neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin, and by increasing insulin sensitivity. However, in human, an association between 26RFa and the regulation of glucose homeostasis is poorly documented. In this study, we have thus investigated in detail the distribution of 26RFa and its receptor, GPR103, in the gut and the pancreas, and determined the response of this peptidergic system to an oral glucose challenge in obese patients.

Design and Methods: Distribution of 26RFa and GPR103 was examined by immunohistochemistry using gut and pancreas tissue sections. Circulating 26RFa was determined using a specific radioimmunoassay in plasma samples collected during an oral glucose tolerance test.

Results: 26RFa and GPR103 are present all along the gut but are more abundant in the stomach and duodenum. In the stomach, the peptide and its receptor are highly expressed in the gastric glands, whereas in the duodenum, ileum and colon they are present in the enterocytes and the goblet cells. In the pancreatic islets, the 26RFa/GPR103 system is mostly present in the β cells. During an oral glucose tolerance test, plasma 26RFa profile is different between obese patients and healthy volunteers, and we found strong positive correlations between 26RFa blood levels and the BMI, and with various parameters of insulin secretion and insulin resistance.

Conclusion: the present data suggest an involvement of the 26RFa/GPR103 peptidergic system in the control of human glucose homeostasis.

Open access

Michaela Keuper

The crosstalk between macrophages (MΦ) and adipocytes within white adipose tissue (WAT) influences obesity-associated insulin resistance and other associated metabolic disorders, such as atherosclerosis, hypertension and type 2 diabetes. MΦ infiltration is increased in WAT during obesity, which is linked to decreased mitochondrial content and activity. The mechanistic interplay between MΦ and mitochondrial function of adipocytes is under intense investigation, as MΦ and inflammatory pathways exhibit a pivotal role in the reprogramming of WAT metabolism in physiological responses during cold, fasting and exercise. Thus, the underlying immunometabolic pathways may offer therapeutic targets to correct obesity and metabolic disease. Here, I review the current knowledge on the quantity and the quality of human adipose tissue macrophages (ATMΦ) and their impact on the bioenergetics of human adipocytes. The effects of ATMΦ and their secreted factors on mitochondrial function of white adipocytes are discussed, including recent research on MΦ as part of an immune signaling cascade involved in the ‘browning’ of WAT, which is defined as the conversion from white, energy-storing adipocytes into brown, energy-dissipating adipocytes.

Open access

Eva Jakobsson Ung, Ann-Charlotte Olofsson, Ida Björkman, Tobias Hallén, Daniel S Olsson, Oskar Ragnarsson, Thomas Skoglund, Sofie Jakobsson and Gudmundur Johannsson

Objective: Experiences and need of support during surgery and start of replacement therapy in patients with pituitary tumours are highly unknown. This study therefore aimed at exploring patient experiences during pre- and postoperative care and recovery after pituitary surgery in patients with a pituitary tumour.

Methods: Within a qualitative study design, 16 consecutive patients who underwent surgery for pituitary tumours were repeatedly interviewed. In total 42 interviews were performed before and after surgery. Analysis was performed using qualitative interpretation.

Results: Suffering a pituitary tumour was overwhelming for many patients and struggling with existential issues was common. Patients expressed loneliness and vulnerability before and after surgery. How professionals handled information in connection with diagnosis greatly affected the patients. Other patients with the same diagnosis were experienced as the greatest support. Normalisation of bodily symptoms and relationships with others were reported during postoperative recovery. However, a fear that the tumour would return was present.

Conclusions: Patients with pituitary tumours need structured support, including peer support, which acknowledges physical, cognitive as well as emotional and existential concerns. Information related to diagnosis and surgery should be adapted in relation to the loneliness and the existential seriousness of the situation. Care and support for patients with pituitary tumours should preferably be organised based on continuity and an unbroken care pathway from the first pre-operative evaluation through to post-operative care and the start of a life-long endocrine treatment and tumour surveillance.

