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Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in

Background Randomized controlled trials evaluating acute sciatica have not demonstrated prolonged improvements in terms of patient-reported pain and function. For chronic sciatica, however, microdiscectomy has been found to be superior at 1 year. Whether this effect persists during the second year is not known. The purpose of the present study was to report the 2-year outcomes following lumbar microdiscectomy as compared with standardized nonoperative care for the treatment of chronic sciatica resulting from a lumbar disc herniation. Methods The present study is a secondary analysis of a previously reported randomized controlled trial with extension to 2 years of follow-up. Patients with radiculopathy for 4 to 12 months resulting from an L4-L5 or L5-S1 disc herniation were randomized to microdiscectomy or 6 months of nonoperative care followed by surgery if needed. Intention-to-treat analysis was performed at 2 years for the primary outcome (the intensity of leg pain) (range of possible scores, 0 [no pain] to 10 [worst pain]) as well as for secondary outcomes (including the Oswestry Disability Index score, the intensity of back pain, and quality of life). Results One hundred and twenty-eight patients were randomized in the present study. Twenty-four (38%) of the 64 patients who had been randomized to nonoperative care crossed over to surgical treatment by 2 years following enrollment. At the 2-year time point, the follow-up rate was approximately 70%. At 2 years, the operative group had less leg pain than the nonoperative group (mean, 2.8 ± 0.4 compared with 4.2 ± 0.4; treatment effect, 1.3 [95% confidence interval, 0.3 to 2.4]). The treatment effect favored surgery for all secondary outcome measures at 6 months and 1 year and for back pain intensity and physical function at 2 years. Conclusions At 2 years, the present study showed that microdiscectomy was superior to nonoperative care for the treatment of chronic sciatica resulting from an L4-L5 or L5-S1 disc herniation. However, the difference between the groups did not surpass the minimal clinically important difference at 2 years as was reached at earlier follow-up points, likely as the result of patients crossing over from nonoperative to operative treatment. Level of evidence Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Background A recent randomized controlled trial (RCT), performed by the authors, comparing early surgical microdiscectomy with 6 months of nonoperative care for chronic lumbar radiculopathy showed that early surgery resulted in improved outcomes. However, estimates of the incremental cost-utility ratio (ICUR), which is often expressed as the cost of gaining one quality-adjusted life year (QALY), of microdiscectomy versus nonsurgical management have varied. Radiculopathy lasting more than 4 months is less likely to improve without surgical intervention and may have a more favorable ICUR than previously reported for acute radiculopathy. Question/purpose In the setting of chronic radiculopathy caused by lumbar disc herniation, defined as symptoms and/or signs of 4 to 12 months duration, is surgical management more cost-effective than 6 months of nonoperative care from the third-party payer perspective based on a willingness to pay of less than CAD 50,000/QALY? Methods A decision analysis model served as the vehicle for the cost-utility analysis. A decision tree was parameterized using data from our single-center RCT that was augmented with institutional microcost data from the Ontario Case Costing Initiative. Bottom-up case costing methodology generates more accurate cost estimates, although institutional costs are known to vary. There were no major surgical cost drivers such as implants or bone graft substitutes, and therefore, the jurisdictional variance would be minimal for tertiary care centers. QALYs derived from the EuroQoL-5D were the health outcome and were derived exclusively from the RCT data, given the paucity of studies evaluating the surgical treatment of lumbar radiculopathy lasting 4 to 12 months. Cost-effectiveness was assessed using the ICUR and a threshold of willingness to pay CAD 50,000 (USD 41,220) per QALY in the base case. Sensitivity analyses were performed to account for the uncertainties within the estimate of cost utility, using both a probabilistic sensitivity analysis and two one-way sensitivity analyses with varying crossover rates after the 6-month nonsurgical treatment had concluded. Results Early surgical treatment of patients with chronic lumbar radiculopathy (defined as symptoms of 4 to 12 months duration) was cost-effective, in that the cost of one QALY was lower than the CAD 50,000 threshold (note: the purchasing power parity conversion factor between the Canadian dollar (CAD) and the US dollar (USD) for 2019 was 1 USD = 1.213 CAD; therefore, our threshold was USD 41,220). Patients in the early surgical treatment group had higher expected costs (CAD 4118 [95% CI 3429 to 4867]) than those with nonsurgical treatment (CAD 2377 [95% CI 1622 to 3518]), but they had better expected health outcomes (1.48 QALYs [95% CI 1.39 to 1.57] versus 1.30 [95% CI 1.22 to 1.37]). The ICUR was CAD 5822 per QALY gained (95% CI 3029 to 30,461). The 2-year probabilistic sensitivity analysis demonstrated that the likelihood that early surgical treatment was cost-effective was 0.99 at the willingness-to-pay threshold, as did the one-way sensitivity analyses. Conclusion Early surgery is cost-effective compared with nonoperative care in patients who have had chronic sciatica for 4 to 12 months. Decision-makers should ensure adequate funding to allow timely access to surgical care given that it is highly likely that early surgical intervention is potentially cost-effective in single-payer systems. Future work should focus on both the clinical effectiveness of the treatment of chronic radiculopathy and the costs of these treatments from a societal perspective to account for occupational absences and lost patient productivity. Parallel cost-utility analyses are critical so that appropriate decisions about resource allocation can be made. Level of evidence Level III, economic and decision analysis.

Background: The coronavirus disease 2019 (COVID-19) pandemic raised concern for exposure to healthcare providers through aerosol generating procedures, such as bronchoalveolar lavage (BAL). Current society guidelines recommended limiting use of BAL to reduce operators' risk for infection, yet data on the infection rate for providers after BAL is sparse. Since March 2020, our institution used a modified protocol to perform over 450 BALs on intubated COVID-19 patients. We therefore sought to describe the subsequent infectious risks to providers associated with BAL. Methods: Fifty-two pulmonary and critical care providers (faculty and fellows) at our tertiary-care, urban medical center were surveyed. Survey participants were asked to provide the number of BALs on COVID-19 patients they performed, the number of weeks they cared for intensive care unit (ICU) patients with COVID-19, and the results of any SARS-CoV-2 testing that they received. Participants were asked to assess the difficulty of BAL on intubated COVID-19 patients as compared to routine ICU BAL using a numeric perceived difficulty score ranging from 1 (easier) to 10 (harder). Results: We received forty-seven responses from fifty-two surveyed (90% response rate), with 2 declining to participate. Many respondents (19/45, 42%) spent >5 weeks on an ICU service with COVID-19 patients. The number of BALs performed by providers ranged from 0 to >60. Sixteen of the 35 providers (46%) who performed BALs underwent at least one nasopharyngeal (NP) swab to test for SARS-CoV-2, but none were positive. Twenty-seven of the 35 providers (77%) who performed BALs underwent SARS-CoV-2 serology testing, and only one (3.7%) was positive. Respondents indicated occasionally not being able to follow aerosol-minimizing steps but overall felt BALs in COVID-19 patients was only slightly more difficult than routine ICU BAL. Discussion: At a high-volume center having performed >450 BALs on intubated COVID-19 patients with aerosol-limiting precautions, our survey of bronchoscopists found no positive NP SARS-CoV-2 tests and only one positive antibody test result. While the optimal role for COVID-19 BAL remains to be determined, these data suggest that BAL can be safely performed in intubated COVID-19 patients if experienced providers take precautions to limit aerosol generation and wear personal protective equipment.

