Reliability of the Spinal Instability Neoplastic Score (SINS) among radiation oncologists: an assessment of instability secondary to spinal metastases

BACKGROUND: The Spinal Instability Neoplastic Score (SINS) categorizes tumor related spinal instability. It has the potential to streamline the referral of patients with established or potential spinal instability to a spine surgeon. This study aims to define the inter- and intra-observer reliability and validity of SINS among radiation oncologists. METHODS: Thirty-three radiation oncologists, across ten international sites, rated 30 neoplastic spinal disease cases. For each case, the total SINS (0-18 points), three clinical categories (stable: 0-6 points, potentially unstable: 7-12 points, and unstable: 13-18 points), and a binary scale (‘stable’: 0-6 points and ‘current or possible instability’; surgical consultation recommended: 7-18 points) were recorded. Evaluation was repeated 6-8 weeks later. Inter-observer agreement and intra-observer reproducibility were calculated by means of the kappa statistic and translated into levels of agreement (slight, fair, moderate, substantial, and excellent). Validity was determined by comparing the ratings against a spinal surgeon’s consensus standard. RESULTS: Radiation oncologists demonstrated substantial (κ = 0.76) inter-observer and excellent (κ = 0.80) intra-observer reliability when using the SINS binary scale (‘stable’ versus ‘current or possible instability’). Validity of the binary scale was also excellent (κ = 0.85) compared with the gold standard. None of the unstable cases was rated as stable by the radiation oncologists ensuring all were appropriately recommended for surgical consultation. CONCLUSIONS: Among radiation oncologists SINS is a highly reliable, reproducible, and valid assessment tool to address a key question in tumor related spinal disease: Is the spine ‘stable’ or is there ‘current or possible instability’ that warrants surgical assessment

The effect of sepsis and its inflammatory response on mechanical clot characteristics: a prospective observational study

Purpose: Sepsis and its progression are known to have a major influence on the coagulation system. Current coagulation tests are of limited use when assessing coagulation in sepsis patients. This study aims to assess the potential for a new functional biomarker of clot microstructure, fractal dimension, to identify changes in the mechanical properties of clot microstructure across the sepsis spectrum (sepsis, severe sepsis and septic shock). Methods: A total of 100 patients that presented acutely to a large teaching hospital were included in this prospective observational study (50 sepsis, 20 severe sepsis and 30 septic shock) against a matched control of 44 healthy volunteers. Fractal analysis was performed, as well as standard markers of coagulation, and six plasma markers of inflammation. Results: Fractal dimension was significantly higher in the sepsis and severe sepsis groups than the healthy control (1.78 ± 0.07 and 1.80 ± 0.05 respectively vs 1.74 ± 0.03) (p < 0.001), indicating a significant increase in mechanical clot strength and elasticity consistent with a hypercoagulable state. Conversely, fractal dimension was significantly lower in septic shock (1.66 ± 0.10, p < 0.001), indicating a significant reduction in mechanical clot strength and functionality consistent with a hypocoagulable state. This corresponded with a significant increase in the inflammatory response. Conclusions: This study confirms that clot microstructure is significantly altered through the various stages of sepsis. Of particular importance was the marked change in clot development between severe sepsis and septic shock, which has not been previously reported

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.)

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

An evidence-based medicine process to determine outcomes after cervical spine trauma: what surgeons should be telling their patients

STUDY DESIGN: A systematic review of the available medical literature from 1980 to 2010 was conducted and combined with expert opinion from a recent survey of experts regarding cervical spine fractures. Using an objective, hierarchical approach, the best available evidence is presented for health-related quality-of-life outcomes for these injuries. OBJECTIVE: To provide an evidence-based set of guidelines for cervical spine injuries in order to reduce variability in the information given to patients and their families. SUMMARY OF BACKGROUND DATA: Patients\u27 expectations regarding quality-of-life outcomes are highly dependent on the information provided by surgeons early in the treatment course. Our previous work has demonstrated that there is substantial variability in what surgeons tell patients regarding outcomes of cervical spine injuries, thus patients\u27 expectations will differ and outcomes vary. METHODS: Four common cervical spine injuries (C1 burst, Hangman fracture, odontoid fracture, and unilateral facet fracture) treated both surgically and nonsurgically were considered. We assessed the evidence regarding 5 health-related quality-of-life outcomes: time to return to work, activity level, hospital stay, the proportion of patients who are pain free and patients who have regained full range of motion at 1 year after the injury. RESULTS: Published outcome data were available for most injuries. Using consensus expert opinion and the literature, answers to each question were achieved. Overall, expert opinion was relatively homogeneous across injury types, suggesting that experts do not distinguish between specific injuries when advising patients of expected outcomes such as pain. CONCLUSION: By overcoming gaps in the literature with consensus expert opinion, our study provides surgeons and others with evidence-based medicine guidelines for patient-centered outcomes after cervical spine injury. This information can be presented to patients to frame expectations of typical outcomes during and after treatment to optimize patient care and quality of life

Reliability of the Spinal Instability Neoplastic Score (SINS) among radiation oncologists: an assessment of instability secondary to spinal metastases

Abstract Background The Spinal Instability Neoplastic Score (SINS) categorizes tumor related spinal instability. It has the potential to streamline the referral of patients with established or potential spinal instability to a spine surgeon. This study aims to define the inter- and intra-observer reliability and validity of SINS among radiation oncologists. Methods Thirty-three radiation oncologists, across ten international sites, rated 30 neoplastic spinal disease cases. For each case, the total SINS (0-18 points), three clinical categories (stable: 0-6 points, potentially unstable: 7-12 points, and unstable: 13-18 points), and a binary scale (‘stable’: 0-6 points and ‘current or possible instability’; surgical consultation recommended: 7-18 points) were recorded. Evaluation was repeated 6-8 weeks later. Inter-observer agreement and intra-observer reproducibility were calculated by means of the kappa statistic and translated into levels of agreement (slight, fair, moderate, substantial, and excellent). Validity was determined by comparing the ratings against a spinal surgeon’s consensus standard. Results Radiation oncologists demonstrated substantial (κ = 0.76) inter-observer and excellent (κ = 0.80) intra-observer reliability when using the SINS binary scale (‘stable’ versus ‘current or possible instability’). Validity of the binary scale was also excellent (κ = 0.85) compared with the gold standard. None of the unstable cases was rated as stable by the radiation oncologists ensuring all were appropriately recommended for surgical consultation. Conclusions Among radiation oncologists SINS is a highly reliable, reproducible, and valid assessment tool to address a key question in tumor related spinal disease: Is the spine ‘stable’ or is there ‘current or possible instability’ that warrants surgical assessment

Analysis of genetically modified red-fleshed apples reveals effects on growth and consumer attributes

Consumers of whole foods, such as fruits, demand consistent high quality and seek varieties with enhanced health properties, convenience or novel taste. We have raised the polyphenolic content of apple by genetic engineering of the anthocyanin pathway using the apple transcription factor MYB10. These apples have very high concentrations of foliar, flower and fruit anthocyanins, especially in the fruit peel. Independent lines were examined for impacts on tree growth, photosynthesis and fruit characteristics. Fruit were analysed for changes in metabolite and transcript levels. Fruit were also used in taste trials to study the consumer perception of such a novel apple. No negative taste attributes were associated with the elevated anthocyanins. Modification with this one gene provides near isogenic material and allows us to examine the effects on an established cultivar, with a view to enhancing consumer appeal independently of other fruit qualities. © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd