Influence of Home Monitoring on the clinical status of heart failure patients: Design and rationale of the IN-TIME study

BACKGROUND: Despite optimal drug and device therapy, frequent hospitalisations due to decompensated heart failure remain an issue. Early detection of decompensation could prevent hospitalisation in patients with congestive heart failure. The recently introduced Home Monitoring functionality of implanted devices is a promising new telecardiology technique which provides information on the status of heart failure. Home Monitoring observation of heart failure patients could lead to early detection of preclinical decompensation, enable early intervention before clinical decompensation, and thus could prevent hospitalisations. OBJECTIVE: The IN-TIME study is designed to assess the impact of Home Monitoring on the early detection of worsening congestive heart failure and the clinical status of heart failure patients. STUDY DESIGN: Approximately 620 patients will be prospectively randomised to patient management guided by Home Monitoring analysis or standard care and followed for 12 months. The endpoints committee will adjudicate events in a blinded fashion. The primary endpoint is a composite of all-cause mortality, unplanned hospitalisation due to worsening heart failure, NYHA class and patient global self assessment (Packer score). The study should complete recruitment during 2009 and report in late 2010.     

Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon

AF Ablation Technologies and Silent Cerebral Ischemic Lesions. Introduction: Silent cerebral ischemic lesions have recently emerged as the most frequent complications after pulmonary vein isolation (PVI). To reduce thromboembolic complications, new types of catheters and energy source have been introduced in clinical practice. The study purpose is to compare the incidence of new silent cerebral ischemic events in patients with paroxysmal atrial fibrillation (PAF) undergoing PVI with different ablation technologies. Methods and Results: One hundred and eight patients (67% men; age 56 ± 9 years) with PAF were enrolled in a consecutive manner to undergo PVI performed with irrigated radiofrequency (RF) catheter (Group 1, 36 patients), multielectrode catheter (PVAC) associated with duty‐cycled RF generator (Group 2, 36 patients) and cryoballoon (Group 3, 36 patients). The protocol included a cerebral magnetic resonance imaging before and after the procedure. After PVI, the following patients showed new silent cerebral ischemic lesions at postprocedural cerebral MRI: 3 patients in Group 1 (8.3%), 14 patients in Group 2 (38.9%), 2 patients in Group 3 (5.6%). PVAC related to higher incidence of silent cerebral ischemic events compared to irrigated RF (P = 0.002) and cryoballoon (P = 0.001), whereas no statistical differences were found between irrigated RF catheter and cryoballoon groups (8.3% vs 5.6%, P = 0.5). At the multivariate analysis, the only independent predictor of new ischemic asymptomatic cerebral lesions after PVI was ablation performed with PVAC (OR 1.48 95% CI 1.19–1.62, P < 0.001). Conclusion: The incidence of silent cerebral lesions after PVI is different depending on technologies used: PVAC increases the risk of 1.48 times compared to irrigated RF and cryoballoon ablation. (J Cardiovasc Electrophysiol, Vol. 22, pp. 961‐968, September 2011)     

Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection

OBJECTIVES: The characterization of primary HIV infection by the analysis of serial plasma samples from newly infected persons using multiple standard viral assays. DESIGN: A retrospective study involving two sets of archived samples from HIV-infected plasma donors. (A) 435 samples from 51 donors detected by anti-HIV enzyme immunoassays donated during 1984-1994; (B) 145 specimens from 44 donors detected by p24 antigen screening donated during 1996-1998. SETTING: Two US plasma products companies. MAIN OUTCOME MEASURES: The timepoints of appearance of HIV-1 markers and viral load concentrations during primary HIV infection. RESULTS: The pattern of sequential emergence of viral markers in the 'A' panels was highly consistent, allowing the definition and estimation of the duration of six sequential stages. From the 'B' panels, the viral load at p24 antigen seroconversion was estimated by regression analysis at 10 000 copies/ml (95% CI 2000-93 000) and the HIV replication rate at 0.35 log copies/ml/day, corresponding to a doubling time in the preseroconversion phase of 20.5 h (95% CI 18.2-23.4 h). Consequently, an RNA test with 50 copies/ml sensitivity would detect HIV infection approximately 7 days before a p24 antigen test, and 12 days before a sensitive anti-HIV test. CONCLUSION: The sequential emergence of assay reactivity allows the classification of primary HIV-1 infection into distinct laboratory stages, which may facilitate the diagnosis of recent infection and stratification of patients enrolled in clinical trials. Quantitative analysis of preseroconversion replication rates of HIV is useful for projecting the yield and predictive value of assays targeting primary HIV infection.     