Superconducting electronics often require high-density microwave interconnects capable of transporting signals between temperature stages with minimal loss, cross talk, and heat conduction. We report the design and fabrication of superconducting 53 wt% Nb-47 wt% Ti (Nb47Ti) FLexible coAXial ribbon cables (FLAX). The ten traces each consist of a 0.076 mm O.D. NbTi inner conductor insulated with PFA (0.28 mm O.D.) and sheathed in a shared 0.025 mm thick Nb47Ti outer conductor. The cable is terminated with G3PO coaxial push-on connectors via stainless steel capillary tubing (1.6 mm O.D., 0.13 mm thick) soldered to a coplanar wave guide transition board. The 30 cm long cable has 1 dB of loss at 8 GHz with -60 dB nearest-neighbor forward cross talk. The loss is 0.5 dB more than commercially available superconducting coax likely due to impedance mismatches caused by manufacturing imperfections in the cable. The reported cross talk is 30 dB lower than previously developed laminated NbTi-onKapton microstrip cables. We estimate the heat load from 1 K to 90 mK to be 20 nW per trace, approximately half the computed load from the smallest commercially available superconducting coax from CryoCoax, Comment: in IEEE Transactions on Applied Superconductivity

Uninsured risk impedes agricultural production, but traditional indemnity insurance is not a viable option for smallholder farmers due to market failures. Weather index insurance is often touted as an alternative risk management tool. Demand for weather index insurance, however, has been weak. One possible reason is basis risk, the mismatch between index insurance payouts and individual outcomes. We estimate the impact of two interventions on preferred coverage under a real index insurance product, as revealed through an auction: (a) a reduction in basis risk, and (b) an experiential game that teaches farmers how index insurance works, with an emphasis on basis risk. We show all farmers demonstrate strong sensitivity to basis risk. The experiential game modestly increased knowledge, and experiential game participants indicate higher levels of preferred insurance coverage. Although offering a lower basis risk insurance product and playing an experiential game both increase preferred coverage in isolation, there is no additional impact of doing both. We adapt a theoretical model of misattribution bias to demonstrate how reference‐dependent learning with loss aversion could lead to this unexpected result.

We present an on-sky demonstration of a post-processing technique for companion detection called Stochastic Speckle Discrimination (SSD) and its ability to improve the detection of faint companions using SCExAO and the MKID Exoplanet Camera (MEC). Using this SSD technique, MEC is able to resolve companions at a comparable signal to noise to other integral field spectrographs solely utilizing photon arrival time information and without the use of any PSF subtraction techniques. SSD takes advantage of photon counting detectors, like the MKID detector found in MEC, to directly probe the photon arrival time statistics that describe the speckle field and allows us to identify and distinguish problematic speckles from companions of comparable brightness in an image. This technique is especially effective at close angular separations where the speckle intensity is large and where traditional post-processing techniques, like ADI, suffer.

Daniel Meza, Basil Khuder, Joseph I Bailey, Sharon R Rosenberg, Ravi Kalhan, Paul A Reyfman Northwestern University, Feinberg School of Medicine, Division of Pulmonary and Critical Care Medicine, Chicago, IL, USACorrespondence: Paul A ReyfmanNorthwestern University Feinberg School of Medicine, Department of Medicine (Pulmonary and Critical Care Medicine), 240 East Huron St. 2-415, Chicago, IL, 60611, USATel +312-503-0325Email paul.reyfman@northwestern.edu

Objectives:. Determine the variation in outcomes and respiratory mechanics between the subjects who are intubated earlier versus later in their coronavirus disease 2019 course. Design:. Retrospective cohort study. Setting:. Northwestern Memorial Hospital ICUs. Patients:. All patients intubated for coronavirus disease 2019 between March 2020 and June 2020. Interventions:. Patients were stratified by time to intubation: 30 subjects were intubated 4–24 hours after presentation and 24 subjects were intubated 5–10 days after presentation. Baseline characteristics, hospitalization, ventilator mechanics, and outcomes were extracted and analyzed. Ten clinically available CT scans were manually reviewed to identify evidence of pulmonary vascular thrombosis and intussusceptive angiogenesis. Measurements and Main Results:. Median time from symptom onset to intubation was significantly different between the early and late intubation cohorts, with the latter being intubated later in the course of their illness (7.9 vs 11.8 d; p = 0.04). The early intubation cohort had a lower mortality rate than the late intubation cohort (6% vs 30%, p < 0.001) without significantly different respiratory mechanics at the time of intubation. The late intubation cohort was noted to have higher dead space ratio (0.40 vs 0.52; p = 0.03). On review of CT scans, the late intubation cohort also had more dilated peripheral segments on imaging (two segments vs five segments). Conclusions:. The question as to whether delaying intubation is beneficial or harmful for patients with coronavirus disease 2019-induced hypoxemic respiratory failure has yet to be answered. As our approaches to coronavirus disease 2019 continue to evolve, the decision of timing of intubation remains paramount. Although noninvasive ventilation may allow for delaying intubation, it is possible that there are downstream effects of delayed intubation that should be considered, including the potential for pulmonary vascular thrombosis and intussusceptive angiogenesis with delayed intubation.

We present the development of a second generation digital readout system for photon counting microwave kinetic inductance detector (MKID) arrays operating in the optical and near-IR wavelength bands. Our system retains much of the core signal processing architecture from the first generation system, but with a significantly higher bandwidth, enabling readout of kilopixel MKID arrays. Each set of readout boards is capable of reading out 1024 MKID pixels multiplexed over 2 GHz of bandwidth; two such units can be placed in parallel to read out a full 2048 pixel microwave feedline over a 4 -- 8 GHz band. As in the first generation readout, our system is capable of identifying, analyzing, and recording photon detection events in real time with a time resolution of order a few microseconds. Here, we describe the hardware and firmware, and present an analysis of the noise properties of the system. We also present a novel algorithm for efficiently suppressing IQ mixer sidebands to below -30 dBc., 12 pages, 12 figures

