Effect of known history of heart disease on survival outcomes after out‐of‐hospital cardiac arrests

Objective

We aimed to investigate the effect of known heart disease on post‐out‐of‐hospital cardiac arrest (OHCA) survival outcomes, and its association with factors influencing survival.

Methods

This was an observational, retrospective study involving an OHCA database from seven Asian countries in 2009–2012. Heart disease was defined as a documented diagnosis of coronary artery disease or congenital heart disease. Patients with non‐traumatic arrests for whom resuscitation was attempted and with known medical histories were included. Differences in demographics, arrest characteristics and survival between patients with and without known heart disease were analysed. Multivariate logistic regression was performed to identify factors influencing survival to discharge.

Results

Of 19 044 eligible patients, 5687 had known heart disease. They were older (77 vs 72 years) and had more comorbidities like diabetes (40.9 vs 21.8%), hypertension (60.6 vs 36.0%) and previous stroke (15.2 vs 10.1%). However, they were not more likely to receive bystander cardiopulmonary resuscitation (P = 0.205) or automated external defibrillation (P = 0.980). On univariate analysis, known heart disease was associated with increased survival (unadjusted odds ratio 1.16, 95% confidence interval 1.03–1.30). However, on multivariate analysis, heart disease predicted poorer survival (adjusted odds ratio 0.76, 95% confidence interval 0.58–1.00). Other factors influencing survival corresponded with previous reports.

Conclusions

Known heart disease independently predicted poorer post‐OHCA survival. This study may provide information to guide future prospective studies specifically looking at family education for patients with heart disease and the effect on OHCA outcomes.     

Mouse models in liver cancer research： A review of current literature

Primary liver cancer remains one of the most lethal malignancies worldwide. Due to differences in prevalence of etiological factors the incidence of primary liver cancer varies among the world, with a peak in East-Asia. As this disease is still lethal in most of the cases, research has to be done to improve our understanding of the disease, offering insights for possible treatment options. For this purpose, animal models are widely used, especially mouse models. In this review, we describe the different types of mouse models used in liver cancer research, with emphasis on genetically engineered mice used in this field. We focus on hepatocellular carcinoma （HCC）, as this is by far the most common type of primary liver cancer, accounting for 70%-85% of cases.     

Coronary-cameral fistulas in adults(first of two parts)

This is a case series and review of the literature adding11 new cases.Coronary-cameral fistulas(CCFs)are infrequent anomalies which are in general co-incidentally found during diagnostic coronary angiography(CAG).To delineate the characteristics of congenital and acquired CCFs in adults,we performed a PubMed search for papers dealing with congenital or acquired CCFs in adults.Publications on coronary-vascular fistulas or paediatric subjects were not included.From the world literature,a total of 243 adult patients were identified who had congenital(65%)or acquired(35%)CCFs.In this review,which is part one of a two-part series on CCFs,we describe and discuss the congenital fistulas,give an overview on the published literature and report details of our own series of 11 patients with MMFs and solitary macro CCFs.Of the congenital group,56%were small or large solitary macro CCFs(cut-off 1.5mm)and 9%were coronary artery-ventricular multiple micro-fistulas(MMFs).Apical hypertrophic cardiomyopathy was reported in some of the reviewed subjects with MMFs(3/24=13%)but not was seen in our own series.Conservative medical management was generally the treatment of choice in congenital MMFs;prophylactic implantable cardioverter defibrillators(ICD)were implanted in 2/24(8%)of subjects,especially when extensive micro-fistulisations were involved.None of the patients of our own series required an ICD,as the MMFs were of limited size.Congenital or acquired CCFs in adults are infrequent anomalies having a wide spectrum of clinical presentation may varies from asymptomatic to severely devastating states requiring different treatment modalities.     