Diagnosis and monitoring of central nervous system involvement in systemic lupus erythematosus: value of F-18 fluorodeoxyglucose PET

OBJECTIVE: To investigate prospectively abnormalities of brain glucose utilisation in relation to major or minor neuropsychiatric symptoms in systemic lupus erythematosus (SLE). METHODS: Positron emission tomography (PET) using F-18-labelled fluorodeoxyglucose was performed in 28 patients with SLE. Patients were classified as having severe neuropsychiatric manifestations (seizures, focal neurological deficits, acute confusional states, mood disorders) (n=12), or mild neuropsychiatric manifestations (headache, reactive depression, cognitive dysfunction, anxiety disorders) (n=11) and five patients without signs of central nervous system (CNS) involvement. Ten clinically and neurologically healthy volunteers served as controls. In 26 patients magnetic resonance imaging (MRI) was performed and autoantibodies against CNS tissue, ribosomal P protein and cardiolipin were measured. In 14 patients follow up PET scans were performed after a mean (SD) period of 11.6 (9.5) months. RESULTS: PET scans showed hypometabolism in at least one brain region in all patients with severe or mild CNS symptoms (100%) as compared with patients without cerebral symptoms (40%) (p<0.0025). Parieto-occipital regions were most commonly affected (96%), followed by parietal regions (32%). In contrast, MRI images were abnormal in only 11 of 22 patients (50%) with neuropsychiatric symptoms and in one of four patients (25%) without symptoms. In 12 of 14 patients examined in follow up PET scans persistence, improvement or worsening of cerebral symptoms were associated with unchanged, decreased or increased brain hypometabolism, respectively. No significant correlation was found between PET or MRI findings and autoantibody profiles. CONCLUSIONS: PET imaging represents a sensitive tool to detect manifest or subclinical CNS involvement in SLE and PET findings correlate well with the clinical course of disease.     

Natriuretic peptides in patients with diastolic dysfunction due to idiopathic dilated cardiomyopathy.

AIMS: The degree of systolic dysfunction does not always correlate with functional impairment in patients with congestive heart failure. In contrast, diastolic dysfunction correlates well with functional impairment. In heart failure, both elevation of N-terminal proatrial natriuretic peptide and B-type natriuretic peptide are markers of a poor prognosis.METHODS: We investigated 32 patients (26 male, 6 female; mean age 55+/-2 years) with dilated cardiomyopathy and sinus rhythm. M-mode echocardiography and 2D-echocardiography were carried out in each patient. Pulsed-wave Doppler inflow signals were obtained and the following parameters were measured: maximal E wave and maximal A wave velocity, E/A ratio, E wave deceleration time, A wave deceleration time. Immediately after echocardiography blood samples were collected from patients in the supine position. N-terminal proANP and brain natriuretic peptide were measured using a radioimmuno assay.RESULTS: The left ventricular ejection fraction was 34+/-1%, the left ventricular end-diastolic diameter on M-mode echocardiography was 68+/-1 mm, while left atrial diameter was 45+/-1 mm. Univariate analysis revealed a significant correlation between both left atrial diameter and ejection fraction and N-terminal proANP and brain natriuretic peptide. All transmitral Doppler parameters showed a significant correlation with N-terminal proANP and brain natriuretic peptide. On forward stepwise regression analysis, left atrial diameter and ejection fraction were able to predict both N-terminal proANP and brain natriuretic peptide. However, of the diastolic parameters only the E/A ratio remained significant. Mildly symptomatic patients differed significantly from severely symptomatic patients in all Doppler parameters. Mildly symptomatic patients had significantly lower levels of N-terminal proANP (0.571+/-0.079 vs 2.282+/-0.340 nmol. l(-1);P<0.001) and brain natriuretic peptide (51+/-14.8 vs 474.2+/- 86.8 pg. ml(-1);P<0. 001).CONCLUSION: There is a close relationship between natriuretic peptides and diastolic Doppler parameters of left ventricular filling in patients with dilated cardiomyopathy. There is also a significant difference between patients with mild and severe functional impairment regarding both natriuretic peptides and transmitral Doppler parameters.     