The Planetary Imaging Concept Testbed Using a Recoverable Experiment-Coronagraph (PICTURE-C) experiment is a balloon-borne observatory for high-contrast imaging of debris disks and exoplanets around nearby stars. This experiment will use a 10,000-pixel Microwave Kinetic Inductance Detector (MKID) instrument as its science camera. The PICTURE-C MKID Camera is an integral field spectrograph (IFS) with a bandpass of λ = 540 − 660 nm that sits behind a modest adaptive optics system and coronagraph which promise to achieve contrast ratios down to 10-7 from 1.7 to 10 λ/D (0.35” to 2.1”). The MKIDs are photon counting detectors promising a resolution R up to 20 for the PICTURE-C mission. The ability to count photons with microsecond time resolution will allow the MKID camera to double as a Focal Plane Wavefront Sensor (FPWFS), helping to discriminate between speckles and circumstellar objects in real time and in post-processing. The intrinsic spectral resolution of the detectors will allow for further characterization of the debris disks and exoplanets around the stars targeted during its flight. The visible light observations taken with this instrument will complement infrared observations taken from the ground and serve to demonstrate MKIDs utility in a space-like environment. For this poster, we will introduce and discuss the PICTURE-C MKID Camera.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic raised concern for exposure to healthcare providers through aerosol generating procedures, such as bronchoalveolar lavage (BAL). Current society guidelines recommended limiting use of BAL to reduce operators’ risk for infection, yet data on the infection rate for providers after BAL is sparse. Since March 2020, our institution used a modified protocol to perform over 450 BALs on intubated COVID-19 patients. We therefore sought to describe the subsequent infectious risks to providers associated with BAL.MethodsFifty-two pulmonary and critical care providers (faculty and fellows) at our tertiary-care, urban medical center were surveyed. Survey participants were asked to provide the number of BALs on COVID-19 patients they performed, the number of weeks they cared for intensive care unit (ICU) patients with COVID-19, and the results of any SARS-CoV-2 testing that they received. Participants were asked to assess the difficulty of BAL on intubated COVID-19 patients as compared to routine ICU BAL using a numeric perceived difficulty score ranging from 1 (easier) to 10 (harder).ResultsWe received forty-seven responses from fifty-two surveyed (90% response rate), with 2 declining to participate. Many respondents (19/45, 42%) spent >5 weeks on an ICU service with COVID-19 patients. The number of BALs performed by providers ranged from 0 to >60. Sixteen of the 35 providers (46%) who performed BALs underwent at least one nasopharyngeal (NP) swab to test for SARS-CoV-2, but none were positive. Twenty-seven of the 35 providers (77%) who performed BALs underwent SARS- CoV-2 serology testing, and only one (3.7%) was positive. Respondents indicated occasionally not being able to follow aerosol-minimizing steps but overall felt BALs in COVID-19 patients was only slightly more difficult than routine bronchoscopy.DiscussionAt a high-volume center having performed >450 BALs on intubated COVID-19 patients with aerosol-limiting precautions, our survey of bronchoscopists found no positive NP SARS-CoV-2 tests and only one positive antibody test result. While the optimal role for COVID-19 BAL remains to be determined, these data suggest that BAL can be safely performed in intubated COVID-19 patients if experienced providers take precautions to limit aerosol generation and wear personal protective equipment.

© 2020 Massachussetts Medical Society. All rights reserved. BACKGROUND The treatment of chronic sciatica caused by herniation of a lumbar disk has not been well studied in comparison with acute disk herniation. Data are needed on whether diskectomy or a conservative approach is better for sciatica that has persisted for several months. METHODS In a single-center trial, we randomly assigned patients with sciatica that had lasted for 4 to 12 months and lumbar disk herniation at the L4-L5 or L5-S1 level in a 1:1 ratio to undergo microdiskectomy or to receive 6 months of standardized nonoperative care followed by surgery if needed. Surgery was performed by spine surgeons who used conventional microdiskectomy techniques. The primary outcome was the intensity of leg pain on a visual analogue scale (ranging from 0 to 10, with higher scores indicating more severe pain) at 6 months after enrollment. Secondary outcomes were the score on the Oswestry Disability Index, back and leg pain, and quality-of-life scores at 6 weeks, 3 months, 6 months, and 1 year. RESULTS From 2010 through 2016, a total of 790 patients were screened; of those patients, 128 were enrolled, with 64 in each group. Among the patients assigned to undergo surgery, the median time from randomization to surgery was 3.1 weeks; of the 64 patients in the nonsurgical group, 22 (34%) crossed over to undergo surgery at a median of 11 months after enrollment. At baseline, the mean score for legpain intensity was 7.7 in the surgical group and 8.0 in the nonsurgical group. The primary outcome of the leg-pain intensity score at 6 months was 2.8 in the surgical group and 5.2 in the nonsurgical group (adjusted mean difference, 2.4; 95% confidence interval, 1.4 to 3.4; P

Study design This was a retrospective study of 2 different fusion techniques for the treatment of lumbar degenerative spondylolisthesis. Objective To determine whether posterior lumbar interbody fusion (IF) is associated with improved patient-rated satisfaction and functional outcome when compared with posterolateral fusion (PLF). Summary of background data IF and PLF are widely used surgical approaches in the treatment of spondylolisthesis. Numerous studies have compared IF and PLF techniques, but inconsistent results, heterogeneous cohorts, and conflicting scientific evidence have made it difficult to reach a consensus on the optimal fusion technique. Materials and methods A consecutive cohort of 87 patients who had single-level degenerative spondylolisthesis and either PLF or IF were identified from a prospectively maintained database. Short Form-36 physical and mental component score, Oswestry Disability Index, back and leg pain, and complication rate were assessed to 24 months postoperatively. Patient characteristics, clinical outcome, and complications were compared between groups. Results Of the 87 patients identified, 29 patients (33%) had PLF and 58 patients (67%) had IF. Patient follow-up was ≥85%. Foraminal stenosis (PLF, 13.8% vs. IF, 34.5%; P=0.046) was more common among the participants in the IF group. Intraoperative and postoperative complications were not different between groups (P>0.05). The reoperation rate was 3.4% in the PLF group and 10.3% in the IF group (P=0.416). Patients in the PLF group experienced similar gains in improvement in all outcome measures as those in the IF group (P>0.05). Four patients in the IF group and 3 in the PLF group were lacking evidence of radiographic fusion. These patients did have increased moderate back pain compared with patients demonstrating radiographic fusion but did not differ in any other postoperative outcomes measures. Conclusions Type of fusion, IF or PLF, does not affect patient outcome or postoperative complication rates. Level of evidence Level IV.

A prospective cohort study of consecutive patients.Determination of the quality of life (QoL) and prevalence of slip progression in patients with degenerative lumbar spondylolisthesis managed nonoperatively.Lumbar spinal stenosis secondary to degenerative lumbar spondylolisthesis is a common radiographic diagnosis associated with chronic back pain and radicular symptoms. There is limited evidence as to the clinical course in terms of validated QoL measures, and the extent of slip progression in patients with this condition treated nonoperatively.Validated disease-specific and generic QoL metrics including SF12 physical and mental scores [SF12-physical component summary (PCS) and SF12-mental component summary (MCS)], Oswestry Disability Index (ODI), and numeric scales for back and leg pain as well as radiographic assessment of slip extent were evaluated at initial consultation (baseline) and at a minimum of 5 years after the baseline assessment. Slip progression was defined by a5% increase in slip percentage.Thirty-nine of 160 (24.4%) patients elected to switch to operative management, despite no slip progression on preoperative radiographs. Seventy spondylolisthetic levels in 66 participants were assessed after a minimum of 5 years of nonoperative management. Twenty-one participants (31.8%) had slip progression. SF12-PCS, ODI, and leg pain improved similarly in both groups (P 0.05). SF12-MCS did not change significantly in either group. Back pain improved only in the nonprogressing group.The majority of cases of low-grade spondylolisthesis do not progress over 5 years with nonoperative management. Regardless of whether there was progression or not, the mean PCS, ODI, and leg pain improved from baseline, although symptoms remained and a significant number elected to switch to surgical management before 5 years. Back pain improved with nonoperative treatment only in those without progression.2.

Objectives To compare the effect of delaying surgery on clinical outcome in patients with chronic sciatica secondary to lumbar disc herniation. Methods Patients with sciatica lasting 4–12 months and lumbar disc herniation at the L4–L5 or L5–S1 level were randomized to undergo microdiscectomy (early surgery) or to receive 6 months of nonoperative treatment followed by surgery if needed (delayed surgery). Outcomes were leg pain, Oswestry Disability Index score (ODI), back pain, SF–36 physical component (PCS) and mental component (MCS) summary scores, employment, and satisfaction measured preoperatively and at 6 weeks, 3 months, 6 months, and 1 year after surgery. Results Of the 64 patients in the early surgery group, 56 underwent microdiscectomy an average of 3 ± 2 weeks after enrollment. Of the 64 patients randomized to nonoperative care, 22 patients underwent delayed surgery an average of 53 ± 24 weeks after enrollment. The early surgery group experienced less leg pain than the delayed surgery group, which was the primary outcome, at 6 months after surgery (early surgery 2.8 ± .4 vs delayed surgery 4.8 ± .7; difference, 2.0; 95% confidence interval, .5–3.5). The overall estimated mean difference between groups significantly favored early surgery for leg pain, ODI, SF36-PCS, and back pain. The adverse event rate was similar between groups. Conclusions Patients presenting with chronic sciatica treated with delayed surgery after prolonging standardized non-operative care have inferior outcomes compared to those that undergo expedited surgery.