Behavior and psychological functioning of young children of HIV-positive mothers in South Africa

Adults with HIV are living longer due to earlier diagnosis and increased access to antiretroviral medications. Therefore, fewer young children are being orphaned and instead, are being cared for by parents who know they are HIV positive, although they may be asymptomatic. Presently, it is unclear whether the psychological functioning of these young children is likely to be affected or, alternatively, whether it is only when a mother is ill, that children suffer adverse effects. We, thus, aimed to compare the behavior and psychological functioning of young children (aged 6–10 years) of HIV-positive and HIV-negative mothers. We also aimed to examine the association between HIV status disclosure and child outcomes. This study uses cross-sectional data from the baseline assessment of a randomized controlled trial conducted in Tshwane, South Africa. Participants (n=509) and their children were recruited from area health clinics. Among the 395 mothers with HIV, 42% reported symptoms of HIV disease. Multivariate linear regression models suggested that after adjusting for socio-demographic characteristics, children of HIV-positive mothers had significantly greater externalizing behaviors than children of HIV-negative mothers. Importantly, children whose mothers were symptomatic had greater internalizing and externalizing behaviors compared with children of HIV-negative mothers, but this was not true for children of asymptomatic mothers. Additionally, among children of HIV-positive mothers, those who had been told their mothers were sick compared with children who had been told nothing had less internalizing and externalizing behaviors and improved daily living skills. This study, therefore, provides evidence that maternal HIV disease can affect the behaviors of young children in South Africa but, importantly, only when the mothers are symptomatic from their disease. Furthermore, results suggest that disclosure of maternal illness but not HIV status was associated with improved behavior and psychological functioning among young children.     

Clinical investigation of human alpha interferon in chronic myelogenous leukemia

Fifty-one patients with previously untreated or minimally treated chronic myelogenous leukemia in chronic phase received human alpha interferon 3 to 9 X 10(6) units intramuscularly (IM) daily until complete hematologic remission, then at doses ranging from 3 X 10(6) units every other day to 9 X 10(6) units daily. Forty-one (80%) patients achieved a hematologic response, 36 (71%) of them attaining a complete hematologic remission with normal peripheral WBC and differential counts. Responding patients showed continuous but slow normalization of several other blood and marrow parameters including platelet counts, serum lactic dehydrogenase and B12 levels, and marrow cellularity and maturation index. Suppression of the Philadelphia chromosome on serial cytogenetic studies of marrow metaphases was documented in 20 of the 36 patients who achieved complete hematologic remission (56%; 39% of total group), eight of whom (22%) had a decrease of the Philadelphia chromosome-positive metaphases to less than 35%. These changes were persistent for 6 months or longer in 18 patients, seven of whom had continuous suppression of the Philadelphia chromosome to less than 90% for a median of 30+ months (range 21+ to 39+ months). After a median follow-up period of 37 months, 25 patients remain in continued disease control with interferon therapy. The projected 3-year survival rate is 76%, with a yearly death rate of 6%, 9%, and 9% in the first 3 years. Response, Philadelphia chromosome suppression, and survival were significantly better among patients in the low-risk category compared to intermediate- and high-risk categories, as defined by a multivariate analysis-derived prognostic model. The projected 3- year survival rate was 94% for patients who achieved a complete hematologic remission on interferon therapy and 45% for those who did not. Thirteen patients have developed blastic crisis, six with lymphoid and three with undifferentiated morphology. We conclude that human leukocyte alpha interferon effectively controls chronic myeloid leukemia and allows reappearance of diploid hemopoietic cells in some patients.     

p16INK4A and p15INK4B gene deletions in primary leukemias

The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene.     

The value of flow cytometric analysis of platelet glycoprotein expression of CD34+ cells measured under conditions that prevent P- selectin-mediated binding of platelets

In the present study, we show by adhesion assays and ultrastructural studies that platelets can bind to CD34+ cells from human blood and bone marrow and that this interaction interferes with the accurate detection of endogenously expressed platelet glycoproteins (GPs). The interaction between these cells was found to be reversible, dependent on divalent cations, and mediated by P-selectin. Enzymatic characterization showed the involvement of sialic acid residues, protein(s). The demonstration of mRNA for the P-selectin glycoprotein ligand 1 (PSGL-1) in the CD34+ cells by polymerase chain reaction (PCR) analysis suggests that this molecule is present in these cells. Under conditions that prevent platelet adhesion, a small but distinct subpopulation of CD34+ cells diffusely expressed the platelet GPIIb/IIIa complex. These cells were visualized by immunochemical studies. Furthermore, synthesis of mRNA for GPIIb and GPIIIa by CD34+ cells was shown using PCR analysis. The semiquantitative PCR results show relatively higher amounts of GPIIb mRNA than of PF4 mRNA in CD34+CD41+ cells in comparison with this ratio in platelets. This finding is a strong indication that the PCR results are not caused by contaminating adhering platelets. MoAbs against GPIa GPIb alpha, GPV, P- selectin, and the alpha-chain of the vitronectin receptor did not react with CD34+ cells. The number of CD34+ cells expressing GPIIb/IIIa present in peripheral blood stem cell (PBSC) transplants was determined and was correlated with platelet recovery after intensive chemotherapy in 27 patients. The number of CD34+CD41+ cells correlated significantly better with the time of platelet recovery after PBSC transplantation (r = .83, P = .04) than did the total number of CD34+ cells (r = .55). Statistical analysis produced a threshold value for rapid platelet recovery of 0.34 x 10(6) CD34+CD41+ cells/kg. This study suggests that if performed in the presence of EDTA the flow cytometric measurement of GPIIb/IIIa on CD34+ cells provides the most accurate indication of the platelet reconstitutive capacity of the PBSC transplant.     

