Tissue factor antisense deoxyoligonucleotide prevents monocrotaline/LPS hepatotoxicity in mice

Tissue factor (TF) is a membranous glycoprotein that functions as a receptor for coagulation factor VII/VIIa and activates the coagulation system when blood vessels or tissues are damaged. TF was upregulated in our monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. We tested the hypothesis that TF‐dependent fibrin deposition and lipid peroxidation in the form of oxidized low‐density‐lipoprotein (ox‐LDL) accumulation contribute to liver inflammation induced by MCT/LPS in mice. In the present study, we blocked TF using antisense oligodeoxynucleotides against mouse TF (TF‐ASO). TF‐ASO (5.6 mg kg^?1) was given i.v. to ND4 male mice 30 min after administration of MCT (200 mg kg^?1) p.o. followed after 3.5 h by LPS i.p. (6 mg kg^?1). Blood alanine aminotransferase (ALT), TF, ox‐LDL, platelets, hematocrit and keratinocyte‐derived chemokine (KC) levels were evaluated in different treatment groups. Fibrin deposition and ox‐LDL accumulation were also analyzed in the liver sections using immunofluorescent staining. The results showed that TF‐ASO significantly restored blood ALT, hematocrit and KC levels, distorted after MCT/LPS co‐treatment, as well as preventing the accumulation of ox‐LDL and the deposition of fibrin in the liver tissues, and thereby inhibited liver injury caused by MCT/LPS. In a separate experiment, TF‐ASO administration significantly prolonged animal survival. The current study demonstrates that TF is associated with MCT/LPS‐induced liver injury. Administration of TF‐ASO successfully prevented this type of liver injury. Copyright © 2012 John Wiley & Sons, Ltd.     

Metabolic and target organ outcomes after total pancreatectomy: Mayo Clinic experience and meta‐analysis of the literature

Introduction Total pancreatectomy (TP) has been associated with substantial metabolic abnormalities and poor glycaemic control limiting its use. Because data reported to date are limited, we evaluated outcomes related to the diabetes mellitus obligated by TP. Methods A case series study of all patients who underwent TP from 01/01/1985 to 12/31/2006 at Mayo Clinic was conducted. TP cases were summarized according to perioperative procedures, mortality and morbidity after TP. To complement this retrospective examination, a survey was developed to measure DM treatment modality, target organ failure and complications in patients alive in 2007. We performed a meta‐analysis to compare our results with similar previous studies and provide overall estimates of outcomes. Results A total of 141 cases were studied (97 malignant diseases, 44 benign diseases). The median survival was much less for malignant pathology (2·2 vs 8·7 years, Log rank P = 0·0009). In 2007, there were 59 patients that were presumed alive and 47 (80%) responded to the survey. Mean HbA1c at last follow‐up was 7·5% with 89% of respondents on a complex insulin programme (mean daily insulin requirement 35 ± 13 units). Episodic hypoglycaemia was experienced by 37 (79%); 15 (41%) experienced severe hypoglycaemia. In contrast, diabetic ketoacidosis developed in only 2 (4%). Target organ complications and chronic diarrhoea developed in 13 patients (28%) each. Conclusion The primary factor determining survival after TP is the aetiology necessitating TP, i.e. pancreatic malignancy. Most respondents used complex insulin programmes, but hypoglycaemia continues to be a problem.     

Treatment of type I gastric neuroendocrine tumors with somatostatin analogs

Background and Aim: There are limited data on response and long‐term follow‐up of octreotide therapy in type‐I gastric neuroendocrine tumors. The objective of the present study was to assess the response of type‐I gastric neuroendocrine tumors to octreotide‐long acting, repeatable (LAR) therapy and evaluate long‐term follow up of such patients after therapy. Methods: Three patients with documented type‐I gastric neuroendocrine tumors from a tertiary gastroenterology centre were studied. Octreotide‐LAR therapy 20 mg intramuscularly every 28 days was administered for one year. Serum gastrin and chromogranin levels, gastroscopies and biopsies from tumor nodules at 6 months and one year on therapy and every 6 months after completion of drug therapy were taken. Follow‐up after completion of therapy extended for 3 years in two and 2.5 years in one patient. Results: During octreotide therapy there was normalization of serum gastrin levels and serum chromogranin levels. Tumors in all three patients had regressed at 6 months of treatment. Following cessation of therapy, there was progressive rise of serum gastrin to pre‐treatment levels. Serum chromogranin levels remained within normal limits. Gastroscopic and histologic examination of gastric biopsies did not reveal recurrence of tumors in any patients. All patients tolerated therapy well and became asymptomatic soon after drug therapy. Conclusions: Octreotide‐LAR therapy causes regression of type‐I gastric neuroendocrine tumors. After completion of drug therapy there was no recurrence of tumors even with continued hypergastrinemia. Octreotide therapy should be considered as one of the treatment options in such patients.     

CORR Insights®: Débridement and Reconstruction Improve Postoperative Sagittal Alignment in Kyphotic Cervical Spinal Tuberculosis

Clinical Orthopaedics and Related Research® -     

A Deep Learning Solution for Automatic Fetal Neurosonographic Diagnostic Plane Verification Using Clinical Standard Constraints

During routine ultrasound assessment of the fetal brain for biometry estimation and detection of fetal abnormalities, accurate imaging planes must be found by sonologists following a well-defined imaging protocol or clinical standard, which can be difficult for non-experts to do well. This assessment helps provide accurate biometry estimation and the detection of possible brain abnormalities. We describe a machine-learning method to assess automatically that transventricular ultrasound images of the fetal brain have been correctly acquired and meet the required clinical standard. We propose a deep learning solution, which breaks the problem down into three stages: (i) accurate localization of the fetal brain, (ii) detection of regions that contain structures of interest and (iii) learning the acoustic patterns in the regions that enable plane verification. We evaluate the developed methodology on a large real-world clinical data set of 2-D mid-gestation fetal images. We show that the automatic verification method approaches human expert assessment.     

Serum Interleukine-6 Concentration,But Not Interleukine-18, is Associated with Head and Neck Squamous Cell Carcinoma Progression

Inflammation has been linked to various steps in tumorigenesis. Interleukin (IL)-6 and IL-18 are two inflammatory cytokines whose serum concentrations are elevated in several types of cancer, including head and neck squamous cell carcinoma (HNSCC) in some studies. This study was designed to analyze the serum concentrations of these cytokines in Iranian HNSCC patients. Serum IL-6 and IL-18 concentrations were assayed by ELISA commercial kits in 65 untreated patients and 20 healthy volunteers. Serum IL-6 concentration was significantly increased in patients compared to healthy individuals (p < 0.000). IL-6 concentration increased as the tumor stage progressed, and a significant difference appeared between stage IV vs. stage I/II/III (p = 0.03) disease. Although serum IL-18 concentration was higher in patients than in healthy individuals, the difference was not statistically significant (p = 0.06). Moreover, there was no association between serum IL-18 concentration and tumor stage (p = 0.47). A significant difference was observed in serum IL-18 concentration according to the gender with higher IL-18 concentration in male patients (p = 0.01). In conclusion, serum concentration of IL-6 might correlate with the stage of tumor progression in Iranian HNSCC patients. Further studies with larger numbers of patients are required to exclude the possible minor correlation of serum IL-18 concentration with tumor stage.