This phase 2, open-label, placebo-controlled examines topical itraconazole as a treatment for basal cell carcinoma.

Background Chronic pruritus causes major morbidity in epidermolysis bullosa (EB). The substance P-neurokinin 1 receptor (SP-NK1) pathway is a promising target for treating EB-related pruritus. Objective To evaluate the safety and efficacy of the oral NK1 receptor antagonist serlopitant in treating moderate-severe pruritus in EB. Methods The study randomized 14 patients to serlopitant or placebo for 8 weeks, followed by a 4-week washout and optional open-label extension. The primary end point was change in itch as measured by the Numeric Rating Scale. Secondary end points were change in itch during dressing changes and wound size. Results We observed greater itch reduction with serlopitant, equivalent to a 0.64-point comparative reduction on the 11-point Numeric Rating Scale by week 8, although this failed to meet statistical significance (P = .11). More serlopitant patients achieved ≥3-point reduction compared with placebo (43% vs 14%, P = .35). In post hoc analysis excluding 1 patient with a concurrent seborrheic dermatitis flare, serlopitant achieved significantly greater median itch reduction from baseline by week 4 (−2 points vs 0, P = .01). We observed no statistically significant differences in secondary end points. Serlopitant was well-tolerated. Limitations Small sample size due to disease rarity. Conclusion The potential itch reduction with serlopitant observed in this trial will be pursued by a larger powered trial ( NCT03836001 ).

OBJECTIVEA multicenter, prospective, randomized equivalence trial comparing a thoracolumbosacral orthosis (TLSO) to no orthosis (NO) in the treatment of acute AO Type A3 thoracolumbar burst fractures was recently conducted and demonstrated that the two treatments following an otherwise similar management protocol are equivalent at 3 months postinjury. The purpose of the present study was to determine whether there was a difference in long-term clinical and radiographic outcomes between the patients treated with and those treated without a TLSO. Here, the authors present the 5- to 10-year outcomes (mean follow-up 7.9 ± 1.1 years) of the patients at a single site from the original multicenter trial.METHODSBetween July 2002 and January 2009, a total of 96 subjects were enrolled in the primary trial and randomized to two groups: TLSO or NO. Subjects were enrolled if they had an AO Type A3 burst fracture between T-10 and L-3 within the previous 72 hours, kyphotic deformity < 35°, no neurological deficit, and an age of 16–60 years old. The present study represents a subset of those patients: 16 in the TLSO group and 20 in the NO group. The primary outcome measure was the Roland Morris Disability Questionnaire (RMDQ) score at the last 5- to 10-year follow-up. Secondary outcome measures included kyphosis, satisfaction, the Numeric Rating Scale for back pain, and the 12-Item Short-Form Health Survey (SF-12) Mental and Physical Component Summary (MCS and PCS) scores. In the original study, outcome measures were administered at admission and 2 and 6 weeks, 3 and 6 months, and 1 and 2 years after injury; in the present extended follow-up study, the outcome measures were administered 5–10 years postinjury. Treatment comparison between patients in the TLSO group and those in the NO group was performed at the latest available follow-up, and the time-weighted average treatment effect was determined using a mixed-effects model of longitudinal regression for repeated measures averaged over all time periods. Missing data were assumed to be missing at random and were replaced with a set of plausible values derived using a multiple imputation procedure.RESULTSThe RMDQ score at 5–10 years postinjury was 3.6 ± 0.9 (mean ± SE) for the TLSO group and 4.8 ± 1.5 for the NO group (p = 0.486, 95% CI −2.3 to 4.8). Average kyphosis was 18.3° ± 2.2° for the TLSO group and 18.6° ± 3.8° for the NO group (p = 0.934, 95% CI −7.8 to 8.5). No differences were found between the NO and TLSO groups with time-weighted average treatment effects for RMDQ 1.9 (95% CI −1.5 to 5.2), for PCS −2.5 (95% CI −7.9 to 3.0), for MCS −1.2 (95% CI −6.7 to 4.2) and for average pain 0.9 (95% CI −0.5 to 2.2).CONCLUSIONSCompared with patients treated with a TLSO, patients treated using early mobilization without orthosis maintain similar pain relief and improvement in function for 5–10 years.

Intermittent claudication can be neurogenic or vascular. Physicians use a profile based on symptom attributes to differentiate the 2 types of claudication, and this guides their investigations for diagnosis of the underlying pathology. We evaluated the validity of these symptom attributes in differentiating neurogenic from vascular claudication.Patients with a diagnosis of lumbar spinal stenosis (LSS) or peripheral vascular disease (PVD) who reported claudication answered 14 questions characterizing their symptoms. We determined the sensitivity, specificity and positive and negative likelihood ratios (PLR and NLR) for neurogenic and vascular claudication for each symptom attribute.We studied 53 patients. The most sensitive symptom attribute to rule out LSS was the absence of "triggering of pain with standing alone" (sensitivity 0.97, NLR 0.050). Pain alleviators and symptom location data showed a weak clinical significance for LSS and PVD. Constellation of symptoms yielded the strongest associations: patients with a positive shopping cart sign whose symptoms were located above the knees, triggered with standing alone and relieved with sitting had a strong likelihood of neurogenic claudication (PLR 13). Patients with symptoms in the calf that were relieved with standing alone had a strong likelihood of vascular claudication (PLR 20.0).The classic symptom attributes used to differentiate neurogenic from vascular claudication are at best weakly valid independently. However, certain constellation of symptoms are much more indicative of etiology. These results can guide general practitioners in their evaluation of and investigation for claudication.La claudication intermittente peut avoir une étiologie neurogène ou vasculaire. Les médecins utilisent un profil fondé sur les particularités des symptômes pour distinguer l’une de l’autre et ceci oriente leur choix des méthodes de diagnostic de la pathologie sous-jacente. Nous avons évalué la validité de ces particularités des symptômes utilisées pour distinguer la claudication d’origine neurogène de la claudication d’origine vasculaire.Des patients atteints d’une sténose spinale lombaire (SSL) ou d’une maladie vasculaire périphérique (MVP) avérées qui se plaignaient de claudication ont réponduà 14 questions afin de caractériser leurs symptômes. Nous avons déterminé la sensibilité, la spécificité et les rapports de probabilité positifs et négatifs (RPP et RPN) à l’égard de la claudication neurogène ou vasculaire pour chacune des particularités des symptômes.Notre étude a regroupé 53 patients. La particularité des symptômes dotée de la sensibilité la plus élevée pour ce qui est d’écarter le diagnostic de SSL a été l’absence de « déclenchement de la douleur à la simple station debout » (sensibilité 0,97; RPN 0,050). Les données sur ce qui soulageait la douleur et sur la localisation des symptômes ont eu une faible portée clinique en ce qui a trait à la SSL et à la MVP. La présence d’une constellation de symptômes a donné lieu aux associations les plus solides : les patients qui manifestaient un signe du « panier d’épicerie » positif et dont les symptômes étaient localisés au-dessus du genou, déclenchés par la station debout seule et soulagés en position assise présentaient une forte probabilité de claudication d’origine neurogène (RPP 13). Chez les patients dont les symptômes étaient localisés au mollet et qui étaient soulagés par la station debout, on notait une forte probabilité de claudication d’origine vasculaire (RPP 20,0).Considérés individuellement, les attributs classiques des symptômes utilisés pour distinguer la claudication d’origine neurogène de la claudication d’origine vasculaire sont au mieux faiblement valides. Toutefois, certaines constellations de symptômes éclairent bien davantage l’étiologie. Ces résultats peuvent guider l’omnipraticien dans son examen et dans son diagnostic de la claudication.

