Certolizumab Pegol Compared to Natalizumab in Patients with Moderate to Severe Crohn’s Disease: Results of a Decision Analysis

Introduction  

A significant proportion of patients with Crohn’s disease (CD) lose response to antibodies directed against tumor necrosis factor α (TNF). Prior TNF-antagonist failure is associated with lower rates of response to subsequent TNF-antagonist therapy. In patients failing two anti-TNF agents, a choice exists between using a third-anti-TNF therapy or natalizumab (NAT), an α-4 integrin inhibitor. A cost-effectiveness analysis comparing these competing strategies has not been performed.     

Living donor intestinal transplant using a standardized technique: first report from India

Aim

We describe the first living donor intestinal transplant (LDIT) in India and discuss the indications and problems of this complex procedure.

Methods

A 43-year-old male patient required massive bowel resection for gangrene due to thrombosis of the superior mesenteric artery. He was maintained on parenteral nutrition but developed cholestasis and well as repeated catheter related infections with progressive loss of venous access due to thrombosis of central veins. A LDIT was performed using 200?cm of small intestine from the patient's son. The graft was based on the continuation of the superior mesenteric vessels beyond the ileocolic branch. The artery was anastomosed directly to the aorta and the vein to the venacava.

Results

The graft functioned well and he was weaned off parenteral nutrition. However, he later developed complications (wound dehiscence and enterocutaneous fistula) and developed sepsis. He succumbed to sepsis with a functioning graft 6?weeks after the transplant. The donor recovered uneventfully and was discharged on the 4th postoperative day.

Conclusions

LDIT can be life saving in patients with intestinal failure and failure of parenteral nutrition. There is a need to introduce this modality in India. In a setting of scarcity of deceased donor organs the living donor option has advantages.     

Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation

Hu antigen R (HuR) is a central RNA-binding protein regulating cell dedifferentiation, proliferation, and survival, which are well-established hallmarks of cancer. HuR is frequently overexpressed in tumors correlating with tumor malignancy, which is in line with a role for HuR in tumorigenesis. However, the precise mechanism leading to changes in HuR expression remains unclear. In the liver, HuR plays a crucial role in hepatocyte proliferation, differentiation, and transformation. Here, we unraveled a novel mean of regulation of HuR expression in hepatocellular carcinoma (HCC) and colon cancer. HuR levels correlate with the abundance of the oncogene, murine double minute 2 (Mdm2), in human HCC and colon cancer metastases. HuR is stabilized by Mdm2-mediated NEDDylation in at least three lysine residues, ensuring its nuclear localization and protection from degradation. Conclusion: This novel Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells, which, in turn, unveils a novel signaling paradigm that is pharmacologically amenable for cancer therapy.     

Gastrointestinal stromal tumour of the duodenum: single institution experience

Background

Primary gastrointestinal stromal tumours (GISTs) of the duodenum are rare. The aim of this study was to review the surgical management of GISTs in this anatomically complex region.

Methods

Retrospective review from January 1999 to August 2011 of patients with primary GISTs of the duodenum.

Results

Forty-one patients underwent resection of duodenal GISTs. All operations were performed with intent to cure with negative margins of resection. The most common location of origin was the second portion of the duodenum. Local excision (n = 19), segmental resection with primary anastomosis (n = 11) and a pancreatoduodenectomy (n = 11) were performed. Two patients underwent an ampullectomy with local excision. Peri-operative mortality and overall morbidity were 0 and 12, respectively. Patients with high-risk GISTs (P = 0.008) and those who underwent a pancreatoduodenectomy (P = 0.021) were at a greater risk for morbidity. The median follow-up was 18 months. Eight patients developed recurrence. High-risk GISTs and neoplasms with ulceration had the greatest risk for recurrence (P = 0.017, P = 0.029 respectively). The actuarial 3- and 5-year survivals were 85% and 74%, respectively.

Conclusion

The choice and type of resection depends on the proximity to the ampulla of Vater, involvement of adjacent organs and the ability to obtain negative margins. The morbidity depends on the type of procedure for GIST.     

Case-control association study of 36 single-nucleotide polymorphisms within 10 candidate genes for major depression and bipolar disorder

In this study we investigated 36 single nucleotide polymorphisms within 10 genes previously associated with major depression and bipolar disorder, as well as with the response to their treatment (ABCB1, ABCB4, TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2). No association with mood disorders and clinical outcomes was observed.     

Radiofrequency lesioning through deep brain stimulation electrodes: A pilot study of lesion geometry and temperature characteristics

Deep brain stimulation (DBS) electrodes have been used effectively to perform radiofrequency lesions in the brain. This study aimed to characterize lesion geometry and peak tissue temperature achieved when lesioning through DBS electrodes. Fresh bovine liver was chosen for a medium as the tissue reliably changes color between 45 and 50°C. Medtronic 3387 DBS electrodes (Medtronic Sofamor Danek, Inc., Memphis, TN, USA) and the Cosman G4 Radiofrequency Generator (Cosman Medical, Inc., Burlington, MA, USA) were used for lesioning. Bipolar lesions were created at currents between 25 mA and 100 mA for 60–120 seconds. Peak tissue temperature was monitored with Cosman disposable cordotomy electrode (LCED; Cosman Medical Inc.) and recorded. Photographic analysis of the lesions was performed. Tissue impedance ranged between 800–900 Ohms, and tissue temperature was maintained at 20°C. With lesions at 25 mA for up to 120 seconds, maximal tissue temperature achieved was 36°C. This correlated with no visible lesions. At 50 mA, maximal tissue temperature exceeded 100°C, which was associated with tissue charring. Lesions created at 35 mA and 40 mA led to an increase in tissue temperature of 63°C and 75°C, respectively. Lesion size was highly reproducible, increasing from 4.5 mm × 7 mm at 35 mA, to 6 mm × 7.5 mm at 50 mA. Preliminary analysis suggests that caution should be exerted in using lesion amplitudes exceeding 40 mA (at 800 Ohms), as peak tissue temperatures in vivo could exceed 100°C. Further in vivo experiments with imaging correlates are needed to further test the safety of this technique.     

Correction to: Epilepsy related multimorbidity,polypharmacy and risks in adults with intellectual disabilities: a national study

Journal of Neurology -