Proof of Concept of Telemedicine-Assisted Abdominal Ultrasound Examinations to Improve the Quality of Patient Care in Rural Areas.

(1) Background: Unclear sonographic findings without adequate specialist expertise in abdominal ultrasound (AU) may harm patients in rural areas, due to overlooked diagnoses, unnecessary additional imaging (e.g., CT scan), and/or patient transport to referral expert centers. Appropriate telemedical sonography assistance could lead to corresponding savings. (2) Methods: The study was designed as a randomized trial. Selected study centers performed AU with the best local expertise. Patients were selected and monitored according to the indication that they required AU. The study depicted three basic scenarios. Group 1 corresponds to the telemedically assisted cohort, group 2 corresponds to the non-telemedically assisted cohort, and group 3 corresponds to a telemedically supported cohort for teaching purposes. The target case number of all three groups was 400 patients (20 calculated dropouts included). (3) Discussion: This study might help to clarify whether telemedicine-assisted ultrasound by a qualified expert is non-inferior to presence sonography concerning technical success and whether one of the interventions is superior in terms of efficacy and safety in one or more secondary endpoints. Randomization was provided, as every patient who needed an AU was included and then randomized to one of the groups. The third group consisted of a lower number of patients who were selected from group 1 or 2 for teaching purposes in case of rare diseases or findings. (4) Conclusions: The study investigates whether there are benefits of telemedical ultrasound for patients, medical staff, and the health care system.

Evolutionary Distance Predicts Recurrence After Liver Transplantation in Multifocal Hepatocellular Carcinoma.

BACKGROUND: Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single-nucleotide polymorphism data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after LTx for multifocal HCC. METHODS: In a retrospective multicenter study, clinical data and formalin-fixed paraffin-embedded specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from formalin-fixed paraffin-embedded specimens followed by genome wide single-nucleotide polymorphism genotyping. RESULTS: Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (P = 0.04) and in the replication data sets (P = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined P = 0.0002). In a univariate analysis, evolutionary distance (P = 7.4 × 10) and microvascular invasion (P = 1.31 × 10) were significantly associated with survival in a Cox regression analysis. CONCLUSIONS: Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered.

Gastrointestinal endoscopy in patients receiving novel direct oral anticoagulants: results from the prospective Dresden NOAC registry.

BACKGROUND: Patients receiving direct-acting, non-vitamin K oral anticoagulants (NOAC) frequently undergo gastrointestinal endoscopies (GIE) but little is known on the management and outcome of these interventions. METHODS: With use of data from an ongoing, prospective, noninterventional registry of NOAC patients, the management and outcome of GIE were evaluated with use of standard event definitions. Patients undergoing GIE were categorized into two subgroups: (1) scheduled GIE (scheduled appointment, no acute bleeding) and (2) unscheduled GIE (unscheduled including management of acute gastrointestinal bleeding). The rates of major bleeding complications, cardiovascular complications, and all-cause death within 30 days after the procedure were evaluated. RESULTS: Between October 1, 2011, and March 31, 2015, 492 patients underwent a total of 713 GIE (44.5% gastroscopies, 53.0% colonoscopies, 2.5% endoscopic retrograde cholangiopancreatography procedures), with 70.0% being scheduled procedures and 30.0% being unscheduled procedures. Endoscopies were performed within 24 h after the last NOAC intake in 45 of 713 cases (6.3%), between 24 and 48 h after the last intake in 336 cases (47.1%), and after NOAC therapy interruption for more than 48 h in 213 cases (29.9%). Heparin bridging therapy was used in 180 of 713 procedures (25.3%) and predominantly (170/180; 94.4%) in cases of NOAC therapy interruption for longer than 72 h. Until day 30 after the procedure, the event rates were 1.4% for cardiovascular events and 0.7% for major bleeding events. CONCLUSION: Continuation or short-term interruption of NOAC therapy seems to be a safe strategy for GIE. Heparin bridging therapy is predominantly used in cases of prolonged NOAC therapy interruption.

Management and outcome of gastrointestinal bleeding in patients taking oral anticoagulants or antiplatelet drugs.

BACKGROUND: Non-vitamin K dependent oral anticoagulants (NOACs) significantly decrease overall major bleeding rates compared with vitamin K antagonists (VKAs) but there is conflicting evidence regarding the relative risk of gastrointestinal bleeding. Since data regarding the types, the management, and the outcome of NOAC-associated gastrointestinal bleeding are scarce, we aimed to fill this gap by comparing cases of gastrointestinal bleeding associated with NOAC, VKA, or antiplatelet therapy. METHODS: All major gastrointestinal bleeding events documented in the prospective Dresden NOAC registry were identified, and bleeding location, lesion type, endoscopic treatment, use of blood and coagulation factor transfusion, length of stay, and in-hospital mortality were compared with historical data from a large cohort of consecutive gastrointestinal bleeding patients. RESULTS: In the 143 NOAC therapy cases, upper gastrointestinal tract bleeding was seen in 44.1%, lower gastrointestinal tract bleeding was seen in 42.0%, and no lesion could be identified in the remaining 14.0%. In contrast, upper gastrointestinal tract bleeding was commoner in the 185 VKA therapy cases (53.0%) and in the 711 antiplatelet therapy cases (68.1%). Among cases with upper gastrointestinal tract bleeding during VKA or antiplatelet therapy, 54.1% and 61.4% respectively presented with ulcers, compared with 27.0% for NOAC therapy. In contrast, hemorrhoid bleeding was the predominant lesion type for lower gastrointestinal tract bleeding with NOAC therapy, with a rate of 33.3%, compared with 10.6% with VKA therapy and 8.7% with antiplatelet therapy. NOAC-associated gastrointestinal bleeding resulted in comparatively low resource consumption, shorter hospitalization, and low in-hospital mortality (1.6%) compared with gastrointestinal bleeding historically seen with use of VKAs (in-hospital mortality 5.6%) or antiplatelet agents (in-hospital mortality 11.9%). CONCLUSIONS: Gastrointestinal bleeding in NOAC recipients is different from that seen with VKA or antiplatelet therapy and has a better short-term prognosis.

