How much oxygen for the injured brain - can invasive parenchymal catheters help?

PURPOSE OF REVIEW: Each year in the United States there are over 2.5 million visits to emergency departments for traumatic brain injury (TBI), 300,000 hospitalizations, and 50,000 deaths. TBI initiates a complex cascade of events which can lead to significant secondary brain damage. Great interest exists in directly measuring cerebral oxygen delivery and demand after TBI to prevent this secondary injury. Several invasive, catheter-based devices are now available which directly monitor the partial pressure of oxygen in brain tissue (PbtO2), yet significant equipoise exists regarding their clinical use in severe TBI. RECENT FINDINGS: There are currently three ongoing multicenter randomized controlled trials studying the use of PbtO2 monitoring in severe TBI: BOOST-3, OXY-TC, and BONANZA. All three have similar inclusion/exclusion criteria, treatment protocols, and outcome measures. Despite mixed existing evidence, use of PbtO2 is already making its way into new TBI guidelines such as the recent Seattle International Brain Injury Consensus Conference. Analysis of high-fidelity data from multimodal monitoring, however, suggests that PbtO2 may only be one piece of the puzzle in severe TBI. SUMMARY: While current evidence regarding the use of PbtO2 remains mixed, three ongoing clinical trials are expected to definitively answer the question of what role PbtO2 monitoring plays in severe TBI.

Traumatic brain injury in pregnancy.

Trauma is the leading cause of nonobstetric maternal mortality and affects up to 8% of all pregnancies. Pregnant patients with traumatic brain injury (TBI) are an especially vulnerable population, and their management is complex, with multiple special considerations that must be taken into account. These include but are not limited to alterations in maternal physiology that occur with pregnancy, potential teratogenicity of pharmacologic therapies and diagnostic studies using ionizing radiation, need for fetal monitoring, Rh immunization status, placental abruption, and preterm labor. Despite these challenges, evidence regarding management of the pregnant patient with a TBI is lacking, limited to only case reports/series and retrospective analyses. Despite this uncertainty, expert opinion on management of these patients seems to be that, overall, the standard therapies for management of TBI are safe and effective in pregnancy, with a few notable exceptions described in this chapter. Significant work is needed to continue to develop best-practice and evidence-based guidelines for the management of TBI pregnancy.

Influence of smoking on aneurysm recurrence after endovascular treatment of cerebrovascular aneurysms.

OBJECTIVE Smoking is a known risk factor for aneurysm development and aneurysmal subarachnoid hemorrhage, as well as subsequent vasospasm in both untreated individuals and patients who have undergone surgical clipping of cerebrovascular aneurysms. However, there is a lack of data in the current scientific literature about the long-term effects that smoking has on the integrity of endovascular repairs of cerebral aneurysms. This study was designed to determine if any smoking history increased the risk of poorer outcomes and/or aneurysm recurrence in patients who have had endovascular repair of cerebral aneurysms. METHODS The authors retrospectively analyzed the medical records of patients admitted to the University of Michigan Health System from January 1999 to December 2011 with coiled aneurysms and angiography, CT angiography, or MR angiography follow-up. Patients were identified and organized based on many criteria including age, sex, smoking history, aneurysm recurrence, aneurysm location, and Hunt and Hess grade. Analysis was targeted to the patient population with a history of smoking. Bivariate chi-square tests were used to analyze the association between a positive smoking history and documented aneurysm recurrence and were adjusted for potential confounders by fitting multivariate logistic regression models of recurrence. RESULTS A total of 247 patients who had undergone endovascular treatment of 296 documented cerebral aneurysms were included in this study. The recurrence rate among all patients treated with endovascular repair was 24.3%, and the average time to the most recent follow-up imaging studies was 1.62 years. Smokers accounted for 232 aneurysms and were followed up for an average of 1.57 years, with a recurrence rate of 26.3%. Never smokers accounted for the remaining 64 aneurysms and were followed up for an average of 1.82 years, with a recurrence rate of 17.2%. Multivariate analysis revealed that, after controlling for potential confounders, a history of smoking-whether current or former-was associated with a significantly increased risk of aneurysm recurrence. The odds ratios for aneurysm recurrence for current and former smokers were 2.739 (95% CI 1.127-7.095, p = 0.0308) and 2.698 (95% CI 1.078-7.212, p = 0.0395), respectively, compared with never smokers. CONCLUSIONS A positive smoking history is associated with a significantly increased risk of aneurysm recurrence in patients who have undergone endovascular repair of a cerebral aneurysm, compared with the risk in patients who have never smoked.

