Introducing a Clinical Practice Guideline Using Early CT in the Diagnosis of Scaphoid and Other Fractures

Objective: We developed and implemented clinical practice guideline (CPG) using computerized tomography (CT) as the initial imaging method in the emergency department management of scaphoid fractures. We hypothesized that this CPG would decrease unnecessary immobilization and lead to earlier return to work.Methods: This observational study evaluated implementation of our CPG, which incorporated early wrist CT in patients with “clinical scaphoid fracture”: a mechanism of injury consistent with scaphoid fracture, anatomical snuff box tenderness, and normal initial plain x-rays. Outcome measures were the final diagnosis as determined by orthopaedic review of the clinical and imaging data. Patient outcomes included time to return to work and patient satisfaction as determined by telephone interview at ten days.Results: Eighty patients completed the study protocol in a regional emergency department.In this patient population CT detected 28 fractures in 25 patients, including six scaphoid fractures, five triquetral fractures, four radius fractures, and 13 other related fractures. Fifty-three patients had normal CT. Eight of these patients had significant ongoing pain at follow up and had an MRI, with only two bone bruises identified. The patients with normal CTs avoided prolonged immobilization (mean time in plaster 2.7 days) and had no or minimal time off work (mean 1.6 days). Patient satisfaction was an average 4.2/5.Conclusion: This CPG resulted in rapid and accurate management of patients with suspected occult scaphoid injury, minimized unnecessary immobilization and was acceptable to patients.[WestJEM. 2009;10(4):227-232.

Invest Ophthalmol Vis Sci

Purpose: We investigated the cross-sectional associations between macular pigment optical density (MPOD), plasma lutein (L), and zeaxanthin (Z) concentrations and cognitive function in 184 older adults of the 3-City-Bordeaux cohort. Methods: MPOD was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma L and Z (L+Z) concentrations were determined by high-performance liquid chromatography and were considered either crude or expressed as a ratio of the concentration of plasma lipids (total cholesterol [TC] + triglycerides [TG]). Cognitive performances were assessed using the following four separate neuropsychological tests: the Mini-Mental State Examination (MMSE), the Isaacs Set Test (IST), the Benton Visual Retention Test (BVRT), and the sum of the three free recalls of the Free and Cued Selective Reminding Test (FCSRT). These test results were summarized by a composite global cognitive z-score. Results: Higher MPOD at 0.5 degrees was significantly associated with a higher composite z-score (beta = 0.15, 95% confidence interval [CI] 0.04-0.26), higher BVRT (beta = 0.39, 95%CI 0.08-0.70), and higher IST (beta = 1.16, 95%CI 0.11-2.22) performances. Higher plasma L+Z concentrations were significantly associated with higher IST scores (beta = 0.97, 95%CI 0.01-1.94). Furthermore, a higher L+Z/TC+TG ratio was associated with a higher composite z-score (beta = 0.12, 95%CI 0.01-0.23), along with higher IST (beta = 1.02, 95%CI 0.002-2.04) and FCSRT (beta = 1.55, 95%CI 0.41-2.69) performances. Conclusions: This analysis suggested that both higher MPOD and L+Z concentrations were significantly associated with higher cognitive performances. However, MPOD measurements have the advantage of being a fast and representative measure of long-term carotenoid intake

CT-guided radiofrequency ablation of osteoid osteoma: correlation of clinical outcome and imaging features

PURPOSEWe aimed to retrospectively evaluate the computed tomography (CT) and magnetic resonance imaging (MRI) findings of patients with osteoid osteoma treated with CT-guided radiofrequency ablation (RFA) along with the clinical outcome and long-term success.MATERIALS AND METHODSSeventy-three CT-guided RFA procedures were performed in 72 patients. The long-term success was assessed using a questionnaire including several visual analog scale scores. The CT evaluation included pre- and immediate postprocedural imaging of all 72 patients, and MRI was performed in 18 patients with follow-up imaging (mean, 3.4±2.2 months). The evaluation criteria included nidus morphology and a correlation with markers of clinical success.RESULTSThe primary technique effectiveness rate was 71/72 (99%). One relapse was successfully retreated, leading to a secondary technique effectiveness rate of 72/72 (100%). The long-term follow-up (mean, 51.2±31.2 months; range, 3–109 months) revealed a highly significant reduction of all assessed limitation scores (P < 0.001). The CT morphology was typical in all cases and did not change during the short-term follow-up. The follow-up MRI patterns varied considerably, including persistent nidus contrast enhancement in one-third (6/18) and persistent marrow edema in half (9/18) of the patients. None of the investigated MRI and CT patterns correlated with the clinical outcome.CONCLUSIONThe long-term outcome of CT-guided RFA of osteoid osteoma is excellent. There is no correlation of the CT and MRI patterns with the clinical outcome. Thus, the treatment decisions should not be solely based on the imaging findings. Investigators should also be aware of the variety of imaging patterns after RFA

Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity

Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large HIV-1 cohort screen. By establishing comprehensive antibody signatures based on IgG1, IgG2, and IgG3 activity to 13 HIV-1 antigens in 4,281 individuals in the same cohort, we now show that the same four parameters that are significantly linked with neutralization breadth, namely viral load, infection length, viral diversity, and ethnicity, also strongly influence HIV-1-binding antibody responses. However, the effects proved selective, shaping binding antibody responses in an antigen and IgG subclass-dependent manner. IgG response landscapes in bnAb inducers indicated a differentially regulated, IgG1-driven HIV-1 antigen response, and IgG1 binding of the BG505 SOSIP trimer proved the best predictor of HIV-1 neutralization breadth in plasma. Our findings emphasize the need to unravel immune modulators that underlie the differentially regulated IgG response in bnAb inducers to guide vaccine development

