Association of polymorphisms of glutamate‐cystein ligase and microsomal triglyceride transfer protein genes in non‐alcoholic fatty liver disease

Background and Aims: Although the metabolic risk factors for non‐alcoholic fatty liver disease (NAFLD) progression have been recognized, the role of genetic susceptibility remains a field to be explored. The aim of this study was to examine the frequency of two polymorphisms in Brazilian patients with biopsy‐proven simple steatosis or non‐alcoholic steatohepatitis (NASH): ?493 G/T in the MTP gene, which codes the protein responsible for transferring triglycerides to nascent apolipoprotein B, and ?129 C/T in the GCLC gene, which codes the catalytic subunit of glutamate‐cystein ligase in the formation of glutathione. Methods: One hundred and thirty‐one biopsy‐proven NAFLD patients (n = 45, simple steatosis; n = 86, NASH) and 141 unrelated healthy volunteers were evaluated. Genomic DNA was extracted from peripheral blood cells, and the ?129 C/T polymorphism of the GCLC gene was determined by restriction fragment length polymorphism (RFLP). The ?493 G/T polymorphism of the MTP gene was determined by direct sequencing of the polymerase chain reaction products. Results: The presence of at least one T allele in the ?129 C/T polymorphism of the GCLC gene was independently associated with NASH (odds ratio 12.14, 95% confidence interval 2.01–73.35; P = 0.007), whereas, the presence of at least one G allele in the ?493 G/T polymorphism of the MTP gene differed slightly between biopsy‐proven NASH and simple steatosis. Conclusion: This difference clearly warrants further investigation in larger samples. These two polymorphisms could represent an additional factor for consideration in evaluating the risk of NAFLD progression. Further studies involving a larger population are necessary to confirm this notion.     

Effects of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the Treatment of Goblet Cell Carcinoma: A Prospective Cohort Study

Background

Goblet cell carcinoma (GCC) of the appendix is a rare disease. Treatment options vary according to disease staging. Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) may improve survival in patients with peritoneal spreading.

Objective

The aim of this study was to examine the prognosis of patients with appendiceal GCC treated per protocol, and to evaluate the results of CRS+HIPEC in cases of peritoneal spreading.

Methods

From 2009 to 2016, a total of 48 GCC patients were referred to the European Neuroendocrine Tumour Center of Excellence, Aarhus University Hospital. All patients received treatment per protocol according to disease staging. In patients with localized disease, the treatment was a right hemicolectomy. Patients with peritoneal spread who met the inclusion criteria for CRS + HIPEC, as well as patients with high-risk features of developing peritoneal spread, received CRS + HIPEC. If too-extensive disease was found, palliative chemotherapy was offered.

Results

Overall survival for patients with localized disease (n = 6) or deemed at risk of peritoneal spread (n = 8) was 100% after a median follow-up of 3.5 years. In patients with peritoneal spread and eligible for CRS+HIPEC(n = 27), the median survival was 3.2 years [95% confidence interval (CI) 2.3–4.1] and the 5-year survival rate was 57%. In contrast, the median survival for patients with too-extensive intraperitoneal disease (n = 7) was 1.3 years (95% CI 0.6–2.0), with a 3-year survival rate of 20%.

Conclusions

Long-term survival can be achieved in patients with peritoneal spread treated with CRS + HIPEC. CRS+HIPEC was associated with a favorable outcome in GCC patients at high-risk of developing peritoneal spread.

     

Spirometric changes in normal children with upper respiratory infections

Recent evidence that certain uncomplicated upper respiratory infections induce pulmonary function abnormalities in adults prompted a prospective study in children, in whom such infections occur more frequently. In a longitudinal study, 55 children 2.5 to 11 years of age were observed for a mean duration of 2 years. Spirometry and lung volume studies were obtained routinely every 3 months, during each upper respiratory infection, and 4 weeks after illnes, providing data for 617 "well" and 237 "illness" observations. After grouping of data by sex and age (less than 84 of greater than 84 months), each spirometric parameter was analyzed using linear regression with individual identification, height, and clinical status (normal versus upper respiratory illness) as independent variables. Adjusted mean values of forced vital capacity, 1-sec forced expiratory volume, peak expiratory flow, maximal mid-expiratory flow, and expiratory flow at 50 per cent of the forced vital capacity all decreased during upper respiratory illness. The data suggest that lower respiratory tract involvement without signs or symptoms of lower airway or alveolar disease occurs with upper respiratory illnesses of varied etiologic origin in childhood.     

A metaanalysis of predischarge risk stratification after acute myocardial infarction with stress electrocardiographic, myocardial perfusion, and ventricular function imaging

We assessed the relation of abnormal predischarge noninvasive test results to outcomes in postmyocardial infarction patients. We included series published from 1980 to 1995 containing only myocardial infarction patients, enrolling most patients after 1980, testing within 6 weeks of infarction, having follow-up rates > 80%, and having 2 × 2 frequency outcome rates for test results, that were the latest of multiple reports. Sensitivity, specificity, and predictive values were calculated for test results for 1-year outcomes (cardiac death, cardiac death or reinfarction). Univariable and summary odds were calculated for test results. Reports (n = 54) included a total of 19,874 patients and were primarily retrospective (76%) and small series (35% of reports included < 5 deaths). One-year mortality ranged from 2.5% for pharmacologic stress echocardiography to 9.3% for exercise radionuclide angiography. Positive predictive values for most noninvasive risk markers were < 0.10 for cardiac death and 0.20 for death or reinfarction. Electrocardiographic, symptomatic, and scintigraphic risk markers of ischemia (ST-segment depression, angina, a reversible defect) were less sensitive (≤44%) for identifying morbid and fatal outcomes than markers of left ventricular dysfunction or heart failure (exercise duration, impaired systolic blood pressure response, and peak left ventricular ejection fraction). The positive predictive value of predischarge noninvasive testing is low. Markers of left ventricular dysfunction appear to be better predictors than markers of ischemia. Limitations of the literature—small samples and widely varying event rates—impede our ability to discern the accuracy of predischarge noninvasive testing. More rigorous, controlled trials are required to elucidate the relative value of these tests for risk stratification.     

Magnesium deficiency after ileal resections for Crohn's disease

The magnesium status of the body was studied in 87 patients with various lengths of small-bowel resections for Crohn's disease. The urinary magnesium excretion decreased with increasing resection length, and so did the concentration of magnesium in muscle. Muscular fatigue, an early symptom of magnesium deficiency, was positively correlated to a pathologically low concentration of muscle magnesium. It was concluded that clinically important magnesium deficiency, which was not detected by determination of serum magnesium, occurred in patients with ileal resections exceeding 75 cm.