Aortic-vertebral interaction in ankylosing spondylitis: syndesmophyte development at the juxta-aortic vertebral rim.

OBJECTIVES: The aorta inhibits paravertebral ossification in diffuse idiopathic skeletal hyperostosis. We investigated if syndesmophytes in ankylosing spondylitis (AS) occurred less often at the vertebral rim near the aorta. METHODS: We performed thoracolumbar CT scans in 60 subjects in this cross-sectional study. The mid-thoracic spine was also scanned in 22 subjects. We divided the rim of each intervertebral disc space (IDS) into 72 angular sectors, each of 5°. We computed syndesmophyte height in each sector, and the distance from the sector to the aorta. We evaluated if syndesmophyte size or frequency in a sector was associated with its distance from the aorta. RESULTS: In the 180° region of the vertebral rim centered on the sector closest to the aorta, syndesmophyte height and/or frequency varied with the distance of the sector to the aorta, with the lowest frequency and smallest mean syndesmophyte height at the sector along the rim nearest the aorta. Additionally, syndesmophytes were less common in subjects and at IDSs where the aorta was anatomically closer to the vertebra. No syndesmophytes were present in the sector closest to the aorta in subjects whose aorta-vertebral distance was less than 2 mm, but syndesmophytes were progressively more common among subjects whose aortas lay further from the rim. CONCLUSIONS: Syndesmophytes occurred less commonly and were smaller at the thoracolumbar vertebral rim near the aorta. These findings suggest that mechanical factors extrinsic to the spine and not solely vertebral inflammation, influence syndesmophyte development in AS.

Physician's Global Assessment in Psoriatic Arthritis: A Multicenter GRAPPA Study.

OBJECTIVE: Physician's global assessment (PGA) of disease activity is a major determinant of therapeutic decision making. This study assesses the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional use of separate VAS scales for musculoskeletal (PhysMSK) and dermatologic (PhysSk) manifestations in patients with psoriatic arthritis (PsA). METHODS: Sixteen centers from 8 countries enrolled 319 consecutive patients with PsA. PGA, PhysMSK, and PhysSk evaluation forms were administered at enrollment (W0) and after 1 week (W1). Detailed clinical data regarding musculoskeletal (MSK) manifestations, as well as dermatological assessment, were recorded. RESULTS: Comparison of W0 and W1 scores showed no significant variation (intraclass correlation coefficients were PGA 0.87, PhysMSK 0.86, PhysSk 0.78), demonstrating the reliability of the instrument. PGA scores were dependent on PhysMSK and PhysSk (p < 0.0001) with a major effect of the MSK component (B = 0.69) compared to skin (B = 0.32). PhysMSK was correlated with the number of swollen joints, tender joints, and presence of dactylitis (p < 0.0001). PhysSk scores were correlated with the extent of skin psoriasis and by face, buttocks or intergluteal, and feet involvement (p < 0.0001). Finally, physician and patient assessments were compared showing frequent mismatch and a scattered dot plot: PGA versus patient's global assessment (r = 0.36), PhysMSK versus patient MSK (r = 0.39), and PhysSk versus patient skin (r = 0.49). CONCLUSION: PGA assessed by means of VAS is a reliable tool to assess MSK and dermatological disease activity. PGA may diverge from patient self-evaluation. Because MSK and skin/nail disease activity may diverge, it is suggested that both PhysMSK and PhysSk are assessed.

Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses.

Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate the HIV-1-specific CD8+ T cell response, which has been shown to play an important role in HIV-1 immunity and control. We found that stimulation of peripheral blood mononuclear cells (PBMCs) from HIV-1-positive subjects with microbial peptides that were cross-reactive with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1-specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different from that of cells stimulated with cross-reactive microbial peptides in some HIV-1-positive subjects. Despite these differences, CD8+ T cells stimulated with either HIV-1 or cross-reactive peptides effectively suppressed HIV-1 replication in autologous CD4+ T cells. These data suggest that exposure to cross-reactive microbial antigens can modulate HIV-1-specific immunity.

Strategic Review Process for an Accountable Care Organization and Emerging Accountable Care Best Practices.

