Charles D. Burger

Effect of Pramipexole in Treatment of Resistant Restless Legs Syndrome

OBJECTIVE To report the results of an open-label trial with a dopaminergic agent, pramipexole, in patients with treatment-resistant restless legs syndrome (RLS). MATERIAL AND METHODS We studied the response to pramipexole in a consecutive series of 16 patients with symptomatic RLS who had previously experienced failure with other dopaminergic therapies. Patients assessed their posttreatment change in symptoms of RLS on a visual analog scale and indicated drug-related side effects with use of a checklist. RESULTS With a mean dose of pramipexole of 0.3 mg, most patients reported clinically significant improvement. From 2 to 3 months after initiation of pramipexole therapy, nocturnal leg restlessness, involuntary leg movements, and insomnia had decreased in 12, 10, and 11 patients, respectively. The most frequent adverse effects were fatigue and stiffness, which occurred in a third of the patients. Overall, the drug was well tolerated. CONCLUSION On the basis of these findings, we propose that pramipexole, a D2 subgroup receptor agonist, is an effective agent for treatment of RLS.

Pulmonary complications in bone marrow transplantation: a practical approach to diagnosis and treatment.

Pulmonary complications occur in 40% to 60% of recipients of bone marrow trans-plants, account for more than 90% of mortality, and develop during identifiable phases. Phase 1 (Days 1-30) includes pulmonary edema; diffuse alveolar hemorrhage; and various bacterial, fungal, and viral infections; Phase 2 (Days 31-100) usually requires a distinction between cytomegalovirus pneumonitis and idiopathic pneumonia syndrome; and Phase 3 (Day 100+) includes complications that are due to chronic graft-versus-host disease and associated bronchiolitis obliterans. The spectrum of pulmonary complications has been influenced by changes in transplantation technique, prophylactic treatment for infections, and the use of new chemotherapeutic agents that contribute to lung injury. Nonetheless, infections remain a leading cause of morbidity and mortality. The most serious complications result in respiratory failure, for which the prognosis has not improved significantly over the last 2 decades. In this article, we describe our algorithmic approach to the diagnosis and management of these complications.

An alternative echocardiographic method to estimate mean pulmonary artery pressure: diagnostic and clinical implications.

BACKGROUND The aim of this study was to evaluated an alternative echocardiographic method to calculate mean pulmonary arterial pressure (MPAP). METHODS One hundred two patients were studied with simultaneous right-heart catheterization (RHC) and echocardiography. MPAP was calculated by adding the right ventricular-right atrial mean systolic gradient to right atrial pressure. RESULTS The mean difference between MPAP calculated using this method and RHC-derived MPAP was -1.6 mm Hg, less than that of traditional systolic pulmonary arterial pressure (SPAP; -6.4 mm Hg) and MPAP estimated using the pulmonary regurgitation method (-13.9 mm Hg). The median absolute percentage difference of the MPAP calculations relative to RHC was significantly less with this method than with the pulmonary regurgitation method (18% vs 71%; P < .001) and similar to the SPAP method (both 18%; P = .30). CONCLUSION MPAP calculated using the proposed method is as accurate as SPAP calculation and less variable than previous methods, thus allowing widespread clinical use.

Accuracy and Precision of Three Echocardiographic Methods for Estimating Mean Pulmonary Artery Pressure

BACKGROUND Pulmonary hypertension is defined as resting mean pulmonary artery pressure (MPAP) ≥ 25 mm Hg. MPAP pressure estimation by right-sided heart catheterization (RHC) is considered the gold standard; however, its invasiveness limits repeated and frequent use. The purpose of this study was to compare the accuracy and precision of three echocardiographic methods for estimating MPAP. METHODS We prospectively studied 117 patients with simultaneous RHC and echocardiography. MPAP was calculated by three echocardiographic methods: (1) mean gradient method (adding the right ventricular-right atrial mean systolic gradient to the right atrial pressure), (2) Chemla equation (0.61 × systolic pulmonary artery pressure + 2 mm Hg), and (3) Syyed equation (0.65 × systolic pulmonary artery pressure + 0.55 mm Hg). MPAP calculated by these three methods was compared with that obtained invasively by RHC. RESULTS The mean ± SD of the differences between invasive MPAP and the three echocardiographic methods were -1.6 ± 7.7 mm Hg for the mean gradient method, -3.7 ± 7.4 mm Hg for the Chemla formula, and -3.2 ± 7.6 mm Hg for the Syyed formula. Median absolute differences were 5.5 mm Hg (mean gradient), 5.7 mm Hg (Chemla; P = .45 vs mean gradient), and 6.0 mm Hg (Syyed; P = .23 vs mean gradient). Accuracy (calculated MPAP within 10 mm Hg of RHC-measured MPAP) was 81% (mean gradient), 77% (Chemla), and 76% (Syyed). CONCLUSIONS Echocardiographic estimation of MPAP by the mean gradient method had similar accuracy and precision compared with the Chemla and Syyed methods. The acceptable accuracy of these methods suggests that they are equally suitable for clinical use.

