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.

Familial pulmonary hypoplasia: plain film appearances with histopathological correlation.

Familial pulmonary hypoplasia is a rare cause of bilateral pulmonary hypoplasia. We describe the plain film appearances and correlate these with the histopathological findings in an infant who survived 5 weeks. In this case, improved technology prolonged survival, allowing the radiological appearance of the primitive lung architecture to become more clearly defined.

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.

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.

A distinct form of spondyloepimetaphyseal dysplasia with multiple dislocations.

Three unrelated patients with identical radiological features are presented. Hypotonia was noted at birth and one patient was diagnosed as having congenital fibre type disproportion in the neonatal period. Later muscle biopsies, however, were entirely normal. All patients, now in their teens and twenties, are of normal intelligence, show striking epiphyseal and metaphyseal changes of the long bones, and have joint laxity and multiple dislocations of large joints, which are particularly incapacitating at the knees. These three cases represent a sporadic, previously unreported skeletal dysplasia with spondyloepimetaphyseal distribution and multiple large joint dislocations.

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.

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.

Inflammatory pseudotumours in children: CT and ultrasound appearances with histopathological correlation.

Inflammatory pseudotumour is an uncommon benign lesion that presents in children and young adults. The rarity of these lesions, particularly at extrapulmonary sites, has resulted in poor documentation of its radiological manifestations. The casenotes, radiology and histology of five patients with inflammatory pseudotumour were reviewed. Two lesions were intra-abdominal, one oesophageal, one intrapulmonary and one lower limb. CT demonstrated inflammatory pseudotumours as well circumscribed masses of soft tissue density producing displacement of surrounding structures rather than local invasion. Sonography depicted these lesions as well defined masses with homogeneous echo patterns. Surgical removal resulted in dramatic symptomatic improvement.

Childhood soft tissue chondroma: a case report.

In this paper we draw attention to the existence of soft tissue chondromas in childhood. This entity is well recognized in adults, where over 90% of the recorded cases have occurred in the hands and feet. Our case is unusual in that the child was only 10 years of age and the lesion was on the back, not in the extremity. The importance of recognizing this condition is that these chondromas may exhibit increased cellularity and mitoses and should not be mistaken for a malignant condition.

Radiographic features of limb lengthening in children.

We report our experience in radiographic imaging in limb lengthening procedures using callotasis for limb lengthening discrepancy with the Orthofix dynamic monoaxial external fixator. Seventeen patients (average age at operation 10.8 years) completed 22 bone segments (7 femora, 11 tibiae, 4 ulnae) lengthening procedures. The average time for formation of good medullary bridging was over 6 months. The commonest radiographic abnormality was a periosteal reaction around the pin sites seen in 14 patients, while evidence of pin loosening was present in 10. All patients with pin loosening also showed periosteal reaction which pre-dated the loosening in 5 of 12 patients by an average of 47 days. Angulation was detected in 9 patients in the a.p. plane, and in 6 in the lateral plane. Six patients developed a ragged radiolucent region through the newly forming bone at an average of 95 days from the corticotomy but with uneventful healing.

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.