Centromedial amygdala is more relevant for phobic confrontation relative to the bed nucleus of stria terminalis in patients with spider phobia.

Recent studies indicate differential involvement of the centromedial amygdala (CM) and the bed nucleus of the stria terminalis (BNST) during processing (anticipation and confrontation) of threat stimuli. Here, temporal predictability was shown to be a relevant factor. In this study, we want to investigate the relevance of these effects, which were found in healthy subjects, for anxiety disorders. Therefore, we investigated the differential involvement of CM and BNST in the anticipation and confrontation of phobic stimuli under variation of temporal predictability in spider phobia. 21 patients with spider phobia and 21 healthy controls underwent a temporally predictable/unpredictable phobic and neutral anticipation and confrontation paradigm using functional magnetic resonance imaging (fMRI) and ROI analyses. During the anticipation phase, healthy controls showed higher CM and BNST activity during the predictable compared with the unpredictable condition compared with the anxiety patients. During a confrontation phase that followed the anticipation phase, CM was more activated than BNST during the phobic compared with the neutral confrontation. While this effect was independent of threat predictability in patients, healthy controls showed higher activation in the CM compared with the BNST only during the predictable spider confrontation compared with the predictable bird confrontation. The results contribute to a better understanding of the separate roles of the CM and BNST during phobic processes. The CM was found to be more relevant to phobic confrontation in patients with spider phobia compared with the BNST.

Differential prognostic accuracy of right ventricular dysfunction, the Seattle heart failure model and the MAGGIC score in patients with severe mitral regurgitation undergoing the MitraClip® procedure.

BACKGROUND: MitraClip ® (MC) is an established procedure for severe mitral regurgitation (MR) in patients deemed unsuitable for surgery.Right ventricular dysfunction (RVD) is associated with a higher mortality risk. The prognostic accuracy of heart failure risk scores like the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in pts undergoing MC with or without RVD has not been investigated so far. METHODS: SHFM and MAGGIC score were calculated retrospectively. RVD was determined as tricuspid annular plane systolic excursion (TAPSE) ≤15 mm. Area under receiver operating curves (AUROC) of SHFM and MAGGIC were performed for one-year all-cause mortality after MC. RESULTS: N = 103 pts with MR III° (73 ± 11 years, LVEF 37 ± 17%) underwent MC with a reduction of at least I° MR. One-year mortality was 28.2%.In Kaplan-Meier analysis, one- year mortality was significantly higher in RVD-pts (34.8% vs 2.8%, p = 0.009).Area under the Receiver Operating Characteristic (AUROC) for SHFM and MAGGIC were comparable for both scores (SHFM: 0.704, MAGGIC: 0.692). In pts without RVD, SHFM displayed a higher AUROC and therefore better diagnostic accuracy (SHFM: 0.776; MAGGIC: 0.551, p < 0.05). In pts with RVD, MAGGIC and SHFM displayed comparable AUROCs. CONCLUSION: RVD is an important prognostic marker in pts undergoing MC. SHFM and MAGGIC displayed adequate over-all prognostic power in these pts. Accuracy differed in pts with and without RVD, indicating higher predictive power of the SHFM score in pts without RVD.

[Early onset pneumonia after successful resuscitation : Incidence after mild invasive hypothermia therapy]. / Early-onset-Pneumonien nach prähospitaler Reanimation : Inzidenz nach milder intravasaler Hypothermiebehandlung.

BACKGROUND: Targeted temperature management (TTM) represents an effective therapy to improve neurologic outcome in patients who survive an out-of-hospital cardiac arrest (OHCA). First publications about this therapy reported a higher incidence of infections in patients who underwent TTM induced by external cooling devices. Whether intravascular cooling devices are also associated with an increased infection rate has not been investigated so far. METHODS: In a single center retrospective study, the incidence of early onset pneumonia (EOP) in OHCA patients with or without intravascular TTM at 33 °C target temperature for 24 h who survived at least 24 h after admission was analyzed. RESULTS: A total of 68 OHCA survivors (mean age 65 ± 15 years) were included in this analysis. The most common causes of OHCA were myocardial infarction (35 %), primary ventricular fibrillation (24 %), asystole (15 %), and pulmonary embolism (7 %). Of those, 32 patients (48 %) received TTM. The overall incidence of EOP was 38 %. Incidence of EOP did not differ significantly between groups, was more frequent in the group without TTM (42 % vs. 34 %, p = 0.57) and had no impact on mortality (hazard ratio = 1.02; 95 % confidence interval 0.25-4.16; p = 0.97). CONCLUSION: Intravascular TTM at 33 °C with a cooling catheter is not associated with more infective complications in OHCA patients. This finding underscores the safety of TTM.

