Clinical Management of Malignant Insulinoma: a single Institution’s experience over three decades

Background

Malignant insulinoma is extremely rare and accounts for only 10% of total insulinoma cases. The goal of this study is to retrospectively analyze clinical data from 15 patients with malignant insulinoma treated at Peking Union Medical College Hospital (PUMCH) from 1984 to April 2017.

Methods

“Malignant insulinoma” was used as the keywords in the PUMCH medical record retrieval system to search and obtain patients’ clinical information. We identified subjects diagnosed with malignant insulinoma based on clinical or surgical pathological signs and subsequently analyzed their clinical data.

Results

Eight males and seven females with a median age at diagnosis of 40?years (38–54?years) were included. Eight patients (53%) had developed metastases at diagnosis, while the others (46.67%) developed metastases during the follow-up visits. The major sites of metastasis were the liver (86.7%), local tissues and blood vessels (33%) and abdominal lymph nodes (13%). All patients displayed neuroglycopenic (100%) and/or autonomic (60%) symptoms, mostly during fasting periods (73.3%), with an average blood glucose level of 1.66?±?0.51?mmol/L. A total of 93% of the patients had one primary pancreatic lesion, 53% had a lesion in the head of the pancreas, and 47% had a lesion in the tail of the pancreas, with diameters ranging between 0.9 and 6.0?cm. Most liver metastases were multiple lesions. Selective celiac arteriography yielded 100% sensitivity for both primary pancreatic lesions and liver metastases. Most patients received synthetical treatments, including surgery, chemoembolization, and octreotide.

Conclusions

Malignant insulinomas have a similar diagnostic process to that of benign insulinomas but require far more comprehensive therapies to alleviate hypoglycemic symptoms and extend patients’ survival.

     

NMR metabolomics of fibroblasts with inherited mitochondrial Complex I mutation reveals treatment-reversible lipid and amino acid metabolism alterations

Introduction

Elucidating molecular alterations due to mitochondrial Complex I (CI) mutations may help to understand CI deficiency (CID), not only in mitochondriopathies but also as it is caused by drugs or associated to many diseases.

Objectives

CID metabolic expression was investigated in Leber’s hereditary optic neuropathy (LHON) caused by an inherited mutation of CI.

Methods

NMR-based metabolomics analysis was performed in intact skin fibroblasts from LHON patients. It used several datasets: one-dimensional ¹H-NMR spectra, two-dimensional ¹H-NMR spectra and quantified metabolites. Spectra were analysed using orthogonal partial least squares-discriminant analysis (OPLS-DA), and quantified metabolites using univariate statistics. The response to idebenone (IDE) and resveratrol (RSV), two agents improving CI activity and mitochondrial functions was evaluated.

Results

LHON fibroblasts had decreased CI activity (??43%, p?<?0.01). Metabolomics revealed prominent alterations in LHON including the increase of fatty acids (FA), polyunsaturated FA and phosphatidylcholine with a variable importance in the prediction (VIP)?>?1 in OPLS-DA, p?<?0.01 in univariate statistics, and the decrease of amino acids (AA), predominantly glycine, glutamate, glutamine (VIP?>?1) and alanine (VIP?>?1, p?<?0.05). In LHON, treatment with IDE and RSV increased CI activity (+?40 and +?44%, p?<?0.05). IDE decreased FA, polyunsaturated FA and phosphatidylcholine (p?<?0.05), but did not modified AA levels. RSV decreased polyunsaturated FA, and increased several AA (VIP?>?1 and/or p?<?0.05).

Conclusion

LHON fibroblasts display lipid and amino acid metabolism alterations that are reversed by mitochondria-targeted treatments, and can be related to adaptive changes. Findings bring insights into molecular changes induced by CI mutation and, beyond, CID of other origins.

     

Progression of idiopathic thoracic or thoracolumbar scoliosis and pelvic obliquity in adolescent patients with and without limb length discrepancy

Βackground

Both limb length inequality and scoliosis are associated with pelvic obliquity.