OBJECTIVE The object of this study was to determine the association between postoperative sagittal spinopelvic alignment and patient-rated outcome measures following decompression and fusion for lumbar degenerative spondylolisthesis. METHODS The authors identified a consecutive series of patients who had undergone surgery for lumbar degenerative spondylolisthesis between 2008 and 2012, with an average follow-up of 3 years (range 1–6 years). Surgery was performed to address the clinical symptoms of spinal stenosis, not global sagittal alignment. Sagittal alignment was only assessed postoperatively. Patients were divided into 2 groups based on a postoperative sagittal vertical axis (SVA) < 50 mm (well aligned) or ≥ 50 mm (poorly aligned). Baseline demographic, procedure, and outcome measures were compared between the groups. Postoperative outcome measures and postoperative spinopelvic parameters were compared between groups using analysis of covariance. RESULTS Of the 84 patients included in this study, 46.4% had an SVA < 50 mm. Multiple levels of spondylolisthesis (p = 0.044), spondylolisthesis at the L3–4 level (p = 0.046), and multiple levels treated with fusion (p = 0.028) were more common among patients in the group with an SVA ≥ 50 mm. Patients with an SVA ≥ 50 mm had a worse SF-36 physical component summary (PCS) score (p = 0.018), a worse Oswestry Disability Index (ODI; p = 0.043), and more back pain (p = 0.039) than those with an SVA < 50 mm after controlling for multiple levels of spondylolisthesis and multilevel fusion. The spinopelvic parameters differing between the < 50-mm and ≥ 50-mm groups included lumbar lordosis (LL; 56.4° ± 4.7° vs 49.8° ± 4.3°, respectively, p = 0.040) and LL < pelvic incidence ± 9° (51% vs 23.1%, respectively, p = 0.013) after controlling for type of surgical procedure. CONCLUSIONS Data in this study revealed that patient-rated outcome is influenced by the overall postoperative sagittal balance as defined by the SVA.

Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of "high risk" patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.

STUDY DESIGN A biomechanical analysis of soft-tissue restraints to passive motion in odontoid fractures. OBJECTIVE To quantify the role of the C1-C2 facet joint capsules and anterior longitudinal ligaments (ALLs) in the setting of a type II odontoid fracture in the elderly. SUMMARY OF BACKGROUND DATA The odontoid process itself is the primary stabilizer at the C1-C2 level; however, little is known about the role of the soft-tissue structures that remain intact in the setting of an odontoid fracture after a low-energy mechanism. METHODS Ten cadaveric C0-C2 spinal segments were studied. Specimens were tested under simulated axial rotation with an applied moment of ±1 Nm and with an application of a 10 N anteriorly directed force to the body of C2 to induce sagittal translation. Optical motion data were initially collected for the intact state and after a simulated dens fracture. The specimens were then divided into 2 groups, where 1 group underwent unilateral and then bilateral C1-C2 facet capsular injuries followed by an ALL injury. The second group underwent the ALL injury before the same capsular injuries. Changes in axial range of motion and C1-C2 translation were analyzed using 2-way repeated measures analyses of variance and post hoc Student-Newman-Keuls tests (α = 0.05). RESULTS In axial rotation, there was an increase in range of motion by approximately 13%, with the fracture of the dens compared with the intact state (P < 0.05). An increase was also present for each subsequent soft-tissue injury state compared with the previous (P < 0.05); however, there was no difference found between the 2 sectioning protocols. For sagittal translation testing, it was found that the odontoid fracture alone showed an increase of 3 mm of C1-C2 translation compared with intact (P < 0.05). Further soft-tissue injuries did not show an increase until the complete injury state. CONCLUSION This study identifies that type II odontoid fractures without associated soft-tissue injury may be stable under certain loading modes.

Study design A calcium triglyceride bone cement (CTBC) was compared with the gold-standard polymethylmethacrylate (PMMA) to assess the stability of augmented sacral screw fixation under cyclic loading. Objective To determine whether CTBC augmentation of a pedicle screw would provide a similar level of fixation in the S1 pedicles compared with PMMA augmentation. Summary of background data Numerous studies have shown the advantages of using PMMA to augment screw fixation; however, its biomechanical properties are not ideal. CTBC offers potential benefits such as being low exothermic, a modulus of elasticity closer to bone, and the potential for osteoconductivity, but its comparative performance in this situation has not been previously evaluated. Methods Six cadaveric sacra were used in this study; 3.0 mL volumes of PMMA (Simplex P) and CTBC (Kryptonite™ Bone Cement) were injected into contralateral screw tracts, with the screw immediately inserted after cement injection. After a 12-hour setting period, the sacrum was potted in a custom fixture and mounted to the frame of a materials testing machine. Alternating flexion and extension bending moments were applied at 1 Hz. Flexion moments were applied starting at 0.5 Nm and increased by 1 Nm after every 1000 cycles until the screw had reached 6° of rotation relative to its starting position. Extension moments were maintained at 0.5 Nm. Screw rotation relative to bone was determined in real time by a custom optical tracking system and was analyzed using two-way repeated-measures analyses of variance (ANOVAs) and post hoc Student-Newman-Keuls tests (α = 0.05). Results To reach 6° of screw rotation, the PMMA-augmented screw required more loading cycles (15,464 ± 2526 vs. 10,277 ± 1762 cycles; P = 0.006) and a larger applied moment (15.3 ± 2.2 vs. 10.5 ± 1.7 Nm; P = 0.010) than CTBC-augmented screw. Conclusion The PMMA augmentation provided increased resistance to cyclic loading compared with the CTBC augmentation for sacral pedicle screw fixation, but both augmentations well exceeded previously published findings for nonaugmented screws.

Object The authors compared the outcome of patients with thoracolumbar burst fractures treated with and without a thoracolumbosacral orthosis (TLSO). Methods As of June 2002, all consecutive patients satisfying the following inclusion criteria were considered eligible for this study: 1) the presence of an AO Classification Type A3 burst fractures between T-11 and L-3, 2) skeletal maturity and age < 60 years, 3) admission within 72 hours of injury, 4) initial kyphotic deformity < 35°, and 5) no neurological deficit. The study was designed as a multicenter prospective randomized clinical equivalence trial. The primary outcome measure was the score based on the Roland-Morris Disability Questionnaire assessed at 3 months postinjury. Secondary outcomes are assessed until 2 years of follow-up have been reached, and these domains included pain, functional outcome and generic health-related quality of life, sagittal alignment, length of hospital stay, and complications. Patients in whom no orthotic was used were encouraged to ambulate immediately following randomization, maintaining “neutral spinal alignment” for 8 weeks. The patients in the TLSO group began being weaned from the brace at 8 weeks over a 2-week period. Results Sixty-nine patients were followed to the primary outcome time point, and 47 were followed for up to 1 year. No significant difference was found between treatment groups for any outcome measure at any stage in the follow-up period. There were 4 failures requiring surgical intervention, 3 in the TLSO group and 1 in the non-TLSO group. Conclusions This interim analysis found equivalence between treatment with a TLSO and no orthosis for thoracolumbar AO Type A3 burst fractures. The influence of a brace on early pain control and function and on long-term 1- and 2-year outcomes remains to be determined. However, the authors contend that a thoracolumbar burst fracture, in exclusion of an associated posterior ligamentous complex injury, is inherently a very stable injury and may not require a brace.