Accountable Care Organizations (ACOs), like other care entities, must be strategic about which initiatives they support in the quest for higher value. This article reviews the current strategic planning process for the Johns Hopkins Medicine Alliance for Patients (JMAP), a Medicare Shared Savings Program Track 1 ACO. It reviews the 3 focus areas for the 2017 strategic review process - (1) optimizing care coordination for complex, at-risk patients, (2) post-acute care, and (3) specialty care integration - reviewing cost savings and quality improvement opportunities, associated best practices from the literature, and opportunities to leverage and advance existing ACO and health system efforts in each area. It then reviews the ultimate selection of priorities for the coming year and early thoughts on implementation. After the robust review process, key stakeholders voted to select interventions targeted at care coordination, post-acute care, and specialty integration including Part B drug and imaging costs. The interventions selected incorporate a mixture of enhancing current ACO initiatives, working collaboratively and synergistically on other health system initiatives, and taking on new projects deemed targeted, cost-effective, and manageable in scope. The annual strategic review has been an essential and iterative process based on performance data and informed by the collective experience of other organizations. The process allows for an evidence-based strategic plan for the ACO in pursuit of the best care for patients.

Zygapophyseal Joint Fusion in Ankylosing Spondylitis Assessed by Computed Tomography: Associations with Syndesmophytes and Spinal Motion.

OBJECTIVE: Because zygapophyseal joints (ZJ) are difficult to visualize on radiographs, little is known about the relationship of ZJ fusion to other features of spinal damage in ankylosing spondylitis (AS). We used computed tomography (CT) to investigate the concordance of ZJ fusion and syndesmophytes, and examined the contribution of both features to spinal motion. METHODS: We performed thoracolumbar CT scans (T10-T11 to L3-L4) on 55 patients. Two readers scored scans for ZJ fusion, which were compared to syndesmophyte height and extent of bridging, measured by computer algorithm at the same levels. We used multiple regression analysis to evaluate the relative contributions of ZJ fusion and syndesmophytes to spinal mobility. RESULTS: Fifty-one percent of patients had ZJ fusion in at least 1 vertebral level. Fusion was present in 129 of 652 individual ZJ. Syndesmophytes and bridging were often present in vertebral levels without ZJ fusion, suggesting that syndesmophytes most often develop first. ZJ fusion was present in 34% of vertebral levels with syndesmophytes and 55.9% of levels with bridging, suggesting a closer association with bridging. Syndesmophytes and ZJ fusion had similar associations with the modified Schober test, but syndesmophytes were more strongly associated with limitations in lateral thoracolumbar flexion. ZJ rarely showed new fusion over 4 years. CONCLUSION: Thoracolumbar ZJ fusion in AS is rarely present at vertebral levels without syndesmophytes. Syndesmophytes, therefore, likely appear before ZJ fusion at a given vertebral level. Both syndesmophytes and ZJ fusion contribute to limited forward lumbar flexion, but syndesmophytes contribute more to limited lateral flexion.

Spatial distribution of syndesmophytes along the vertebral rim in ankylosing spondylitis: preferential involvement of the posterolateral rim.

OBJECTIVE: Syndesmophytes in ankylosing spondylitis (AS) can occur anywhere along the vertebral rim, but little is known about how and where they develop, and particularly if they first form in certain locations along the rim. This information might provide clues to their aetiology. We examined the spatial distribution of syndesmophytes in the thoracolumbar spine in patients with AS using CT. METHODS: We performed lumbar spine CT scans in 50 patients and used a validated computer algorithm to measure syndesmophyte heights in six intervertebral disc spaces. We measured heights every five radial degrees around the rim of each superior and inferior vertebral endplate. RESULTS: Syndesmophytes were observed in 208 of 296 intervertebral disc spaces. Both ascending and descending syndesmophytes were non-randomly distributed along the vertebral rim (p<0.0001 for deviation from uniform distribution). Syndesmophytes occurred most often at the posterolateral vertebral rim, and least commonly at the posterior rim and anterior rim. In disc spaces with only small isolated syndesmophytes, these were also most likely to occur at the posterolateral rim. Syndesmophyte distribution varied with the vertebral level. Localisation at the posterolateral rim was most pronounced at T10-T11, T12-T12 and T12-L1, while L2-L3 and L3-L4 exhibited little localisation. CONCLUSIONS: Syndesmophytes are not randomly distributed around the vertebral rim, as might be expected if they develop solely in response to inflammation. Rather, they preferentially occur, and likely develop first, at the posterolateral rim. Studying factors that can lead to this pattern may help elucidate how syndesmophytes develop.

Quantitation of circumferential syndesmophyte height along the vertebral rim in ankylosing spondylitis using computed tomography.