Outcomes after surgery for spinal metastasis of colorectal origin: case series.

STUDY DESIGN: Retrospective study. PURPOSE: The aim of this study was to evaluate the clinical management and outcomes of patients who underwent surgical intervention for metastatic colorectal adenocarcinoma of the spine. OVERVIEW OF LITERATURE: Gastrointestinal (GI) cancer metastasis to the spine are relatively rare and represent later manifestations of the disease. Studies and reports on the outcomes of patients who undergo surgery for spinal metastasis of GI origin are scarce. METHODS: A retrospective chart review of all patients who underwent surgery for spinal metastasis of colorectal origin was performed. Four patients were identified. Patient characteristics, outcomes, and survival were analyzed. RESULTS: Two patients experienced improvement in pain or myelopathic symptoms. Although the mean survival was 15.3 months, this average included a patient still living at 57.1 months. The mean survival was just 1.3 months for the 3 patients who expired. CONCLUSIONS: In certain cases, symptomatic improvement with prolonged survival is possible after surgery for metastatic spinal lesions of colorectal origin; however, survival is poor in the majority of cases.

Independent predictors of complication following surgery for spinal metastasis.

PURPOSE: Surgery for spinal metastasis is often associated with significant morbidity. Despite a number of preoperative scoring systems/scales and identified variables that have been reported to predict complication risk, clinical studies that directly evaluate this issue using multivariate analysis are scarce. The goal of our study was to assess independent predictors of complication after surgery for spinal metastasis. METHODS: We queried electronic medical records to identify a consecutive population of adult patients who underwent surgery for spinal metastasis for the period June 2005 through June 2011. Utilizing multivariate logistic regression, we assessed independent predictors of perioperative and postoperative adverse events. RESULTS: A total of 106 patients were included in the final analysis. Overall complication rate was 21.7 %. Independent predictors for higher rates of complication were age greater than 40 years [40-65 years had odds ratio (OR) 1.91, 95 % confidence interval (CI) 1.02-16.78 and >65 years had OR 5.17, 95 % CI 1.54-29.81] and metastatic lesions involving three or more contiguous levels of the spine (OR 2.76, 95 % CI 1.09-9.61). CONCLUSIONS: Patients older than 40 years or patients who have metastatic lesions involving three or more contiguous vertebral levels appear to be at higher risk for complication. Patients older than 65 years have the greatest likelihood of complication.

Independent predictors of survival and the impact of repeat surgery in patients undergoing surgical treatment of spinal metastasis.

OBJECT: Surgery for spinal metastasis is considered palliative, and postoperative survival is often less than a year. Recurrence of metastatic lesions is quite common, and it remains unclear whether repeat surgery is effective. In this study, the authors assessed independent predictors for survival at 6 months, 1 year, and 2 years after surgery, and examined whether repeat surgery for recurrence of spinal metastasis influenced survival rates. METHODS: Retrospective review of the electronic medical records was performed to identify a consecutive population of adult patients who underwent surgery for spinal metastasis during the period 2005-2011. Utilizing a Cox proportional hazard regression model, the authors assessed independent predictors and risk factors for survival at 6 months, 1 year, and 2 years after surgery. In addition, the impact of repeat surgery on survival was specifically assessed via multivariable analysis. RESULTS: A total of 99 patients were included in the final analysis. The overall mean postoperative duration of survival was 9.6 months. In addition to previously identified predictors of survival (preoperative ambulation, Karnofsky Performance Status [KPS], radiotherapy, primary cancer type, presence of extraspinal metastasis, and number of spinal segments with metastasis), pain on presentation and body mass index (BMI) of 25-30 were both independently associated with survival. Patients with recurrence who underwent repeat surgery had longer mean survival times than patients with recurrence who did not undergo repeat surgery (19.6 months vs 12.8 months, respectively). Repeat surgery was also independently associated with higher survival rates on multivariate analysis. Follow-up KPS was significantly higher in patients who underwent repeat surgery as well. CONCLUSIONS: In addition to confirming previously identified predictors of survival following surgery for spinal metastasis, the authors identified BMI and pain on presentation as independent predictors of survival. They also found that repeat surgery may be a viable option in patients with metastatic recurrence and may offer prolonged survival, likely due to improved functionality, mitigating complications associated with immobility.

