Comparison of Diet, Metformin and Insulin in the Treatment of Gestational Diabetes Mellitus

Objective: The aim of the study was to compare maternal and neonatal outcomes in patients with gestational diabetes mellitus (GDM) treated with metformin versus those with insulin, or diet alone. Material and methods: The study included 24 GDM women treated with metformin, 21 treated with insulin, and 17 women only on diet. All patients were from Outpatient Department of Endocrinology in the period from May, 2008 to October, 2010. Results: The three groups were comparable with respect to age, pre-pregnancy body mass index (BMI), weight gain during pregnancy, gestational week at enrolment, smoking cigarettes and positive family history for diabetes. Mean glycosylated haemoglobin (HbA1c) at 37 gestation week was lower in diet and metformin groups than insulin group (4,5±0,9, 5,3±0,7, and 6,1± 1,3 %, respectively, p< 0,01). Postprandial glycaemia (PPG) statistically significant differed in diet from metformin group (6,2±2,1 v.s. 7,5±1,1 mmol/L, p< 0,05) and in diet as to insulin group (6,2±2,1 v.s. 8,3±2,3 mmol/L, p< 0,01). There were statistically significant difference in mean gestational age at delivery, between the three (diet, metformin and insulin) groups (39,1±2,2; 38,7±1,6 and 37,3±2,4 gestation week, respectively, p< 0,05). The incidence of neonatal hypoglycemia was higher in the insulin group (52,4%) than in the metformin (33,3%) and diet group (17,6%), but there was statistically difference between insulin and diet group (p=0,04). No differences between the groups were observed in mode of delivery, birth weight, and incidence for large or small for gestational age. Conclusion: Metformin is effective, easy and safe in controlling GDM. Author Keywords: Gestational diabetes mellitus, metformin, insulin, glycaemia

Drug sensitivity testing on patient-derived sarcoma cells predicts patient response to treatment and identifies c-Sarc inhibitors as active drugs for translocation sarcomas

BACKGROUND: Heterogeneity and low incidence comprise the biggest challenge in sarcoma diagnosis and treatment. Chemotherapy, although efficient for some sarcoma subtypes, generally results in poor clinical responses and is mostly recommended for advanced disease. Specific genomic aberrations have been identified in some sarcoma subtypes but few of them can be targeted with approved drugs. METHODS: We cultured and characterised patient-derived sarcoma cells and evaluated their sensitivity to 525 anti-cancer agents including both approved and non-approved drugs. In total, 14 sarcomas and 5 healthy mesenchymal primary cell cultures were studied. The sarcoma biopsies and derived cells were characterised by gene panel sequencing, cancer driver gene expression and by detecting specific fusion oncoproteins in situ in sarcomas with translocations. RESULTS: Soft tissue sarcoma cultures were established from patient biopsies with a success rate of 58%. The genomic profile and drug sensitivity testing on these samples helped to identify targeted inhibitors active on sarcomas. The cSrc inhibitor Dasatinib was identified as an active drug in sarcomas carrying chromosomal translocations. The drug sensitivity of the patient sarcoma cells ex vivo correlated with the response to the former treatment of the patient. CONCLUSIONS: Our results show that patient-derived sarcoma cells cultured in vitro are relevant and practical models for genotypic and phenotypic screens aiming to identify efficient drugs to treat sarcoma patients with poor treatment options.Peer reviewe

Regional and experiential differences in surgeon preference for the treatment of cervical facet injuries: a case study survey with the AO Spine Cervical Classification Validation Group

Purpose: The management of cervical facet dislocation injuries remains controversial. The main purpose of this investigation was to identify whether a surgeon’s geographic location or years in practice influences their preferred management of traumatic cervical facet dislocation injuries. Methods: A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. The survey included clinical case scenarios of cervical facet dislocation injuries and asked responders to select preferences among various diagnostic and management options. Results: A total of 189 complete responses were received. Over 50% of responding surgeons in each region elected to initiate management of cervical facet dislocation injuries with an MRI, with 6 case exceptions. Overall, there was considerable agreement between American and European responders regarding management of these injuries, with only 3 cases exhibiting a significant difference. Additionally, results also exhibited considerable management agreement between those with ≤ 10 and &gt; 10&nbsp;years of practice experience, with only 2 case exceptions noted. Conclusion: More than half of responders, regardless of geographical location or practice experience, identified MRI as a screening imaging modality when managing cervical facet dislocation injuries, regardless of the status of the spinal cord and prior to any additional intervention. Additionally, a majority of surgeons would elect an anterior approach for the surgical management of these injuries. The study found overall agreement in management preferences of cervical facet dislocation injuries around the globe

Screening out irrelevant cell-based models of disease

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates

Ehogenicity of thyroid gland on ultrasonography in primary hypothyroidism

Background. The aim of this study was to investigate the association between echogenicity of thyroid gland and low thyroid function. Methods. The study group included 60 patients, with normal and low thyroid function, who visited the Outpatient Department of the Clinic of Endocrinology, Diabetes and Metabolic Disorders in the period from April 2008 to October 2009. Echogenicity of the thyroid gland in all patients was evaluated by ultrasonography as well as serum concentrations of TSH, fT4 and thyroid autoantibody (anti-TPO). To find out the association between thyroid ehogenicity with mean TSH and anti-TPO in different ages, we divided the patients into five subgroups according to age. Results. Patients with decreased echogenicity had a higher mean TSH compared with patients with normal echogenicity (2.77 mIU/l vs. 1.75 mIU/l) (p=0.04). Differences were more significant in patients with markedly decreased echogenicity (6.34 mIU/l vs. 1.75 mIU/l) (p< 0.0001). Patients with reduced echogenicity had a higher risk of having anti-TPO than patients without normal echogenicity (p<0.001). This association was stronger when echogenicity was markedly decreased. According to age, only younger population (19-29 years) with decreeased and markedly decreased echogenicity had significantly higher mean TSH and anti-TPO values. Conclusions. Thyroid ultrasonography changes can be used as an early sign of low thyroid function, especially in younger population