Traumatic injury can cause a systemic inflammatory response, increasing oxidative activity of circulating leukocytes and potentially exacerbating the original injury, as well as causing damage to initially unaffected organs. Although the importance of intraspinal inflammation after human spinal cord injury is appreciated, the role of the systemic inflammatory response to this injury is not widely recognised. We investigated oxidative activity of blood leukocytes from nine cord-injured subjects and six trauma controls (bone fractures without CNS injury) at 6 h–2 weeks after injury, comparing values to those of ten uninjured subjects. Neutrophil and monocyte free radical production, evaluated by flow cytometry, increased significantly more in cord injury subjects than in trauma controls (6-fold vs 50% increases). In leukocyte homogenates, the concentration of free radicals increased significantly more in cord injury subjects (2-fold) than in the trauma controls (1.6-fold) as did activity of myeloperoxidase (2.3-fold vs. 1.7-fold). Moreover, in homogenates and blood smears, expression of the NADPH oxidase subunit gp91 phox and of the oxidative enzyme, inducible nitric oxide synthetase was 20–25% greater in cord injury subjects than in trauma controls. Expression of the pro-inflammatory transcription factor NF-κB and of cyclooxygenase-2 increased similarly after both injuries. Finally, aldehyde products of tissue-damaging lipid peroxidation also increased significantly more in the plasma of spinal cord injury subjects than in trauma controls (2.6 fold vs. 1.9-fold). Spinal cord injury causes a particularly intense systemic inflammatory response. Limiting this response briefly after cord injury should protect the spinal cord and tissues/organs outside the CNS from secondary damage.

Most cutaneous basal cell carcinomas (BCCs) are successfully treated by surgical resection. However, locally advanced (unresectable) or metastatic BCC (mBCC) have a poor prognosis, with a mean survival ranging from 8 months to 3.6 years.1 Basal cell carcinomas require the hedgehog (HH) pathway for growth. Hedgehog pathway inhibitors, such as vismodegib2 and sonidegib phosphate, target the G-protein–coupled receptor Smoothened (SMO) and are recommended as first-line treatment for advanced BCC or mBCC by the National Comprehensive Cancer Network.3 The emergence of resistance has limited vismodegib's efficacy2,4 and led the search for therapeutics downstream from SMO. Investigators5 found that 50% of SMO inhibitor–resistant BCCs had SMO mutations with disruption of ligand responsiveness or release of autoinhibition. Itraconazole, a widely used oral antifungal agent, is a potent HH pathway antagonist that suppresses BCC carcinogenesis and reduces messenger RNA (mRNA) expression of the GLI family zinc finger 1 (GLI1 [OMIM 165220]) gene in murine BCCs6 and in patients with nonadvanced cutaneous BCCs.7 Arsenic trioxide, which is approved by the US Food and Drug Administration for treatment of acute promyelocytic leukemia, inhibits the HH pathway downstream from SMO by preventing ciliary trafficking and destabilizing GLI2. Arsenic trioxide can bypass acquired mutations in SMO found in resistant tumors.8 Combined treatment with arsenic trioxide and itraconazole (ATO-ITRA) has an additive HH inhibitory effect shown to be effective in murine BCCs.9 To assess the HH inhibitory effect and clinical efficacy of ATO-ITRA in human BCC, we performed an open-label proof-of-concept, phase 2 biomarker trial in patients with mBCC whose tumors were clinically resistant to SMO inhibitors.10 The primary goal of our study was to determine whether administration of intravenous (IV) arsenic trioxide and oral itraconazole in patients with mBCC is associated with a reduction in GLI1 mRNA expression in tumor and/or normal skin biopsy samples. Secondary end points included the evaluation of tumor response, safety profile, and presence of HH pathway mutations in SMO inhibitor–resistant BCCs before treatment.

Summary: Women with phenylketonuria (PKU) must follow a strict low-phenylalanine diet during pregnancy in order to protect the fetus from the deleterious effects of high maternal blood phenylalanine. The Resource Mothers Study of Maternal PKU was undertaken to determine whether a home visitation programme was effective in helping women with PKU attain blood phenylalanine control earlier during pregnancy. Resource Mothers were trained to provide social support and practical assistance to women with PKU during pregnancy. Eight metabolic clinics in the United States participated in the study. Women with PKU who were planning pregnancy or already pregnant were enrolled in the study and were treated with a low-phenylalanine diet aimed at controlling blood phenylalanine to 120–360 µmol/L. They were randomly assigned to receive the services of a Resource Mother (RM group) or to a control group. Fifty women were enrolled, and accounted for 44 pregnancies which resulted in 28 live births, and 6 spontaneous abortions. Ten women are currently pregnant and another 6 have not become pregnant. Fifty-six percent of enrolled women began the diet prior to becoming pregnant. Fifty-three percent of women in the Resource Mother group were in metabolic control by 10 weeks gestation as compared to 39% in the control group. In addition, women who began diet after pregnancy and had a Resource Mother attained metabolic control earlier (mean gestational age of 22.4 weeks in the RM group vs 29.8 weeks in the control group). There was no difference in birth measurement z-scores of offspring born to women in the RM group compared to controls. All but 4 women rated themselves as feeling worse about the diet at the end of pregnancy than at the beginning, and few women in either group remained on diet after delivery.

Fiber-fed multi-object spectrographs have proven to be powerful tools in astronomy, capable of developing large kinematic samples in a fraction of the time required by single-object spectroscopy. The recently commissioned Michigan Magellan Fiber System (M2FS) is a multi-mode, multi-object, fiber-fed optical spectrograph capable of observing up to 256 targets with its 1.2" fibers. By using M2FS’s adjustable slit mechanism with telluric lines as a wavelength reference we have developed an instrument capable of measuring absolute velocities to 25 m/s for up to 256 objects simultaneously. We briefly describe M2FS’s baseline capabilities and then discuss the fiber slit mechanism we created for M2FS. Finally we review our analysis methods, highlighting both the additional calibration opportunities presented by multi-object observations and the effects of atmospheric models on our achieved precision.

Background Vismodegib is an oral hedgehog-pathway inhibitor approved for advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery, excision of large tumors in aesthetically sensitive sites may compromise function or cosmesis. Objective We sought to evaluate the reduction in BCC surgical defect area after 3 to 6 months of neoadjuvant vismodegib. Methods This was an open-label, single-arm intervention trial with a primary outcome of change in target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary outcomes were change in tumor area and tolerability. Results Eleven of 15 enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target tumors were excised after a mean of 4 ± 2 months of vismodegib. In all, 29% (4 of 14 patients) could not complete more than 3 months because of vismodegib-related side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13 tumors occurred on the face. Overall, vismodegib reduced the surgical defect area by 27% (95% confidence interval –45.7% to –7.9%; P = .006) from baseline. Vismodegib was not effective in patients who received less than 3 months. Over a mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred at 17 months post-Mohs micrographic surgery. Limitations Short follow-up time and no placebo control are limitations. Conclusion Neoadjuvant vismodegib appears to reduce surgical defect area when taken for 3 months or longer for nonrecurrent BCCs in functionally sensitive locations. Further studies with larger sample sizes and long-term follow-up are warranted.

