Although BSCM surgery has significant associated risks, including perioperative complications, new neurological deficits, and death, most patients have favorable outcomes. Overall, surgery markedly improved the risk of rehemorrhage and related symptoms and should be considered in patients with accessible lesions.

Lumbar interbody fusion involves insertion of a structural graft into an intervertebral disc space to promote bony arthrodesis. It is a well-established surgical strategy for multiple spinal disorders ranging from degenerative conditions to trauma, neoplastic diseases, and deformities requiring correction. Since the inception of lumbar interbody fusion, the most established techniques have been two posterior approaches, the posterior lumbar interbody fusion (PLIF) and the transforaminal lumbar interbody fusion (TLIF). Within the past 15 years, multiple anterolateral approaches to the spine have become widely adopted. These approaches can be performed minimally invasively and spare disruption of the paraspinal muscles and posterior spinal column while enabling wide exposure of the disc space for insertion of interbody grafts much larger than PLIF and TLIF instrumentation. This review highlights three minimally invasive anterolateral approaches: the anterior lumbar interbody fusion (ALIF), the transpsoas lateral lumbar interbody fusion (LLIF), and prepsoas or anterior to the psoas oblique lumbar interbody fusion (OLIF). Relevant topics for discussion and comparison include patient selection, surgical techniques, outcomes, and complications for the three surgical approaches.

OBJECTIVE This study evaluated the utility, specificity, and sensitivity of intraoperative confocal laser endomicroscopy (CLE) to provide diagnostic information during resection of human brain tumors. METHODS CLE imaging was used in the resection of intracranial neoplasms in 74 consecutive patients (31 male; mean age 47.5 years; sequential 10-month study period). Intraoperative in vivo and ex vivo CLE was performed after intravenous injection of fluorescein sodium (FNa). Tissue samples from CLE imaging–matched areas were acquired for comparison with routine histological analysis (frozen and permanent sections). CLE images were classified as diagnostic or nondiagnostic. The specificities and sensitivities of CLE and frozen sections for gliomas and meningiomas were calculated using permanent histological sections as the standard. RESULTS CLE images were obtained for each patient. The mean duration of intraoperative CLE system use was 15.7 minutes (range 3–73 minutes). A total of 20,734 CLE images were correlated with 267 biopsy specimens (mean number of images/biopsy location, in vivo 84, ex vivo 70). CLE images were diagnostic for 45.98% in vivo and 52.97% ex vivo specimens. After initiation of CLE, an average of 14 in vivo images and 7 ex vivo images were acquired before identification of a first diagnostic image. CLE specificity and sensitivity were, respectively, 94% and 91% for gliomas and 93% and 97% for meningiomas. CONCLUSIONS CLE with FNa provided intraoperative histological information during brain tumor removal. Specificities and sensitivities of CLE for gliomas and meningiomas were comparable to those for frozen sections. These data suggest that CLE could allow the interactive identification of tumor areas, substantially improving intraoperative decisions during the resection of brain tumors.

OBJECTIVEMinimally invasive anterolateral retroperitoneal approaches for lumbar interbody arthrodesis have distinct advantages attractive to spine surgeons. Prepsoas or transpsoas trajectories can be employed with differing complication profiles because of the inherent anatomical differences encountered in each approach. The evidence comparing them remains limited because of poor quality data. Here, the authors sought to systematically review the available literature and perform a meta-analysis comparing the two techniques.METHODSA systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A database search was used to identify eligible studies. Prepsoas and transpsoas studies were compiled, and each study was assessed for inclusion criteria. Complication rates were recorded and compared between approach groups. Studies incorporating an analysis of postoperative subsidence and pseudarthrosis rates were also assessed and compared.RESULTSFor the prepsoas studies, 20 studies for the complications analysis and 8 studies for the pseudarthrosis outcomes analysis were included. For the transpsoas studies, 39 studies for the complications analysis and 19 studies for the pseudarthrosis outcomes analysis were included. For the complications analysis, 1874 patients treated via the prepsoas approach and 4607 treated with the transpsoas approach were included. In the transpsoas group, there was a higher rate of transient sensory symptoms (21.7% vs 8.7%, p = 0.002), transient hip flexor weakness (19.7% vs 5.7%, p < 0.001), and permanent neurological weakness (2.8% vs 1.0%, p = 0.005). A higher rate of sympathetic nerve injury was seen in the prepsoas group (5.4% vs 0.0%, p = 0.03). Of the nonneurological complications, major vascular injury was significantly higher in the prepsoas approach (1.8% vs 0.4%, p = 0.01). There was no difference in urological or peritoneal/bowel injury, postoperative ileus, or hematomas (all p > 0.05). A higher infection rate was noted for the transpsoas group (3.1% vs 1.1%, p = 0.01). With regard to postoperative fusion outcomes, similar rates of subsidence (12.2% prepsoas vs 13.8% transpsoas, p = 0.78) and pseudarthrosis (9.9% vs 7.5%, respectively, p = 0.57) were seen between the groups at the last follow-up.CONCLUSIONSComplication rates vary for the prepsoas and transpsoas approaches owing to the variable retroperitoneal anatomy encountered during surgical dissection. While the risks of a lasting motor deficit and transient sensory disturbances are higher for the transpsoas approach, there is a reciprocal reduction in the risks of major vascular injury and sympathetic nerve injury. These results can facilitate informed decision-making and tailored surgical planning regarding the choice of minimally invasive anterolateral access to the spine.

