Identification of subclinical lung involvement in ACPA-positive subjects through functional assessment and serum biomarkers

Lung involvement is related to the natural history of anti-citrullinated proteins antibodies (ACPA)-positive rheumatoid arthritis (RA), both during the pathogenesis of the disease and as a site of disease-related injury. Increasing evidence suggests that there is a subclinical, early lung involvement during the course of the disease, even before the onset of articular manifestations, which can potentially progress to a symptomatic interstitial lung disease. To date, reliable, noninvasive markers of subclinical lung involvement are still lacking in clinical practice. The aim of this study is to evaluate the diagnostic potential of functional assessment and serum biomarkers in the identification of subclinical lung involvement in ACPA-positive subjects. Fifty ACPA-positive subjects with or without confirmed diagnosis of RA (2010 ARC-EULAR criteria) were consecutively enrolled. Each subject underwent clinical evaluation, pulmonary function testing (PFT) with assessment of diffusion lung capacity for carbon monoxide (DLCO), cardiopulmonary exercise testing (CPET), surfactant protein D (SPD) serum levels dosage and high-resolution computed tomography (HRCT) of the chest. The cohort was composed of 21 ACPA-positive subjects without arthritis (ND), 10 early (disease duration < 6 months, treatment-naïve) RA (ERA) and 17 longstanding (disease duration < 36 months, on treatment) RA (LSRA). LSRA patients had a significantly higher frequency of overall HRCT abnormalities compared to the other groups (p = 0.001). SPD serum levels were significantly higher in ACPA-positive subjects compared with healthy controls (158.5 ± 132.3 ng/mL vs 61.27 ± 34.11 ng/mL; p < 0.0001) and showed an increasing trend from ND subjects to LSRD patients (p = 0.004). Patients with HRCT abnormalities showed significantly lower values of DLCO (74.19 ± 13.2% pred. vs 131.7 ± 93% pred.; p = 0.009), evidence of ventilatory inefficiency at CPET and significantly higher SPD serum levels compared with subjects with no HRCT abnormalities (213.5 ± 157.2 ng/mL vs 117.7 ± 157.3 ng/mL; p = 0.018). Abnormal CPET responses and higher SPD levels were also associated with specific radiological findings. Impaired DLCO and increased SPD serum levels were independently associated with the presence of HRCT abnormalities. Subclinical lung abnormalities occur early in RA-associated autoimmunity. The presence of subclinical HRCT abnormalities is associated with several functional abnormalities and increased SPD serum levels of SPD. Functional evaluation through PFT and CPET, together with SPD assessment, may have a diagnostic potential in ACPA-positive subjects, contributing to the dentification of those patients to be referred to HRCT scan

Cerebral venous thrombosis: A case series and a neuroimaging review of the literature

Cerebral venous thrombosis (CVT) is a rare condition, difficult to diagnose because of its non specific clinical symptoms. In some cases CVT can mimic other conditions as subarachnoid hemorrhage, ischemia or tumor and for these reasons diagnosis is delayed or missed. CT, DSA and MRI findings help to obtain an early diagnosis and to distinguish it from other diseases. Our cases involved four patients with no signs or symptoms suspected for CVT and without risk factors associated to this disease; furthermore some early imaging findings observed in these patients could mimic other diseases. The aim of presenting these cases is to underline the importance of some findings at imaging techniques in obtaining an early diagnosis of CVT; in particular we describe the usefulness of MRI with gradient echo sequences (GRE) in detecting the venous thrombus, suggesting that GRE sequences should be included in the MRI protocol when a CVT is suspected. We also underline the role of radiologists in helping neurologists to make an early diagnosis of CVT or when in doubt to encourage further investigations in order to begin the anticoagulation therapy as soon as possible avoiding the onset of complications as permanent parenchymal damage, cerebral hemorrhage and venous infarction

Conversion of osteoporotic vertebral fracture severity score to osteoporosis T-score equivalent status: a framework and a comparative study of Hong Kong Chinese and Rome Caucasian older women

