CD6 and Syntaxin Binding Protein 6 Variants and Response to Tumor Necrosis Factor Alpha Inhibitors in Danish Patients with Rheumatoid Arthritis

<div><h3>Background</h3><p>TNFα inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, however at least 30% do not respond. We aimed to investigate insertions and deletions (INDELS) associated with response to TNFα inhibitors in patients with rheumatoid arthritis (RA).</p> <h3>Methodology and Principal Findings</h3><p>In the DANBIO Registry we identified 237 TNFα inhibitor naïve patients with RA (81% women; median age 56 years; disease duration 6 years) who initiated treatment with infliximab (n = 160), adalimumab (n = 56) or etanercept (n = 21) between 1999 and 2008 according to national treatment guidelines. Clinical response was assessed at week 26 using EULAR response criteria. Based on literature, we selected 213 INDELS potentially related to RA and treatment response using the GeneVa® (Compugen) <em>in silico</em> database of 350,000 genetic variations in the human genome. Genomic segments were amplified by polymerase chain reaction (PCR), and genotyped by Sanger sequencing or fragment analysis. We tested the association between genotypes and EULAR good response versus no response, and EULAR good response versus moderate/no response using Fisher’s exact test. At baseline the median DAS28 was 5.1. At week 26, 68 (29%) patients were EULAR good responders, while 81 (34%) and 88 (37%) patients were moderate and non-responders, respectively. A 19 base pair insertion within the CD6 gene was associated with EULAR good response vs. no response (OR = 4.43, 95% CI: 1.99–10.09, p = 7.211×10⁻⁵) and with EULAR good response vs. moderate/no response (OR = 4.54, 95% CI: 2.29–8.99, p = 3.336×10⁻⁶). A microsatellite within the syntaxin binding protein 6 (STXBP6) was associated with EULAR good response vs. no response (OR = 4.01, 95% CI: 1.92–8.49, p = 5.067×10⁻⁵).</p> <h3>Conclusion</h3><p>Genetic variations within CD6 and STXBP6 may influence response to TNFα inhibitors in patients with RA.</p> </div

Perianesthetic Management of Laparoscopic Kidney Surgery

Laparoscopic kidney surgery is commonly used for living donor, partial, and total tumor nephrectomy. The successful emergence of laparoscopic technique was justified by the many benefits offered such as reduced blood loss, tissue trauma, pain, and hospital stay. However, this comes at the expense of physiologic changes and complications secondary to pneumoperitoneum, surgical technique, and patient positioning with significant challenges in anesthetic management. A variety of laparoscopic approaches (transperitoneal, retroperitoneal, hand-assisted, robotic) are used with some having advantages over others. The kidneys are particularly sensitive to hemodynamic changes and pneumoperitoneum. Controversies in perioperative fluid administration exist. New modalities for postoperative pain control have been suggested. Laparoscopic kidney surgery is associated with multiple physiologic changes and adverse events but offers advantages of reduced postoperative pain, faster recovery, and shorter hospital stay. Understanding these physiologic changes and related anesthetic considerations is key for safe patient outcome