OBJECTIVE: Using the 3-D imaging capability of computed tomography (CT), we developed an algorithm quantitating syndesmophyte height along the entire vertebral rim. We investigated its reliability and sensitivity to change, performed a 2-year longitudinal study, and compared it to CT measures of syndesmophyte volume. METHODS: We performed thoracolumbar spine CT scans on 33 patients at baseline, Year 1, and Year 2, and computed syndesmophyte height in 4 intervertebral disc spaces (IDS). Height was computed every 5° (72 angular sectors) along the vertebral rim. These 72 measures were summed to form the circumferential height per IDS, and results from 4 IDS were summed to provide results per patient. To assess reliability, we compared results between 2 scans performed on the same day in 9 patients. Validity was assessed by associations with spinal flexibility. RESULTS: Coefficient of variation for circumferential syndesmophyte height was 0.893% per patient, indicating excellent reliability. Based on the Bland-Altman analysis, an increase in circumferential height of more than 3.44% per patient represented a change greater than measurement error. At years 1 and 2, mean (SD) circumferential syndesmophyte height increases were 10.2% (11.7%) and 16.1% (14.0%), respectively. Sensitivity to change was 0.72 and 0.87 at years 1 and 2, respectively. Circumferential syndesmophyte height correlated with the Schober test (r = -0.56, p = 0.0003) and lateral thoracolumbar flexion (r = -0.73, p < 0.0001). CONCLUSION: CT-based circumferential syndesmophyte height had excellent reliability and good sensitivity to change. It was more highly correlated with spine flexibility than syndesmophyte volume. The algorithm shows promise for longitudinal studies of syndesmophyte growth.

Dynamics of syndesmophyte growth in AS as measured by quantitative CT: heterogeneity within and among vertebral disc spaces.

OBJECTIVE: Syndesmophytes in AS typically grow slowly, but it is not known whether growth is uniform among syndesmophytes in the same intervertebral disc space (IDS) or among different IDSs in the same patient or if growth is heterogeneous. We examined the dynamics of syndesmophyte growth over 24 months using CT, with the main aim of determining if syndesmophytes in the same IDS or the same patient grow at similar rates. METHODS: We performed lumbar spine CT scans on 33 patients and measured syndesmophytes in four IDSs using a validated computer algorithm. Scans were done at baseline and 12 and 24 months. We compared absolute and percentage changes in volume from baseline to 12 months and to 24 months among syndesmophytes in the same IDS and among four IDSs of each patient. We also examined whether growth among all IDSs differed between study years. RESULTS: Among 60 IDSs with at least two syndesmophytes at baseline (range 2-6), there was substantial heterogeneity in both absolute (P < 0.0001) and percentage (P = 0.0002) volume increases among syndesmophytes in the same IDS. Several IDSs had both syndesmophytes with no growth and syndesmophytes that increased by >100 mm(3). Similarly there was significant heterogeneity in syndesmophyte growth among IDSs of individual patients. Increases in total syndesmophyte volume for each patient also tended to differ between study years (P = 0.07). CONCLUSION: Syndesmophytes in AS do not all grow continuously. Rates of growth over 24 months commonly differ between syndesmophytes in the same IDS and between different IDSs in the same patient, suggesting that local factors regulate syndesmophyte growth.

Quantitative syndesmophyte measurement in ankylosing spondylitis using CT: longitudinal validity and sensitivity to change over 2†years.

OBJECTIVES: Accurate measurement of syndesmophyte development and growth in ankylosing spondylitis (AS) is needed for studies of biomarkers and of treatments to slow spinal fusion. We tested the longitudinal validity and sensitivity to change of quantitative measurement of syndesmophytes using CT. METHODS: We performed lumbar spine CT scans on 33 patients with AS at baseline, 1 year and 2 years. Volumes and heights of syndesmophytes were computed in four intervertebral disk spaces. We compared the computed changes to a physician's ratings of change based on CT scan inspection. Sensitivity to change of the computed measures was compared with that of the modified Stoke AS Spinal Score (radiography) and a scoring method based on MRI. RESULTS: At years 1 and 2, respectively 24 (73%) and 26 (79%) patients had syndesmophyte volume increases by CT. At years 1 and 2, the mean (SD) computed volume increases per patient were, respectively 87 (186) and 201 (366) mm(3). Computed volume changes were strongly associated with the physician's visual ratings of change (p<0.0002 and p<0.0001 for changes at years 1 and 2, respectively). The sensitivity to change over 1 year was higher for the CT volume measure (1.84) and the CT height measure (1.22) than either the MRI measure (0.50) or radiography (0.29). CONCLUSIONS: CT-based syndesmophytes measurements had very good longitudinal validity and better sensitivity to change than radiography or MRI. This method shows promise for longitudinal clinical studies of syndesmophyte development and growth.