A randomized open label phase-II clinical trial with or without infusion of plasma from subjects after convalescence of SARS-CoV-2 infection in high-risk patients with confirmed severe SARS-CoV-2 disease (RECOVER): a structured summary of a study protocol for a randomised controlled trial

OBJECTIVES: Primary objectives • To assess the time from randomisation until an improvement within 84 days defined as two points on a seven point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of SARS-CoV-2 infection or standard of care. Secondary objectives • To assess overall survival, and the overall survival rate at 28 56 and 84 days. • To assess SARS-CoV-2 viral clearance and load as well as antibody titres. • To assess the percentage of patients that required mechanical ventilation. • To assess time from randomisation until discharge. TRIAL DESIGN: Randomised, open-label, multicenter phase II trial, designed to assess the clinical outcome of SARS-CoV-2 disease in high-risk patients (group 1 to group 4) following treatment with anti-SARS-CoV-2 convalescent plasma or standard of care. PARTICIPANTS: High-risk patients >18 years of age hospitalized with SARS-CoV-2 infection in 10-15 university medical centres will be included. High-risk is defined as SARS-CoV-2 positive infection with Oxygen saturation at ≤ 94% at ambient air with additional risk features as categorised in 4 groups: • Group 1, pre-existing or concurrent hematological malignancy and/or active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or less. • Group 2, chronic immunosuppression not meeting the criteria of group 1. • Group 3, age ≥ 50 - 75 years meeting neither the criteria of group 1 nor group 2 and at least one of these criteria: Lymphopenia 1μg/mL. • Group 4, age ≥ 75 years meeting neither the criteria of group 1 nor group 2. Observation time for all patients is expected to be at least 3 months after entry into the study. Patients receive convalescent plasma for two days (day 1 and day 2) or standard of care. For patients in the standard arm, cross over is allowed from day 10 in case of not improving or worsening clinical condition. Nose/throat swabs for determination of viral load are collected at day 0 and day 1 (before first CP administration) and subsequently at day 2, 3, 5, 7, 10, 14, 28 or until discharge. Serum for SARS-Cov-2 diagnostic is collected at baseline and subsequently at day 3, 7, 14 and once during the follow-up period (between day 35 and day 84). There is a regular follow-up of 3 months. All discharged patients are followed by regular phone calls. All visits, time points and study assessments are summarized in the Trial Schedule (see full protocol Table 1). All participating trial sites will be supplied with study specific visit worksheets that list all assessments and procedures to be completed at each visit. All findings including clinical and laboratory data are documented by the investigator or an authorized member of the study team in the patient's medical record and in the electronic case report forms (eCRFs). INTERVENTION AND COMPARATOR: This trial will analyze the effects of convalescent plasma from recovered subjects with SARS-CoV-2 antibodies in high-risk patients with SARS-CoV-2 infection. Patients at high risk for a poor outcome due to underlying disease, age or condition as listed above are eligible for enrollment. In addition, eligible patients have a confirmed SARS-CoV-2 infection and O2 saturation ≤ 94% while breathing ambient air. Patients are randomised to receive (experimental arm) or not receive (standard arm) convalescent plasma in two bags (238 - 337 ml plasma each) from different donors (day 1, day 2). A cross over from the standard arm into the experimental arm is possible after day 10 in case of not improving or worsening clinical condition. MAIN OUTCOMES: Primary endpoints: The main purpose of the study is to assess the time from randomisation until an improvement within 84 days defined as two points on a seven-point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of a SARS-CoV-2 infection or standard of care. Secondary endpoints: • Overall survival, defined as the time from randomisation until death from any cause 28-day, 56-day and 84-day overall survival rates. • SARS-CoV-2 viral clearance and load as well as antibody titres. • Requirement mechanical ventilation at any time during hospital stay (yes/no). • Time until discharge from randomisation. • Viral load, changes in antibody titers and cytokine profiles are analysed in an exploratory manner using paired non-parametric tests (before - after treatment). RANDOMISATION: Upon confirmation of eligibility (patients must meet all inclusion criteria and must not meet exclusion criteria described in section 5.3 and 5.4 of the full protocol), the clinical site must contact a centralized internet randomization system ( https://randomizer.at/ ). Patients are randomized using block randomisation to one of the two arms, experimental arm or standard arm, in a 1:1 ratio considering a stratification according to the 4 risk groups (see Participants). BLINDING (MASKING): The study is open-label, no blinding will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total number of 174 patients is required for the entire trial, n=87 per group. TRIAL STATUS: Protocol version 1.2 dated 09/07/2020. A recruitment period of approximately 9 months and an overall study duration of approximately 12 months is anticipated. Recruitment of patients starts in the third quarter of 2020. The study duration of an individual patient is planned to be 3 months. After finishing all study-relevant procedures, therapy, and follow-up period, the patient is followed in terms of routine care and treated if necessary. Total trial duration: 18 months Duration of the clinical phase: 12 months First patient first visit (FPFV): 3rd Quarter 2020 Last patient first visit (LPFV): 2nd Quarter 2021 Last patient last visit (LPLV): 3rd Quarter 2021 Trial Report completed: 4th Quarter 2021 TRIAL REGISTRATION: EudraCT Number: 2020-001632-10, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE , registered on 04/04/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). The eCRF is attached (Additional file 3)

Technical Design Report for the: PANDA Micro Vertex Detector

This document illustrates the technical layout and the expected performance of the Micro Vertex Detector (MVD) of the PANDA experiment. The MVD will detect charged particles as close as possible to the interaction zone. Design criteria and the optimisation process as well as the technical solutions chosen are discussed and the results of this process are subjected to extensive Monte Carlo physics studies. The route towards realisation of the detector is outlined.Comment: 189 pages, 225 figures, 41 table

Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial

Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial (https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response