The prevalence and characteristics of pulmonary hypertension in adults with sickle cell disease have not been clearly established.
In this prospective study, we evaluated 398 outpatients with sickle ...cell disease (mean age, 34 years) at referral centers in France. All patients underwent Doppler echocardiography, with measurement of tricuspid-valve regurgitant jet velocity. Right heart catheterization was performed in 96 patients in whom pulmonary hypertension was suspected on the basis of a tricuspid regurgitant jet velocity of at least 2.5 m per second. Pulmonary hypertension was defined as a mean pulmonary arterial pressure of at least 25 mm Hg.
The prevalence of a tricuspid regurgitant jet velocity of at least 2.5 m per second was 27%. In contrast, the prevalence of pulmonary hypertension as confirmed on catheterization was 6%. The positive predictive value of echocardiography for the detection of pulmonary hypertension was 25%. Among the 24 patients with confirmed pulmonary hypertension, the pulmonary-capillary wedge pressure was 15 mm Hg or less (indicating precapillary pulmonary hypertension) in 11 patients. Patients with confirmed pulmonary hypertension were older and had poorer functional capacity and higher levels of N-terminal pro-brain natriuretic peptide than other patients. In contrast, patients who had a tricuspid regurgitant jet velocity of at least 2.5 m per second without pulmonary hypertension and patients with a tricuspid regurgitant jet velocity of less than 2.5 m per second had similar clinical characteristics.
In this study of adults with sickle cell disease, the prevalence of pulmonary hypertension as confirmed on right heart catheterization was 6%. Echocardiographic evaluation alone had a low positive predictive value for pulmonary hypertension. (Funded by the French Ministry of Health and Assistance Publique-Hôpitaux de Paris; ClinicalTrials.gov number, NCT00434902.).
To assess the survival and prognostic factors in patients with newly diagnosed incident systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) in the modern management era.
...Prospectively enrolled SSc patients in the French PAH Network between January 2006 and November 2009, with newly diagnosed PAH and no interstitial lung disease, were analysed (85 patients, mean age 64.9±12.2 years). Median follow-up after PAH diagnosis was 2.32 years.
A majority of patients were in NYHA functional class III-IV (79%). Overall survival was 90% (95% CI 81% to 95%), 78% (95% CI 67% to 86%) and 56% (95% CI 42% to 68%) at 1, 2 and 3 years from PAH diagnosis, respectively. Age (HR: 1.05, 95% CI 1.01 to 1.09, p=0.012) and cardiac index (HR: 0.49, 95% CI 0.27 to 0.89, p=0.019) were significant predictors in the univariate analysis. We also observed strong trends for gender, SSc subtypes, New York Heart Association functional class, pulmonary vascular resistance and capacitance to be significant predictors in the univariate analysis. Conversely, six-min walk distance, mean pulmonary arterial and right atrial pressures were not significant predictors. In the multivariate model, gender was the only independent factor associated with survival (HR: 4.76, 95% CI 1.35 to 16.66, p=0.015 for male gender).
Incident SSc-associated PAH remains a devastating disease even in the modern management era. Age, male gender and cardiac index were the main prognosis factors in this cohort of patients. Early detection of less severe patients should be a priority.
The prevalence of HIV-associated pulmonary arterial hypertension (PAH) has not been evaluated since introduction of combined, highly active antiretroviral treatments.
To establish the current ...prevalence of PAH in a large HIV-positive population.
Prospective study conducted in 7,648 consecutive HIV-positive adults in 14 HIV clinics in France. PAH was identified through screening with a predefined algorithm. Patients with dyspnea unexplained by other causes underwent transthoracic Doppler echocardiography. PAH was suspected if peak velocity of tricuspid regurgitation was greater than 2.5 m/second and was confirmed by right heart catheterization.
PAH was diagnosed if mean pulmonary arterial pressure at rest was 25 mm Hg or greater (with pulmonary capillary wedge pressure < or = 15 mm Hg) or 30 mm Hg or greater on exercise. A total of 739 patients had dyspnea, of which 312 met exclusion criteria and 150 refused to participate. Among the remaining 277, 30 had known PAH and 247 had unexplained dyspnea and underwent echocardiography; PAH was suspected in 18 and confirmed in 5, to give a total of 35 cases. The prevalence was thus 0.46% (95% confidence interval, 0.32-0.64%). All new cases had relatively milder PAH.
The prevalence of HIV-associated PAH is about the same as it was in the early 1990s. Given the current good long-term prognosis of patients with HIV, the severity of PAH in HIV-infected patients, and the absence of predictive factors, careful screening for PAH is warranted for patients with unexplained dyspnea.