Comparison of Body Habitus in Patients With Pulmonary Arterial Hypertension Enrolled in the Registry to Evaluate Early and Long-term PAH Disease Management With Normative Values From the National Health and Nutrition Examination Survey

OBJECTIVE To investigate the correlation between body mass index (BMI) and pulmonary artery systolic pressure in a large population of patients with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS The BMI of patients with group 1 PAH enrolled in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) was compared with that of age- and sex-matched controls in the National Health and Nutrition Examination Survey (NHANES) to clarify whether obesity is linked with PAH. The diagnosis of PAH was defined in REVEAL by right-sided heart catheterization. Differences in BMI and the percentage of patients considered obese (BMI ≥30) and underweight (BMI <18.5) in various subgroups of patients enrolled in REVEAL from March 30, 2006, through September 11, 2007, were determined. RESULTS Mean BMI was no different for patients with PAH (n=2141) than for the NHANES normal comparison group; however, the proportion of obese and underweight patients was increased in patients with PAH. Subgroup analysis demonstrated that subgroups with idiopathic PAH and those with PAH associated with drugs and toxins had both higher BMI and percentage of obese patients, whereas 3 other subgroups (those with PAH associated with congenital heart disease, connective tissue disease, and human immunodeficiency virus) had lower mean BMI. CONCLUSION Mean BMI of the REVEAL patients was the same as that of the NHANES normal comparison group; however, there were higher percentages of obese and underweight patients in REVEAL. This discrepancy can be explained by the balancing effect of more overweight and underweight patients in different PAH subgroups. The reason for the increased frequency of obesity in idiopathic PAH is unknown, and additional study is needed.

Spectrum of Pneumonia in the Current Era of Liver Transplantation and Its Effect on Survival

OBJECTIVE To examine the frequency and microbial pattern of pneumonia and its effect on survival in the current era of orthotopic liver transplantation (OLT). PATIENTS AND METHODS At the Mayo Clinic in Jacksonville, Fla, the medical records of consecutive patients who underwent their first OLT between February 1998 and January 2001 were retrospectively reviewed through the end of the first year posttransplantation. RESULTS Of 401 study patients, 20 developed pneumonia; estimates of incidence with corresponding 95% confidence interval (CI) at 1 and 12 months were 3% (1%-5%) and 5% (3%-7%), respectively. Pseudomonas aeruginosa was the predominant microorganism identified (in 8 of 14 patients) during the first month after transplantation. Between the second and sixth months, 2 of the 4 cases of pneumonia were due to fungal infections of Aspergillus fumigatus. Cytomegalovirus was associated with Aspergillus in 1 patient. No other viral or Pneumocystis carnil pneumonia was diagnosed. There were only 2 cases of pneumonia between 7 months and 1 year after transplantation, neither of which was fungal. Approximately 40% (95% CI, 14%-58%) of patients with pneumonia died within 1 month after diagnosis. The relative risk of mortality in the first month after onset of pneumonia was estimated to be 24 (95% CI, 10-54), which is strong evidence of increased risk of mortality with pneumonia (P<0.001). CONCLUSIONS Pneumonia appears to occur less often after OLT than previously reported but still has a substantial negative effect on survival. In the early period after OLT, P. aeruginosa continues to be the predominant organism causing pneumonia.

Echocardiographic Assessment of Estimated Right Atrial Pressure and Size Predicts Mortality in Pulmonary Arterial Hypertension

