Pericardial complications and postcardiac injury syndrome after cardiovascular implantable electronic device placement : A meta-analysis and systematic review.

BACKGROUND: Postcardiac injury syndrome (PCIS) is an emerging condition including pericarditis with or without pericardial effusion after an injury to cardiac tissue. Data are lacking on its incidence and clinical predictors after cardiovascular implantable electronic device (CIED) placement. We therefore performed this meta-analysis to determine the incidence of PCIS. METHODS: Medline, Embase, and Cochrane CENTRAL databases were searched according to PRISMA guidelines from February 2007 to February 2017 for studies evaluating pericardial complications subsequent to CIED implantation. Primary outcome was the total number of cases of pericarditis, pericardial effusion, and cardiac tamponade documented. RESULTS: Of 2931 references, 22 articles (enrolling 188,944 patients) were included. Pooled estimates from random-effects analysis showed an overall incidence of 5.82 per 1000 patients (95% confidence interval [CI], 4.33-8.17) at 30 days, and 1.60 per 1000 (95% CI: 0.13-3.07) at 1 year. Advanced age and prior coronary artery bypass graft (CABG) surgery were associated with increased rates of pericardial complications. CONCLUSION: Our analysis revealed that CIED implantations are associated with a low incidence (0.6%) of pericardial complications at 30 days. Patients with advanced age and prior CABG are high-risk patients for pericardial complications.

Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy.

AIMS: Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. METHODS: Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥ 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. RESULTS: Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P < 0.01). Heart-rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P < 0.05). Area under the receiver-operating characteristic curve revealed good diagnostic performance of all heart-rate recovery parameters (range 0.80-0.83, P < 0.001). Optimal cut-offs for heart-rate recovery at 1-, 2- and 3-min post-exercise were ≤ 28 beats/min (sensitivity 93%, specificity 69%), ≤ 50 beats/min (sensitivity 96%, specificity 63%) and ≤ 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P < 0.05). CONCLUSIONS: Post-exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation.

Reliability of heart rate variability in patients with type 2 diabetes mellitus.

AIMS: Heart rate variability may be used to assess diabetic cardiac autonomic neuropathy. The aim of the present study was to determine the reliability of standard short-term clinical measurements of heart rate variability in patients with Type 2 diabetes. METHODS: In 24 patients with Type 2 diabetes (11 male, age 61 ± 9 years), parameters of heart rate variability in the time domain (standard deviation of RR intervals, coefficient of variation of RR intervals and root mean square of successive RR interval differences) and frequency domain (very low frequency, low frequency, high frequency and total spectral power) were derived from a 5-min electrocardiograph recorded during two laboratory visits separated by 16 ± 8 days. Absolute and relative reliability were assessed by 95% limits of random variation and the intraclass correlation coefficient, respectively. Categorical agreement of classifications of heart rate variability and sample size estimates for clinical trials were calculated. RESULTS: Despite no significant difference in mean heart rate variability between tests, 95% limits of random variation indicated that repeated measurements were between 58% higher/37% lower (most reliable parameter; coefficient of variation of RR intervals) and 443% higher/82% lower (least reliable parameter; very low frequency power) than the first measure. The intraclass correlation coefficient ranged from 0.58 to 0.90 and sample size requirements from 20 to 93 patients per group. Agreement of categories of heart rate variability ranged from 79 to 96%. CONCLUSIONS: Short-term clinical measurements of heart rate variability in patients with Type 2 diabetes are characterized by poor absolute reliability, but substantial to good relative reliability, suggesting greater clinical utility in diagnosis than in sequential follow-up.

Genomic organization of the gene coding for the costimulatory human B-lymphocyte antigen B7-2 (CD86).

The generation of an antigen-specific T-cell response requires that the T lymphocyte receive two signals from the antigen presenting cell. The specificity of this response is provided by antigen presented to the T lymphocyte and involves stimulation of the T lymphocyte via the T-cell receptor (TCR)/CD3 complex. The second, or costimulatory signal, can be provided by ligation of the B-lymphocyte activation antigens B7-1 (CD80) and B7.2 (CD86) to TCR antigen CD28. The cDNAs for both CD80 and CD86 have been isolated and are predicted to encode type 1 membrane proteins of the immunoglobulin (Ig) superfamily. The predicted protein is composed of a signal peptide followed by two Ig-like extracellular domains, a transmembrane domain, and a cytoplasmic tail. Here we report that the genomic organization of CD86 reflects its functional structure, and is similar to that found for CD80. The gene is composed of eight exons which span more than 22 kilobases. The predicted protein functional domains of signal peptide, extracellular IgV- and IgC-like regions, and transmembrane domain coincide with the genomic structure. Two independent sequences had been reported for CD86 cDNA which differed in their 5'untranslated (UT) regions. We find CD86 exons 1 and 2 correspond to these alternate 5'UT sequences. Splicing of exon 1 or 2 with the signal peptide encoding exon 3 would produce mRNA transcripts complementary to the reported cDNA clones. Exons 4 and 5 correspond to IgV- and IgC-like extracellular domains, respectively. Exon 6 encodes the transmembrane region and beginning of the cytoplasmic tail. Exons 7 and 8 encode the remainder of the cytoplasmic tail and 3'UT sequences.