The role of Ca 2؉ signaling in triggering hypertrophy was investigated in neonatal rat cardiomyocytes in vitro. We show that an increase in cell size and sarcomere reorganization were elicited by receptor agonists such as Angiotensin II, aldosterone, and norepinephrine and by a small rise in medium KCl concentration, a treatment devoid of direct effects on receptor functions. All these treatments increased the frequency of spontaneous [Ca 2؉ ] transients, caused nuclear translocation of transfected NFAT(GFP), and increased the expression of a NFAT-sensitive reporter gene. There was no increase in Ca 2؉ spark frequency in the whole cell or in the perinuclear region under these conditions. Hypertrophy and NFAT translocation but not the increased frequency of [Ca 2؉ ] transients were inhibited by the calcineurin inhibitor cyclosporine A. Hypertrophy by the different stimuli was insensitive to inhibition of myofilament contraction. We concluded that calcineurin-NFAT can act as integrators of the contractile Ca 2؉ signal, and that they can decode alterations in the frequency even of rapid Ca 2؉ oscillations. C ardiac hypertrophy accompanies many forms of heart pathologies, such as genetic or congenital defects, ischemia, and hypertension. The molecular signaling pathways through which the different hypertrophic stimuli modulate cardiac cell size include mitogen-activated protein kinase, Gp130/Stat3, Calmodulin (CaM)-dependent kinases, and the calcineurin-regulated pathway (1). The latter has recently received much attention, in part because it can be the target of therapeutic intervention with well known drugs. For example, in transgenic mice, it has been demonstrated that overexpression of the Ca 2ϩ -dependent phosphatase calcineurin causes a dramatic increase in the size of the heart, inhibited by cyclosporine A (CsA), a calcineurin blocker (2). Along the same line, overexpression of Cain/Cabin (molecules that associate with the calcineurin and inhibit its activity) attenuate cardiac hypertrophy caused not only by calcineurin overexpression but also by pressure overload or ␤-adrenergic receptor stimulation (3). The effect of CsA on cardiac hypertrophy, however, has led to contradictory results in different model systems (4,5).At the cellular level, cardiomyocyte hypertrophy is characterized by an increase in cell size, enhanced protein synthesis, activation of fetal genes, and cytoskeleton reorganization (4, 5). A number of treatments are known to induce cardiac cell hypertrophy in vitro, including angiotensin II (Ang II) (6), catecholamines (7), endothelin (8), and aldosterone (9). Many, but not all, of these hormones are known to be coupled to alterations in Ca 2ϩ homeostasis. In particular, (i) Ang II (6) and endothelin (10) are coupled to IP 3 generation and Ca 2ϩ mobilization from stores; (ii) catecholamines, in particular through ␤1 receptors, are known to induce an increase in the frequency and amplitude of Ca 2ϩ spiking in cardiomyocytes (7); and (iii) the mechanism of aldosterone-induced hypertrophy in vit...