[Aspiration and pneumonia risk after preclinical invasive resuscitation: Endotracheal intubation and supraglottic airway management with the laryngeal tube S]. / Aspirations- und Pneumonierisiko nach präklinischer invasiver Beatmung : Endotracheale Intubation und supraglottische Atemwegssicherung mittels Larynxtubus S.

BACKGROUND: Laryngeal tubes (LT) have substantially facilitated emergency airway management. However, it remains unclear whether LTs provide comparable protection against aspiration or even higher rates of aspiration and pneumonia compared to endotracheal intubation (ET) as the former gold standard. METHODS: The indices for aspiration and early onset pneumonia in patients after preclinical airway management by either LT or ET were retrospectively analyzed. Furthermore, in-hospital mortality was analyzed. RESULTS: A total of 90 patients with invasive ventilation by either ET (n = 69) or LT (n = 21) were analyzed. Patients were excluded if indication for ventilation was pneumonia, aspiration, drowning, or if they had preexisting tracheotomy. The ET and LT groups did not differ regarding age (ET: 62 ± 16 years, LT: 64 ± 8 years, p = 0.56), female gender (ET: 23.2%, LT: 33.3%, p = 0.25), or first paO2/FIO2 (ET: 300 ± 164, LT: 342 ± 178, p = 0.3). The majority of patients were survivors of out-of-hospital cardiac arrest (OHCA, 72.2%), with a significantly higher OHCA rate in the LT group (LT: 95.2% ET: 65.2%, p = 0.006). Analysis for radiological or endoscopic evidence of pulmonary aspiration revealed a higher aspiration rate in the ET group (43.5%, LT: 23.8%, p = 0.08), especially after OHCA (ET: 48.9%, LT: 20%, p = 0.025). In parallel, early onset pneumonia as a correlate for microaspiration in patients without evident aspiration was observed more frequently in ET patients (41% vs. 25%, p = 0.21). In OHCA patients without aspiration, rates of pneumonia were similar (ET: 26.1%, LT: 25%; p = 0.62). Analysis of in-hospital mortality showed significantly higher mortality in the LT group (57.1% vs 30.4%, p = 0.026). Also in OHCA patients, higher mortality was observed in the LT group (60 vs. 28.9%, p = 0.018). DISCUSSION AND CONCLUSION: Airway management by LT was not associated with higher risk of aspiration. In contrast, higher rates of aspiration and pneumonia were observed after ET, especially in OHCA patients. However, a possible prognostic impact of supraglottic airway devices remains to be elucidated.

An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy.

AIM/HYPOTHESIS: Monocytes/macrophages play important roles in adipose and vascular tissues and can be polarised as inflammatory M1 or anti-inflammatory M2. We sought to analyse monocyte polarisation status in type 2 diabetes, which is characterised by chronic inflammation. METHODS: We enrolled 60 individuals without diabetes and 53 patients with type 2 diabetes. We quantified standard monocyte subsets defined by cluster of differentiation (CD)14 and CD16. In addition, based on the phenotype of polarised macrophages in vitro, we characterised and quantified more definite M1 (CD68(+)CCR2(+)) and M2 (CX3CR1(+)CD206(+)/CD163(+)) monocytes. We also analysed bone marrow (BM) samples and the effects of granulocyte-colony stimulating factor (G-CSF) stimulation in diabetic and control individuals. RESULTS: We found no alterations in standard monocyte subsets (classical, intermediate and non-classical) when comparing groups. For validation of M1 and M2 phenotypes, we observed that M2 were enriched in non-classical monocytes and had lower TNF-α content, higher LDL scavenging and lower transendothelial migratory capacity than M1. Diabetic patients displayed an imbalanced M1/M2 ratio compared with the control group, attributable to a reduction in M2. The M1/M2 ratio was directly correlated with waist circumference and HbA1c and, among diabetic patients, M2 reduction and M1/M2 increase were associated with microangiopathy. A decrease in M2 was also found in the BM from diabetic patients, with a relative M2 excess compared with the bloodstream. BM stimulation with G-CSF mobilised M2 macrophages in diabetic but not in healthy individuals. CONCLUSIONS/INTERPRETATION: We show that type 2 diabetes markedly reduces anti-inflammatory M2 monocytes through a dysregulation in bone-marrow function. This defect may have a negative impact on microangiopathy.

[Veno-arterial ECMO as bridge to recovery. Cardiogenic shock and suspected myocarditis in a 37-year-old patient]. / Venoarterielle ECMO als "bridge to recovery". Kardiogener Schock und Verdacht auf Myokarditis bei einer 37-Jährigen.

