Bleeding Duodenal Ulcer: Strategies in High-Risk Ulcers.

BACKGROUND: Acute peptic ulcer bleeding is still a major reason for hospital admission. Especially the management of bleeding duodenal ulcers needs a structured therapeutic approach due to the higher morbidity and mortality compared to gastric ulcers. Patient with these bleeding ulcers are often in a high-risk situation, which requires multidisciplinary treatment. SUMMARY: This review provides a structured approach to modern management of bleeding duodenal ulcers and elucidates therapeutic practice in high-risk situations. Initial management including pharmacologic therapy, risk stratification, endoscopy, surgery, and transcatheter arterial embolization are reviewed and their role in the management of bleeding duodenal ulcers is critically discussed. Additionally, a future perspective regarding prophylactic therapeutic approaches is outlined. KEY MESSAGES: Beside pharmacotherapeutic and endoscopic advances, bleeding management of high-risk duodenal ulcers is still a challenge. When bleeding persists or rebleeding occurs and the gold standard endoscopy fails, surgical and radiological procedures are indicated to manage ulcer bleeding. Surgical procedures are performed to control hemorrhage, but they are still associated with a higher morbidity and a longer hospital stay. In the meantime, transcatheter arterial embolization is recommended as an alternative to surgery and more often replaces surgery in the management of failed endoscopic hemostasis. Future studies are needed to improve risk stratification and therefore enable a better selection of high-risk ulcers and optimal treatment. Additionally, the promising approach of prophylactic embolization in high-risk duodenal ulcers has to be further investigated to reduce rebleeding and improve outcomes in these patients.

[What Do Young Surgeons Want? Modern Requirements for Senior Surgeons]. / Was wollen die jungen Chirurgen? Moderne Anforderungen an chirurgische Chefs.

Due to the shortage of surgical specialists, the question arises as to what surgical residents want and how the fascination of general and visceral surgery may be highlighted. The surgical working group "Young Surgeons" (CAJC) of the German Society for General and Visceral Surgery (DGAV) has organised and subdivided the aspects of an attractive surgical workplace and provides solutions. On the one hand, there is the structured and transparent residency which includes a defined curriculum, assistance of sub-steps during surgery, residency dialogues held on a regular basis, logbooks, the possibility of training and simulation in the clinic as well as permission to participate in further education and training. This has to go hand in hand with a "livable surgery" that is characterised by the compatibility of family and work, better planning of the routine in the clinic, a positive feedback culture, work-life balance, new work (time) models and more time for teaching and research. For many of these aspects, the head of surgery has to be the central role model to initiate structural changes in the clinic, especially as many of these key points may be easily implemented. In this way, the attraction of surgery can be rapidly enhanced and a "livable surgery" may be lived.

Prophylactic Transcatheter Arterial Embolization After Successful Endoscopic Hemostasis in the Management of Bleeding Duodenal Ulcer.

GOALS: The aim of this study was to demonstrate the new strategy of prophylactic transcatheter arterial embolization (TAE) of the gastroduodenal artery after endoscopic hemostasis of bleeding duodenal ulcers. BACKGROUND: TAE is a well-established method for the treatment of recurrent or refractory ulcer bleeding resistant to endoscopic intervention, which increasingly replaces surgical procedures. A new approach for improving outcome and reducing rebleeding episodes is the supplemental and prophylactic TAE after successful endoscopic hemostasis. STUDY: This retrospective study included all patients (n=117) treated from 2008 to 2012 for duodenal ulcer bleeding. After initial endoscopic hemostasis, patients were assessed regarding their individual rebleeding risk. Patients with a low rebleeding risk (n=47) were conservatively treated, patients with a high risk for rebleeding (n=55) had prophylactic TAE of the gastroduodenal artery, and patients with endoscopically refractory ulcer bleeding received immediate TAE. RESULTS: The technical success of prophylactic TAE was 98% and the clinical success was 87% of cases. Rebleeding occurred in 11% of patients with prophylactic TAE and was successfully treated with repeated TAE or endoscopy. The major complication rate was 4%. Surgery was necessary in only 1 prophylactic TAE patient (0.9%) during the whole study period. Mortality associated with ulcer bleeding was 4% in patients with prophylactic TAE. CONCLUSIONS: Prophylactic TAE in patients with duodenal ulcers at high risk for rebleeding was feasible, effective at preventing the need for surgery, and had low major complication rates. Given these promising outcomes, prophylactic TAE should be further evaluated as a preventative therapy in high-risk patients.

A molecular switch between the outer and the inner vestibules of the voltage-gated Na+ channel.

Voltage-gated ion channels are transmembrane proteins that undergo complex conformational changes during their gating transitions. Both functional and structural data from K(+) channels suggest that extracellular and intracellular parts of the pore communicate with each other via a trajectory of interacting amino acids. No crystal structures are available for voltage-gated Na(+) channels, but functional data suggest a similar intramolecular communication involving the inner and outer vestibules. However, the mechanism of such communication is unknown. Here, we report that amino acid Ile-1575 in the middle of transmembrane segment 6 of domain IV (DIV-S6) in the adult rat skeletal muscle isoform of the voltage-gated sodium channel (rNa(V)1.4) may act as molecular switch allowing for interaction between outer and inner vestibules. Cysteine scanning mutagenesis of the internal part of DIV-S6 revealed that only mutations at site 1575 rescued the channel from a unique kinetic state ("ultra-slow inactivation," I(US)) produced by the mutation K1237E in the selectivity filter. A similar effect was seen with I1575A. Previously, we reported that conformational changes of both the internal and the external vestibule are involved in the generation of I(US). The fact that mutations at site 1575 modulate I(US) produced by K1237E strongly suggests an interaction between these sites. Our data confirm a previously published molecular model in which Ile-1575 of DIV-S6 is in close proximity to Lys-1237 of the selectivity filter. Furthermore, these functional data define the position of the selectivity filter relative to the adjacent DIV-S6 segment within the ionic permeation pathway.

C2C12 skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment.

Intracardiac transplantation of undifferentiated skeletal muscle cells (myoblasts) has emerged as a promising therapy for myocardial infarct repair and is already undergoing clinical trials. The fact that cells originating from skeletal muscle have different electrophysiological properties than cardiomyocytes, however, may considerably limit the success of this therapy and, in addition, cause side effects. Indeed, a major problem observed after myoblast transplantation is the occurrence of ventricular arrhythmias. The most often transient nature of these arrhythmias may suggest that, once transplanted into cardiac tissue, skeletal muscle cells adopt more cardiac-like electrophysiological properties. To test whether a cardiac cell environment can indeed modify electrophysiological parameters of skeletal muscle cells, we treated mouse C(2)C(12) myocytes with medium preconditioned by primary cardiocytes and compared their functional sodium current properties with those of control cells. We found this treatment to significantly alter the activation and inactivation properties of sodium currents from "skeletal muscle" to more "cardiac"-like ones. Sodium currents of cardiac-conditioned cells showed a reduced sensitivity to block by tetrodotoxin. These findings and reverse transcription PCR experiments suggest that an upregulation of the expression of the cardiac sodium channel isoform Na(v)1.5 versus the skeletal muscle isoform Na(v)1.4 is responsible for the observed changes in sodium current function. We conclude that cardiomyocytes alter sodium channel isoform expression of skeletal muscle cells via a paracrine mechanism. Thereby, skeletal muscle cells with more cardiac-like sodium current properties are generated.