Brainstem cavernous malformations (CMs) are low-flow vascular lesions in eloquent locations. Their presentation is often marked with symptomatic hemorrhages that appear to occur more frequently than hemorrhage from supratentorial cavernomas. Brainstem CMs can be removed using 1 of the 5 standard skull-base approaches: retrosigmoid, suboccipital (with or without telovelar approach), supracerebellar infratentorial, orbitozygomatic, and far lateral. Patients being referred to a tertiary institution often have lesions that are aggressive with respect to bleeding rates. Nonetheless, the indications for surgery, in the authors' opinion, are the same for all lesions: those that are symptomatic, those that cause mass effect, or those that abut a pial surface. Patients often have relapsing and remitting courses of symptoms, with each hemorrhage causing a progressive and stepwise decline. Many patients experience new postoperative deficits, most of which are transient and resolve fully. Despite the risks associated with operating in this highly eloquent tissue, most patients have had favorable outcomes in the authors' experience. Surgical treatment of brainstem CMs protects patients from the potentially devastating effects of rehemorrhage, and the authors believe that the benefits of intervention outweigh the risks in patients with the appropriate indications.

Pedicled VBGs can feasibly be applied to posterior spinal arthrodesis from occiput to T12. Patients at high risk for nonunion may benefit from this strategy.

Rationale: Uncoupling protein (UCP)2 is a mitochondrial inner membrane protein that is expressed in mammalian myocardium under normal conditions and upregulated in pathological states such as heart failure. UCP2 is thought to protect cardiomyocytes against oxidative stress by dissipating the mitochondrial proton gradient and mitochondrial membrane potential (⌬⌿ m ), thereby reducing mitochondrial reactive oxygen species generation. However, in apparent conflict with its uncoupling role, UCP2 has also been proposed to be essential for mitochondrial Ca 2؉ uptake, which could have a protective action by stimulating mitochondrial ATP production. Objective: The goal of this study was to better understand the role of myocardial UCP2 by examining the effects of UCP2 on bioenergetics, Ca 2؉ homeostasis, and excitation-contraction coupling in neonatal cardiomyocytes. Methods and Results: Adenoviral-mediated expression of UCP2 caused a mild depression of ⌬⌿ m and increased the basal rate of oxygen consumption but did not affect total cellular ATP levels. Mitochondrial Ca 2؉ uptake was examined in permeabilized cells loaded with the mitochondria-selective Ca 2؉ probe, rhod-2. UCP2 overexpression markedly inhibited mitochondrial Ca 2؉ uptake. Pretreatment with the UCP2-specific inhibitor genipin largely reversed the effects UCP2 expression on mitochondrial Ca 2؉ handling, bioenergetics, and oxygen utilization. Electrically evoked cytosolic Ca 2؉ transients and spontaneous cytosolic Ca 2؉ sparks were examined using fluo-based probes and confocal microscopy in line scan mode. UCP2 overexpression significantly prolonged the decay phase of [Ca 2؉ ] c transients in electrically paced cells, increased [Ca 2؉ ] c spark activity and increased the probability that Ca 2؉ sparks propagated into Ca 2؉ waves. This dysregulation results from a loss of the ability of mitochondria to suppress local Ca 2؉ -induced Ca 2؉ release activity of the sarcoplasmic reticulum. Conclusion: Increases in UCP2 expression that lower ⌬⌿ m and contribute to protection against oxidative stress, also have deleterious effects on beat-to-beat [Ca 2؉ ] c handling and excitation-contraction coupling, which may contribute to the progression of heart disease. (Circ Res. 2010;106:730-738.) Key Words: uncoupling protein-2 Ⅲ mitochondria Ⅲ calcium Ⅲ calcium sparks Ⅲ excitation-contraction coupling I n ventricular myocytes, the majority of the sarcolemmal Ca 2ϩ current comes from voltage-gated L-type Ca 2ϩ channels. These L-type Ca 2ϩ channels are primarily found at the junctions of the sarcolemma with the sarcoplasmic reticulum (SR) where they are coupled to SR Ca 2ϩ -release channels, ryanodine receptors (RyRs), forming junctional complexes. 1 The coupling of RyRs to L-type Ca 2ϩ channels serves to amplify [Ca 2ϩ ] c increases through Ca 2ϩ -induced Ca 2ϩ release (CICR), to meet the threshold needed to initiate cellular contraction.It is well established that mitochondria have a large capacity to accumulate Ca 2ϩ and that mitochondrial Ca 2ϩ ([Ca 2ϩ ] m ...