Epithelial expression of the cytosolic retinoid chaperone cellular retinol binding protein II is essential for in vivo imprinting of local gut dendritic cells by lumenal retinoids.

Dendritic cells (DCs) use all-trans retinoic acid (ATRA) to promote characteristic intestinal responses, including Foxp3(+) Treg conversion, lymphocyte gut homing molecule expression, and IgA production. How this ability to generate ATRA is conferred to DCs in vivo remains largely unstudied. Here, we observed that among DCs, retinaldehyde dehydrogenase (ALDH1), which catalyzes the conversion of retinal to ATRA, was preferentially expressed by small intestine CD103(+) lamina propria (LP) DCs. Retinoids induced LP CD103(+) DCs to generate ATRA via ALDH1 activity. Either biliary or dietary retinoids were required to confer ALDH activity to LP DCs in vivo. Cellular retinol-binding protein II (CRBPII), a cytosolic retinoid chaperone that directs enterocyte retinol and retinal metabolism but is redundant to maintain serum retinol, was required to confer ALDH activity to CD103(+) LP DCs. CRBPII expression was restricted to small intestine epithelial cells, and ALDH activity in CRBPII(-/-) DCs was restored by transfer to a wild-type recipient. CD103(+) LP DCs from CRBPII(-/-) mice had a decreased capacity to promote IgA production. Moreover, CD103(+) DCs preferentially associated with the small intestine epithelium and LP CD103(+) DC ALDH activity, and the ability to promote IgA production was reduced in mice with impaired DC-epithelia associations. These findings demonstrate in vivo roles for the expression of epithelial CRBPII and lumenal retinoids to imprint local gut DCs with an intestinal phenotype.

Aging impacts isolated lymphoid follicle development and function.

BACKGROUND: Immunosenescence is the age-related decline and dysfunction of protective immunity leading to a marked increase in the risk of infections, autoimmune disease, and cancer. The majority of studies have focused on immunosenescence in the systemic immune system; information concerning the effect of aging on intestinal immunity is limited. Isolated lymphoid follicles (ILFs) are newly appreciated dynamic intestinal lymphoid structures that arise from nascent lymphoid tissues, or cryptopatches (CP), in response to local inflammatory stimuli. ILFs promote "homeostatic" responses including the production of antigen-specific IgA, thus playing a key role in mucosal immune protection. ILF dysfunction with aging could contribute to immunosenescence of the mucosal system, and accordingly we examined phenotypic and functional aspects of ILFs from young (2 month old) and aged (2 year old) mice. RESULTS: We observed that aged mice have increased numbers of ILFs and increased numbers of structures corresponding to an early stage of CPs transforming into ILFs. The cellular composition of ILFs in aged mice is altered with a smaller B-lymphocyte population and an increased T-lymphocyte population. The ILF T-lymphocyte population is notable by the presence of CD4+ CD8αα+ T-lymphocytes, which are absent from the systemic compartment. The smaller B-lymphocyte population in ILFs from aged mice is directly correlated with decreased mRNA and protein expression of CCL20 and CXCL13, two chemokines that play crucial roles in recruiting B-lymphocytes into ILFs. Aged mice had elevated levels of serum and fecal immunoglobulins and despite the decreased B-lymphocyte population, ILFs from aged mice displayed increased IgA production. The immunoglobulin repertoire was skewed in aged mice, and ILFs demonstrated a repertoire usage similar to that of the systemic pool in both young and aged mice. CONCLUSIONS: Here we observed that ILF development, cellular composition, and immunoglobulin production are altered with aging suggesting that ILF dysfunction contributes to mucosal immunosenescence.