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.

Discoid lateral meniscus in children: clinical manifestations and morphology.

The authors investigated the correlation between the clinical manifestations and the morphology of discoid lateral meniscus. Thirty-eight children, age 5 to 17 years, with 39 cases of discoid lateral meniscus underwent an arthroscopic procedure and magnetic resonance imaging. The two most frequent preoperative clinical manifestations were pain and extension block. In 19 cases without surface tear, the most frequent clinical manifestation was extension block. In the sagittal magnetic resonance images, the mean thickness of the anterior portion of the discoid lateral meniscus (7.77 mm) in the group with extension block exceeded that (4.02 mm) in the group without extension block. Extension block was significantly more common in patients with the anterior hypertrophy type and the slab (anterior-posterior diffusely hypertrophic) type than in the posterior hypertrophy type by the modified Hall classification. As a result, extension block was significantly correlated with the morphology of the menisci. Also, the thickened anterior portion of the discoid lateral meniscus may be considered one of the mechanical factors that limit knee extension.

Hemophilus aphrophilus osteomyelitis.

Hemophilus aphrophilus is a slow-growing, aerobic (capnophilic), gram-negative bacillus. H. aphrophilus was the cause of hematogenous vertebral osteomyelitis in a patient who had a lip laceration. This was successfully treated with parenteral penicillin. The antimicrobial susceptibilities of 14 antimicrobial agents are presented.

Proteoglycan structure and metabolism in normal and osteoarthritic cartilage of guinea pigs.

Sulfated proteoglycan structure and metabolism in osteoarthritic articular cartilage from the hind-limb joints of guinea pigs in which the disease had been surgically induced were evaluated and compared with those from nonoperated or sham-operated controls. In these studies, conducted on animals receiving high and low dietary levels of ascorbic acid, the effect of vitamin C on these variables was also examined. Sulfated proteoglycan biosynthesis per unit of DNA as reflected by in vivo uptake of 35S-sulfate was stimulated both by arthritic development and high dietary vitamin C. Under these conditions, the specific activities, 35S-cpm/micrograms uronic acid, of the proteoglycans were elevated. Neither arthritic development nor variation in dietary levels of vitamin C altered the structure of the proteoglycans. Two species of proteoglycans that exhibited the same electrophoretic mobilities in agarose/acrylamide gels, the same elution profiles on high performance liquid chromatography,, and the same galactosamine/glucosamine ratios were found in all normal and osteoarthritic cartilage specimens tested. The specific activities of these two specimens tested. The specific activities of these two species were dissimilar. In all samples, the larger of the two species had a higher specific activity.

Experimentally-induced osteoarthritis in guinea pigs: effect of surgical procedure and dietary intake of vitamin C.

The effect of variation in dietary ascorbic acid on surgically induced osteoarthritis was examined in the stifle joints of guniea pigs. Two different surgical procedures were used to induce osteoarthritis in the right stifle joint of these animals. Guinea pigs were maintained either on a high (150 mg/day) or low (2.4 mg/day) dietary intake of vitamin C. Regardless of the surgical procedure used to induce osteoarthritis, the animals maintained on the high level of vitamin C consistently showed severe joint damage than animals on the low level of the vitamin.

Experimentally induced osteoarthritis in guinea pigs: metabolic responses in articular cartilage to developing pathology.

Developing osteoarthritis, surgically induced in the right hind knee joint of guinea pigs by different procedures (A or B), was studied in animals maintained on either minimal or supplemented levels of dietary vitamin C. Procedure A, consisting of transecting the anterior cruciate and major portion of the medial collateral ligaments, resulted in a slower developing and less severe form of the disease than procedure B which also included a partial menisectomy. Regardless of the surgical procedure used, animals on minimal levels of ascorbate always exhibited more severe pathology than those on high levels. When compared with controls, a significant enhancement of acid phosphatase characterized arthritic cartilage in both supplemented and minimal diet groups, although the increase was 2-fold greater in the latter. In addition, a significant elevation of arylsulfatase A and B activities was observed only in the minimal diet group. Early stages of pathology in both diet groups were characterized by formation of repair cartilage which stained strongly with Safranin O on histologic sections. As the disease progressed, pitting, ulcerations, and eburnation occurred in the minimal diet group. Cartilage weight in normal joints was greater for guinea pigs kept on high levels of vitamin C. It is likely that this stimulated synthesis of cartilage in the supplemented animals protected against the erosion of the articular cartilage which characterized the more severe disease process in the guinea pigs on minimal levels of ascorbate.

Adjuvant treatment of osteogenic sarcoma with high-dose cyclophosphamide.

Six patients with osteosarcoma and no evidence of metastases received postoperative adjuvant chemotherapy with high-dose cyclophosphamide (25 mg/kg iv every other day for five doses). Three of these patients are alive without evidence of disease at 2 1/2, 3, and 5 years following diagnosis. The regimen was tolerable in terms of toxicity. Cyclophosphamide in high doses may be effective adjuvant therapy in some patients with osteosarcoma.

Combined therapy of osteosarcoma: preoperative irradiation, surgery, and chemotherapy.

The rationale for prebiopsy and preoperative irradiation in a multimodal approach to treatment of osteosarcoma is presented. Six patients with osteosarcoma underwent preoperative irradiation, amputation, and elective chemotherapy. Five of these also received prebiopsy irradiation: three survive without metastases at 29, 36, and 56 months, with no therapy for 10, 16, and 37 months, respectively; two patients died at 6 and 19 months of pulmonary metastases which appeared at 2 and 10 months, respectively. The latter two did not receive prebiopsy irradiation. Another patient, whose pulmonary metastasis regressed at 6 months with adriamycin and was later resected, died of cardiac failure at 59 months without evident metastasis. Immunologic aspects of the disease are also discussed.

Dislocation of the hip in birth defects.

Several heritable disorders--although rare--are reviewed that are directly or indirectly related to dislocation of the hip. With the ever increasing list of clinical syndromes and our growing understanding of genetics, the physician who first sees these patients should broaden his views to identify these conditions and establish the diagnosis. The effectiveness of treatment often depends upon such knowledge.

Arthrogryposis multiplex congenita of the lower extremity: report of two siblings.

The purpose of treatment of arthrogryposis of the lower extremities is to achieve a stable functional weight bearing position of the affected joints. One cannot expect to achieve normal mobility and gait unless the process is mild. Achieving a functional weight bearing position of a joint may be extremely difficult, requiring repeated surgical procedures. Maintenance of correction, although often imperfect, is vital during the growing period.