Adjuvant Use of Ivabradine in Acute Heart Failure due to Myocarditis

We report two cases of young men in whom acute heart failure due to myocarditis was diagnosed. The patients had been transferred to the intensive care unit (ICU) with commencing symptoms of acute heart failure and consecutive multiorgan failure for further treatment and to evaluate the indication for implantation of a ventricular assist device or for high urgent orthotopic heart transplantation. In both patients, the If-channel inhibitor ivabradine was administered off-label to provide selective heart rate reduction, and thus support hemodynamic stabilization. Though currently considered off-label use in patients suffering from severe hypotension and acute heart failure, the use of ivabradine may beneficially influence outcome by allowing optimization of the patient's heart rate concomitant to initial measures of clinical stabilization

Correlation of EGFR expression, gene copy number and clinicopathological status in NSCLC

Background: Epidermal Growth Factor Receptor (EGFR) targeting therapies are currently of great relevance for the treatment of lung cancer. For this reason, in addition to mutational analysis immunohistochemistry (IHC) of EGFR in lung cancer has been discussed for the decision making of according therapeutic strategies. The aim of this study was to obtain standardization of EGFR-expression methods for the selection of patients who might benefit of EGFR targeting therapies. Methods: As a starting point of a broad investigation, aimed at elucidating the expression of EGFR on different biological levels, four EGFR specific antibodies were analyzed concerning potential differences in expression levels by Immunohistochemistry (IHC) and correlated with fluorescence in situ hybridization (FISH) analysis and clinicopathological data. 206 tumor tissues were analyzed in a tissue microarray format employing immunohistochemistry with four different antibodies including Dako PharmDx kit (clone 2-18C9), clone 31G7, clone 2.1E1 and clone SP84 using three different scoring methods. Protein expression was compared to FISH utilizing two different probes. Results: EGFR protein expression determined by IHC with Dako PharmDx kit, clone 31G7 and clone 2.1E1 (≤ 0.05) correlated significantly with both FISH probes independently of the three scoring methods; best correlation is shown for 31G7 using the scoring method that defined EGFR positivity when ≥ 10% of the tumor cells show membranous staining of moderate and severe intensity (p = 0.001). Conclusion: Overall, our data show differences in EGFR expression determined by IHC, due to the applied antibody. Highest concordance with FISH is shown for antibody clone 31G7, evaluated with score B (p = 0.001). On this account, this antibody clone might by utilized for standard evaluation of EGFR expression by IHC

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) in association with an adenocarcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder and information on this disease is limited, especially with regard to its management and prognosis. It has become generally accepted that DIPNECH is a precursor lesion to pulmonary carcinoid tumors.</p> <p>Case presentation</p> <p>Here we report on a 60-year-old female patient with DIPNECH and an associated pulmonary adenocarcinoma.</p> <p>Conclusion</p> <p>This case contributes to a better understanding of the disorder and its associated pathologies.</p

Simultaneous computed tomography-guided biopsy and radiofrequency ablation of solitary pulmonary malignancy in high-risk patients

Background: In recent years experience has been accumulated in percutaneous radiofrequency ablation (RFA) of lung malignancies in nonsurgical patients. Objectives: In this study, we retrospectively evaluated a simultaneous diagnostic and therapeutic approach including CT-guided biopsy followed immediately by RFA of solitary malignant pulmonary lesions. Methods: CT-guided transthoracic core needle biopsy of solitary pulmonary lesions suspicious for malignancy was performed and histology was proven based on immediate frozen sections. RFA probes were placed into the pulmonary tumors under CT guidance and the ablation was performed subsequently. The procedure-related morbidity was analyzed. Follow-up included a CT scan and pulmonary function parameters. Results: A total of 33 CT-guided biopsies and subsequent RFA within a single procedure were performed. Morbidity of CT-guided biopsy included pulmonary hemorrhage (24%) and a mild pneumothorax (12%) without need for further interventions. The RFA procedure was not aggravated by the previous biopsy. The rate of pneumothorax requiring chest tube following RFA was 21%. Local tumor control was achieved in 77% with a median follow-up of 12 months. The morbidity of the CT-guided biopsy had no statistical impact on the local recurrence rate. Conclusions: The simultaneous diagnostic and therapeutic approach including CT-guided biopsy followed immediately by RFA of solitary malignant pulmonary lesions is a safe procedure. The potential of this combined approach is to avoid unnecessary therapies and to perform adequate therapies based on histology. Taking the local control rate into account, this approach should only be performed in those patients who are unable to undergo or who refuse surgery. Copyright (C) 2012 S. Karger AG, Base