We explored how the severity of radiological osteoporotic vertebral fracture (OVF) can be converted to the equivalent T-score values.Introduction To perform a study to define what portion of older community women with what severity of radiographic OVF correspond to what low T-score status.Methods There were age-matched 301 Italian community women and 301 Chinese community women (sub-group A, age, 73.6 +/- 6.1 years). In addition, Chinese sub-groups B and C included 110 community women (age, 68.9 +/- 5.5 years) and 101 community women (age: 82.2 +/- 4.3 years), respectively. For each vertebra in women, a score of 0, - 0.5, - 1, - 1.5, - 2, - 2.5, and - 3 was assigned for no OVF or OVF of < 20%, >= 20 similar to 25%, >= 25% similar to 1/3, >= 1/3 similar to 40%, >= 40%-2/3, and >= 2/3 vertebral height loss, respectively, OVFss was defined as the summed score of vertebrae T4 to L5. OVFss and T-scores were ranked from the smallest to the largest values.Results For the Chinese total group (sub-groups A, B, and C together), OVFss = - 1 corresponded to lowest T-score (lowest T-score of lumbar spine, femoral neck, and total hip) of - 3.4 similar to - 3.2. OVFss <= - 1.5 corresponded to femoral neck T-score <= - 2.5. OVFss = -1.5 corresponded to a mean femoral neck T-score of - 3.0, - 2.6, and - 2.4, among Chinese sub-groups B, A, and C subjects, respectively. For Italians, all cases with OVFss <= - 1 had lowest T-score <= - 2.5. For cases with femoral neck T-score = - 2.5, 41.7% had OVFss = - 1.5, and 58.3% had OVFss = - 1.Conclusion For older women, statistically OVFss <= -1 suggests this subject is osteoporotic according to lowest T-score. If using femoral neck T-score, OVFss <= - 1.5 qualifies osteoporosis diagnosis

ACCURACY OF VERTEBRAL FRACTURE ASSESSMENT BY DUAL-ENERGY X-RAY ABSORPTIOMETRY USING GE IDXA COMPARED TO CONVENTIONAL RADIOGRAPHY

26 subjects (9.5%) had multiple vertebral fractures detected by SQ Rx technique and 28 subjects (10.2%) by iDXA . Considering radiological SQ assessment as the gold standard, iDXA sensitivity was 87% and the specificity was 96% (Positive Predictive Value 88%; Objective: This prospective investigation was carried out in order to evaluate the accuracy of vertebral fracture assessment by dual-energy X-ray absorptiometry using GE iDXA device (GE Medical Systems Lunar, Madison, WI, USA) compared to conventional radiography.Subjects and Methods: We enrolled 273 subjects (207 females and 68 males, age range 28-85 years) consecutively studied at our Mineral Metabolism Centre, which were undergoing a spine vertebral X-ray evaluation. Lateral images of the spine, from T4 to L4, by both conventional X-ray and iDXA device, were acquired in each subject on the same day, after informed consent was obtained. The radiographs were evaluated by an experienced skeletal radiologist (D.D.), using the semiquantitative (SQ) method. The iDXA images were evaluated by a trained operator using a specific software (enCORE).Results: By means of SQ radiological technique, we evaluated 3515 (99%) of the 3549 available vertebrae, and identified 151 vertebral deformities (101 mild and 50 moderate or severe). By means of iDXA we visualized 3405 (96%) vertebrae and identified 150 vertebral deformities (100 mild and 50 moderate or severe). Ninety-two subjects (33.7% of the total sample) were identified as having vertebral fractures by SQ Rx technique and eighty-seven subjects (31.9%) fractured were recognized by iDXA (χ2 = n.s.). A single fracture was detected in 66 patients (24.2%) by conventional radiographs and in 59 subjects (21.6%) by iDXA; Negative Predictive Value 97%). Agreement between radiographs and iDXA was 96% with a kappa statistic of 0.91 (confidence interval 0.82-0.96).Conclusions: According to the results obtained, iDXA and SQ radiological technique demonstrated good agreement in classifying vertebrae as normal or deformed. Therefore, since iDXA performs spine images with good resolution and lower dose, it proves to be useful in the clinical evaluation of patients at risk of osteoporosis or for the selection of patients for osteoporosis-related clinical trials