CTLA4 mediates antigen-specific apoptosis of human T cells.

The regulation of T cell-mediated immune responses requires a balance between amplification and generation of effector function and subsequent selective termination by clonal deletion. Although apoptosis of previously activated T cells can be induced by signaling of the tumor necrosis factor receptor family, these molecules do not appear to regulate T-cell clonal deletion in an antigen-specific fashion. We demonstrate that cross-linking of the inducible T-cell surface molecule CTLA4 can mediate apoptosis of previously activated human T lymphocytes. This function appears to be antigen-restricted, since a concomitant signal T-cell receptor signal is required. Regulation of this pathway may provide a novel therapeutic strategy to delete antigen-specific activated T cells.

Defining critical residues in the epitope for a HIV-neutralizing monoclonal antibody using phage display and peptide array technologies.

A peptide display library [Scott and Smith, Science 249 (1990) 386-390] was constructed that expressed 1.5 x 10(8) unique 20-amino-acid (aa) peptides fused to the N-terminus of the pIII coat protein of filamentous phage fd. This phage display library (PDL-20) was prepared using a degenerate oligodeoxyribonucleotide designed to minimize bias towards most aa. Characterization of the PDL-20 showed that all aa were present at the expected frequency and that there was no positional bias. Screening of this library with a HIV-1 isotype MN envelope reactive monoclonal antibody (mAb 58.2) using two different panning procedures showed that the biopanning technique was sensitive to one phage in 10(8). Analysis of peptide sequences from panning the mAb identified a core antibody recognition sequence of four aa residues (GPGR) and two preferred flanking residues on either side. This epitope occurred at various locations within the random aa segment demonstrating an absence of positional or nearest neighbor effects. Parallel panning experiments using an array of 266 synthetic peptides identified an epitope similar to that defined by the phage display library.

Expression and functional significance of an additional ligand for CTLA-4.

Effective T-cell activation requires antigen/major histocompatibility complex engagement by the T-cell receptor complex in concert with one or more costimulatory molecules. Recent studies have suggested that the B7 molecule, expressed on most antigen presenting cells, functions as a costimulatory molecule through its interaction with CD28 on T cells. Blocking the CD28/B7 interaction with CTLA4Ig inhibits T-cell activation in vitro and induces unresponsiveness. We demonstrate that another molecule(s), termed B7-2, is expressed constitutively on dendritic cells, is differentially regulated on B cells, and costimulates naive T cells responding to alloantigen. B7-2 is up-regulated by lipopolysaccharide in < 6 hr and is maximally expressed on the majority of B cells by 24 hr. In contrast, B7 is detected only on a subset of activated B cells late (48 hr) after stimulation. In addition, Con A directly induces B7-2 but not B7 expression on B cells. Finally, although both anti-B7 monoclonal antibodies and CTLA4Ig blocked T-cell proliferation to antigen-expressing B7 transfectants, only CTLA4Ig had any significant inhibitory effect on T-cell proliferation to antigens expressed on natural antigen presenting cells, such as dendritic cells. Thus, B7 is not the only costimulatory molecule capable of initiating T-cell responses since a second ligand, B7-2, can provide a necessary second signal for T-cell activation.

Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein.

The principal neutralizing determinant of human immunodeficiency virus type 1 (HIV-1) is located in the external envelope protein, gp120, and has previously been mapped to a 24-amino acid-long sequence (denoted RP135). We show here that deletion of this sequence renders the envelope unable to elicit neutralizing antibodies. In addition, using synthetic peptide fragments of RP135, we have mapped the neutralizing determinant to 8 amino acids and found that a peptide of this size elicits neutralizing antibodies. This sequence contains a central Gly-Pro-Gly that is generally conserved between different HIV-1 isolates and is flanked by amino acids that differ from isolate to isolate. Antibodies elicited by peptides from one isolate do not neutralize two different isolates, and a hybrid peptide, consisting of amino acid sequences from two isolates, elicits neutralizing antibodies to both isolates. By using a mixture of peptides of this domain or a mixture of such hybrid peptides the type-specificity of the neutralizing antibody response to this determinant can perhaps be overcome.