Flexible percutaneous endoscopic retroperitoneal necrosectomy as rescue therapy for pancreatic necroses beyond the reach of endoscopic ultrasonography: A case series.

Minimally invasive or endoscopic transluminal drainage and necrosectomy are the standard of care for infected pancreatic fluid collections and necroses after pancreatitis. In an endoscopic treatment algorithm, necroses beyond the reach of safe endoscopic access are typically treated by percutaneous drainage. We aimed to evaluate percutaneous minimally invasive necrosectomy using a purely endoscopic technique in patients with extensive necrosis. In patients with necroses beyond safe transluminal reach, the percutaneous drainage canal was used for flexible endoscopic access and dilatation of the tract to 20 mm. Percutaneous endoscopic necrosectomy was carried out through this canal. We present a case series of 14 patients in whom between one and four necrosectomy (median two) sessions were done to remove solid necroses successfully in 13 out of 14 patients. There were no major complications apart from one patient with abdominal compartment syndrome secondary to delayed erosion of the splenic artery. Percutaneous flexible necrosectomy might evolve into an alternative to surgical minimally invasive necrosectomy in anatomical sites beyond transluminal endoscopic reach.

[New oral anticoagulants and endoscopy--what do you have to consider?]. / Neue orale Antikoagulanzien und Endoskopie--was ist zu beachten?

Anti-coagulated patients often undergo endoscopic procedures and non-vitamin-K-antagonist oral anticoagulants (NOAC) are increasingly prescribed. Consequently, a comprehensive knowledge about the adequate peri-interventional handling of these substances is required. A standardized approach needs to be planned for elective and emergency situations. As a result of their pharmacokinetics, the peri-endoscopic management of NOAC is relatively easy - an heparin "bridging"/"switching" is usually not required. In case of a severe NOAC bleeding endoscopic treatment must be considered at an early stage.

Selection, management, and outcome of vitamin K antagonist-treated patients with atrial fibrillation not switched to novel oral anticoagulants. Results from the Dresden NOAC registry.

Atrial fibrillation (AF) patients treated with well-controlled vitamin K antagonists (VKAs) may benefit less from non-vitamin K antagonist oral anticoagulants (NOACs) because they are supposed to be at low risk of thromboembolic and bleeding complications. However, little is known about the selection, management, and outcome of such "stable" VKA patients in current practice. We assessed characteristics, VKA persistence and 12 months' outcome of AF patients selected for VKA continuation. On March 1, 2013, the Dresden NOAC registry opened recruitment of patients continuing on VKA for sites that had been actively recruiting AF patients treated with NOACs in the prior 18 months. Patient characteristics were compared with those of NOAC patients from the same sites. Four hundred twenty-seven VKA patients had a significantly lower bleeding risk profile compared with 706 patients selected for NOAC treatment. For VKA, international normalised ratio time-in-therapeutic range before enrolment was 71 % and increased to 75 % during a mean follow-up of 15 months. Rates of stroke/transient ischaemic attack/systemic embolism were 1.3/100 patient-years (intention-to-treat) and 0.94/100 patient-years (as-treated). On-treatment rate of ISTH major bleeding was 4.15/100 patient-years (95 % CI 2.60-6.29) with a case-fatality rate of 16.3 % (all-cause mortality at day 90 after major bleeding). In conclusion, in daily care, AF patients selected for VKA therapy are healthier than those treated with NOAC, demonstrate a high quality of anticoagulant control and very low stroke rates. However, despite adequate patient selection and INR control, the risk of major VKA bleeding is unacceptably high and bleeding outcome is poor.

Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry.

