Role of IgG against N-protein of SARS-CoV2 in COVID19 clinical outcomes.

The Nucleocapsid Protein (N Protein) of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) is located in the viral core. Immunoglobulin G (IgG) targeting N protein is detectable in the serum of infected patients. The effect of high titers of IgG against N-protein on clinical outcomes of SARS-CoV2 disease has not been described. We studied 400 RT-PCR confirmed SARS-CoV2 patients to determine independent factors associated with poor outcomes, including Medical Intensive Care Unit (MICU) admission, prolonged MICU stay and hospital admissions, and in-hospital mortality. We also measured serum IgG against the N protein and correlated its concentrations with clinical outcomes. We found that several factors, including Charlson comorbidity Index (CCI), high levels of IL6, and presentation with dyspnea were associated with poor clinical outcomes. It was shown that higher CCI and higher IL6 levels were independently associated with in-hospital mortality. Anti-N protein IgG was detected in the serum of 55 (55%) patients at the time of admission. A high concentration of antibodies, defined as signal to cut off ratio (S/Co) > 1.5 (75 percentile of all measurements), was found in 25 (25%) patients. The multivariable logistic regression models showed that between being an African American, higher CCI, lymphocyte counts, and S/Co ratio > 1.5, only S/Co ratio were independently associated with MICU admission and longer length of stay in hospital. This study recommends that titers of IgG targeting N-protein of SARS-CoV2 at admission is a prognostic factor for the clinical course of disease and should be measured in all patients with SARS-CoV2 infection.

Cross calibration of Hologic QDR2000 and GE lunar prodigy for whole body bone mineral density and body composition measurements.

The objective of this study was to undertake an in vivo cross calibration of body composition, whole body bone mineral content (BMC) and bone mineral density (BMD) between a Hologic QDR2000 and a GE Healthcare Lunar Prodigy. Twenty-one subjects attending for routine bone densitometry were recruited to the study (19 female and 2 male, aged 30-79 yr). Phantom cross calibrations were carried out using the Bio-Imaging Variable Composition Phantom (VCP) for percentage fat (%fat) and the Bona Fide Phantom (BFP) for BMD. There was no significant difference in whole body lean body mass between the QDR2000 and the Prodigy. Fat mass (FM) and %fat were significantly higher on the QDR2000. BMC and whole body BMD were significantly higher on Prodigy. As the BMC increased, so did the difference between the 2 instruments. The VCP did not provide an adequate cross calibration of %fat compared with in vivo. The BFP provided a good cross calibration of whole body BMD compared with in vivo. The results suggest that the partitioning of the soft tissue component between lean and fat in the 2 instruments is systematically different. The variation between instruments from the same and different manufacturers reported in the literature varies widely, as does the comparison with criterion methods. This makes it difficult to generalize the results of this study to other centers and it is recommended that each center would have to cross calibrate when changing equipment.

Cross calibration of DXA as part of an equipment replacement program.

The purpose of this study was to develop cross calibrations when replacing three dual-energy X-ray absorptiometers (GE Lunar DPXL [Madison, WI], DPXL, GE Lunar Expert [Madison, WI], Expert, Hologic QDR2000 [Waltham, MA]) with two new GE Lunar Prodigy instruments. Subjects previously scanned on the Expert or QDR2000 were transferred to Prodigy 1 and those previously scanned on the DPXL to Prodigy 2. A cohort of subjects was recalled for each old instrument, and approximately 20 subjects had lumbar spine and hip scans on each old instrument and the appropriate new instrument. An in vitro calibration was carried out using a Bona Fide Phantom (Bio-Imaging Technologies, Inc., Newtown, PA). Calibrations were fitted using a standardized principal components method. A Bland and Altman plot was used to calculate the mean difference and limits of agreement between instruments. Standardized bone mineral density (BMD) was also used to calibrate the Hologic to Prodigy 1. There was good agreement between instruments from the same manufacturer. As expected, BMD measured on the Prodigy was about 15% higher than the Hologic. Using standardized BMD to cross calibrate gave a mean difference of 3% at the lumbar spine. The limits of agreement following calibration are clinically significant, so it is not possible to apply a calibration to an individual subject for trending purposes, as the error is similar to the expected annual change in BMD, but can be used for cross calibration in clinical trials. The in vivo calibration gave better agreement than using standardized BMD. The phantom calibration was close to the in vivo calibrations at the spine, but not in some hip regions. When introducing a new instrument, a new baseline BMD has to be obtained for each subject.

Vertebral morphometry by DXA: a comparison of supine lateral and decubitus lateral densitometers.

