Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2\u2009cm; P\u20091.5\u2009cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8\u2009cm vs 652.8\u2009cm (94% vs 85% by 10 years; P\u2009=\u20090.020; 80% vs 50% at 10 years; P\u2009=\u20090.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8\u2009cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Neu: Nationale VersorgungsLeitlinie Typ-2-Diabetes : Wichtige Teile der Langfassung publiziert!

Eigentlicher deutscher Titel unter der oben angegebenen DOI: Wichtige Teile der Langfassung publiziert! Neu: Nationale VersorgungsLeitlinie Typ-2-Diabete

Regimen simplification and medication adherence: Fixed-dose versus loose-dose combination therapy for type 2 diabetes.

BackgroundSuboptimal patient adherence to pharmacological therapy of type 2 diabetes may be due in part to pill burden. One way to reduce pill burden in patients who need multiple medications is to use fixed-dose combinations. Our study aimed to compare the effects of fixed-dose combination versus loose-dose combination therapy on medication adherence and persistence, health care utilization, therapeutic safety, morbidities, and treatment modification in patients with type 2 diabetes over three years.MethodsUsing administrative data, we conducted a retrospective controlled cohort study comparing type 2 diabetes patients who switched from monotherapy to either a fixed-dose combination or a loose-dose combination. Adherence was assessed as the primary endpoint and calculated as the proportion of days covered with medication. After using entropy balancing to eliminate differences in observable baseline characteristics between the two groups, we applied difference-in-difference estimators for each outcome to account for time-invariant unobservable heterogeneity.ResultsOf the 990 type 2 diabetes patients included in our analysis, 756 were taking a fixed-dose combination and 234 were taking a loose-dose combination. We observed a statistically significantly higher change in adherence (year one: 0.22, pConclusionOur results indicate that taking a fixed-dose combination can lead to a significant improvement in adherence to pharmacological therapy of type 2 diabetes compared to a loose-dose combination. In particular, these findings suggest that reducing pill burden may improve disease management among patients with more complex medication demand and patients who have demonstrated poor medication adherence

4K 3-dimensional video microscope system (orbeye) for transsphenoidal pituitary surgery

Background!#!In previous reports on experiences with an exoscope, this new technology was not found to be applicable for transsphenoidal pituitary surgery. As a specialized center for pituitary surgery, we were using a 4K 3D video microscope (Orbeye, Olympus) to evaluate the system for its use in transsphenoidal pituitary surgery in comparison to conventional microscopy.!##!Method!#!We report on 296 cases performed with the Orbeye at a single institution. An observational study was conducted with standardized subjective evaluation by the surgeons after each procedure. An objective measurement was added to compare the exoscopic and microscopic methods, involving surgery time and the initial postoperative remission rate in matched cohorts.!##!Results!#!The patients presented with a wide range of pathologies. No serious events or minor complications occurred based on the usage of the 4K 3D exoscope. There was no need for switching back to the microscope in any of the cases. Compared to our microsurgically operated collective, there was no significant difference regarding duration of surgery, complications, or extent of resection. The surgeons rated the Orbeye beneficial in regard to instrument size, positioning, surgeon's ergonomics, learning curve, image resolution, and high magnification.!##!Conclusions!#!The Orbeye exoscope presents with optical and digital zoom options as well as a 4K image resolution and 3D visualization resulting in better depth perception and flexibility in comparison to the microscope. Split screen mode offers the complementary benefit of the endoscope which may increase the possibilities of lateral view but has to be evaluated in comparison to endoscopic transsphenoidal procedures in the next step