Methods

This is an observational study of adolescents with growth potential presenting for evaluation of thoracic or thoracolumbar idiopathic scoliosis at an outpatient pediatric orthopedic clinic. Patients were evaluated for limb length discrepancy (LLD) (using bilateral femoral head height difference), pelvic obliquity (using bilateral iliac crest height difference and sacral takeoff angle), and scoliotic curve (using Cobb angle and rotation) on full spine standing radiographs. The same radiographic parameters were measured at a follow-up visit at least 2 years later.

Results

Seventy-three consecutive patients with a mean (SD) age of 13.3 (0.2) years at initial examination were included in the study. Scoliosis (major curve Cobb angle ≥?10°) was confirmed in all 73 patients, pelvic obliquity (iliac crest height difference >?1 cm or sacral takeoff angle >?5°) appeared in 23 (31.5%) patients with scoliosis, and LLD (>?1 cm femoral head height difference) was identified in 6 (8.2%) patients with scoliosis and pelvic obliquity. At a subsequent visit, a mean of 2.8 (range 2–5.8) years later, no significant change (p?>?0.05) in limb length inequality was observed but a statistically significant increase (p?<?0.05) in scoliotic and pelvic deformity parameters was found.

Conclusions

In adolescent patient population with thoracic or thoracolumbar scoliosis, the anisomelia remains stable with growth but both the scoliotic deformity and pelvic obliquity progress.

Trial registration

MGH no 2012-P-000774/1

     

Comparison of mitral annulus geometry between patients with ischemic and non-ischemic functional mitral regurgitation: implications for transcatheter mitral valve implantation

Background

Transcatheter mitral valve replacement (TMVR) is a new therapeutic option for high surgical risk patients with mitral regurgitation (MR). Mitral valve (MV) geometry quantification is of paramount importance for success of the procedure and transthoracic 3D echocardiography represents a useful screening tool. Accordingly, we sought to asses MV geometry in patients with functional MR (FMR) that would potentially benefit of TMVR, focusing on the comparison of mitral annulus (MA) geometry between patients with ischemic (IMR) and non ischemic mitral regurgitation (nIMR).

Methods

We retrospectively selected 94 patients with severe FMR: 41 (43,6%) with IMR and 53 (56,4%) with nIMR. 3D MA analysis was performed on dedicated transthoracic 3D data sets using a new, commercially-available software package in two moments of the cardiac cycle (early-diastole and mid-systole). We measured MA dimension and geometry parameters, left atrial and left ventricular volumes.

Results

Maximum (MA area 10.7?±?2.5 cm² vs 11.6?±?2.7 cm², p?>?0.05) and the best fit plane MA area (9.9?±?2.3 cm² vs 10.7?±?2.5 cm², p?>?0.05, respectively) were similar between IMR and nIMR. nIMR patients showed larger mid-systolic 3D area (9.8?±?2.3 cm² vs 10.8?±?2.7 cm², p?<?0.05) and perimeter (11.2?±?1.3 cm vs 11.8?±?1.5 cm, p?<?0.05) with longer and larger leaflets, and wider aorto-mitral angle (135?±?10° vs 141?±?11°, p?<?0.05). Conversely, the area of MA at the best fit plane did not differ between IMR and nIMR patients (9?±?1.1 cm² vs 9.9?±?1.5 cm², p?>?0.05).

Conclusions

Patients with ischemic and non-ischemic etiology of FMR have similar maximum dimension, yet systolic differences between the two groups should be taken into account to tailor prosthesis’s selection.

Trial registration

N.A.

     

Effect of food intake on myocardial performance index

Background

Myocardial performance index (MPI) has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether myocardial performance index is affected by food intake in healthy subjects.

Methods

Twenty-three healthy subjects aged 25.6?±?4.5 years were investigated. MPI was measured before, 30 min after, and 110 min after a standardized meal.

Results

MPI decreased significantly (P?<?0.05) from fasting values 30 min after the meal, and had almost returned to baseline after 110 min. MPI decreased from 0.28?±?0.06 (fasting) to 0.20?±?0.07 30 min after eating. At 110 min after eating the index value was almost back to the baseline value 0.26?±?0.06. (P?=?0.15).

