Efficacy and safety of convalescent plasma to treat hospitalised COVID-19 patients with or without underlying immunodeficiency: a randomized clinical trial

Efficacy of COVID-19 convalescent plasma (CCP) in COVID-19 pneumonia is uncertain. The CORIPLASM study was an open-label, Bayesian randomised clinical trial evaluating the efficacy of CCP in patients with moderate COVID-19, including immunocompromised patients. Patients hospitalised with COVID-19 and less than 9 days since symptoms onset were assigned to receive 4 units of plasma over 2 days ({approx} 840 ml)(CCP) or usual care alone (UC). Primary outcomes were the proportion of patients with a WHO-Clinical Progression Score (CPS) [≥]6 on the 10-point scale on day (d) 4 and survival without ventilation or additional immunomodulatory treatment by d14. A total of 120 patients were recruited and assigned to CCP (n=60) or UC (n=60), including 22 (CCP) and 27 (UC) immunocompromised patients. Thirteen (22%) patients with CCP had a WHO-CPS [≥]6 at d4 versus 8 (13%) with UC, adjusted odds ratio (aOR) 1.88 [95%CI 0.71 to 5.24]. By d14, 19 (31.6%) patients with CCP and 20 (33.3%) patients with UC had ventilation, additional immunomodulatory treatment or had died. Cumulative incidence of death was 3 (5%) with CCP and 8 (13%) with UC at d14 (aHR 0.40 [95%CI 0{middle dot}10 -1{middle dot}53]), and 7 (12%) with CCP and 12 (20%) with UC at d28 (aHR 0.51 [95%CI 0.20-1.32]). Subgroup analysis indicated that CCP might be associated with a lower mortality in immunocompromised patients (HR 0.37 [95%CI 0.14-0.97]). CCP treatment did not improve early outcomes in patients with moderate COVID-19 but was associated with reduced mortality in the subgroup of immunocompromised patients.

The Importance of Characterizing the Hemoglobin Instability of New Variants: The Case of Hb Dompierre [ß29(B11)Gly→Arg, HBB: c.88G>C].

Hb Dompierre [ß29(B11)Gly→Arg, HBB: c.88G>C] is a rare ß-globin gene variant that was previously described in the heterozygous state in a 24-year-old female patient. It is defined in the HbVar database as being clinically and biologically asymptomatic. A few years after the first description, we had an opportunity of reassessing the index case because she presented with splenomegaly and clinical and biological manifestations of hemolysis. After ruling out the most common causes of hemolysis, further analyses on the variant hemoglobin (Hb) using brilliant cresyl blue staining, indicated that it showed mild instability, which may explain the clinical and biological manifestations. A structural bioinformatic analysis on the Hb variant suggested that the amino acid replacement may be deleterious to the integrity of the Hb. This report confirms the importance of completely characterizing all new Hb variants in order to guide the patients' clinical management and follow-up, as well as to provide the probands and their family members with appropriate genetic counseling.

Postoperative evaluation of tibial footprint and tunnels characteristics after anatomic double-bundle anterior cruciate ligament reconstruction with anatomic aimers.

Following anatomic double-bundle anterior cruciate ligament (ACL) reconstruction with hamstring tendon autografts, 38 consecutive patients were evaluated with high-speed three-dimensional computed tomography. Scans were performed within 3 days following surgery. The length and width of the reconstructed ACL footprint were measured on axial images. Then, 3D images were converted into 2D with radiologic density for measurement purposes. Tunnel orientation was measured on AP and lateral views. In the sagittal plane, the center of the anteromedial (AMB) and posterolateral bundle (PLB) tibial attachment positions was calculated as the ratio between the geometric insertion sites with respect to the sagittal diameter of the tibia. In addition, the length from the anterior tibial plateau to the retro-eminence ridge was measured; the relationship of this line with the centers of the AM and PL tunnels was then measured. The AP length of the reconstructed footprint was 17.1 mm ± 1.9 mm and the width 7.3 mm ± 1.2 m. The distance from retro-eminence ridge to center of AM tunnel was 18.8 mm ± 2.8 mm, and the distance from RER to center of PL tunnel was 8.7 mm ± 2.6 mm. The distance between tunnels center was 10.1 mm ± 1.7 mm. There were no significant differences between the intra- and inter-observer measurements. The bone bridge thickness was 2.1 mm ± 0.8 mm. In the sagittal plane, the centers of the tunnel apertures were located at 35.7% ± 6.7% and 53.7% ± 6.8% of the tibia diameter for the AMB and PLB, respectively. The surface areas of the tunnel apertures were 46.3 mm(2) ± 4.4 mm(2) and 36.3 mm(2) ± 4.0 mm(2) for the AM and PL tunnels, respectively. The total surface area occupied by both tunnels was 82.6 mm(2) ± 7.0 mm(2). In the coronal plane, tunnel orientation showed the AM tunnel was more vertical than the PL tunnel with a 10° divergence (14.8° vs. 24.1°). In the sagittal plane, both tunnels were almost parallel (29.9° and 25.4° for the AM and PL tunnels, respectively). When using anatomic aimers, the morphometric parameters of the reconstructed tibial footprint in terms of length and distances to the surrounding bony landmarks were similar to the native ACL tibial footprint. However, the native footprint width was not restored, and the surface area of the two tunnel apertures was in the lower range of the published values for the native footprint area.

