Pharmacogenetic workup of perioperative serotonin syndrome

Serotonin syndrome is gaining attention in perioperative and chronic pain settings due to the growing prevalence of multimodal therapies that increase serotonin levels and thereby heighten patient risk. A patient's genetic make-up may further increase the risk of serotonin syndrome. A case of serotonin syndrome on emergence after general anesthesia is presented. A subsequent cytochrome P4502D6 genetic test result suggested a potential alteration in metabolism. For this patient, who was taking combination antidepressant medications and receiving common perioperative medicines, additive pharmacodynamic effects converged with a pharmacogenetic predisposition, resulting in serotonin syndrome.     

Peripheral platelet count correlates with liver atrophy and predicts long‐term mortality on the liver transplant waiting list

Several studies have shown a direct role of liver atrophy in the pathogenesis of thrombocytopenia of cirrhosis via reduced production of thrombopoeitin. About 181 patients listed for liver transplantation at a single transplant center were evaluated at the time of listing with laboratory tests and volumetric liver measurements using computed tomography. Expected normal liver volume was calculated using the Heinemann formula. Liver volume ratio (LVR) was calculated as actual liver volume over expected liver volume. Patients were predominantly male (70.7%), with viral hepatitis (60.2%), had a mean age of 51.8 years (SD 8.7), model for end stage liver disease (MELD) of 14 (SD 6.4), LVR of 0.95 (SD 0.3), and platelet count of 105 000/mcL (SD 66 000). Platelet count (P < 0.0001) correlated more strongly with LVR than MELD, MELD components (P = 0.27) or serum albumin (P = 0.003). Platelet count (HR 0.987, 95% CI 0.979–0.994, P = 0.001) was a strong independent predictor of mortality. Patients with platelet count < 100 000/mcL had a shorter survival (935 vs. 1396 days, P = 0.002) and higher death rate (42.2% vs. 23.6%, P = 0.01), but no different transplantation rate (36.7% vs. 33.3%, P = 0.64) compared to those with platelet count ≥ 100 000/mcL. Low platelet count corresponds to higher waiting list mortality and is a sign of advanced liver atrophy.     

Orbital Preservation in Patients with Esthesioneuroblastoma

Objectives Surgical resection in addition to adjuvant radiation with or without chemotherapy is the mainstay of treatment for esthesioneuroblastoma (ENB). However, management of patients with orbital involvement remains controversial. Historically, orbital exenteration has been advocated when there is evidence of periorbital invasion. Recently, the indications for orbital exenteration have become more selective and orbital preservation has been advocated. We report our experience with anterior craniofacial resection and orbital preservation in patients with ENB.Design Retrospective review of all patients diagnosed with esthesioneuroblastoma who underwent traditional open anterior craniofacial resection at the Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary Cranial Base Center from 1997 to 2008.Results Sixteen patients were identified with a mean follow-up of 76 months. All patients underwent anterior craniofacial resection via an open approach and adjuvant proton beam radiation. Six of the 16 patients had evidence of either periorbital or lacrimal sac involvement at the time of surgery. All of these patients underwent periorbital resection to negative histologic margins with preservation of the orbit.Conclusion In our study, patients with ENB and periorbital invasion—who were treated with anterior craniofacial resection and periorbital resection with orbital preservation—had no evidence of decreased survival. In all patients, negative histologic margins of the periorbital resection were achieved.     

Management of ruptured dissecting intracranial aneurysms in infants: report of four cases and review of the literature

Backgound

Intracranial cerebral aneurysms in the pediatric population are infrequent, and those occurring in infants less than 1 year old are extremely rare. Of intracranial aneurysms in children, dissecting aneurysms are the most common type seen. While spontaneous dissecting aneurysms usually present with ischemia, hemorrhage can also occur.