Conclusions

This study shows that myocardial performance index is affected by food intake in healthy subjects.

     

Gastrointestinal stromal tumor: clinicopathological characteristics and pathologic prognostic analysis

Objective

This study aimed to understand clinicopathological characteristics of gastrointestinal stromal tumors (GISTs) and correlation between pathologic features and clinical outcome.

Methods

We used 76 cases diagnosed as primary GISTs during January 2007 to July 2017 at Army Institute of Pathology, Thailand. Clinical, survival, and pathological data were collected and analyzed.

Results

Ages of the patients ranged from 15 to 88?years (M:F?=?1:1). The most common presentation was gastrointestinal bleeding (39.7%). The most common site was the stomach (64.5%). Tumor size ranged from 0.6 to 25.5?cm (average 8.78?cm). Histologic types were spindle cell type (75%), mixed spindled-epithelioid type (17.1%), and epithelioid type (7.9%). The majority of histologic subtype was diffuse hypercellularity (67.1%). Tumor necrosis was found in 38.1% and 80% showed low mitotic counts. Most gastrointestinal stromal tumors (27.6%) are low-risk category according to Miettinen and Lasota’s algorithm. Metastasis was found in 27.7%, mostly occurs within 2?years, and is correlated with tumor size >?10?cm (P?=?0.023), non-spindle cell histologic type (P?=?0.027), mitotic count >?5/5mm² (P?=?0.000), myxoid change (P?=?0.011), and mucosal invasion (P?=?0.002). Recurrence was found in 8.1%, mostly occurs within 7?years, and correlated with myxoid change (P?=?0.045).

Conclusion

We found that most of GISTs show spindle cell type and low-risk category. Metastasis was correlated with tumor size >?10?cm, non-spindle cell histologic type, mitotic count >?5/5mm², myxoid change, and mucosal invasion. Recurrence was correlated with myxoid change.

     

Proteomic distinction of renal oncocytomas and chromophobe renal cell carcinomas

Background

Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5–7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns.

Methods

We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases.

Results

At 1% false discovery rate, we identified?>?3900 proteins, of which?>?2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO.

Conclusion

We present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.

     

Proliferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies

Background

Ki67 labeling index (Ki67 LI), the percentage Ki67 immunoreactive cells, is a measure of tumor proliferation, with important clinical relevance in breast cancer, and it is extremely important to standardize its evaluation.

Aim

To test the efficacy of computer assisted image analysis (CAIA) applied to completely digitized slides and to assess its feasibility in routine practice and compare the results obtained using two different Ki67 monoclonal antibodies.

Materials and methods

315 consecutive breast cancer routinely immunostained for Ki-67 (223 with SP6 and 92 with MM1 antibodies previously examined by an experienced pathologist, have been re-evaluated using Aperio Scanscope Xs.

Results

Mean human Ki67 LI values were 36%± 14.% and 28% ± 18% respectively for SP6 and MM1 antibodies; mean CAM Ki67 LI values were 31%± 19% and 22% ± 18% respectively for SP6 and MM1. Human and CAIA evaluation are statistically highly correlated (Pearson: 0.859, p<0.0001), although human LI are systematically higher. An interobserver variation study on CAIA performed on 84 cases showed that the correlation between the two evaluations was linear to an excellent degree.

Discussion

Our study shows that a) CAIA can be easily adopted in routine practice, b) human and CAIA Ki67 LI are highly correlated, although human LI are systematically higher, c) Ki67 LI using different evaluation methods and different antibodies shows important differences in cut-off values.

     

The clinical assessment of amyotrophic lateral sclerosis patients’ prognosis by ZNF512B gene,neck flexor muscle power score and body mass index (BMI)

Background

Assessment on the prognosis of amyotrophic lateral sclerosis (ALS) is becoming a focus of research in recent years since there is no effective treatment. The aim of the research is to explore the major factors involving in prognosis of ALS patients through long-term follow-up.

