Prognostic value of simple frailty and malnutrition screening tools in patients with acute heart failure due to left ventricular systolic dysfunction

Background: Frailty and malnutrition are common in patients with heart failure (HF), and are associated with adverse outcomes. We studied the prognostic value of three malnutrition and three frailty indices in patients admitted acutely to hospital with HF. Methods: 265 consecutive patients [62% males, median age 80 (interquartile range (IQR): 72–86) years, median NTproBNP 3633 (IQR: 2025–6407) ng/l] admitted with HF between 2013 and 2014 were enrolled. Patients were screened for frailty using the Derby frailty index (DFI), acute frailty network (AFN) frailty criteria, and clinical frailty scale (CFS) and for malnutrition using the geriatric nutritional risk index (GNRI), controlling nutritional status (CONUT) score and prognostic nutritional index (PNI). Results: According to the CFS (> 4), DFI, and AFN, 53, 50, and 53% were frail, respectively. According to the GNRI (≤ 98), CONUT score (> 4), and PNI (≤ 38), 46, 46, and 42% patients were malnourished, respectively. During a median follow-up of 598 days (IQR 319–807 days), 113 patients died. One year mortality was 1% for those who were neither frail nor malnourished; 15% for those who were either malnourished or frail; and 65% for those who were both malnourished and frail. Amongst the malnutrition scores, PNI, and amongst the frailty scores, CFS increased model performance most compared with base model. A final model, including CFS and PNI, increased c-statistic for mortality prediction from 0.68 to 0.84. Conclusion: Worsening frailty and malnutrition indices are strongly related to worse outcome in patients hospitalised with HF

Budd-Chiari Syndrome: Long term success via hepatic decompression using transjugular intrahepatic porto-systemic shunt

<p>Abstract</p> <p>Background</p> <p>Budd-Chiari syndrome (BCS) generally implies thrombosis of the hepatic veins and/or the intrahepatic or suprahepatic inferior vena cava. Treatment depends on the underlying cause, the anatomic location, the extent of the thrombotic process and the functional capacity of the liver. It can be divided into medical treatment including anticoagulation and thrombolysis, radiological procedures such as angioplasty and transjugular intrahepatic porto-systemic shunt (TIPS) and surgical interventions including orthotopic liver transplantation (OLT). Controlled trials or reports on larger cohorts are limited due to rare disease frequency. The aim of this study was to report our single centre long term results of patients with BCS receiving one of three treatment options i.e. medication only, TIPS or OLT on an individually based decision of our local expert group.</p> <p>Methods</p> <p>20 patients with acute, subacute or chronic BCS were treated between 1988 and 2008. Clinical records were analysed with respect to underlying disease, therapeutic interventions, complications and overall outcome.</p> <p>Results</p> <p>16 women and 4 men with a mean age of 34 ± 12 years (range: 14-60 years) at time of diagnosis were included. Myeloproliferative disorders or a plasmatic coagulopathy were identified as underlying disease in 13 patients, in the other patients the cause of BCS remained unclear. 12 patients presented with an acute BCS, 8 with a subacute or chronic disease. 13 patients underwent TIPS, 4 patients OLT as initial therapy, 2 patients required only symptomatic therapy, and one patient died from liver failure before any specific treatment could be initiated. Eleven of 13 TIPS patients required 2.5 ± 2.4 revisions (range: 0-8). One patient died from his underlying hematologic disease. The residual 12 patients still have stable liver function not requiring OLT. All 4 patients who underwent OLT as initial treatment, required re-OLT due to thrombembolic complications of the graft. Survival in the TIPS group was 92.3% and in the OLT group 75% during a median follow-up of 4 and 11.5 years, respectively.</p> <p>Conclusion</p> <p>Our results confirm the role of TIPS in the management of patients with acute, subacute and chronic BCS. The limited number of patients with OLT does not allow to draw a meaningful conclusion. However, the underlying disease may generate major complications, a reason why OLT should be limited to patients who cannot be managed by TIPS.</p

Psychosocial adaptation of adolescent migrants in a Swiss community survey

OBJECTIVE: The aim of this study was to compare psychosocial adaptation in adolescent (first generation) migrants, double-citizens (mainly second generation with one migrant parent), and native Swiss, and to compare migrants from various European regions. METHOD: Data from a community survey were based on 1,239 participants (mean age 13.8, SD = 1.6 years) with 996 natives, 55 double-citizens, and 188 migrants. The adolescents completed the youth self-report measuring emotional and behavioural problems, and various questionnaires addressing life events, personality variables, perceived parental behaviour (PPB), family functioning, school environment, and social network. RESULTS: Adolescent migrants had significantly higher scores for internalizing and externalizing problems. There was a pattern of various unfavourable psychosocial features including life events, coping, self-related cognitions, and PPB that was more common among adolescent migrants than natives. Double-citizens were similar to natives in all domains. Young adolescents from South and South-East Europe differed from natives in terms of more unfavourable psychosocial features. Migrant status was best predicted by adverse psychosocial features rather than emotional and behavioural problems. CONCLUSION: There is some indication that certain migrant adolescents are at risk of psychosocial mal-adaptation. Obviously, ethnic origin is an important moderator

Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in breast cancer.</p> <p>Methods</p> <p>The expression levels of TLR3, TLR4 and TLR9 were analyzed on tumors from 74 patients with breast cancer. The analysis was performed by immunohistochemistry.</p> <p>Results</p> <p>Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4 and TLR9. Tumors showed high expression of TLRs expression levels by cancer cells, especially TLR4 and 9. Nevertheless, a significant percentage of tumors also showed TLR4 expression by mononuclear inflammatory cells (21.6%) and TLR9 expression by fibroblast-like cells (57.5%). Tumors with high TLR3 expression by tumor cell or with high TLR4 expression by mononuclear inflammatory cells were significantly associated with higher probability of metastasis. However, tumours with high TLR9 expression by fibroblast-like cells were associated with low probability of metastasis.</p> <p>Conclusions</p> <p>The expression levels of TLR3, TLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness in breast cancer. TLRs may represent therapeutic targets in breast cancer.</p

Genetic and environmental influences on the stability of withdrawn behavior in children: A longitudinal, multi-informant twin study.

We examined the contribution of genetic and environmental influences on the stability of withdrawn behavior (WB) in childhood using a longitudinal multiple rater twin design. Maternal and paternal ratings on the withdrawn subscale of the Child Behavior Checklist (CBCL) were obtained from 14,889 families when the twins were 3, 7, 10 and 12 years old. A longitudinal psychometric model was fitted to the data and the fit of transmission and common factor models were evaluated for each variance component. WB showed considerable stability throughout childhood, with correlation coefficients ranging from about .30 for the 9-year time interval to .65 for shorter time intervals. Individual differences in WB as observed by the mother and the father were found to be largely influenced by genetic effects at all four time points, in both boys (50–66%) and girls (38–64%). Shared environmental influences explained a small to modest proportion (0–24%) of the variance at all ages and were slightly more pronounced in girls. Non-shared environmental influences were of moderate importance to the variance and slightly increased with age, from 22–28% at age 3 to 35–41% at age 12 years. The stability of WB was largely explained by genetic effects, accounting for 74% of stability in boys and 65% in girls. Shared environmental effects explained 7% (boys) and 17% (girls) of the behavioral stability. Most shared environmental effects were common to both raters, suggesting little influence of rater bias in the assessment of WB. The shared environmental effects common to both raters were best described by a common factor model, indicating that these effects are stable and persistent throughout childhood. Non-shared environmental effects accounted for the remaining covariance over time

The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells

The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR) as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNα treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner, inducing phosphorylation of the protein synthesis translation initiation factor eIF-2α and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNα combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug

Host Cell Invasion and Virulence Mediated by Candida albicans Ssa1

Candida albicans Ssa1 and Ssa2 are members of the HSP70 family of heat shock proteins that are expressed on the cell surface and function as receptors for antimicrobial peptides such as histatins. We investigated the role of Ssa1 and Ssa2 in mediating pathogenic host cell interactions and virulence. A C. albicans ssa1Δ/Δ mutant had attenuated virulence in murine models of disseminated and oropharyngeal candidiasis, whereas an ssa2Δ/Δ mutant did not. In vitro studies revealed that the ssa1Δ/Δ mutant caused markedly less damage to endothelial cells and oral epithelial cell lines. Also, the ssa1Δ/Δ mutant had defective binding to endothelial cell N-cadherin and epithelial cell E-cadherin, receptors that mediate host cell endocytosis of C. albicans. As a result, this mutant had impaired capacity to induce its own endocytosis by endothelial cells and oral epithelial cells. Latex beads coated with recombinant Ssa1 were avidly endocytosed by both endothelial cells and oral epithelial cells, demonstrating that Ssa1 is sufficient to induce host cell endocytosis. These results indicate that Ssa1 is a novel invasin that binds to host cell cadherins, induces host cell endocytosis, and is critical for C. albicans to cause maximal damage to host cells and induce disseminated and oropharyngeal disease

Contrasting Roles for TLR Ligands in HIV-1 Pathogenesis

The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs). Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs) 5 and 9, we examined their effect on human immunodeficiency virus (HIV)-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist) treatment enhanced replication of CC chemokine receptor 5 (CCR 5)-tropic and CXC chemokine receptor 4 (CXCR4)-tropic HIV-1, treatment with oligodeoxynucleotide (ODN) M362 (TLR9 agonist) suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD) 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA)-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention

ICAR: endoscopic skull‐base surgery

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