Safe and Effective Use of Bilateral Erector Spinae Block in Patient Suffering from Post-Operative Coagulopathy Following Hepatectomy.

BACKGROUND Regional nerve blocks ideally provide safe and effective post-operative pain control, decrease opiate requirements, and enhance recovery from intense pain following major thoracic, abdominal, and musculoskeletal surgeries. The erector spinae plane block, a recently described novel treatment for chronic neuropathic pain and acute pain after thoracic surgery, can be performed with in plane infiltration and placement of a continuous infusion catheter deep to the erector spinae muscle at the tip of the transverse process, resulting in diffusion of local anesthetic between vertebrae and the paravertebral space with sensory blockade of spinal nerves as well as sympathetic branches. CASE REPORT We describe the novel use of the erector spinae block for primary pain control and uncomplicated catheter removal in the setting of anticoagulation following a major hepatectomy for intrahepatic cholangiocarcinoma. The use of the erector spinae block in this context provided effective post-operative analgesia. CONCLUSIONS Additional evidence from clinical trials will be helpful to evaluate the role of this relatively new block for peri-operative analgesia.

Urologic Surgery with Multisystem Comorbidities: A Case Report.

BACKGROUND Originally implemented for colorectal surgery, enhanced perioperative protocols have been incorporated into many surgical fields in an effort to improve outcomes. The cornerstone of many strategies includes patient education, liberalized oral intake on the day of surgery, no routine bowel prep, targeted multimodal analgesia, cautious use of IV hydration, early extubation, avoidance of NG tubes and/or surgical drains, and encouraging early postoperative ambulation. CASE REPORT We report on the successful outcome of a single patient with a rare autosomal dominant disorder (hereditary hemorrhagic telangiectasia) with multisystem involvement including pulmonary, cardiac, hematologic, gastrointestinal, renal, oncologic, and hepatic comorbidities, scheduled for open nephrectomy. CONCLUSIONS Prospective and retrospective studies are needed to specifically elucidate the role of similar management in higher-risk surgical candidates.

High-affinity interaction between IKKbeta and NEMO.

The Ser/Thr-specific IkappaB kinase (IKK), which comprises IKKalpha or IKKbeta and the regulatory protein NEMO, is at the bottleneck for NF-kappaB activation. IKK activity relies on interaction between NEMO and IKKalpha or IKKbeta. A conserved region in the C-terminal tail of IKKbeta or IKKalpha (NEMO-binding domain, NBD, residues 734-745 of IKKbeta) is important for interaction with NEMO. Here we show that the NBD peptide of IKKbeta is not sufficient for interaction with NEMO. Instead, a longer region of the IKKbeta C-terminal region provides high affinity for NEMO. Quantitative measurements using surface plasmon resonance and isothermal titration calorimetry confirm the differential affinities of these interactions and provide insight into the kinetic and thermodynamic behaviors of the interactions. Biochemical characterization using multiangle light scattering (MALS) coupled with refractive index shows that the longer IKKbeta C-terminal region forms a 2:2 stoichiometirc complex with NEMO.

TAK1-dependent signaling requires functional interaction with TAB2/TAB3.

Transforming growth factor beta-activated kinase 1 (TAK1), a member of the MAPKKK family, was initially described to play an essential role in the transforming growth factor beta-signaling pathway, but recent evidence has emerged implicating TAK1 in the interleukin (IL)-1 and tumor necrosis factor (TNF) pathways. Notably, two homologous proteins, TAB2 and TAB3, have been identified as adaptors linking TAK1 to the upstream adaptors TRAFs. However, it remains unclear whether the interaction between TAB2/TAB3 and TAK1 is necessary for its kinase activation and subsequent activation of the IKK and MAPK pathways. Here, we characterized the TAB2/TAB3-binding domain in TAK1 and further examined the requirement of this interaction for IL-1, TNF, and RANKL signaling. Through deletion mapping experiments, we demonstrated that the binding motif for TAB2/TAB3 is a non-contiguous region located within the last C-terminal 100 residues of TAK1. However, residues 479-553 of TAK1 appear to be necessary and sufficient for TAB2/TAB3 interaction. Conversely, residues 574-693 of TAB2 were shown to interact with TAK1. A green fluorescent protein fusion protein containing the last 100 residues of TAK1 (TAK1-C100) abolished the interaction of endogenous TAB2/TAB3 with TAK1, the phosphorylation of TAK1, and prevented the activation of IKK and MAPK induced by IL-1, TNF, and RANKL. Furthermore, TAK1-C100 blocked RANKL-induced nuclear accumulation of NFATc1 and consequently osteoclast differentiation consistent with the ability of a catalytically inactive TAK1 to block RANKL-mediated signaling. Significantly, our study provides evidence that the TAB2/TAB3 interaction with TAK1 is crucial for the activation of signaling cascades mediated by IL-1, TNF, and RANKL.

Partial rescue of the p35-/- brain phenotype by low expression of a neuronal-specific enolase p25 transgene.

Cyclin-dependent kinase 5 (Cdk5) is activated on binding of activator proteins p35 and p39. A N-terminally truncated p35, termed p25, is generated through cleavage by the Ca(2+)-dependent protease calpain after induction of ischemia in rat brain. p25 has been shown to accumulate in brains of patients with Alzheimer's disease and may contribute to A-beta peptide-mediated toxicity. Studies from transfected neurons as well as p35 and p25 transgenic mice have indicated that Cdk5, when activated by p25, gains some toxic function compared with p35/Cdk5. It remains unclear, however, whether p25/Cdk5 signaling additionally channels into pathways usually used by p35/Cdk5 and whether p25 is associated with a loss of p35 function. To clarify these issues, we have generated p25-transgenic mice in a p35-null background. We find that low levels of p25 during development induce a partial rescue of the p35-/- phenotype in several brain regions analyzed, including a rescue of cell positioning of a subset of neurons in the neocortex. In accordance with the partial rescue of brain anatomy, phosphorylation of the Cdk5 substrate mouse disabled 1 is partially restored during development. Besides this, p25/Cdk5 fails to phosphorylate other substrates that are normally phosphorylated by p35/Cdk5. Our results show that p25 can substitute for p35/Cdk5 under certain circumstances during development. In addition, they suggest that p25 may have lost some functions of p35.