Methods

ALS patients’ DNA extracted from peripheral blood white cells were detected for the risk allele by single nucleotide polymorphism (SNP) analysis. Neck flexor muscle score and body mass index (BMI) were recorded during Medical Research Council follow-up using manual muscle testing method.

Results

ALS patients with risk alleles (C) deteriorated rapidly with poor clinical outcome. It seemed that the higher neck flexor muscle strength score in ALS patients with the longer survival time but without significant correlation (p?>?0.05). The lower the basal body mass index, the shorter the survival time and the faster deterioration (p?<?0.05). The patients with body mass index less than 22.04 seemed to have short survival time than those with BMI more than 22.04 (p?<?0.05), however, the speed of deterioration in two groups of patients had no significant difference (p?>?0.05).

Conclusion

The risk (C) allele of the SNP (rs2275294) in the ZNF512B gene, cervical flexor muscle power and body weight index might have clinical potential for ALS prognostication, since these indicators is so simple to perform that they might be very suitable for primary clinics and even community medical institutions to carry out.

     

Low serum insulin-like growth factor-1 in patients with erectile dysfunction

Objective

Endothelial dysfunction and microvascular damage play a crurical role in the pathogenesis of erectile dysfunction (ED). Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues. The purpose of the current study was to determine the association between IGF-1 levels and ED.

Materials and methods

All men were evaluated for ED and divided into two groups: 80 patients suffering from ED for >?1 year and 80 subjects without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score-5. IGF-1 levels were measured in serum by an automated chemiluminescence immunoassay. The relationship between IGF-1 levels and ED scores in patients was statistically evaluated.

Results

The mean age of patients in ED group was 60.4?±?11.3 years and 55.4?±?9.6 in control group. The plasma IGF-1 levels were significantly lower in ED than in control group (96.5?±?38.3 and 132.5?±?53.3 ng/ mL, respectively, P?<?0.001). The IGF-1 levels were positively correlated with ED score (r?=?0.623, P?<?0.01).

Conclusion

In this study serum IGF-1 levels were found to be associated with endothelial dysfunction that predicts ED. Serum IGF-1 level appears to be a specific predictor of ED, and it might be used in early prediction of ED in male population.

     

Over-expression of miR-146b and its regulatory role in intestinal epithelial cell viability,proliferation, and apoptosis in piglets

Background

Weaning stress affects the small intestine of piglets. MiR-146b is differentially expressed in suckling and weaned piglets. In this study, we evaluated the effects of miR-146b on cell viability, proliferation, and apoptosis in IPEC-J2 cells.

Results

Transfection with miR-146b mimics successfully increased miR-146b levels by 1000× (P?<?0.001). The over-expression of miR-146b significantly promoted the apoptosis (P?<?0.01) of IPEC-J2 cells, with no significant effects on cell viability or proliferation. MiR-146b suppressed the luciferase activity of the miR-TLR4-wt by 57% compared with the negative control, while mutation of the miR-146b binding site significantly blocked the suppressive effect (P?<?0.05). Western blot results showed that TLR4 levels decreased in IPEC-J2 cells transfected with miR-146b mimics (P?<?0.05).

Conclusions

The over-expression of miR-146b promotes IPEC-J2 cell apoptosis. TLR4 is a direct target of miR-146b in IPEC-J2 cells.

Reviewers

This article was reviewed by Eugene Berezikov and Jan B Hoek.

     

The reliability and validity for Japanese type 2 diabetes patients of the Japanese version of the acceptance and action diabetes questionnaire

Background

The purpose of this study was to determing which psychological traits of Japanese type 2 diabetes patients would provide reliability and validity to the Japanese version of the Acceptance and Action Diabetes Questionnaire (AADQ-J).

Methods

Various questionnaires were administered to type 2 diabetes patients who were registered on the database of the research service provider; data from a total of 600 patients (mean?±?SD age was 57.50?±?9.87 years, female 21.83%) were analyzed.