Quantitative measurement of syndesmophyte volume and height in ankylosing spondylitis using CT.

OBJECTIVE: Syndesmophyte growth in ankylosing spondylitis can be difficult to measure using radiographs because of poor visualisation and semiquantitative scoring methods. We developed and tested the reliability and validity of a new computer-based method that fully quantifies syndesmophyte volumes and heights on CT scans. METHODS: In this developmental study, we performed lumbar spine CT scans on 38 patients and used our algorithm to compute syndesmophyte volume and height in four intervertebral disk spaces. To assess reliability, we compared results between two scans performed on the same day in nine patients. To assess validity, we compared computed measures to visual ratings of syndesmophyte volume and height on both CT scans and radiographs by two physician readers. RESULTS: Coefficients of variation for syndesmophyte volume and height, based on repeat scans, were 2.05% and 2.40%, respectively. Based on Bland-Altman analysis, an increase in syndesmophyte volume of more than 4% or in height of more than 0.20 mm represented a change greater than measurement error. Computed volumes and heights were strongly associated with physician ratings of syndesmophyte volume and height on visual examination of both the CT scans (p<0.0001) and plain radiographs (p<0.002). Syndesmophyte volumes correlated with the Schober test (r=-0.48) and lateral thoracolumbar flexion (r=-0.60). CONCLUSIONS: This new CT-based method that fully quantifies syndesmophytes in three-dimensional space had excellent reliability and face and construct validity. Given its high precision, this method shows promise for longitudinal clinical studies of syndesmophyte development and growth.

The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project).

OBJECTIVE: To develop new composite disease activity indices for psoriatic arthritis (PsA). METHODS: Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). RESULTS: 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index>10) both nonparametric and AUC curve statistics were nonsignificant for all measures. CONCLUSIONS: Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.

Ethical concerns related to grateful patient philanthropy: the physician's perspective.

BACKGROUND: Philanthropic contributions to academic medical centers from grateful patients support research, patient care, education, and capital projects. The goal of this study was to identify the ethical concerns associated with philanthropic gifts from grateful patients. METHODS: A qualitative study design was selected. Investigators conducted in-depth semi-structured interviews with 20 Department of Medicine physicians at Johns Hopkins who were identified by Development Office staff as experienced and successful in this realm-those having relationships with multiple patients who have made philanthropic contributions. Interview transcripts were independently coded by two investigators. Content analysis identified several themes related to ethical concerns. RESULTS: Eighteen informants (90 %) were Associate Professors or Professors; two (10 %) were females. Four thematic domains emerged related to ethical concerns associated with philanthropy from grateful patients: (i) impact of gift on the doctor-patient relationship; (ii) gift acquisition considered beyond the physician's professional role; (iii) justice and fairness; and (iv) vulnerability of patients. Despite acknowledging at least one of the aforementioned concerns, eleven physician informants (55 %) expressed the view that there were no ethical issues involved with grateful patient philanthropy. CONCLUSIONS: In this paper, we report that physicians involved in grateful patient philanthropy are aware of, and in some cases troubled by, the ethical concerns related to this activity. Further studies could examine how best to prepare faculty for the challenges that may accompany these gifts so as to help them maintain expected professional and ethical standards when accepting grateful patient philanthropy.

Patient global assessment in psoriatic arthritis: a multicenter GRAPPA and OMERACT study.

OBJECTIVE: During OMERACT 8, delegates selected patient global assessment (PGA) of disease as a domain to be evaluated in randomized controlled trials in psoriatic arthritis (PsA). This study assessed the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional utility of separate VAS scales for joints (PJA) and skin (PSA). METHODS: In total, 319 consecutive patients with PsA (186 men, 133 women, mean age 51 ± 13 yrs) were enrolled. PGA, PJA, and PSA were administered at enrolment (W0) and after 1 week (W1). Detailed clinical data, including ACR joint count, Psoriasis Area and Severity Index (PASI), and Hospital Anxiety and Depression Scale, were recorded. RESULTS: Comparison of W0 and W1 scores showed no significant variations (intraclass correlation coefficients for PGA 0.87, PJA 0.86, PSA 0.78), demonstrating the reliability of the instrument. PGA scores were not influenced by patient anxiety or depression, but were dependent on PJA and PSA (p = 0.00001). PJA was dependent on the number of swollen and tender joints (p < 0.00001). PSA scores were influenced by the extent of skin psoriasis and by hand skin involvement (p = 0.00001). Joint and skin disease were found not to correlate in terms of disease activity as evidenced by the swollen joint count compared to PASI (r = 0.11) and by the PJA compared to PSA (r = 0.38). CONCLUSION: PGA assessed by means of VAS is a reliable tool related to joint and skin disease activity. Because joint and skin disease often diverge it is suggested that in some circumstances both PJA and PSA are also assessed.