Methods

A retrospective review of our patients revealed that from July 1, 2007 to June 30, 2012, four infants were treated for ruptured distal dissecting intracranial aneurysms at Texas Children’s Hospital. Mycotic aneurysms and collagen vascular disorder were excluded in all four cases. All patients presented in our series presented with subarachnoid hemorrhage, and three had intraventricular hemorrhage. All patients underwent conventional catheter angiography for diagnosis. All patients in this series were managed in the acute or subacute period with surgical or endovascular trapping without distal bypass procedures. All four patients tolerated sacrifice of the parent vessels feeding these distal aneurysms well.

Case report and review of literature

We describe the presentation and management of these rare cases and then review the current literature on the management of these dissecting aneurysms in infants.     

Monitoring information processing efficiency after stroke or head injury: A comparison of four computerised tests for use in single case experiments

Abstract

Single case experiments on cognitive rehabilitation can only be valid if adequate methods of monitoring cognitive change are developed. The sensitivity and reliability of four computer-based tests of information processing efficiency (continuous choice reaction time, visual tracking, memory for pairs, and critical flicker fusion) were compared. Performance of 16 left hemisphere stroke patients and 17 patients with severe closed head injury was compared with age-matched controls. The reaction time task proved the most useful in detecting effects of brain damage in both groups and showing good test-retest reliability.     

The relationship between negative trauma-related cognitions and psychosocial functioning in veterans with posttraumatic stress disorder and alcohol use disorder

Abstract

Background: The comorbidity of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is highly prevalent and associated with especially poor psychosocial functioning. Negative trauma-related cognitions are theoretically proposed to be associated with poor psychosocial functioning in PTSD, but few studies have examined the association between negative trauma-related cognitions and psychosocial functioning in PTSD/AUD. Evaluating this association may provide evidence of a potential treatment target for improving psychosocial functioning in PTSD/AUD. We hypothesized that negative trauma-related cognitions, including cognitions about the self, world, and self-blame, would be independently associated with poor psychosocial functioning in the following domains: vitality, psychosocial well-being, role limitations due to emotional distress, and social functioning. Methods: We examined the relationship between negative trauma-related cognitions and psychosocial functioning in 145 treatment-seeking veterans with PTSD/AUD using multiple linear regression analyses while controlling for PTSD and alcohol abuse and dependence severity. Results: Our hypotheses were partially supported. We found that negative trauma-related cognitions were uniquely associated with greater psychosocial functional impairment, independent of PTSD and alcohol abuse and dependence severity. Specifically, negative trauma-related cognitions about the self were associated with greater psychosocial functional impairment across all domains, cognitions about the world were associated with worse social functioning and psychological well-being, and self-blame was associated with impaired psychological well-being. Conclusions: Given that improvements in negative trauma-related cognitions are a mechanism of trauma-focused treatment, future studies should examine whether changes in negative trauma-related cognitions through trauma-focused treatment are associated with improved psychosocial functioning.     

Chromosomal reinsertion of broken RSS ends during T cell development

The V(D)J recombinase catalyzes DNA transposition and translocation both in vitro and in vivo. Because lymphoid malignancies contain chromosomal translocations involving antigen receptor and protooncogene loci, it is critical to understand the types of "mistakes" made by the recombinase. Using a newly devised assay, we characterized 48 unique TCRbeta recombination signal sequence (RSS) end insertions in murine thymocyte and splenocyte genomic DNA samples. Nearly half of these events targeted "cryptic" RSS-like elements. In no instance did we detect target-site duplications, which is a hallmark of recombinase-mediated transposition in vitro. Rather, these insertions were most likely caused by either V(D)J recombination between a bona fide RSS and a cryptic RSS or the insertion of signal circles into chromosomal loci via a V(D)J recombination-like mechanism. Although wild-type, p53, p53 x scid, H2Ax, and ATM mutant thymocytes all showed similar levels of RSS end insertions, core-RAG2 mutant thymocytes showed a sevenfold greater frequency of such events. Thus, the noncore domain of RAG2 serves to limit the extent to which the integrity of the genome is threatened by mistargeting of V(D)J recombination.