Association of Subclinical hypothyroidism with clinical symptomatology

Introduction: Subclinical hypothyroidism (SCH) often remains undetected because of the absence of clinical symptoms or unspecific symptomatology. The aim of the study was to discover whether SCH is associated with relevant clinical symptomatology. Material and methods: The study included 69 consecutive patients, in whom SCH was detected for the first time (level of serum thyrotropin (TSH) between 4.2-20 mU/l with the reference values of free thyroxine (fT4) 10.3-24.45 pmol/l) and a control group of 30 healthy subjects without goiter and with reference values of fT4 and TSH (0.2-4.2 U/l). All participants completed a previously prepared anamnestic questionnaire and blood was taken for evaluation of TSH and fT4. Results: Patients with SCH unlike the control group presented significantly more often with: fatigue, dry skin, insomnia and menorrhagia (in all cases p<0.05). There was a positive correlation between serum concentrations of TSH and percentage of symptoms of hypothyroidism (r= 0.25, p=0.04). Value of TSH over 7.1mU/l was associated with a significantly larger number of symptoms. Conclusion: SCH is associated with fatigue, dry skin, insomnia and menorrhagia, that justifies initiating thyroid replacement therapy at low values of TSH. Instead of the current recommendations for beginning thyroid replacement therapy when TSH >10mU/l, the cut-off value should be moved to TSH >7,1mU/l

Gestational Diabetes Mellitus – The Impact оf Maternal Body Mass Index аnd Glycaemic Control оn Baby’s Birth Weight

Abstract: Objectives. To asses the influence of the maternal BMI and glycaemic control in women with GDM on the baby's birth weight (BW). Material and methods: We analysed 180 women with GDM. Macrosomia has been defined as BW > 4000 gm, small for gestational age < 2700 gm and appropriate for gestational age between both. According to the baby´s BW the pregnant women were divided into three groups: group 1 (G1) with BW < 2700 gm (n = 26); group 2 (G2) with BW between 2700 to 4000 gm (n = 117), and group 3 (G3) with BW > 4000 gm (n = 37). We also analysed BMI (kg/m²), HbA1c (%), PPG (mmol/L) and time of delivery (WG). Results: Comparisons between G1 and G2 showed: BMI (30.7 ± 5 & 31 ± 5.2; p < 0.7), HbA1c (6.4 ± 0.8 & 5.1 ± 0.8, p < 0.002), PPG (8.2 ± 1.7 & 6.9 ± 1.5, p < 0.02), time of delivery (35.2 ± 3.8 & 38.6 ± 1.5, p < 0.0001) and BW (2289 ± 504 & 3474 ± 334, p < 0.0001). Comparisons between G2 and G3 showed: BMI (31 ± 5. 2 & 33.4 ± 6.1; p < 0.02), HbA1c (5.2 ± 1.1 & 6.4 ± 2.3, p < 0.02), PPG (6.9 ± 1.5 & 8.2 ± 1.9, p < 0.02), time of delivery (38.6 ± 1.5 & 39.3 ± 1.4, p < 0.01) and BW (3474 ± 334 & 4431 ± 302, p < 0.0001). Comparisons between G1 and G3 showed the difference at delivery time and the baby's BW (p < 0.0001). Conclusions: Maternal obesity and PPG contribute to macrosomia and also PPG to SGE. Key words: gestational diabetes, large for gestational age, small for gestational age, birth weight, postprandial glycaemia

Maternal 75 g OGTT glucose levels as predictive factors for large-for-gestational age newborns in women with gestational diabetes mellitus

Objective: Our goal was to investigate the effects of glucose levels from 75-g oral glucose tolerance test (OGTT) on large for gestational age (LGA) newborns in women with gestational diabetes mellitus (GDM). Material and methods: A prospective study was undertaken in Outpatient Department of Clinics for Endocrinology, Diabetes and Metabolic Disorders. One hundred and eighteen pregnant women were prospectively screened for GDM between 24 and 28 weeks of pregnancy. Results: From 118 pregnancies, 78 (66.1%) women were with GDM, and 40 (33.9%) without GDM. Twenty-one (30.4%) of the neonates in the GDM group were LGA (adjusted weight at or above the 90th percentile). This proportion significantly differ from the proportion (5.5%) for the control group (P<0.01). There were significant correlations between LGA from GDM pregnancies with fasting, and 1-h OGTT plasma glucose levels (r=0.46 and 0.23 respectively, P<0.05). Gestation week of delivery and fasting glucose levels were independent predictors for LGA (β=0.58 and β=0.37 respectively, P<0.001). Areas under the receiver operator characteristic curve (AUC) were compared for the prediction of LGA. The AUC were: 0.782 (0.685–0.861) for fasting, 0.719 (0.607–0.815) for 1-h, and 0.51 (0.392–0.626) for 2-h OGTT plasma glucose levels. Conclusion: Fasting and 1-h plasma glucose levels from OGTT may predict LGA babies in GDM pregnancies. Key Words: gestational diabetes, oral glucose tolerance test (OGTT), large for gestational age