Performance of the 4-Level Pulmonary Embolism Clinical Probability Score (4PEPS) in the diagnostic management of pulmonary embolism:An external validation study

Background: The recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging testing in patients with clinically suspected pulmonary embolism (PE). Aim: To externally validate the performance of 4PEPS in an independent cohort. Methods: In this post-hoc analysis of the prospective diagnostic management YEARS study, the primary outcome measures were discrimination, calibration, efficiency (proportion of imaging tests potentially avoided), and failure rate (venous thromboembolism (VTE) diagnosis at baseline or follow-up in patients with a negative 4PEPS algorithm). Multiple imputation was used for missing 4PEPS items. Based on 4PEPS, PE was considered ruled out in patients with a very low clinical pre-test probability (CPTP) without D-dimer testing, in patients with a low CPTP and D-dimer &lt;1000 μg/L, and in patients with a moderate CPP and D-dimer below the age-adjusted threshold. Results: Of the 3465 patients, 474 (14 %) were diagnosed with VTE at baseline or during 3-month follow-up. Discriminatory performance of the 4PEPS items was good (area under ROC-curve, 0.82; 95%CI, 0.80–0.84) as was calibration. Based on 4PEPS, PE could be considered ruled out without imaging in 58 % (95%CI 57–60) of patients (efficiency), for an overall failure rate of 1.3 % (95%CI 0.86–1.9). Conclusion: In this retrospective external validation, 4PEPS appeared to safely rule out PE with a high efficiency. Nevertheless, although not exceeding the failure rate margin by ISTH standards, the observed failure rate in our analysis appeared to be higher than in the original 4PEPS derivation and validation study. This highlights the importance of a prospective outcome study.</p

A unified science of concussion

The etiology, imaging, and behavioral assessment of mild traumatic brain injury (mTBI) are daunting fields, given the lack of a cohesive neurobiological explanation for the observed cognitive deficits seen following mTBI. Although subjective patient self-report is the leading method of diagnosing mTBI, current scientific evidence suggests that quantitative measures of predictive timing, such as visual tracking, could be a useful adjunct to guide the assessment of attention and to screen for advanced brain imaging. Magnetic resonance diffusion tensor imaging (DTI) has demonstrated that mTBI is associated with widespread microstructural changes that include those in the frontal white matter tracts. Deficits observed during predictive visual tracking correlate with DTI findings that show lesions localized in neural pathways subserving the cognitive functions often disrupted in mTBI. Unifying the anatomical and behavioral approaches, the emerging evidence supports an explanation for mTBI that the observed cognitive impairments are a result of predictive timing deficits caused by shearing injuries in the frontal white matter tracts

Origin of the hot gas in low-mass protostars, Herschel-PACS spectroscopy of HH 46

Aims. “Water In Star-forming regions with Herschel” (WISH) is a Herschel key programme aimed at understanding the physical and chemical structure of young stellar objects (YSOs) with a focus on water and related species. Methods. The low-mass protostar HH 46 was observed with the Photodetector Array Camera and Spectrometer (PACS) on the Herschel Space Observatory to measure emission in H2O, CO, OH, [O i], and [C ii] lines located between 63 and 186 μm. The excitation and spatial distribution of emission can disentangle the different heating mechanisms of YSOs, with better spatial resolution and sensitivity than previously possible. Results. Far-IR line emission is detected at the position of the protostar and along the outflow axis. The OH emission is concentrated at the central position, CO emission is bright at the central position and along the outflow, and H2O emission is concentrated in the outflow. In addition, [O i] emission is seen in low-velocity gas, assumed to be related to the envelope, and is also seen shifted up to 170 km s−1 in both the red- and blue-shifted jets. Envelope models are constructed based on previous observational constraints. They indicate that passive heating of a spherical envelope by the protostellar luminosity cannot explain the high-excitation molecular gas detected with PACS, including CO lines with upper levels at >2500 K above the ground state. Instead, warm CO and H2O emission is probably produced in the walls of an outflow-carved cavity in the envelope, which are heated by UV photons and non-dissociative C-type shocks. The bright OH and [Oi] emission is attributed to J-type shocks in dense gas close to the protostar. In the scenario described here, the combined cooling by far-IR lines within the central spatial pixel is estimated to be 2 × 10−2 L, with 60–80% attributed to J- and C-type shocks produced by interactions between the jet and the envelope

Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): Study protocol for a randomized controlled trial

Background: Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days. Methods: Patients of 8 years and older undergoing appendectomy for acute complex appendicitis - defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess - are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at α 0.025). Both per-protocol and intention-to-treat analyses will be performed. Discussion: This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly