A genome wide association study identifies new genes potentially associated with eyelid sagging

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10^‐10) and rs4746957 (P = 1.06 × 10^‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.     

Use of i.v. insulin in well-controlled non-insulin-dependent diabetics undergoing major surgery

We conducted a randomized, prospective study to assess the effect of i.v. insulin on blood glucose control, development of ketone bodies and hormonal changes in 60 well-controlled, non-insulin-dependent diabetics (NIDDM) undergoing major surgery. In group A, patients were given only 0.9% saline; in group B, patients were given insulin as a continuous i.v. infusion (1.25 u. h-1); in group C, patients were given insulin 10 u. i.v. boluses every 2 h. Patients in all three groups were given insulin 5 u. when their intraoperative blood glucose concentration increased to greater than 11.1 mmol litre-1. Blood glucose concentrations were measured every 15 min, from just before induction of anaesthesia to 2 h after surgery. Plasma lactate, pyruvate, ketone body, C-peptide and counter-regulatory hormone concentrations were also measured. Blood glucose concentrations in the three groups did not differ significantly. There was a mild-to-moderate increase in plasma ketone body concentrations in group A, but without any deleterious consequences. Plasma C-peptide concentrations decreased significantly in groups B and C, especially in patients given bolus injections of insulin. Plasma growth hormone concentrations also increased significantly in group B and C patients. This study indicated that the "no insulin--no glucose" regimen was a simple, effective way to control blood glucose in well-controlled NIDDM patients, provided blood glucose was measured frequently and insulin used appropriately.      

Multivisceral organ failure related to leptospirosis in pregnant patient

Leptospirosis is the most widespread zoonosis in the world. It is caused by pathogenic leptospira infection. This infection is also an uncommon cause of hepatorenal failure. Indeed, hemolysis, elevated liver enzyme levels and low platelet count syndrome, and acute fatty liver of pregnancy are specific to the pregnant state. Leptospirosis is rarely described in pregnancy; it might mimic puerperal sepsis or hepatorenal failure associated with pregnancy induced hypertension. We report a case of leptospirosis presenting as multiple organ failure during third trimester of pregnancy with a good outcome.     

Myeloid-derived suppressor cells and regulatory T cells share common immunoregulatory pathways-related microRNAs that are dysregulated by acute lymphoblastic leukemia and chemotherapy

BackgroundRelapse remains a critical challenge in children with acute lymphoblastic leukemia (ALL). The emergence of immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs), and T regulatory (T_reg) cells, has been considered one potential mechanism of relapse in children with ALL.AimThis study aimed to address the microRNAs (miRNAs) related to MDSCs and T_reg cells and to explore their targeted immunoregulatory pathways.MethodsAffymetrix microarray was used for global miRNA profiling in B-ALL pediatric patients before, during, and after induction of chemotherapy. Bioinformatics analysis was performed on MDSCs and T_reg cells-related dysregulated miRNAs, and miR-Pathway analysis was performed to explore their targeted immunoregulatory pathways.Results516 miRNAs were dysregulated in ALL patients as compared to the healthy donor. Among them, 13 miRNAs and 8 miRNAs related to MDSCs and T_reg cells, respectively, were common in all patients. Besides, 12 miRNAs were shared between MDSCs and T_reg cells; 4 of them were common in all patients. Four immune-related pathways; TNF, TGF-β, FoxO, and Hippo were found implicated.ConclusionOur pilot study concluded certain miRNAs related to MDSCs and T_reg cells, these miRNAs were linked to immunoregulatory pathways. Our results open avenues for testing those miRNA as molecular biomarkers for the immunosuppressive tumor microenvironment.     

A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease

BACKGROUND: Biochemical markers for liver fibrosis (FibroTest) and necroinflammatory features (ActiTest) are an alternative to liver biopsy in patients with chronic hepatitis C. Our aim was to assess the inter-laboratory variability of these tests, and their 6 components (gamma-glutamyl transpeptidase, alanine aminotransferase, alpha2-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability. RESULTS: Serum of 24 patients with chronic hepatitis C or severe alcoholic liver disease were prospectively recorded and analyzed in one reference center and in 8 additional laboratories. When gamma-glutamyl transpeptidase and alanine aminotransferase were expressed in international units, there was no significant difference between laboratories in the results of FibroTest or ActiTest; kappa statistics were greater than 0.50 with only 0.8% of cases (3/384) with a discordance of more than one stage. The main factor significantly associated with variability was the expression of gamma-glutamyl transpeptidase and alanine aminotransferase, as multiples of upper limit of reference values. The use of standardized method with pyridoxal phosphate reduced the variability of alanine aminotransferase expression, and standardized original Szasz method reduced the variability of gamma-glutamyl transpeptidase expression. CONCLUSIONS: The variability of FibroTest and ActiTest was acceptable without clinical consequences for the prediction of the stage of liver fibrosis and grade of activity. Standardized methods and assay calibration should be used and expression of alanine aminotransferase and gamma-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed.     

Role of matrix metalloproteinase-3 (MMP-3) and magnetic resonance imaging of sacroiliitis in assessing disease activity in ankylosing spondylitis

The objective of this study is to evaluate the role of MMP-3 and MRI in assessing disease activity in sacroiliac joints of AS patients in comparison to the conventional measures Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Serum MMP-3 was measured in 30 patients who fulfilled the modified New York criteria for AS and in ten healthy volunteers. AS patients were categorized into those having high or low MMP-3 according to a cut-off value?=?7.1?ng/ml. MRI of the sacroiliac joints (SIJs) was performed on all patients. SIJs were evaluated for enhancement and subchondral bone marrow edema. Results of MMP-3 and findings on MRI were correlated with multiple clinical parameters including BASDAI, ESR and CRP. Serum MMP-3 was significantly elevated in AS patients with active disease. Elevated MMP-3 levels were significantly associated with high BASDAI (P?=?0.046), but not with ESR or CRP. MRI showed bone marrow edema and enhancement of SIJs in 19/30 patients with one patient showing enhancement only. These MRI findings were not correlated with MMP-3, BASDAI, CRP or ESR. In conclusion, serum MMP-3 is an objective measure reflecting clinical disease activity in AS. Bone marrow edema and enhancement detected by MRI of SIJs is another objective measure of disease activity, but are not correlated with MMP-3 or the conventional parameters as BASDAI, ESR, or CRP. Although both MMP-3 and MRI can reflect disease activity in AS they seem to be unrelated, perhaps each is reflecting a different aspect of disease activity. MMP-3 and MRI should be considered together with BASDAI in assessing disease activity and in guiding the available recommendations for initiation of biologics in AS.     

Transcystic or Transductal Stone Extraction during Single-Stage Treatment of Choledochocystolithiasis: A Systematic Review

Background

Choledochocystolithiasis can be managed by endoscopic retrograde cholangiopancreaticography (ERCP) or laparoscopically by transcystic (TC) or transductal (TD) stone extraction.

Objective

The aim of this study was to systematically review safety and effectiveness of combined endoscopic/laparoscopic management versus total laparoscopic management for choledochocystolithiasis with specific emphasis on TC versus TD stone extraction.

Methods

MEDLINE/PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched systematically to identify trials on combined endoscopic/laparoscopic and total laparoscopic management for choledochocystolithiasis. Laparoscopic common bile duct (CBD) exploration was divided into TD and TC approach. Primary outcomes were successful stone clearance from CBD, postoperative/procedural morbidity, and mortality.

Results

Eight randomized trials with 965 patients were included. Successful bile duct clearance varied between 52.6 and 97 % in the ERCP groups, 80.4 and 100 % in the TC groups, and 58.3 and 100 % in the TD groups. There were more bile leaks after TD stone extraction (11 %) than after ERCP (1 %) and TC stone extraction (1.7 %). Total morbidity varied between 9.1 and 38.3 % in the ERCP groups, 7 and 10.5 % in the TC groups, and 18.4 and 26.7 % in the TD groups. Methodological and statistical heterogeneity among the trials precluded a meaningful meta-analysis.

Conclusion

Stone clearance rates are comparable between the three modalities, but TD stone extraction is associated with a higher risk of bile leaks and should only be performed by highly experienced surgeons. TC stone extraction seems a more accessible technique with lower complication rates. If unsuccessful, per- or postoperative endoscopic stone extraction is a viable option.