Routine Depression Screening in an HIV Clinic Cohort Identifies Patients with Complex Psychiatric Co-morbidities Who Show Significant Response to Treatment

This study described characteristics, psychiatric diagnoses and response to treatment among patients in an outpatient HIV clinic who screened positive for depression. Depressed (25 %) were less likely to have private insurance, less likely to have suppressed HIV viral loads, had more anxiety symptoms, and were more likely to report current substance abuse than not depressed. Among depressed, 81.2 % met diagnostic criteria for a depressive disorder; 78 % for an anxiety disorder; 61 % for a substance use disorder; and 30 % for co-morbid anxiety, depression, and substance use disorders. Depressed received significantly more treatment for depression and less HIV primary care than not depressed patients. PHQ-9 total depression scores decreased by 0.63 from baseline to 6-month follow-up for every additional attended depression treatment visit. HIV clinics can routinely screen and treat depressive symptoms, but should consider accurate psychiatric diagnosis as well as co-occurring mental disorders.     

Contact investigation based on serial interferon-gamma release assays (IGRA) in children from the hematology-oncology ward after exposure to a patient with pulmonary tuberculosis

Background

Interferon-gamma release assays (IGRAs) have high specificity and sensitivity for the diagnosis of tuberculosis (TB) infection. However, their role as a screening tool in children with immunodeficiency disorders is still unclear. In the present study, we performed a contact investigation using serial IGRAs on children with immunodeficiency conditions exposed to a contagious TB patient.

Methods

Children who were exposed to a contagious TB case underwent serial QuantiFERON^® TB Gold In-Tube (QFT-GIT) and T-SPOT^®.TB (T-SPOT) testing.

Results

Eighteen children were tested. At the first testing, only two children (11 %) were positive to T-SPOT. Indeterminate results were more frequent with QFT-GIT (35 %) than with T-SPOT (12 %). In the multivariable analysis, a statistically significant association of lymphocyte count <500 cells/mm³ (p < 0.00005) and low age (p = 0.03) with indeterminate results for the QFT-GIT test but not for T-SPOT (p = 0.10 and p = 0.88, respectively) was found. At the end of October 2012, 15 of the 18 children were alive and none developed active TB disease.

Conclusion

T-SPOT provided more determinate results and was less influenced by low age and lymphocytopenia than QFT-GIT in this population of immunodeficient children. These findings suggest that T-SPOT is a more accurate test for the identification of TB infection in young children with lymphocytopenia and should be preferred to QFT-GIT under such specific conditions.     

Effective graft depletion of MiHAg T-cell specificities and consequences for graft-versus-host disease

Minor histocompatibility antigen (MiHAg) differences between donor and recipient in MHC-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT) often result in graft-versus-host disease (GVHD). While MiHAg-specific T-cell responses can in theory be directed against a large number of polymorphic differences between donor and recipient, in practice, T-cell responses against only a small set of MiHAgs appear to dominate the immune response, and it has been suggested that immunodominance may predict an important contribution to the development of GVHD. Here, we addressed the feasibility of graft engineering by ex vivo removal of T cells with 1 or more defined antigen specificities in a well-characterized experimental HSCT model (B6 --> BALB.B). We demonstrate that immunodominant H60- and H4-specific CD8(+) T-cell responses can be effectively suppressed through MHC class I tetramer-mediated purging of the naive CD8(+) T cell repertoire. Importantly, the development of GVHD occurs unimpeded upon suppression of the immunodominant MiHAg-specific T-cell response. These data indicate that antigen-specific graft engineering is feasible, but that parameters other than immunodominance may be required to select T-cell specificities that are targeted for removal.