Growth factors have been widely used in strategies to regenerate and repair diseased tissues, but current therapies that go directly from bench to bedside have had limited clinical success. We hypothesize that engineering successful therapies with recombinant proteins will often require specific quantitative information of the spatiotemporal role of the factors and the development of sophisticated delivery approaches that provide appropriate tissue exposures. This hypothesis was tested in the context of therapeutic angiogenesis. An in vitro model of angiogenesis was adapted to quantify the role of the concentration/gradient of vascular endothelial growth factor [VEGF(165)] on microvascular endothelial cells, and a delivery system was then designed, based on a mathematical model, to provide the desired profile in ischemic mice hindlimbs. This system significantly enhanced blood vessel formation, and perfusion and recovery from severe ischemia. This general approach may be broadly applicable to growth factor therapies.

Intracranial electroencephalography (iEEG) can be performed using minimally invasive stereo-electroencephalography (SEEG) or by implanting subdural electrodes via a craniotomy or multiple burr holes. There is anecdotal evidence that SEEG is becoming more common in the United States, though this has yet to be quantified. To address this question, all SEEG and burr hole/craniotomy subdural iEEG procedures were extracted from the Centers for Medicare and Medicaid Services Part B data files for the years 2000-2016. National trends were compared over time. In 2016, SEEG became the most frequently performed intracranial monitoring procedure in the Medicare population, increasing from 28.8% of total cases in 2000 to 43.1% in 2016 (p = 0.02). The proportion of strip electrode cases (through burr holes) significantly declined, while the frequency of craniotomies for subdural grid placement did not significantly change. These data are consistent with a nationwide increase in the utilization of SEEG with a concomitant decline in burr hole placement of subdural strip electrodes in the United States. The factors driving these changes are unknown, but are likely due in part to the desire for minimally invasive surgical options.

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Brock AA, Friedman RM, Fan RH, Roe AW. Optical imaging of cortical networks via intracortical microstimulation. J Neurophysiol 110: 2670 -2678. First published September 11, 2013 doi:10.1152/jn.00879.2012.-Understanding cortical organization is key to understanding brain function. Distinct neural networks underlie the functional organization of the cerebral cortex; however, little is known about how different nodes in the cortical network interact during perceptual processing and motor behavior. To study cortical network function we examined whether the optical imaging of intrinsic signals (OIS) reveals the functional patterns of activity evoked by electrical cortical microstimulation. We examined the effects of current amplitude, train duration, and depth of cortical stimulation on the hemodynamic response to electrical microstimulation (250-Hz train, 0.4-ms pulse duration) in anesthetized New World monkey somatosensory cortex. Electrical stimulation elicited a restricted cortical response that varied according to stimulation parameters and electrode depth. Higher currents of stimulation recruited more areas of cortex than smaller currents. The largest cortical responses were seen when stimulation was delivered around cortical layer 4. Distinct local patches of activation, highly suggestive of local projections, around the site of stimulation were observed at different depths of stimulation. Thus we find that specific electrical stimulation parameters can elicit activation of single cortical columns and their associated columnar networks, reminiscent of anatomically labeled networks. This novel functional tract tracing method will open new avenues for investigating relationships of local cortical organization. intrinsic signal optical imaging; electrical microstimulation PRIMATE CEREBRAL CORTEX is composed of a collection of cortical columns. These columns are 100-to 250-m-sized processing units that are interconnected to form distinct stimulusspecific processing networks. With this organization, the cerebral cortex is able to process information in parallel, perhaps best exemplified by the anatomical and functional organization found within visual cortical areas (see, e.g., Hubel 1984a, 1984b; Ts'o and Gilbert 1988). Anatomical and electrophysiological connectivity studies in V1 and V2 have revealed separate networks strongly associated with color processing (in the blobs in V1 and thin stripes in V2) and orientation selectivity (in the interblob regions and thick/pale stripes), respectively. Ongoing research is still revealing how these feature-specific networks generate the perception of the visual world.

OBJECTIVE Overlapping surgery-the performance of parts of 2 or more surgical procedures at the same time by a single lead surgeon-has recently come under intense scrutiny, although data on the effects of overlapping procedures on patient outcomes are lacking. The authors examined the impact of overlapping surgery on complication rates in neurosurgical patients. METHODS The authors conducted a retrospective review of consecutive nonemergent neurosurgical procedures performed during the period from May 12, 2014, to May 12, 2015, by any of 5 senior neurosurgeons at a single institution who were authorized to schedule overlapping cases. Overlapping surgery was defined as any case in which 2 patients under the care of a single lead surgeon were under anesthesia at the same time for any duration. Information on patient demographics, premorbid conditions, surgical variables, and postoperative course were collected and analyzed. Primary outcome was the occurrence of any complication from the beginning of surgery to 30 days after discharge. A secondary outcome was the occurrence of a serious complication-defined as a life-threatening or life-ending event-during this same period. RESULTS One thousand eighteen patients met the inclusion criteria for the study. Of these patients, 475 (46.7%) underwent overlapping surgery. Two hundred seventy-one patients (26.6%) experienced 1 or more complications, with 134 (13.2%) suffering a serious complication. Fourteen patients in the cohort died, a rate of 1.4%. The overall complication rate was not significantly higher for overlapping cases than for nonoverlapping cases (26.3% vs 26.9%, p = 0.837), nor was the rate of serious complications (14.7% vs 11.8%, p = 0.168). After adjustments for surgery type, surgery duration, body mass index, American Society of Anesthesiologists (ASA) physical classification grade, and intraoperative blood loss, overlapping surgery remained unassociated with overall complications (OR 0.810, 95% CI 0.592-1.109, p = 0.189). Similarly, after adjustments for surgery type, surgery duration, body mass index, ASA grade, and neurological comorbidity, there was no association between overlapping surgery and serious complications (OR 0.979, 95% CI 0.661-1.449, p = 0.915). CONCLUSIONS In this cohort, patients undergoing overlapping surgery did not have an increased risk for overall complications or serious complications. Although this finding suggests that overlapping surgery can be performed safely within the appropriate framework, further investigation is needed in other specialties and at other institutions.