The rationale that conjoint use of feedback inhibition could alter the effectiveness of a goitrogen, methylthiouracil (MTU), for achieving pharmacological suppression of thyroid gland function was tested in sheep. Experiment 1 determined the appropriate daily dose of T 3 for achieving feedback suppression of thyroid secretion. Experiment 2 tested the hypothesis that prior treatment with T 3 at such dosage would speed up the thyroid suppressive effect of subsequent administration of MTU, and Experiment 3 determined whether T 3 exerted feedback inhibition on the anterior pituitary gland. In Experiment 1, ewes ( n =6) treated with doses of 0, 1, 5 and 25 μg T 3 per kg live weight as a daily s.c. injection for 2 weeks had a dose-related increase in heart rate and decrease in plasma T 4 concentration. Ewes in Experiment 2 received combinations of daily s.c. injections of T 3 at 5 μg per kg and daily oral dosing with 35 mg per kg MTU ( n =6). Suppression of plasma T 4 concentration by T 3 did not improve the effect of subsequent treatment with MTU. In Experiment 3, plasma TSH responses to TRH stimulation (200 μg, i.v.) were reduced by treatment with T 3 , confirming its feedback inhibition of the anterior pituitary gland. It is concluded that, in spite of the inhibitory actions of T 3 on plasma T 4 concentration in sheep, its use prior to treatment with MTU did not affect the resultant suppression of thyroid hormone secretion.

A Maternal PKU camp provided education and social support for 25 young women with phenylketonuria (PKU). Questionnaires were administered and blood samples were collected on the first and last days of camp to evaluate the psychological and medical impact of the programme. Long-term outcome was assessed through telephone interviews 7-14 months later. Knowledge of maternal PKU and the maternal PKU diet increased significantly. There was a significant increase in campers' ratings of the degree to which others supported the use of birth control to prevent late-treated pregnancies, although campers' comfort with contraception did not change. Mean blood phenylalanine concentrations were significantly reduced by 37% during camp and by 20% at follow-up. Ninety-six per cent of campers remained in contact with other campers after the summer. At follow-up, one pregnancy was reported, in which metabolic control was achieved prior to conception. Overall, attitudes about treatment and perceptions about ability to cope with PKU did not change to a significant degree. It is suggested that camps may be most successful in changing both behaviour and attitudes if they actively involve the campers in food preparation, address the psychological meaning of food in our culture, and provide social support.

Background context Thoracolumbar burst fractures have good outcomes when treated with early ambulation and orthosis (TLSO). If equally good outcomes could be achieved with early ambulation and no brace, resource utilization would be decreased, especially in developing countries where prolonged bed rest is the default option because bracing is not available or affordable. Purpose To determine whether TLSO is equivalent to no orthosis (NO) in the treatment of acute AO Type A3 thoracolumbar burst fractures with respect to their functional outcome at 3 months. Study design A multicentre, randomized, nonblinded equivalence trial involving three Canadian tertiary spine centers. Enrollment began in 2002 and 2-year follow-up was completed in 2011. Patient sample Inclusion criteria included AO-A3 burst fractures between T11 and L3, skeletally mature and older than 60 years, 72 hours from their injury, kyphotic deformity lower than 35°, no neurologic deficit. One hundred ten patients were assessed for eligibility for the study; 14 patients were not recruited because they resided outside the country (3), refused participation (8), or were not consented before independent ambulation (3). Outcome measures Roland Morris Disability Questionnaire score (RMDQ) assessed at 3 months postinjury. The equivalence margin was set at δ=5 points. Methods The NO group was encouraged to ambulate immediately with bending restrictions for 8 weeks. The TLSO group ambulated when the brace was available and weaned from the brace after 8 to 10 weeks. The following competitive grants supported this work: VHHSC Interdisciplinary Research Grant, Zimmer/University of British Columbia Research Fund, and Hip Hip Hooray Research Grant. Aspen Medical provided the TLSOs used in this study. The authors have no financial or personal relationships that could inappropriately influence this work. Results Forty-seven patients were enrolled into the TLSO group and 49 patients into the NO group. Forty-six participants per group were available for the primary outcome. The RMDQ score at 3 months postinjury was 6.8±5.4 (standard deviation [SD]) for the TLSO group and 7.7±6.0 (SD) in the NO group. The 95% confidence interval (−1.5 to 3.2) was within the predetermined margin of equivalence. Six patients required surgical stabilization, five of them before initial discharge. Conclusions Treating these fractures using early ambulation without a brace avoids the cost and patient deconditioning associated with a brace and complications and costs associated with long-term bed rest if a TLSO or body cast is not available.

Patients with basal cell nevus syndrome (BCNS) have a greater risk of developing numerous basal cell carcinomas (BCCs). Risk factors influencing the wide variation in tumor burden are poorly understood.To describe the burden of BCCs in patients with BCNS in the United States and identify potential risk factors for BCCs.Prospective clinical registry with data collected from September 2014 to March 2016. Participants were recruited from a mailing list of patients with BCNS at Children's Hospital Oakland Research Institute and Basal Cell Carcinoma Nevus Syndrome Life Support Network. Patients of all ages with a diagnosis of BCNS were eligible for enrollment. Participants completed a clinical questionnaire on their disease characteristics and risk factors.Number of BCCs in the past 2 years and over lifetime (disease burden), risk factors for BCCs.A consecutive sample of the first 141 participants was included (34% [100 of 297] response rate from paper survey, 23% [41 of 179] from online survey; 85 [60%] female; mean age at start of study, 53 [range, 8-83] years; 131 [93%] white). In the previous 2 years, participants reported a mean of 25 BCCs (median, 11; range, 0-250). Over their lifetime, participants reported a mean of 257 BCCs (median, 160; range, 0-2200). Univariate analysis identified age (odds ratio [OR], 1.05; 95% CI, 1.03-1.07; P .001), number of sunburns (OR, 1.05; 95% CI, 1.00-1.10; P = .047), and history of radiation exposure (OR, 2.26; 95% CI, 1.02-5.03; P = .046) as potential risk factors for lifetime BCC severity. On multivariate analysis, only age (OR, 1.04; 95% CI, 1.02-1.07; P .001) and number of sunburns (OR, 1.06; 95% CI, 1.00-1.11; P = .04) were statistically significant. In our adjusted models, BCC burden increased by 4% per year of age and by 6% per number of sunburns.Patients with BCNS have a high burden of BCCs. Age and number of sunburns were significantly associated with the severity of lifetime BCC. Further interventions to prevent and treat BCCs in patients with BCNS are needed.