Results

Three items were excluded because of psychometric concerns related to the original 11-item AADQ. Confirmation factor analyses revealed that the eight-item version demonstrated the best indicators of a goodness of fit. The questionnaire showed adequate internal consistency. The questionnaire demonstrated high measurement accuracy in broad trait values by the test information function of Item Response Theory. The questionnaire showed stronger positive correlations with self-care activities and HbA1c than with diabetes distress and depressive mood.

Conclusions

The eight-item Japanese version of AADQ has reliability and validity for type 2 diabetes patients.

     

Untargeted metabolomics analysis of ischemia–reperfusion-injured hearts ex vivo from sedentary and exercise-trained rats

Introduction

The effects of exercise on the heart and its resistance to disease are well-documented. Recent studies have identified that exercise-induced resistance to arrhythmia is due to the preservation of mitochondrial membrane potential.

Objectives

To identify novel metabolic changes that occur parallel to these mitochondrial alterations, we performed non-targeted metabolomics analysis on hearts from sedentary and exercise-trained rats challenged with isolated heart ischemia–reperfusion injury (I/R).

Methods

Eight-week old Sprague–Dawley rats were treadmill trained 5 days/week for 6 weeks (exercise duration and intensity progressively increased to 1 h at 30 m/min up a 10.5% incline, 75–80% VO_2max). The recovery of pre-ischemic function for sedentary rat hearts was 28.8?±?5.4% (N?=?12) compared to exercise trained hearts, which recovered 51.9%?±?5.7 (N?=?14) (p?<?0.001).

Results

Non-targeted GC–MS metabolomics analysis of (1) sedentary rat hearts; (2) exercise-trained rat hearts; (3) sedentary rat hearts challenged with global ischemia–reperfusion (I/R) injury; and (4) exercise-trained rat hearts challenged with global I/R (10/group) revealed 15 statistically significant metabolites between groups by ANOVA using Metaboanalyst (p?<?0.001). Enrichment analysis of these metabolites for pathway-associated metabolic sets indicated a?>?10-fold enrichment for ammonia recycling and protein biosynthesis. Subsequent comparison of the sedentary hearts post-I/R and exercise-trained hearts post-I/R further identified significant differences in three metabolites (oleic acid, pantothenic acid, and campesterol) related to pantothenate and CoA biosynthesis (p?≤?1.24E?05, FDR?≤?5.07E?4).

Conclusions

These studies shed light on novel mechanisms in which exercise-induced cardioprotection occurs in I/R that complement both the mitochondrial stabilization and antioxidant mechanisms recently described. These findings also link protein synthesis and protein degradation (protein quality control mechanisms) with exercise-linked cardioprotection and mitochondrial susceptibility for the first time in cardiac I/R.

     

Independent prognostic value of coronary artery calcium score and coronary computed tomography angiography in an outpatient cohort of low to intermediate risk chest pain patients

Background

Limited studies report on the additional prognostic value of coronary computed tomography angiography (CCTA) and the coronary artery calcium score (CACS).

Methods

For a median of 637 days, 1551 outpatients with chest pain, without known coronary artery disease (CAD) and low or intermediate pre-test probability of CAD, were followed for major adverse cardiac events (MACE), defined as death, myocardial infarction or late revascularisation. Cox proportional hazard regression was used to evaluate the independent prognostic value of CCTA and CACS.

Results

MACE occurred in 23 patients (1.5?%): death (3, 0.2?%), myocardial infarction (4, 0.3?%) and late revascularisation (16, 1.3?%). Multivariate analysis showed an independent prognostic value of CCTA (p?<?0.001), CACS of 100–400 (p?=?0.035) and CACS of >?400 (p?=?0.021). CCTA showed obstructive CAD in 3.1?% of patients with CACS?=?0. No events occurred in patients with CACS?=?0 without obstructive CAD at CCTA, whereas 2/23 patients (9?%) with CACS?=?0 with obstructive CAD had a MACE.

Conclusions

Our study shows that both CCTA and higher CACS categories have independent prognostic value in chest pain patients with low to intermediate pre-test probability of obstructive CAD, in which CCTA is appropriate. Furthermore a non-negligible amount of patients with CACS?=?0 have obstructive CAD at CCTA. CCTA can be used in these patients to identify those at risk for MACE.