Crustal structure of the Niuafo’ou Microplate and Fonualei Rift and Spreading Center in the northeastern Lau Basin, Southwestern Pacific

Key points: First insights into the crustal structure of the northeastern Lau Basin, along a 290 km transect at 17°20’S. Crust in southern Fonualei Rift and Spreading Center was created by extension of arc crust and variable amount of magmatism. Magmatic underplating is present in some parts of the southern Niuafo’ou Microplate The northeastern Lau Basin is one of the fastest opening and magmatically most active back‐arc regions on Earth. Although the current pattern of plate boundaries and motions in this complex mosaic of microplates is reasonably understood, the internal structure and evolution of the back‐arc crust are not. We present new geophysical data from a 290 km long east‐west oriented transect crossing the Niuafo’ou Microplate (back‐arc), the Fonualei Rift and Spreading Centre (FRSC) and the Tofua Volcanic Arc at 17°20’S. Our P‐wave tomography model and density modelling suggests that past crustal accretion inside the southern FRSC was accommodated by a combination of arc crustal extension and magmatic activity. The absence of magnetic reversals inside the FRSC supports this and suggests that focused seafloor spreading has until now not contributed to crustal accretion. The back‐arc crust constituting the southern Niuafo’ou Microplate reveals a heterogeneous structure comprising several crustal blocks. Some regions of the back‐arc show a crustal structure similar to typical oceanic crust, suggesting they originate from seafloor spreading. Other crustal blocks resemble a structure that is similar to volcanic arc crust or a ‘hydrous’ type of oceanic crust that has been created at a spreading center influenced by slab‐derived water at distances < 50 km to the arc. Throughout the back‐arc region we observe a high‐velocity (Vp 7.2‐7.5 km s‐1) lower crust, which is an indication for magmatic underplating, which is likely sustained by elevated upper mantle temperatures in this region

Invasive Aspergillus fumigatus infection after Plasmodium falciparum malaria in an immuno-competent host: Case report and review of literature

Invasive fungal infection is rarely reported in association with malaria, even though malaria-associated inhibition of phagocyte function is a well-known condition. Invasive aspergillosis is frequently found in severely immuno-compromised patients but not in healthy individuals. Here, a case of pulmonary invasive aspergillosis in a previously healthy patient with severe P. falciparum malaria is presented, who was successfully treated with voriconazol and caspofungin. This is the first survival of malaria-associated invasive aspergillosis

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Hypoxic Epithelial Necrosis Triggers Neutrophilic Inflammation via IL-1 Receptor Signaling in Cystic Fibrosis Lung Disease

Rationale: In many organs, hypoxic cell death triggers sterile neutrophilic inflammation via IL-1R signaling. Although hypoxia is common in airways from patients with cystic fibrosis (CF), its role in neutrophilic inflammation remains unknown. We recently demonstrated that hypoxic epithelial necrosis caused by airway mucus obstruction precedes neutrophilic inflammation in Scnn1b-transgenic (Scnn1b-Tg) mice with CF-like lung disease

RANTES/CCL5 and risk for coronary events:Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years). Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (&gt;22,000 cases, &gt;60,000 controls), none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years). Conclusions: High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes and (iii) RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a novel coronary risk biomarker. However, the potential relevance of RANTES levels in platelet-poor plasma needs to be investigated in further studies.</p