264 Topical treatments improved periorbital aging J Namkoong, B Cook, D Kern and HE Knaggs Global R&D, Nu Skin Enterprises, Inc., Provo, UT Facial aging is manifested by different symptoms. One area people pay more attention to and use additional cosmetic products to keep healthier is the eye area e the periorbital region. There are multiple reasons why the periorbital region manifests an unhealthy and aged look. The skin in the eye area is thinner than other parts of face, and repetitive muscle movements and UV exposures lead to skin aging. Periorbital aging includes eyelid drooping, dark circles, under eye bags, or fine lines/wrinkles. Topical and mechanical treatments to improve periorbital aging is challenging due to the proximity to eyes. Hypersensitivity to treatment options are common occurrence in the eyes. In order to improve the skin in the eye area, topical ingredients were evaluated for their potential to modulate different skin aging target genes, such as improving skin structures, hydration, anti-inflammation, antioxidant capacity and cell turnover, using normal human skin equivalent cultures. Some interesting finding includes modulation of Prostaglandin E2 (PGE2). Induction of cellular stress with 5mM or 10mM hydrogen peroxide increased PGE2 expression, which would increase inflammation. In addition, PGE2 increase has been suggested in the skin of elderly and inhibition of PGE2 resulted in collagen production in skin organ culture. Experimental ingredients were able to suppress that H2O2-induced PGE2 expression, similar to ascorbic acid. After evaluating ingredients using in vitro models, a specific formula was developed to target clinical signs of periorbital skin aging. Prior to running a clinical study, the formula was evaluated for safety, due to potential hypersensitivity. This eye formulation did not trigger any safety concerns during in vitro evaluations and non-ocular evaluations. The formula was further assessed for safety during the efficacy testing by both dermatological and ophthalmologic evaluations. This formula improved periorbital aging in 50% of subjects with sagging skin, eyelid firmness and puffiness after 12 weeks of application by dermatological evaluations. 265 Pilot trial to evaluate the effect of vitamin D on melanocyte biomarkers E Anderson, M Rezaee, I Bailey-Healy, K Sarin and J Tang 1 School of Medicine, Stanford University, Stanford, CA and 2 Dermatology, Stanford University, Stanford, CA The role of vitamin D for cancer prevention is an expanding area of interest. In clinical and epidemiologic studies, vitamin D has been shown to predict incidence and severity of melanoma skin cancer. Although the role of vitamin D in melanocyte differentiation and melanoma carcinogenesis has been described, a clear mechanism is yet to be established. Previous studies have suggested that vitamin D supplementation and increased serum vitamin D levels are associated with decreased melanoma incidence. We sought to determine the effect of oral vitamin D supplementation on gene expression within melanocytic nevi of women previously diagnosed with non-melanoma skin cancer. A total of 24 healthy women were included in this randomized placebo-controlled study. Half of the cohort received 4,000 IU oral vitamin D3 daily for 8 weeks. Skin checks were performed at baseline and 8 week follow-up, and nevi were biopsied at both time points. RNAwas collected from these nevi for gene expression profiling to identify activity in signaling pathways associated with vitamin D treatment. Women who received vitamin D supplementation experienced a significant increase in vitamin D levels at follow-up (p 1⁄4 0.0001) while women who received placebo did not (p 1⁄4 0.50). Gene expression analysis of melanocytic nevi revealed 1048 genes that were significantly differentially expressed between vitamin D-treated and placebo-controlled women. Ingenuity Pathway Analysis indicated that the most significantly differentiated molecular signaling pathways were related to immune system signaling, including primary immunodeficiency signaling (p 1⁄4 3.53 x 10), T cell receptor signaling (p 1⁄4 4.31 x 10), iCOS-iCOSL signaling in T helper cells (p 1⁄4 1.24 x 10), calcium-induced T lymphocyte apoptosis (p 1⁄4 7.52 x 10), and crosstalk between dendritic cells and natural killer cells (p 1⁄4 1.68 x 10). This finding suggests that increased immune surveillance could underlie the previously described association between vitamin D supplementation and decreased melanoma incidence.

The relative efficiency of the WOMAC, AIMS, and HAQ instruments was compared in 21 patients with osteoarthritis who received total knee replacement surgery. Assessments of pain and physical function were made pre-operatively and 6 months post-operatively and the relative efficiency of the three instruments in detecting change was determined. Overall, the WOMAC Osteoarthritis Index was greater in relative efficiency than the HAQ and AIMS instruments, particularly in the detection of change in functional status. We conclude that the WOMAC Index can be used as an alternative to the HAQ or AIMS instruments in outcome assessment in osteoarthritis clinical trials.

We describe the Michigan/Magellan Fiber System (M2FS) under construction for use on the Magellan/Clay telescope. M2FS consists of four primary components including: (1) A fiber-fed double spectrograph (MSPec) in which each spectrograph is fed by 128 fibers (for a total multiplexing factor of 256) and each is optimized in to operate from 370- 950 nm; (2) A fiber mounting system (MFib) that supports the fibers and fiber plug plates at the telescope f/11 Nasmyth focal surface and organizes the fibers into ‘shoes’ that are used to place the fibers at the image surface of the MSpec spectrographs;, (3) A new wide-field corrector (WFC) that produces high-quality images over a 30 arcmin diameter field; (4) A unit (MCal) mounted near the telescope secondary that provides wavelength and continuum calibration and that supports a key component in a novel automated fiber identification system. We describe the opto-mechanical properties of M2FS, its modes of operation, and its anticipated performance, as well as potential upgrades including the development of a robotic fiber positioner and an atmospheric dispersion corrector. We describe how the M2FS design could serve as the basis of a powerful wide-field, massively multiplexed spectroscopic survey facility.

Fiber-fed multi-object spectrographs have greatly enhanced the spectroscopic capabilities of the world's premiere telescopes, but their flexibility has typically been limited by a fixed effective slit size that constrains the available resolving power. We present a novel mechanism that, for the first time, equips a fiber-fed spectrograph with multiple discreet slits of different widths. In this paper, we detail the mechanical design of our variable slit mechanism, which is capable of positioning any one of six slits in front of the fibers immediately prior to injection into the spectrograph's optical train. Further, we present the details of related systems necessary to achieve closed loop positioning of the slit mechanism given that no encoder is used. We also briefly discuss our use of open source and open hardware projects in the design. Finally, we describe the control system we have implemented for this subsystem.

Approximately 75% of hospitalized patients with a cervical spinal cord injury (CSCI) will require intubation and mechanical ventilation (MV) because of compromised respiratory function. It is difficult to predict those CSCI patients who will require prolonged ventilation and therefore will most benefit from early tracheostomy. This study intended to show the benefits of tracheostomy, particularly early, and to identify predictors of prolonged MV after CSCI.A retrospective review of patients aged 16 years and older with acute CSCI admitted to London Health Science Center from 1991 to 2010 was performed. Demographic data and clinical parameters were extracted from medical records and the trauma registry. Regression analysis was used to identify predictors of prolonged MV.There were 66 eligible patients of which 42 (62%) had a tracheostomy performed. Five patients (7.6%) remained ventilator dependent and seven (10.6%) died more than 7 days after injury secondary to sepsis. After adjusting for the number of ventilator days after injury, patients who had a tracheostomy had fewer pulmonary complications than those who did not have a tracheostomy (p = 0.001). Early tracheostomy resulted in fewer days on the ventilator and a shorter hospital stay. Clinical parameters that predicted MV to be required longer than 7 days were Injury Severity Score32, complete SCI, and a PAO2/FIO2 ratio300 3 days after MV was initiated.We recommend early tracheostomy if the Injury Severity Score is32, the patient has a complete SCI, and the PAO2/FIO2 ratio is300 3 days after MV was initiated.Prognostic study, level III.