Aortic insufficiency in a patient with reactive arthritis: case report and review of the literature.

BACKGROUND: Reactive arthritis (ReA) consists of the classic clinical triad of arthritis, urethritis, and conjunctivitis generally occurring within 6 weeks of an infection, typically of the gastrointestinal or genitourinary systems. Cardiovascular manifestations of ReA and other members of the spondyloarthritis family have long been recognized. CASE REPORT: A 43-year-old male who was human leukocyte antigen-27 (HLA-B27)-positive and who had ReA for 19 years developed severe aortic insufficiency requiring aortic valve replacement. Typically, the onset of musculoskeletal symptoms precedes development of aortic insufficiency by many years. The average calculated from reported cases was 13 years, with a range from 4 days to 61 years. The mechanism by which the aortic valve leaflets become targets in HLA-B27-associated disease is unclear. At one point, interest developed as to whether the HLA-B27 allele was independently associated with lone aortic insufficiency, in the absence of clinical spondylitis. The preponderance of cardiac abnormalities in patients with HLA-B27-positive ReA has led to the suggestion that a genetic syndrome of the heart consisting of aortic insufficiency and conduction-system abnormalities exists, and has been dubbed the "HLA-B27-associated cardiac syndrome". This case highlights the importance of recognizing the association between HLA-B27-associated spondyloarthritis and serious aortic valvular complications. CONCLUSION: Clinicians should maintain a high suspicion for aortic insufficiency in patients with ReA, including a low threshold for echocardiographic evaluation. A heightened awareness can lead to earlier identification and potential avoidance of fatal events in these patients.

Relation of serum uric acid with metabolic risk factors in asymptomatic middle-aged Brazilian men.

This study in 352 asymptomatic middle-aged Brazilian men demonstrated that serum uric acid increases linearly with an increasing number (0 to >/=3) of metabolic risk factors (5.78 +/- 1.1, 6.14 +/- 1.0, 6.27 +/- 1.1, and 6.79 +/- 1.3, p <0.001). In patients who had >/=3 metabolic risk factors, there was a higher prevalence of serum uric acid in the highest quartile (7.2 to 10.3 mg/dl) than in the lowest quartile (2.6 to 5.4 mg/dl, 35% vs 12%, p <0.001). Mean serum levels of uric acid were higher in those who had an abnormal ratio of >/=3 for triglyceride to high-density lipoprotein (suggesting insulin resistance) than in those who had a normal ratio (6.6 +/- 1.2 vs 5.87 +/- 1 mg/dl, p <0.001).

Diagnosis and localization of pheochromocytoma.

This Hypertension Grand Rounds shows how applying new clinical laboratory techniques helped to diagnose pheochromocytoma in a difficult case. In the setting of long-standing, sustained hypertension, the patient had a hypertensive paroxysm during anesthesia induction for surgery, leading to suspicion of a pheochromocytoma. Conventional testing, including CT scanning and fractionated urinary metanephrine test, was not diagnostic. The patient had another hypertensive paroxysm during subsequent anesthesia induction, requiring intensive care. Consistently elevated plasma levels of free normetanephrine provided the first and only biochemical evidence for a pheochromocytoma in this case. 6-[18F]Fluorodopamine positron emission tomography and 123I-metaiodobenzylguanidine scintigraphy subsequently agreed on the existence of a small left adrenal mass, which when removed surgically proved to be a pheochromocytoma. Postoperatively, plasma levels of normetanephrine normalized, and there were no further hypertensive paroxysms, although the patient remained hypertensive. This case illustrates the superiority of plasma levels of free (unconjugated) metanephrines, compared with other biochemical tests, to detect pheochromocytoma. It also confirms that functional imaging by 6-[18F]fluorodopamine or 123I-metaiodobenzylguanidine scanning can localize pheochromocytoma in difficult cases in which other imaging tests are not diagnostic.