     

Role of <Emphasis Type="Italic">PUF60</Emphasis> gene in Verheij syndrome: a case report of the first Chinese Han patient with a de novo pathogenic variant and review of the literature

Background

Verheij syndrome is a rare microdeletion syndrome of chromosome 8q24.3 that harbors PUF60, SCRIB, and NRBP2 genes. Subsequently, loss of function mutations in PUF60 have been found in children with clinical features significantly overlapping with Verheij.

Case presentation

Here we present the first Chinese Han patient with a de novo nonsense variant (c.1357C?>?T, p.Gln453*) in PUF60 by clinical whole exome sequencing. The 5-year-old boy presents with dysmorphic facial features, intellectual disability, and growth retardation but without apparent cardiac, renal, ocular, and spinal anomalies.

Conclusions

Our finding contributes to the understanding of the genotype and phenotype in PUF60 related disorder.

     

The relationship between epicardial adipose tissue and coronary artery stenosis by sex and menopausal status in patients with suspected angina

Background

Evidence suggests that epicardial adipose tissue (EAT) is closely related to coronary artery stenosis (CAS). However, sexual dimorphism may be present in adipose tissue, and its influence on CAS between men and women is controversial. We assessed the relationship between EAT and CAS by sex and menopausal status in patients with suspected angina.

Methods

Six hundred twenty-eight consecutive patients (men/women n?=?257/371; mean age = 59.9?±?10.2?years) who had chest pain for angina and underwent coronary angiography were included. CAS was defined as >?50% luminal narrowing of at least one epicardial coronary artery. EAT thickness was measured by transthoracic echocardiography.

Results

Of the 628 patients, 52.1% (n?=?134) of men and 35.3% (n?=?131) of women had CAS. The mean EAT thickness was not different between men and women and was larger in patients with CAS (8.04?±?2.39 vs 6.58?±?1.88?mm, P?<?0.001). EAT thickness was independently associated with CAS in both sexes (P?<?0.001). The odds ratio (OR) of EAT for the presence of CAS was higher in men (OR?=?1.43, 95% confidence interval [CI] 1.21–1.69) than in women (OR?=?1.24, 95% CI 1.10–1.40). EAT thickness was larger in postmenopausal women than in premenopausal women (7.59?±?2.25 vs 5.80?±?1.57?mm, P?<?0.001) and was independently related with CAS (OR?=?1.24, 95% CI 1.09–1.41). This was not the case in premenopausal women.

Conclusion

In patients with suspected angina, an increase in EAT thickness was independently related to the presence of CAS in both men and women, with it being stronger in men. According to menopausal status in women, EAT thickness is significantly associated with CAS only in postmenopausal women.

     

Metabolomic biomarkers and novel dietary factors associated with gestational diabetes in China

Introduction

Gestational diabetes mellitus (GDM) is impaired glucose tolerance first recognised during pregnancy; its development is associated with many adverse outcomes. Mechanisms of GDM development are not fully elucidated and few studies have used Chinese participants.

Objectives

The aim of this study was to investigate the maternal metabolome associated with GDM in a Chinese population, and explore the relationship with maternal diet.

Methods

Ninety-three participants were recruited at 26–28 weeks’ gestation from Chongqing, China. Maternal urine, serum, and hair metabolomes were analysed using gas and liquid chromatography–mass spectrometry. Dietary intake was assessed using a 96-item food frequency questionnaire.

Results

Of the 1064 metabolites identified, 73 were significantly different between cases and controls (P?<?0.05), but only 2-aminobutyric acid had both a p- and q-value?<?0.05. A “snack-based-dietary-pattern” was associated with an increased likelihood of GDM (odds ratio 2·1; 95% confidence interval 1.1–3.9). The association remained significant after adjustment for calorie intake but not food volume.

Conclusion

This study provides a comprehensive characterization of the maternal metabolome. The snack-based dietary pattern associated with GDM suggests that timing and frequency of consumption are important factors in the relationship between maternal diet and GDM.