Vertebral fracture assessment in postmenopausal women with post-surgical hypoparathyroidism

CONTEXT: Hypoparathyroidism is a rare endocrine disorder whose skeletal features include suppression of bone turnover, greater volume and width of the trabecular compartment. Few and inconsistent data are available on the prevalence of vertebral fractures (VF).OBJECTIVE: To evaluate the prevalence of VF assessed by vertebral fracture assessment (VFA) in postmenopausal women with chronic post-surgical hypoparathyroidism.DESIGN: Cross-sectional study.SETTING: Ambulatory referral center.PATIENTS OR OTHER PARTICIPANTS: Fifty postmenopausal women (mean age 65.4 ± 9 years) with chronic post-surgical hypoparathyroidism and 40 age-matched healthy postmenopausal women (mean age 64.2 ± 8.6).MAIN OUTCOME MEASURES: Lumbar spine, femoral neck and total hip BMD were measured by dual X-ray absorptiometry (DXA) (Hologic Inc., USA) in all subjects. Site-matched spine TBS was calculated by TBS iNsight (Medimaps, Switzerland). Assessment of VF was made by VFA (iDXA, Lunar GE, USA) using the semiquantitative method and the algorithm-based qualitative assessment.RESULTS: All-site BMD values were higher in the hypoparathyroid vs the control group. By VFA, we observed a 16% prevalence of VF in hypoparathyroid women vs 7.5% in control subjects. Among those with hypoparathyroidism who fractured, 5 (62.5%) had grade 1 wedge, 2 (25%) had grade 2 wedge, and 1 (12.5%) grade 2 wedge and grade 2 biconcave VF. In the hypoparathyroid group, among those with VFs, 57% had symptoms of hypoparathyroidism 32% among those without VF.CONCLUSION: We demonstrate for the first time that in postmenopausal women with chronic postsurgical hypoparathyroidism, VFs are demonstrable by VFA despite normal BMD

Much lower prevalence and severity of osteoporotic vertebral facture in elderly Chinese women than in age-matched Italian women: a radiographic comparison study.

Introduction: Many studies reported that East Asian's prevalence of radiographic OVF is similar to that of Caucasian. Since elderly Chinese's osteoporotic hip fracture prevalence is half (or less than half) of that of their age-match Caucasians, we hypothesize that elderly Chinese's OVF prevalence could be only half, or even less than half, of that of their agematch Caucasians.Materials: Age-matched elderly women's radiographs (T4-L5) were from two OVF population-based epidemiological studies conducted in Hong Kong (n=200) and in Rome (n=200). The study subjects had a mean age of 74.1 yrs (range: 65-87 yrs). All radiographs were double read by one reader in Hong Kong and one reader in Rome. Radiological osteoporotic vertebral deformity (ROVD) classification included no ROVD (grade 0), and ROVDs with <20%, 20~25%, ≥25%~1/3, ≥1/3~40%, ≥40%~2/3, and ≥2/3 height loss (grade 1~6). Spinal deformity index (SDI) was calculated with each vertebra assigned a score of 0, 0.5, 1, 1.5, 2, 2.5 and 3 for no ROVD or ROVDs grade 1~6.Results: 77 (38.5%) Chinese subjects and 123 Italian subjects (61.5%) had ROVD respectively (p<0.0001). ROVDs in Italian subjects tended to be more severe (total and mean SDI: 454.5 and 3.71 for Italian, and 212 and 2.72 for Chinese, p<0.05), more likely to be multiple (p<0.001), more likely to have severe and collapsed grades (p<0.001). The slope of the relationship between age vs. SDI was steeper for the Italian subjects than for the Chinese subjects, suggesting aging Italian subjects developed faster for the prevalence of ROVD and their severity. A trend suggested earlier onset of ROVD among Italian.Conclusion: Compared with elderly Italian women, elderly Chinese women have much lower prevalence of OVF. OVF in Chinese women tend to be less severe and less likely to have multiple fractures and less likely to collapse