Validation of the position of the femoral tunnels in anatomic double-bundle ACL reconstruction with 3-D CT scan.

This study compares the positioning of femoral AM and PL tunnels obtained with specific ancillary instruments during anatomic double-bundle ACL reconstruction with the native ACL footprint using three-dimensional computed tomography (3-D CT). In 35 consecutive patients, anatomic double-bundle ACL reconstruction was performed with specific ancillary instruments. Three-dimensional CT reconstruction of both knees was performed using the volume rendering technique. In the controls (contralateral knee, with intact ACL), the angle between the longitudinal axis of the footprint and the axis of the femur, the "footprint angle" (FA) was measured. On the involved side, using the axis passing through the tunnel centers, FA was also measured. In both the groups, footprint's length and width, and distances to cartilage margins were measured. FA was 28.1 degrees +/- 5.0 degrees in the controls and 32.9 degrees +/- 15.8 degrees on the involved side (n.s.). There was no statistical difference between the two groups for the other morphometric parameters: footprint's length and width, and distances to cartilage margins. Using specific ancillary instruments the morphometric parameters of the reconstructed femoral ACL footprint were similar to the native ACL.

Economic impact of migraine and other episodic headaches in France: data from the GRIM2000 study.

BACKGROUND: Migraine is a prevalent and incapacitating condition that affects individuals in the prime of their productive life, thus generating an economic burden for both society and healthcare systems. The direct annual healthcare costs of migraine in France were assessed over 10 years ago, and the current study updates these figures. OBJECTIVE: The objective of this study was to determine the economic cost (primarily direct costs) of migraine and other episodic headache in France based on a general population survey of headache, the GRIM2000 (Groupe de Researche Interdisciplinaire sur la Migraine). DESIGN: From a representative general population sample of 10,585 individuals aged > or = 15 years in France in 1999, 1486 individuals experiencing headaches were identified and interviewed regarding healthcare resource consumption in the previous 6 months. By applying unit costs to the resource data, costings (in 1999 values) were determined for physician consultations, hospitalisation, medication use and diagnostic/laboratory tests, and evaluated from a healthcare system perspective. Information on absenteeism and lost productivity was derived from the Migraine Disability Assessment Score (MIDAS) questionnaire. RESULTS: The prevalence of migraine (including migrainous disorder) was determined to be 17%. Total annual direct healthcare costs were estimated to be Euros 128 per individual with migraine in 1999, corresponding to Euros 1044 million when extrapolated to all individuals experiencing migraine and aged > or = 15 years. Around two-thirds of this cost accrued to the social security system (Euros 698 million; Euros 85 per individual). The total annual direct cost of other forms of episodic headache was much lower at Euros 28 per individual (social security cost Euros 18); with a prevalence of 9.2%, the annual national direct cost for other forms of episodic headache totalled Euros 124 million. The principal cost element was physician consultations. However, it was found that many individuals had never consulted a physician for their headaches, and self-medication contributed substantially to the medication costs (the second greatest cost factor for migraine). The cost per individual rose steeply with increasing severity of headache. CONCLUSIONS: The direct healthcare costs of migraine do not seem to have risen significantly over the past decade. A small minority of individuals with more severe headaches consume most of the healthcare resources devoted to migraine, while most individuals generate relatively low direct costs. The total annual direct costs in France for migraine are almost 10-fold higher than those of other episodic headache.