Pre-capillary pulmonary hypertension (PH) in systemic sclerosis (SSc) is a heterogeneous condition with an overall bad prognosis. The objective of this study was to identify and characterize ...homogeneous phenotypes by a cluster analysis in SSc patients with PH. Patients were identified from two prospective cohorts from the US and France. Clinical, pulmonary function, high-resolution chest tomography, hemodynamic and survival data were extracted. We performed cluster analysis using the k-means method and compared survival between clusters using Cox regression analysis. Cluster analysis of 200 patients identified four homogenous phenotypes. Cluster C1 included patients with mild to moderate risk pulmonary arterial hypertension (PAH) with limited or no interstitial lung disease (ILD) and low DLCO with a 3-year survival of 81.5% (95% CI: 71.4-88.2). C2 had pre-capillary PH due to extensive ILD and worse 3-year survival compared to C1 (adjusted hazard ratio HR 3.14; 95% CI 1.66-5.94; p = 0.0004). C3 had severe PAH and a trend towards worse survival (HR 2.53; 95% CI 0.99-6.49; p = 0.052). Cluster C4 and C1 were similar with no difference in survival (HR 0.65; 95% CI 0.19-2.27, p = 0.507) but with a higher DLCO in C4. PH in SSc can be characterized into distinct clusters that differ in prognosis.
To describe the natural history of ischemic digital ulcers (DU) in systemic sclerosis (SSc).
This single-center, retrospective, longitudinal study identified patients by demographic data, SSc history ...and type, Rodnan score, tobacco use, presence of autoantibodies, ongoing treatment, and DU history.
One hundred three patients were enrolled, 46 with DU history and 57 without; 2 with DU were excluded. The mean duration of followup from the first non-Raynaud SSc symptoms was 12.3 +/- 6.3 years in patients with DU history and 12.1 +/- 7.0 years in patients without. In 43% of cases, first DU occurred within 1 year following first non-Raynaud SSc symptoms, and within 5 years in 73% of cases. In a multivariate analysis, younger patients at occurrence of first non-Raynaud SSc symptoms (HR = 0.77 per each 5 years older, 95% CI 0.66-0.90) with higher Rodnan scores (HR = 1.21 per 5 points, 95% CI 1.05-1.47) experienced earlier DU occurrences, which were delayed by vasodilator therapy (HR = 0.17, 95% CI 0.09-0.32). Patients with shorter durations between first and second DU episodes, particularly with a second episode within 2 years of the first, experienced a higher yearly incidence of DU episodes (0.85 +/- 0.57 and 0.48 +/- 0.26, respectively, if less or more than 2 yrs; p = 0.04). Throughout the duration of followup, the incidence of finger amputation was 1.2% per patient-year in patients with DU history.
Patients who are young at first sign of SSc, with high Rodnan scores and without vasodilator therapy, are at high risk of developing DU. Development of DU typically occurred within 5 years of the first non-Raynaud clinical symptom of SSc in the majority of patients.
Background: Pulmonary arterial hypertension (PAH) is a frequent cause of morbidity and mortality in patients with systemic sclerosis
(SSc). PAH is generally considered to be a late complication of ...limited cutaneous SSc. This study identified and investigated
a subset of SSc patients with early-onset PAH.
Methods: Clinical and hemodynamic data at the time of diagnosis were collected retrospectively for 78 consecutive patients with PAH
associated with SSc. PAH diagnosed within 5 years of the first non-Raynaud phenomenon symptom of SSc was considered to be
an early-onset complication. PAH diagnosed > 5 years following SSc diagnosis was considered to be a late complication.
Results: PAH occurred a mean (± SD) duration of 6.3 ± 6.6 years after the diagnosis of SSc (median delay, 4.0 years; 95% CI, 2.88
to 6.0 years). Early-onset PAH was diagnosed in 43 patients (55.1%), and late-onset PAH was diagnosed in 35 patients (44.9%).
Patients with early-onset PAH were older at SSc diagnosis than patients with late-onset PAH (mean age, 58.0 ± 12.5 vs 46.6
± 12.9 years, respectively; p = 0.0002). No differences in age at the time of PAH diagnosis, or in SSc subtype (limited vs
diffuse; anticentromere vs anti-Scl70 antibodies), were observed between onset subgroups. At diagnosis, early-onset PAH was
more severe than late-onset PAH, with a lower cardiac index (2.4 ± 0.6 vs 2.8 ± 0.6 L/min/m 2 , respectively; p = 0.005) and greater total pulmonary resistance (1,708 ± 777 vs 1,341 ± 530 dyne · s · cm â5 /m 2 , respectively; p = 0.02). Mortality at 3 and 5 years was comparable between subgroups.
Conclusions: In contrast to the expected scenario, early-onset PAH occurred in approximately half of SSc patients. Early-onset PAH was
as frequent among patients with diffuse SSc as those with limited SSc. Annual screening for PAH should be implemented immediately
after SSc diagnosis for all patients.
Background
Serum thymidine kinase 1 (sTK1) activity is closely correlated with DNA synthesis.
Objectives
Evaluate sTK1 activity as a biomarker for treatment response and early detection of relapse in ...dogs with lymphoma.
Animals
Ninety‐seven client‐owned dogs with naive or relapsed lymphoma and 23 healthy dogs.
Methods
Prospective study. Serum TK1 activity measured by refined ELISA‐based method (DiviTum assay, Biovica International) before treatment, at clinical response, and every 4 weeks until relapse or last follow‐up.