We report a case of a 37-year-old patient presenting with fulminant cardiogenic shock, almost noncontractile ventricles, followed by electromechanical dissociation. During performance of cardiopulmonary resuscitation, a veno-arterial extracorporeal membrane oxygenation device (VA ECMO) was implanted, which became necessary for 13 days. Subsequently, a total arrest of ventricular function was observed and prominent multiple organ failure emerged. A rapid test for respiratory syncytial virus was positive, supporting the suspected diagnosis of myocarditis. Despite numerous complications, complete recovery was achieved.

[Ultrasound-guided central venous access in adults and children: Procedure and pathological findings]. / Ultraschallgestützte zentrale Venenpunktion bei Erwachsenen und Kindern : Verfahren und pathologische Befunde.

Central venous line placement is a standard procedure in critical care and peri-operative medicine. This procedure can be associated with severe complications. In contrast to the landmark technique, ultrasound-guided punctures can significantly reduce the rate of complications. Patients with a high risk for difficult vascular access include critical care and emergency patients as well as patients on anticoagulation medication and dialysis. Placement of central venous catheters can be difficult in ventilated patients and if there has been prior surgery in the puncture area. In children and small infants central venous access can also be challenging due to the anatomical relationship in the head and neck region. Puncture techniques are explained briefly by means of ultrasound anatomy. Typical ultrasonographic images visualize pathological findings in order to identify dangers and complications in central venous catheterization.

Platelet-derived growth factor activates production of reactive oxygen species by NAD(P)H oxidase in smooth muscle cells through Gi1,2.

Recent findings indicate that platelet-derived growth factor (PDGF) plays a role in the generation of reactive oxygen species (ROS) as second messengers in smooth muscle cells (SMC). To identify the source and signal transduction pathway of ROS formation in SMC, we investigated PDGF-induced ROS formation. Stimulation of SMC with PDGF resulted in a rapid increase of ROS production. Using an inactivating antibody, we identified the increase to be dependent on p22phox, a NAD(P)H-oxidase subunit. ROS release was completely inhibited by the Gi protein inhibitor PTX as well as an antibody against Galphai1,2, however, not by antibodies against Galphai3/0, Gas, and Gbeta1beta2. The effect of PDGF on ROS production in SMC membranes could likewise be mimicked by the use of a recombinant Galphai2 subunit but not by Galphai3, Galphai0, Gas, and Gbetagamma subunits. Immunoaffinity chromatography demonstrated coupling of Galphai1,2 to the PDGF a-receptor, which, after preincubation of the SMC membranes with PDGF, was increased in the absence of GTPgammaS but decreased in the presence of GTPgammaS and prevented by PTX treatment. These data define a novel G protein-dependent mechanism by which PDGF signaling is transduced through direct coupling of the Gai1,2 subunit of the trimeric G proteins to the PDGF tyrosine kinase receptor.

Fibrinogen induces chemotactic activity in endothelial cells.

Chemotaxis of blood monocytes into the vessel wall together with the change of the relative content of the extracellular matrix (ECM) proteins at sites of predilection is an early cellular marker of atherogenesis. To examine the influence of ECM proteins on secretion of chemoattractants by endothelial cells (EC), porcine EC were seeded on gelatin (G), fibronectin (Fn) and fibrinogen (Fg). After 24 h cells seeded on G and Fn showed the histiotypic 'cobblestone'-morphology whereas cells seeded on Fg did not. Chemotactic activity for monocytes in supernatants from cells seeded on Fg was more than two-fold higher compared with G and was independent of soluble Fn or Fg in the supernatant. Quantification of monocyte chemoattracting protein-1, PDGF-AB and IL-8 in EC supernatants showed that Fg led to a significant increase in secretion of all three proteins compared with cells cultured on G. Preincubation of porcine EC with the tripeptide arginine-glycine-aspartic acid, as inhibitor of binding of Fg to integrin receptors, but not with the control tripeptide arginine-glycine-glutamic acid showed a decrease in chemotactic activity for cells cultured on Fg but not on Fn or G. Inhibition of protein kinase C (PKC) activity in EC by GF109203 resulted in a decrease of fibrinogen-induced chemotactic activity. Also the tyrosine-kinase inhibitor herbimycin inhibited fibrinogen mediated secretion of chemokines. The role of the PKC pathway for matrix mediated signal transduction is further corroborated by Fg-dependent induction of the PKC isoform delta. These data indicate an integrin-dependent signal transduction pathway leading to induction of chemotactic activity by the ECM protein fibrinogen. This mechanism may contribute to induction of chemokines in early atherosclerotic lesions.