Open access

Monika Bilic, Huma Qamar, Akpevwe Onoyovwi, Jill Korsiak, Eszter Papp, Abdullah Al Mahmud, Rosanna Weksberg, Alison D Gernand, Jennifer Harrington and Daniel E Roth

Fetal growth restriction is linked to adverse health outcomes and is prevalent in low- and middle-income countries; however, determinants of fetal growth are still poorly understood. The objectives were to determine the effect of prenatal vitamin D supplementation on the insulin-like growth factor (IGF) axis at birth, to compare the concentrations of IGF-I in newborns in Bangladesh to a European reference population and to estimate the associations between IGF protein concentrations and birth size. In a randomized controlled trial in Dhaka, Bangladesh, pregnant women enrolled at 17–24 weeks of gestation were assigned to weekly oral vitamin D3 supplementation from enrolment to delivery at doses of 4200 IU/week, 16,800 IU/week, 28,000 IU/week or placebo. In this sub-study, 559 woman–infant pairs were included for analysis and cord blood IGF protein concentrations were quantified at birth. There were no significant effects of vitamin D supplementation on cord blood concentrations of IGF-I (P = 0.398), IGF-II (P = 0.525), binding proteins (BPs) IGFBP-1 (P = 0.170), IGFBP-3 (P = 0.203) or the molar ratio of IGF-I/IGFBP-3 (P = 0.941). In comparison to a European reference population, 6% of girls and 23% of boys had IGF-I concentrations below the 2.5th percentile of the reference population. IGF-I, IGF-II, IGFBP-3 and the IGF-I/IGFBP-3 ratio were positively associated with at least one anthropometric parameter, whereas IGFBP-1 was negatively associated with birth anthropometry. In conclusion, prenatal vitamin D supplementation does not alter or enhance fetal IGF pathways.

Open access

Rasha Odeh, Abeer Alassaf, Lubna Gharaibeh, Sarah Ibrahim, Fareed Khdair Ahmad and Kamel Ajlouni


Scientific findings regarding the prevalence of celiac disease (CD) in pediatric patients with type 1 diabetes (T1D) in the Arab world are scarce. We aimed to determine the prevalence of biopsy-proven celiac disease (BPCD) among pediatric patients with T1D from Jordan. We also assessed the possible predictors for developing CD in this cohort of patients and we compared T1D patients who developed BPCD with those who had positive CD serology but negative histology and/or fluctuating CD serology.


Celiac serology and duodenal biopsy results from 2012 to 2017 were collected from patients with T1D. The outcome of positive celiac serology and the risk factors for CD in T1D patients were investigated.


A total of 538 children of which 278 boys (51.7%) were included in the study. The prevalence of positive serology and the diagnosis of BPCD in this cohort of T1D patients were 16.6 and 9.1% respectively. Eighty percent of those with BPCD were asymptomatic and 47% were diagnosed with CD at onset of T1D. Spontaneous normalization of celiac serology occurred in 23.6% of those with positive serology.


CD is prevalent in T1D pediatric patients from Jordan (9.1%). It is often asymptomatic and the majority of cases were diagnosed at onset or within 5 years of T1D diagnosis. Spontaneous normalization of CD serology occurred in some patients with T1D. Hence, a watchful follow-up is recommended in such patients.

Open access

Marloes Emous, Merel van den Broek, Ragnhild Wijma, Ljm de Heide, Anke Laskewitz, Gertjan van Dijk, Erik Totté, Bruce H R Wolffenbuttel and André P van Beek

Objective: Roux-en-Y gastric bypass (RYGB) is an effective way to induce sustainable weight loss and can be complicated by postprandial hyperinsulinemic hypoglycaemia (PHH). To study the prevalence and the mechanisms behind the occurrence of hypoglycaemia after a mixed meal tolerance test (MMTT) in patients with primary RYGB.

Design: This is a cross-sectional study of patients four years after primary RYGB.

Methods: From a total population of 550 patients, a random sample of 44 patients completed the total test procedures. A standardized mixed meal was used as stimulus. Venous blood samples were collected at baseline, every 10 minutes during the first half hour and every 30 minutes until 210 minutes after the start. Symptoms were assessed by questionnaires. Hypoglycaemia defined as a blood glucose below 3.3 mmol/L.

Results: The prevalence of postprandial hypoglycaemia was 48% and was asymptomatic in all patients. Development of hypoglycaemia was more frequent in patients with lower weight at surgery (p = 0.045), with higher weight loss after surgery (p = 0.011), and with higher insulin sensitivity calculated by Homeostasis Model Assessment indexes (HOMA2-IR p = 0.014) and enhanced beta cell function (insulinogenic index at 20 minutes p = 0.001).

