Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial.

BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.

New autosomal dominant form of spondyloepiphyseal dysplasia presenting with atlanto-axial instability.

We present a family with a radiologically distinct new form of autosomal dominant spondyloepiphyseal dysplasia, presenting with cervical instability and attendant neurological compromise and emphasise the radiological characteristics which delineate this condition. Cervical vertebral abnormalities, including malformation of the odontoid process, have been observed in some forms of spondyloepiphyseal dysplasia, but rarely lead to neurological sequelae, in contrast to the pedigree we describe.

The synthetic phosphagen cyclocreatine phosphate inhibits the growth of a broad spectrum of solid tumors.

BACKGROUND: The brain isoform of creatine kinase (CKBB), an enzyme involved in energy metabolism, has been implicated in cellular transformation process. Cyclocreatine (CCr), a creatine kinase (CK) substrate analogue, was shown to inhibit the growth of a broad spectrum of solid tumors expressing high levels of CK. Cyclocreatine phosphate (CCrP) generated by CK, was proposed to be the active form responsible for growth inhibition. MATERIALS AND METHODS: We synthesized CCrP and tested its cellular uptake and anti tumor activity in stem cell assays and in athymic mouse models. RESULTS: CCrP seems to be taken up by cells and inhibits the growth of solid tumors with high levels of CK. CCr and CCrP have similar specificity and potency. CONCLUSION: The observation that only high-CK cell lines were responsive to CCrP, similar to CCr, indicates that the enzyme requirement was not bypassed. We propose that CK is a target for CCrP, and is involved in mediating its antiproliferative activity.

Case report: soft tissue and perivisceral calcification occurring in an infant: a case of brown fat necrosis.

Fat necrosis is a well described cause of widespread subcutaneous calcification occurring in a young infant. In this condition the radiographic demonstration of soft tissue calcification is often dramatic but is clinically irrelevant since the diagnosis is usually evident without recourse to radiology. Visceral fat necrosis and calcification, in the absence of hypercalcaemia, have been reported occasionally in association with subcutaneous fat necrosis. We report a case with calcification largely confined to deep perivisceral sites without clinical signs of subcutaneous fat necrosis.

Accuracy of imaging of the brains of newborn infants by linear-array real-time ultrasound.

Comparisons were made in 69 newborn infants of the appearance of the brain as visualised by linear-array real-time ultrasound, computerised tomography and at autopsy, in order to evaluate the accuracy of ultrasound for the detection of lesions in the brain. Ultrasound was found to give a good estimate of the presence and extent of haemorrhage into the germinal layer and ventricles, and also to be very useful for assessing the appearance of the ventricular system. Ultrasound diagnosed extradural haemorrhages but was unhelpful for identifying subarachnoid haemorrhages or lesions in the posterior fossa.

Lunate subluxation associated with a Salter-Harris type 2 fracture of the distal radius.

A case is reported of lunate subluxation in combination with a Salter-Harris type 2 fracture of the distal radius in a child. Carpal subluxations or dislocations are rare in children. This combination has never been reported before. It significance lies in the combination of injuries, the more common of which led the lunate injury to be overlooked, emphasizing the importance of careful study of all available radiographs of an injury.

Spondyloepiphyseal dysplasia with nephrotic syndrome (Schimke immunoosseous dysplasia).

We report a 3-year-old girl with the association of spondyloepiphyseal dysplasia, nephrotic syndrome, and signs of defective cellular immunity. The findings are similar to those reported by Spranger et al., which have become known as Schimke immunoosseous dysplasia.

Care of the suddenly bereaved in cardiac care units: a review of the literature.

This paper considers the experiences emerging from relatives whose loved ones die suddenly in a Cardiac Care Unit (CCU). It examines how best to address their needs and how to facilitate the normal grieving process during their brief yet traumatic hospital encounter. There appears to be no primary research relating specifically to sudden bereavement in a CCU. Several authors assume that findings can be applied between specialties but there is no empirical evidence to support this assumption. The research which does exist is predominantly in the areas of bereavement generally and in Accident and Emergency (A&E) in particular. This paper contains a critical examination of this literature and consideration of the extent to which findings from these fields can be relied upon to lead practice in the CCUs. It is concluded that recommendations for practice arising from such literature, e.g. those supporting the allocation of an advocate nurse to accompany relatives and allowing observation of resuscitation, may not be readily applicable to CCUs. The paper concludes with a consideration of future cardio-specific research needs.

Trans-vaginal oocyte retrieval and subsequent in vitro production of embryos from a cow involuntarily culled.

A Holstein cow of high genetic merit, in late lactation (205 days) and diagnosed with salpingitis (after 4 infertile services and veterinary consultation), was subjected to 1 trans-vaginal oocyte collection attempt, prior to slaughter. Of an estimated 10 follicles punctured, a total of 4 cumulus-oocyte complexes were retrieved. These were matured in vitro in a maturation medium for 24 hours. After 24 hours maturation, the oocytes were fertilised in vitro with Percoll-processed frozen/thawed imported semen, of the owner's choice. Fertilisation was achieved in a modified Tyrode's medium. At 18 hours post-insemination, the presumptive zygotes were transferred into culture in vitro in Charles Rosenkran's amino-acid medium and supplemented on Day 4 post-insemination with 10% foetal calf serum. All in vitro procedures were conducted in 50 microl medium droplets, under oil, in a humidified incubator at 38.5 degrees C in 5% CO2 in air. Three of the potential zygotes cleaved and, by Day 7 of culture, these had developed to the morula stage. The embryos were frozen in 1.5 M ethylene glycol and later transferred non-surgically to synchronised Holstein recipient heifers. One morula resulted in the only pregnancy and subsequent birth of a healthy heifer calf. An independent commercial company confirmed parentage through standard blood-typing assays. The genetic salvage of oocytes, for in vitro production of embryos, has potential benefits to the producer.