     

Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis,tricarboxylic acid and urea metabolism

Background

Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet.

Objectives

We aimed to study the effects of interventional LAAC on systemic metabolism.

Methods

Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ? p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1).

Results

During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta ?0.19, p?<?0.01) and the increase of sarcosine (beta 0.16, p?<?0.01).

Conclusions

Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future.

     

The ability of left ventricular end-diastolic volume variations measured by TEE to monitor fluid responsiveness in high-risk surgical patients during craniotomy: a prospective cohort study

Background

This study was aimed to evaluate the ability of left ventricular end-diastolic volume variations (LVEDVV) measured by transesophageal echocardiography (TEE) compared with stroke volume variation (SVV) obtained by the FloTrac/Vigileo monitor to predict fluid responsiveness, in patients undergoing craniotomy with goal direct therapy.

Methods

We used SVV obtained by the FloTrac/Vigileo monitor to manage intraoperative hypotension in adult patients undergoing craniotomy (ASA III – IV) after obtaining IRB approval and informed consent. The LVEDVV were measured by TEE through the changes of left ventricular short diameter of axle simultaneously. When cardiac index (CI)?≤?2.5 and SVV?≥?15%, comparisons were made between the two devices before and after volume expansion.

Results

We enrolled twenty-six patients referred for craniotomy in this study and 145 pairs of data were obtained. Mean Vigileo-SVV and TEE-LVEDVV were 17.8?±?2.78% and 22.1?±?7.25% before volume expansion respectively, and were 10.95?±?2.8% and 13.58?±?3.78% after volume expansion respectively (P <?0.001). The relationship between Vigileo-SVV and TEE-LVEDVV was significant (r2?=?0.55; p <?0.001). Agreement between Vigileo-SVV and TEE-LVEDVV was 3.3%?±?3.9% (mean bias ± SD, Bland-Altman).

Conclusions

For fluid responsiveness of patients during craniotomy in ASA III-IV, LVEDVV measured by left ventricular short diameter of axle using M type echocaidiographic measurement seems an acceptable monitoring indicator. This accessible method has promising clinical applications in situations where volume and cardiac function monitoring is of great importance during surgery.

Trial registration

Chinese Clinical Trial Registry, ChiCTR-TRC-13003583, August 20, 2013.

     

Improved patient-reported outcomes in patients with psoriatic arthritis treated with abatacept: results from a phase 3 trial

Background

To explore the effect of abatacept treatment on patient-reported outcomes (PROs) in psoriatic arthritis (PsA).

Methods

Patients with PsA were randomised (1:1) to subcutaneous abatacept 125?mg weekly/placebo for 24?weeks with early escape (EE) to open-label abatacept (week 16). Adjusted mean changes from baseline to weeks 16 (all patients) and 24 (non-EE responders) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 (SF-36; physical and mental component summary and domains), Dermatology Life Quality Index and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Subpopulations were analysed by baseline C-reactive protein (CRP) level (> vs?≤?upper limit of normal [ULN]) and prior tumour necrosis factor inhibitor (TNFi) exposure. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCIDs) and?≥?normative values (NVs) in HAQ-DI, SF-36 and FACIT-F (week 16 before EE) were analysed.

Results

In total population, numerically higher improvements in most PROs were reported with abatacept (n?=?213) versus placebo (n?=?211) at both time points (P?>?0.05). Higher proportions of abatacept versus placebo patients reported PRO improvements ≥ MCID and?≥?NV at week 16. At week 16, all PRO improvements were numerically greater (P?>?0.05) in patients with baseline CRP?>?ULN versus CRP?≤?ULN (all significant [95% confidence interval] for abatacept vs placebo); improvements in SF-36 component summaries and FACIT-F were greater in TNFi-naïve versus TNFi-exposed patients (abatacept > placebo). Week 24 subgroup data were difficult to interpret due to low patient numbers.

Conclusions

Abatacept treatment improved PROs in patients with PsA versus placebo, with better results in elevated baseline CRP and TNFi-naïve subpopulations.

Trial registration

ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb); date of registration: 23 May 2013.