Identification of vertebral fracture has become increasingly important in the diagnosis and management of osteoporosis. This study compares the morphometric techniques on a fan beam dual-energy X-ray absorptiometry (DXA) GE-Lunar Expert system (Expert) using a supine lateral position and a narrow fan beam GE-Lunar Prodigy system (Prodigy; GE Lunar, Madison, WI) that requires lateral decubitus positioning. Patient acceptability, image quality, observer, and equipment variability were determined. Study subjects were recruited from clinical referrals sent for a routine DXA study that included vertebral morphometry. Twenty-five patients underwent lateral vertebral assessment on both machines and completed a questionnaire on comfort and tolerability. Analysis was undertaken by two trained observers. Vertebral height, anterior/posterior height (A/P) and mid/posterior height (M/P) ratios, image quality, and prevalent fractures were assessed. There were no significant differences in patient comfort or image quality scores. More upper thoracic vertebrae could be assessed on the Expert, and good radiographic positioning was easier to achieve on the Expert. Inter-observer coefficients of variance percentage (CV%) of vertebral height was lower on the Prodigy (3.5% in the lumbar spine rising to 12.8% in the thoracic spine) than the Expert (4.2% to 16.9%). Inter-observer CV% for A/P and M/P ratios varied from 2.5% to 10.5% on the Prodigy compared with 3.5% to 12.3% on the Expert, depending on vertebral level. The variation between instruments was similar to the inter-observer CV% (anterior height: -0.11+/-1.65 mm; mid height: 0.54+/-1.51 mm; posterior height: 0.43+/-1.46 mm). There was good agreement between observers and between the Expert and Prodigy in identifying severe fractures, but lack of agreement in identifying moderate fractures. In conclusion, there was no clinically significant difference in patient comfort and image quality between the Expert and the Prodigy. The inter-observer variations in vertebral height and A/P and M/P ratios are similar to the variations between instruments. In making the change from the supine lateral to the decubitus lateral positioning, measurements of vertebral height are reproducible and patient comfort is not compromised.

Total hip bone mass predicts survival in chronic hemodialysis patients.

BACKGROUND: Bone mass measurements are widely used to diagnose osteoporosis and identify patients at risk for fractures. Recent studies have shown that reduced bone mass is also predictive of all-cause and cardiovascular mortality in healthy postmenopausal women. Among chronic hemodialysis patients reduced bone mass resulting from the combined effects of age-related factors and renal osteodystrophy has been associated with vascular calcification. In this prospective study, we investigated the ability of bone mass measurements to predict mortality in chronic hemodialysis patients. METHODS: Eighty eight patients underwent hip bone mass measurements by dual energy x-ray absorptiometry (DEXA) and were followed up for a mean of 3.5 years. Eleven patients received renal transplants and were therefore excluded. Forty of the remaining patients died, predominantly due to cardiovascular causes (43%). RESULT: Cox regression analysis showed patient age, osteoporosis or osteopenia, and baseline average calcium x phosphate product (Ca x P) to be independently predictive of increased mortality. Patients with osteopenia or osteoporosis had a 3.3- and 4.3-fold increased risk of death, respectively. A Ca x P of >or=5.0 mmol2/L2 predicted a threefold increased risk of death. Previous renal transplantation predicted a lower mortality. CONCLUSIONS: This study has shown for the first time that reduced total hip bone mass is an independent predictor of all-cause mortality among chronic hemodialysis patients. Our findings suggest that reduced bone mass and elevated Ca x P may be involved in the pathogenesis of cardiovascular disease in these patients but further research is required to investigate the possible mechanisms for these associations.

The impact of oral corticosteroid use on bone mineral density and vertebral fracture.

The use of oral corticosteroids is associated with an increased risk of fracture, but there is limited information on the relationship between corticosteroid dose, bone mineral density (BMD), and fracture. We examined this relationship in a community population (more than 50 years) taking oral corticosteroids for chronic lung disease. Details of corticosteroid use and lifestyle were obtained by questionnaire, general practice records, and patient interview. BMD was assessed at the lumbar spine and femur and vertebral fracture by morphometric X-ray absorptiometry. Of the 117 patients who participated (median age, 69), 48% were female. Fifty-eight percent had osteoporosis (a T score of less than -2.5), and 61% had a vertebral fracture. The presence of vertebral fracture was related to BMD at the femoral neck, with an odds ratio of 1.6 for a 1 SD reduction in BMD. The cumulative prednisolone dose ranged from 3.4 to 175 g and was strongly associated with vertebral fracture, with the odds ratio between the highest and lowest dose quartiles being 4.4 (95% confidence interval, 1.04, 18.8). The difference in femoral neck BMD between the same dose quartiles was only modest, however (0.5 SD; 95% confidence interval, 0.09, 0.94). In patients taking long-term oral corticosteroids for chronic lung disease, the relationship between vertebral fracture risk and BMD is similar to that seen in other populations. Cumulative prednisolone dose is strongly related to fracture risk, and this effect is independent of its more modest impact on BMD.