Conclusion: In a randomly selected population four years after primary RYGB surgery 48% of patients developed a hypoglycemic event during a mixed meal tolerance test without symptoms, suggesting the presence of hypoglycaemia unawareness in these patients. The findings in this study suggest that the pathophysiology of PHH is multifactorial.

Open access

Shuang Ye, Yuanyuan Xu, Jiehao Li, Shuhui Zheng, Peng Sun and Tinghuai Wang

The role of G protein-coupled estrogen receptor 1 (GPER) signaling, including promotion of Ezrin phosphorylation (which could be activated by estrogen), has not yet been clearly identified in triple-negative breast cancer (TNBC). This study aimed to evaluate the prognostic value of GPER and Ezrin in TNBC patients. Clinicopathologic features including age, menopausal status, tumor size, nuclear grade, lymph node metastasis, AJCC TNM stage, and ER, PR and HER-2 expression were evaluated from 249 TNBC cases. Immunohistochemical staining of GPER and Ezrin was performed on TNBC pathological sections. Kaplan–Meier analyses, as well as logistic regressive and Cox regression model tests were applied to evaluate the prognostic significance between different subgroups. Compared to the GPER-low group, the GPER-high group exhibited higher TNM staging (P = 0.021), more death (P < 0.001), relapse (P < 0.001) and distant events (P < 0.001). Kaplan–Meier analysis showed that GPER-high patients had a decreased OS (P < 0.001), PFS (P < 0.001), LRFS (P < 0.001) and DDFS (P < 0.001) than GPER-low patients. However, these differences in prognosis were not statistically significant in post-menopausal patients (OS, P = 0.8617; PFS, P = 0.1905; LRFS, P = 0.4378; DDFS, P = 0.2538). There was a significant positive correlation between GPER and Ezrin expression level (R = 0.508, P < 0.001) and the effect of Ezrin on survival prognosis corresponded with GPER. Moreover, a multivariable analysis confirmed that GPER and Ezrin level were both significantly associated with poor DDFS (HR: 0.346, 95% CI 0.182–0.658, P = 0.001; HR: 0.320, 95% CI 0.162–0.631, P = 0.001). Thus, overexpression of GPER and Ezrin may contribute to aggressive behavior and indicate unfavorable prognosis in TNBC; this may correspond to an individual’s estrogen levels.

Open access

Sylvia Thiele, Anke Hannemann, Maria Winzer, Ulrike Baschant, Heike Weidner, Matthias Nauck, Rajesh Thakker, Martin Bornhäuser, Lorenz Hofbauer and Martina Rauner

Glucocorticoids (GC) are used for the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited, amongst others, by adverse effects on bone. The Wnt and bone formation inhibitor sclerostin was recently implicated in the pathogenesis of GC-induced osteoporosis. However, data are ambiguous. The aim of this study was to assess the regulation of sclerostin by GC using several mouse models with high GC levels and two independent cohorts of patients treated with GC. Male 24-week-old C57BL/6 and 18-week-old DBA/1 mice exposed to GC and 12-week-old mice with endogenous hypercortisolism displayed reduced bone formation as indicated by reduced levels of P1NP and increased serum sclerostin levels. The expression of sclerostin in femoral bone tissue and GC-treated bone marrow stromal cells, however, was not consistently altered. In contrast, GC dose- and time-dependently suppressed sclerostin at mRNA and protein level in human mesenchymal stromal cells, and this effect was GC receptor-dependent. In line with the human cell culture data, patients with rheumatoid arthritis (RA, n=101) and polymyalgia rheumatica (PMR, n=21) who were exposed to GC had lower serum levels of sclerostin than healthy age- and sex-matched controls (-40%, p<0.01 and -26.5%, p<0.001, respectively). In summary, sclerostin appears to be differentially regulated by GC in mice and humans as it is suppressed by GCs in humans but is not consistently altered in mice. Further studies are required to delineate the differences between GC regulation of sclerostin in mice and humans and assess whether sclerostin mediates GC-induced osteoporosis in humans.