Results
Serum TK1 activity was ≤20 Du/L in 96% (22/23) of healthy dogs. Pretreatment sTK1 activity was >20 Du/L in 88% (85/97) dogs with lymphoma. At clinical response, sTK1 activity was significantly lower in dogs with complete (CR, n = 36) versus partial (PR, n = 29) response (P < .0001). Sensitivity (Se) and specificity (Sp) of sTK1 activity for detecting nonfully responders were 76% and 100%, respectively, with cutoff of 119.5 Du/L (AUC, 0.90; 95%‐CI, 0.81‐0.98; P < .0001). In dogs with CR, a 5‐fold increase in sTK1 activity at a 4‐week interval predicted relapse at the subsequent 4‐week assessment with a Se 50% and Sp 94% (AUC, 0.72; 95%‐CI, 0.55‐0.90; P = .02). An increase of sTK1 activity (>2.7‐fold value measured at clinical response) predicted relapse at subsequent 4‐week assessment with a Se 61% and Sp 88% (AUC, 0.79; 95%‐CI, 0.64‐0.95; P = .004).
Conclusions and Clinical Importance
Monitoring sTK1 activity could help to detect complete responders and early disease progression in dogs with lymphoma.
Background Pulmonary hypertension (PH) complicating systemic sclerosis (SSc)-related interstitial lung disease (ILD) is usually associated with a poor prognosis. However, data are either lacking or ...scarce on prognostic factors in this condition. The objectives of this study were to compare the survival of patients with ILD-associated PH (PH-ILD) or pulmonary arterial hypertension (PAH) and to determine whether the severity of PH has prognostic value in SSc-associated PH-ILD. Methods Consecutive patients with SSc and PH-ILD (n = 47) or PAH (n = 50) confirmed by right-sided heart catheterization were included in a cross-sectional analysis. PH was classified as mild (mean pulmonary arterial pressure mPAP ≤ 35 mm Hg) or moderate to severe (mPAP > 35 mm Hg). Results As compared with patients with PAH, subjects with PH-ILD were younger, were more frequently men with a history of smoking, had more frequently diffuse SSc, less frequently anticentromere antibodies, and a lower FVC/diffusing capacity of lung for carbon monoxide (D lco) ratio. They had a worse prognosis than patients with PAH (3-year survival of 47% vs 71%, respectively; P = .07). Patients with mild PH-ILD had similar poor outcomes when compared with those with moderate to severe PH-ILD. Pericardial effusion (hazard ratio HR, 2.44; P = .04) and lower D lco (HR, 0.96; P = .01) were the only independent factors predictive of a poor survival in the PH-ILD group. Conclusions Patients with SSc with PH-ILD had a different phenotype and a worse prognosis than those with SSc and PAH. Lower D lco and presence of pericardial effusion were predictive of a poor outcome in PH-ILD, whereas mPAP seemed to have no prognostic significance.
BACKGROUNDThe uric acid (UA) level in patients with gout is a key factor in disease management and is typically measured in the laboratory using plasma samples obtained after venous puncture. This ...study aimed to assess the reliability of immediate UA measurement with capillary blood samples obtained by fingertip puncture with the HumaSensplus point-of-care meter.METHODSUA levels were measured using both the HumaSensplus meter in the clinic and the routine plasma UA method in the biochemistry laboratory of 238 consenting diabetic patients. HumaSensplus capillary and routine plasma UA measurements were compared by linear regression, Bland-Altman plots, intraclass correlation coefficient (ICC), and Lin's concordance coefficient. Values outside the dynamic range of the meter, low (LO) or high (HI), were analyzed separately. The best capillary UA thresholds for detecting hyperuricemia were determined by receiver operating characteristic (ROC) curves. The impact of potential confounding factors (demographic and biological parameters/treatments) was assessed. Capillary and routine plasma UA levels were compared to reference plasma UA measurements by liquid chromatography-mass spectrometry (LC-MS) for a subgroup of 67 patients.RESULTSIn total, 205 patients had capillary and routine plasma UA measurements available. ICC was 0.90 (95% confidence interval (CI) 0.87-0.92), Lin's coefficient was 0.91 (0.88-0.93), and the Bland-Altman plot showed good agreement over all tested values. Overall, 17 patients showed values outside the dynamic range. LO values were concordant with plasma values, but HI values were considered uninterpretable. Capillary UA thresholds of 299 and 340 μmol/l gave the best results for detecting hyperuricemia (corresponding to routine plasma UA thresholds of 300 and 360 μmol/l, respectively). No significant confounding factor was found among those tested, except for hematocrit; however, this had a negligible influence on the assay reliability. When capillary and routine plasma results were discordant, comparison with LC-MS measurements showed that plasma measurements had better concordance: capillary UA, ICC 0.84 (95% CI 0.75-0.90), Lin's coefficient 0.84 (0.77-0.91); plasma UA, ICC 0.96 (0.94-0.98), Lin's coefficient 0.96 (0.94-0.98).CONCLUSIONSUA measurements with the HumaSensplus meter were reasonably comparable with those of the laboratory assay. The meter is easy to use and may be useful in the clinic and in epidemiologic studies.
PDF