Quantification of the breakpoint cluster region rearrangement for clinical monitoring in Philadelphia chromosome-positive chronic myeloid leukemia

The purpose of this report was to evaluate scintigraphy analysis of Southern blot hybridization as a method to quantify the breakpoint cluster region (BCR) rearrangement of Philadelphia chromosome (Ph)+ chronic myelogenous leukemia (CML). Cytogenetic and molecular studies performed simultaneously on 474 bone marrow and/or blood samples from 300 patients treated with alpha-interferon-based therapy were compared. Molecular results were expressed as the percentage of rearranged BCR bands versus the total scintigraphic signal. The percentage of Ph+ metaphases was calculated on 25 metaphases. The results of molecular studies obtained on both peripheral blood and bone marrow samples were identical. The rank correlation between the BCR quantification and the percentage of Ph positivity in 465 samples was excellent (r = .78). However, of 99 samples with a normal karyotype, 24% had a BCR rearrangement. Of 86 samples with no BCR rearrangement, 13% showed a Ph chromosome. Of 49 samples with partial cytogenetic remission (Ph+ metaphases, 1% to 34%), 23% had no BCR rearrangement. In samples with a minor or no cytogenetic response (Ph+ metaphases, > 34%), BCR analysis overestimated the degree of response in 73 of 326 samples (22%). Nevertheless, survival analysis by BCR quantification level showed statistically better outcome for patients in complete or partial molecular response (P < .01). Molecular quantification of BCR was useful in monitoring the course of Ph+ CML. This method, which can be used on peripheral blood, detected residual disease not shown by cytogenetic analysis and was prognostically relevant as a measure of disease suppression.     

Collagen-induced arthritis in rhesus monkeys: evaluation of markers for inflammation and joint degradation

The objective of this study was to analyse parameters in rhesus monkey collagen-induced arthritis (CIA) with which the inflammation and destruction of the joints can be described in quantitative terms. CIA was induced in genetically susceptible and resistant monkeys, which can be distinguished on the basis of the dominant resistance marker Mamu- A26. The disease course was monitored daily using a semiquantitative scoring system. Plasma samples were collected once or twice weekly and analysed for C-reactive protein (CRP). Urines were collected overnight once a week and analysed for excretion rates of the collagen cross- links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). The results show that periods of active CIA are characterized by substantial weight loss and increased plasma CRP levels, followed shortly thereafter by increased excretion rates of the collagen cross- links HP and LP. Remission of the disease can be recognized by a decline in plasma CRP levels and especially an increase in body weight. The highest CRP levels were found in the most severely arthritic monkeys, indicating a possible relationship of the absolute plasma CRP levels to the severity of inflammation. During periods of active arthritis, increased excretion rates of collagen cross-links HP and LP in the urine were found. In particular, the major collagen cross-link in articular cartilage, HP, showed a strong increase (9- to 15-fold). The excretion rates of LP, which is considered as a bone-specific degradation marker, only increased 4- to 6-fold, thus indicating predominant destruction of cartilage and less of bone. In conclusion, the severity of CIA can be monitored in a quantitative manner using plasma CRP levels, urinary excretion rates of HP and LP, and body weights, superimposed on semiquantitative clinical scores. The parameters also facilitate a more objective assessment of the effect of anti-arthritic drugs in the model than with the clinical scores alone.