Diagnostic Performance of Vertebral Fracture Assessment by the Lunar iDXA Scanner Compared to Conventional Radiography

The purpose of this study was to evaluate the diagnostic performance of vertebral fracture assessment (VFA) using the Lunar iDXA scanner. Conventional spinal radiographs and images acquired by dual-energy X-ray absorptiometry (DXA) of 350 subjects (269 females, 81 males) were evaluated by two different readers. We visualized 4,476/4,550 (98.4 %) vertebrae from T4 to L4 on VFA images compared to 4,535/4,550 (99.7 %) on radiographs. Among the visualized vertebrae, 205/4,535 (4.5 %) and 190/4,476 (4.2 %) were identified as nonfracture deformities by reading of radiographs and VFA, respectively. Vertebral fractures (VFs) were 231 in 126 patients and 228 in 125 patients by semiquantitative assessment of radiographs (SQ-Rx) and by VFA, respectively. There was excellent agreement between the two techniques and high diagnostic performance of VFA both on a per-vertebra basis (k score = 0.984, 95 % CI 0.972-0.996, sensitivity 98.68 %, specificity 99.91 %, PPV 98.25 %, NPV 99.93 %) and on a per-patient basis (k score = 0.957, 95 % CI 0.925-0.988, sensitivity 96.83 %, specificity 98.66 %, PPV 97.60 %, NPV 98.22 %). In older patients (≥65 years) affected by moderate or severe osteoarthritis, SQ-Rx and VFA identified 96 VFs and 95 versus 90 vertebral deformities, respectively. This study demonstrates that most vertebrae are evaluable using the iDXA scanner, with improved VFA diagnostic performance even in discriminating mild VFs from vertebral deformities. Therefore, VFA may be appropriate as an alternative to conventional radiography in patients at high risk of VF who are undergoing DXA bone densitometry and in the follow-up of osteoporotic patients on treatment

Reliability of Vertebral Fractures Assessment (VFA) in Children with Osteogenesis Imperfecta.

The aim of this study is to evaluate the diagnostic accuracy of vertebral fractures assessment (VFA) in comparison with conventional radiography in identifying vertebral fractures in children and adolescents affected by OI. On 58 patients (33 males, 25 females; age range 1-18 years; 41 children and 17 adolescents) with osteogenesis imperfecta (OI type I, n = 44, OI type III, n = 4; OI type IV, n = 10), lateral spine images by radiographs and by dual-energy X-ray absorptiometry (DXA) were acquired. For vertebral fracture diagnosis, plain radiographs were used as "gold standard" and VFA and morphometric X-ray absorptiometry (MXA) were performed. The visualized vertebrae were 738 (97.9 %) by radiographs and 685 (90.9 %) by DXA of a total of 754 vertebrae from T4 to L4. VFA and MXA identified, respectively, 129 (74 %) and 116 (66 %) of the 175 vertebral fractures detected by radiographs. Radiographs identified 36 patients with vertebral fractures, VFA 35 and MXA 41 (6 false positives). On a per vertebra basis, radiographs and VFA had elevated agreement (93.9 %; k score 0.81, 95 % CI 0.76-0.86), that resulted slightly lower for MXA (90.6 %; k score 0.72, 95 % CI 0.65-0.78). VFA and MXA demonstrated high sensitivity (95.6 and 94.1 %, respectively) while specificity was 100 % for VFA and 90.6 % for MXA on a per patient basis; the agreement was excellent for VFA (98.3 %; k score 0.96, 95 % CI 0.89-1.03) and good for MXA (87.9 %; k score 0.73, 95 % CI 0.55-0.91). The diagnostic performance parameters resulted better for VFA (sensitivity 95.6 %; specificity 100 %; PPV 100 %; NPV 97.2 %), than for MXA (sensitivity 94.1 %; specificity 85.4 %; PPV 72.7 %; NPV 97.2 %). The results of our study demonstrate the reliability of VFA for diagnosis of vertebral fractures in children with OI suggesting its use as a more safe and practical alternative to conventional radiography