BACKGROUND Elevated mean right atrial pressure (RAP) measured by cardiac catheterization is an independent risk factor for mortality. Prior studies have demonstrated a modest correlation with invasive and noninvasive echocardiographic RAP, but the prognostic impact of estimated right atrial pressure (eRAP) has not been previously evaluated in patients with pulmonary arterial hypertension (PAH). METHODS A retrospective analysis of 121 consecutive patients with PAH based on right-sided heart catheterization and echocardiography was performed. The eRAP was calculated by inferior vena cava diameter and collapse using 2005 and 2010 American Society of Echocardiography (ASE) definitions. Accuracy and correlation of eRAP to RAP was assessed. Kaplan-Meier survival analysis by eRAP, right atrial area, and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) risk criteria as well as univariate and multivariate analysis of echocardiographic findings was performed. RESULTS Elevation of eRAP was associated with decreased survival time compared with lower eRAP (P < .001, relative risk = 7.94 for eRAP > 15 mm Hg vs eRAP ≤ 5 mm Hg). Univariate analysis of echocardiographic parameters including eRAP > 15 mm Hg, right atrial area > 18 cm², presence of pericardial effusion, right ventricular fractional area change < 35%, and at least moderate tricuspid regurgitation was predictive of poor survival. However, multivariate analysis revealed that eRAP > 15 mm Hg was the only echocardiographic risk factor that was predictive of mortality (hazard ratio = 2.28, P = .037). CONCLUSIONS Elevation of eRAP by echocardiography at baseline assessment was strongly associated with increased risk of death or transplant in patients with PAH. This measurement may represent an important prognostic component in the comprehensive echocardiographic evaluation of PAH.

Characterization of First-Time Hospitalizations in Patients With Newly Diagnosed Pulmonary Arterial Hypertension in the REVEAL Registry

BACKGROUND: Hospitalization is an important outcome in pulmonary arterial hypertension (PAH), shown previously to correlate with survival. Using the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry), we sought to characterize first-time hospitalizations and their effect on subsequent hospitalization and survival in patients with newly diagnosed disease. METHODS: Patients with newly diagnosed PAH (n = 862, World Health Organization group 1) were evaluated for first-time hospitalization. The hospitalizations were categorized as PAH related or PAH unrelated based on the case report form. Categories for PAH-related and PAH-unrelated hospitalization were defined before independent review. Patient demographics and disease characteristics are described as well as freedom from hospitalization and survival. RESULTS: Of 862 patients, 490 (56.8%) had one or more hospitalizations postenrollment: 257 (52.4%) PAH related, 214 (43.7%) PAH unrelated, and 19 (3.9%) of undetermined causes. The most common causes of PAH-related hospitalization were congestive heart failure and placement/removal of a central venous catheter. Patients with PAH-related hospitalizations were more likely to receive parenteral therapy, be in functional class III/IV, and have higher risk scores before hospitalization at enrollment. Following discharge, 25.4% ± 3.2% and 31.0% ± 4.0% of patients with PAH-related and PAH-unrelated first hospitalization, respectively, remained hospitalization-free for 3 years (P = .11). Survival estimates at 3 years postdischarge were 56.8% ± 3.5% and 67.8% ± 3.6% (P = .037) for patients with PAH-related and PAH-unrelated hospitalization, respectively. CONCLUSIONS: In the REVEAL Registry, PAH-related hospitalization was associated with relatively more rehospitalizations and worse survival at 3 years. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov

Cerebral embolization presenting as delayed, severe obtundation in the postanesthesia care unit after total hip arthroplasty.

Catastrophic neurologic events occur rarely postoperatively and must be diagnosed quickly. A 63-year-old woman who had undergone uneventful total hip arthroplasty experienced obtundation after admission to the postanesthesia care unit. Cranial magnetic resonance imaging revealed multiple lesions consistent with ischemia or infarction, and fat cerebral embolism was diagnosed. We describe the numerous complications that may occur in patients in the postanesthesia care unit and review the differential diagnosis of altered mental status in such patients. Paradoxical cerebral fat embolization must be considered in the differential diagnosis of altered mental status after pelvic or long bone fracture or lower extremity major joint replacement, and this condition may occur despite normal pulmonary function and no patent foramen ovale or right-to-left intracardiac shunt. Magnetic resonance imaging with T2-weighted sequences is the cranial imaging study of choice for early evaluation of patients with sudden multifocal neurologic deficits and suspected fat embolism syndrome.

Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseases

The diffuse cystic lung diseases (DCLDs) are a group of pathophysiologically heterogeneous processes characterised by the presence of multiple, thin-walled, air-filled spaces within the pulmonary parenchyma [1]. The differential diagnosis of DCLDs includes lymphangioleiomyomatosis (LAM), follicular bronchiolitis (FB), lymphocytic interstitial pneumonia (LIP), Birt–Hogg–Dubé syndrome (BHD), pulmonary Langerhans cell histiocytosis (PLCH), amyloidosis, light chain deposition disease, cystic metastases, infectious entities such as Pneumocystis, and other aetiologies [2]. Bronchiectasis and bullous changes seen in chronic obstructive pulmonary disease can also produce high-resolution computed tomography (HRCT) patterns that mimic the DCLDs. Correct diagnosis of diffuse cystic lung diseases is established in most cases by critical review of HRCT features http://ow.ly/NvrCc