Detailed Long-Term Follow-Up of Patients Who Relapsed After the Nordic Mantle Cell Lymphoma Trials: MCL2 and MCL3.

Mantle cell lymphoma (MCL) is an incurable disease with a highly variable clinical course. The prognosis after relapse is generally poor, and no standard of care exists. We investigated the postrelapse outcomes of 149 patients who were initially treated in the Nordic Lymphoma Group trials, MCL2 or MCL3, both representing intensive cytarabine-containing frontline regimens including autologous stem cell transplant. Patients with progression of disease before 24 months (POD24, n = 51, 34%) displayed a median overall survival of 6.6 months compared with 46 months for patients with later POD (n = 98, 66%; P < 0.001). MCL international prognostic index, cell proliferation marker, blastoid morphology, and TP53 mutations showed independent prognostic value irrespective of POD24, and in a combined, exploratory risk score, patients with 0, 1, 2-3, or 4-5 high-risk markers, respectively, displayed a 5-year overall survival of 62%, 39%, 31%, and 0%. By a comparison of median progression-free survival of the different salvage therapies in the relapse setting, bendamustine-rituximab was superior to all other combination chemotherapy regimens; however, it was also associated with longer responses to last line of therapy. Collectively, we confirm the prognostic impact of POD24 and highlight the relevance of other biomarkers, and we emphasize the importance of novel therapies for patients with high-risk features at first POD.

Management of Adults With Congenital Heart Disease and Pulmonary Arterial Hypertension in the UK: Survey of Current Practice, Unmet Needs and Expert Commentary.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a well-recognised complication of adult congenital heart disease (CHD). However, management is not currently standardised between centres and specific guidelines are lacking. In order to identify and understand the unmet needs related to PAH associated with CHD (PAH-CHD), a survey of physicians was performed. METHODS: An electronic survey was sent to two physician groups: (1) cardiologists registered in a UK cardiology directory; (2) specialist pulmonary hypertension (PH) physicians known to manage patients with adult PAH-CHD. The questions related to referral pathways, screening, therapy and palliative care. RESULTS: 821 surveys were distributed and 106 were returned. Respondents included a broad mix of specialist physicians with many patients along with general cardiologists managing only a small number of PAH-CHD patients. Although 97% of respondents have access to a specialist PH centre, patients are still being managed in non-specialist settings. Shared care arrangements are widespread but only 41% have formal shared care protocols. Palliative care services are limited and general cardiologists rarely perform 6-minute walk tests (6MWT) or quality of life assessments. People with PAH-CHD are often undertreated, with 39% of respondents reporting that fewer than 25% of these patients were receiving PAH-specific therapies. CONCLUSIONS: The survey revealed gaps and inconsistencies in the management of patients with PAH-CHD therefore patient-specific guidance is needed for many of these aspects.

Greek health professionals' perceptions of the HPV vaccine, state policy recommendations and their own role with regards to communication of relevant health information.

BACKGROUND: Every year in Europe 60,000 women develop cervical cancer and 30,000 die from the disease. HPV vaccines are currently believed to constitute an important element of cervical cancer control strategy. Currently in Greece, the HPV vaccine is given on demand after prescription by a healthcare professional. Health care professionals' role is key as they are in a position to discuss HPV vaccination with parents, adolescents and young women. This study is aiming to explore health care professionals' perceptions of the HPV vaccine, state policy recommendations and their own role with regards to communication of relevant health information. METHODS: This was an in-depth, qualitative study, employing a stratified, purposeful sampling. Fifteen face-to-face, semi-structured interviews were conducted with health care professionals from a variety of disciplines: pediatrics, obstetrics and gynecology, infectious diseases, pharmacy, dermatology, general practice. Thematic qualitative analysis was used to analyze participants' accounts. RESULTS: Five major themes were identified: health care professionals' perceptions towards the HPV vaccine (recognition of importance, concerns about safety, effectiveness and impact of long-term use), animosity between medical specialties (territorial disputes among professional bodies, role advocacy, role limitations), health care professionals' perceptions of the public's attitudes (effects of cultural beliefs, health professionals' attitudes, media and family), the role of the state (health policy issues, lack of guidance, unmet expectations) and their own role (provision of health information, sex education). CONCLUSIONS: Health professionals' concerns, lack of role definition and uniform information provision have led to territorial disputes among professional bodies and distrust among different medical specialties. Positive and negative judgements deriving from a multitude of sources have resulted in the confusion of the general public, as manifested by low vaccination rates. Due to the lack of clear regulation of vaccination prescription, administration and mode of delivery, factors such as lack of knowledge, cultural beliefs and personal attitudes have shaped the vaccination landscape. These factors have neither been explored nor addressed prior to the initiation of this public health effort and as such there is an evident less than efficient use of resources.

Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United Kingdom National Cohort.

BACKGROUND: Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli. Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA. METHODS AND RESULTS: Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-to-event) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s(-1)·cm(-5) at reassessment correlated with worse long-term survival. CONCLUSIONS: Our data confirm excellent long-term survival and maintenance of good functional status post-PEA. Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery.

Lung function and gas exchange in Eisenmenger syndrome and their impact on exercise capacity and survival.

BACKGROUND: Eisenmenger physiology may contribute to abnormal pulmonary mechanics and gas exchange and thus impaired functional capacity. We explored the relationship between lung function and gas exchange parameters with exercise capacity and survival. METHODS: Stable adult patients with Eisenmenger syndrome (N=32) were prospectively studied using spirometry, lung volumes, diffusion capacity, and blood gas analysis, as well as same day measurement of 6-minute walk distance and cardiopulmonary maximal treadmill exercise. Patients were followed prospectively to determine survival (7.4 ± 0.5 years). Abnormalities were identified and appropriate comparisons were made between affected and unaffected individuals between respiratory mechanics, exercise function, and survival. RESULTS: Obstruction (FEV1/FVC ratio <0.70) was found in 13 patients (41%), who were older but not otherwise different. Restriction was uncommon. Diffusion transfer coefficient, which was <80% in half the patients, correlated with exercise duration (r=0.542, P=0.005), and was worse in non-survivors (N=6). Nearly all patients had a compensated respiratory alkalosis (PaCO2 32 ± 4.4 mm Hg). PaCO2 was less reduced in older patients (r=0.438, P=0.022), and correlated independently with exercise duration (R=-0.463, P=0.03), yet PaO2, not PaCO2, was associated with survival. CONCLUSIONS: Eisenmenger patients show evidence of obstructive lung disease, diffusion abnormalities, and hypocapnia; likely from hyperventilation. Understanding expected lung mechanics and gas exchange may facilitate more appropriate clinical management.

The impact of transcatheter atrial septal defect closure in the older population: a prospective study.

OBJECTIVES: We sought to prove that device closure of atrial septal defect (ASD) in older patients not only improves cardiac function but also results in symptomatic relief by improving functional class. BACKGROUND: Atrial septal defect accounts for approximately 10% of all congenital cardiac defects. It is possible that ASD closure in older patients may derive benefits, though this is not well established. We therefore aim to prospectively assess the clinical status and functional class of older patients after transcatheter ASD closure. METHODS: This was a prospective study of all patients age 40 years or more who underwent device closure of a secundum ASD between April 2004 and August 2006. Investigations including atrial and brain natriuretic peptide levels, electrocardiography, chest X-ray, transthoracic echocardiogram, 6-min walk test, and quality of life questionnaire were performed before and at 6 weeks and 1 year after the procedure. RESULTS: Twenty-three patients (median age 70 years, 13 women) had transcatheter device closure of ASD. Median ASD size was 18 mm (range 9 to 30 mm). Median pulmonary artery pressure was 22 mm Hg (range 12 to 27 mm Hg). At 1 year, New York Heart Association functional class improved (p = 0.004) in 16 patients with significant improvement in 6-min walk-test distance (p = 0.004) and physical (p = 0.002) as well as mental health score (p = 0.03). There were no major complications. One year following closure there was a significant change in left ventricular end-diastolic (p = 0.001) and end-systolic dimensions (p = 0.001) and also significant reduction in right ventricular end-diastolic dimension (p < 0.001). CONCLUSIONS: Our data demonstrated that ASD closure at advanced age results in favorable cardiac remodeling and improvement of functional class.