The effectiveness and safety of dabigatran for stroke prevention in atrial fibrillation (SPAF) demonstrated in RE-LY needs to be confirmed in daily care. To evaluate treatment persistence, effectiveness and safety of dabigatran therapy in SPAF patients in daily care, we used data from an ongoing, prospective, non-interventional registry of more than 2,500 patients on novel oral anticoagulants in daily care. Between October 1, 2011 and February 28, 2013, a total of 341 SPAF patients receiving dabigatran were enrolled. The combined endpoint of stroke/transient ischaemic attack/systemic embolism occurred at a rate of 2.93/100 patient-years in the intention-to-treat analysis (95%-CI 1.6-4.9) and at 1.9/100 patient-years in the on treatment analysis (events within three days after last intake). On-treatment rates were higher in patients selected for 110 mg dabigatran (n=183) BID compared to the 158 patients selected for 150 mg BID (2.88 [95% CI 1.16- 5.93] vs 0.86/100 patient-years [95% CI 0.10, 3.12]). On treatment, major bleeding occurred at a rate of 2.3/100 patient-years and numerically more often in patients receiving the 110 mg BID dose compared to the 150 mg BID dose (2.9 vs 1.7/100 patient-years). Dabigatran treatment discontinuation occurred in a total of 124 patients during follow-up (25.8 per 100 patient-years in Kaplan Meier analysis). Main reasons for treatment discontinuation were non-bleeding side effects. Our data contribute to the confirmation of effectiveness and relative safety of dabigatran in unselected patients in daily care. However, discontinuation rates are not lower than those reported for patients treated with vitamin K antagonists.

Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry.

Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, but little is known about rivaroxaban-related bleeding complications in daily care. Using data from a prospective, noninterventional oral anticoagulation registry of daily care patients (Dresden NOAC registry), we analyzed rates, management, and outcome of rivaroxaban-related bleeding. Between October 1, 2011, and December 31, 2013, 1776 rivaroxaban patients were enrolled. So far, 762 patients (42.9%) reported 1082 bleeding events during/within 3 days after last intake of rivaroxaban (58.9% minor, 35.0% of nonmajor clinically relevant, and 6.1% major bleeding according to International Society on Thrombosis and Haemostasis definition). In case of major bleeding, surgical or interventional treatment was needed in 37.8% and prothrombin complex concentrate in 9.1%. In the time-to-first-event analysis, 100-patient-year rates of major bleeding were 3.1 (95% confidence interval 2.2-4.3) for stroke prevention in atrial fibrillation and 4.1 (95% confidence interval 2.5-6.4) for venous thromboembolism patients, respectively. In the as-treated analysis, case fatality rates of bleeding leading to hospitalizations were 5.1% and 6.3% at days 30 and 90 after bleeding, respectively. Our data indicate that, in real life, rates of rivaroxaban-related major bleeding may be lower and that the outcome may at least not be worse than that of major vitamin K antagonist bleeding, and probably better. This trial was registered at www.clinicaltrials.gov as identifier #NCT01588119.

Association of Oesophageal Varices and Splanchnic Vein Thromboses in Patients with JAK2-Positive Myeloproliferative Neoplasms: Presentation of Two Cases and Data from a Retrospective Analysis.

BACKGROUND: Oesophageal varices and gastrointestinal bleeding are common complications of liver cirrhosis. More rarely, oesophageal varices occur in patients with non-cirrhotic portal hypertension that results from thromboses of portal or splanchnic veins. CASE REPORT: We describe 2 young men who initially presented with varices as a result of portal vein thromboses. In the clinical follow-up, both were tested positive for a JAK2 mutation and consequently diagnosed with myeloproliferative neoplasms (MPNs). In an attempt to characterise the frequency of gastrointestinal complications in patients with JAK2-positive MPNs, we retrospectively analysed all known affected patients from our clinic for the diagnosis of portal vein thromboses and oesophageal varices. Strikingly, 48% of those who had received an oesophagogastroduodenoscopy had detectable oesophageal or gastric varices, and 82% of those suffered from portal or splanchnic vein thromboses. CONCLUSION: While the association between JAK2, myeloproliferative disease and thrombotic events is well established, patients with idiopathic oesophageal varices are not regularly tested for JAK2 mutations. However, the occurrence of oesophageal varices may be the first presenting symptom of a MPN with a JAK2 mutation, and affected patients may profit from a close haematological monitoring to assure the early detection of developing MPN.

Decreased caveolin-1 in atheroma: loss of antiproliferative control of vascular smooth muscle cells in atherosclerosis.

OBJECTIVE: Proliferation of vascular smooth muscle cells (VSMC) is involved in the pathogenesis of primary atherosclerosis and restenosis after angioplasty. On the background of the antiproliferative activities of caveolin-1, the present study focused on the expression of caveolin-1 in proliferating VSMC of human atheroma. METHODS: VSMC were isolated from wild-type (Wt) and caveolin-1 knockout mice (Cav-/-). Proliferation of Wt-VSMC after supplementation of serum or Cav-/-VSMC after adenoviral overexpression of caveolin-1 was documented by either Western blot analysis of the cyclin-dependent kinase (Cdk) inhibitor p27kip1 and the proliferating cell nuclear antigen (PCNA) or BrdU incorporation. Using immunohistochemistry the proliferation of VSMC derived from atheroma of human carotid vessels as well as the expression of caveolin-1 in these cells were investigated ex vivo. RESULTS: Supplementation of serum to Wt-VSMC resulted in an augmented cell cycle entry and a concomitant decrease of caveolin-1 expression. Inversely, adenoviral overexpression of caveolin-1 in Cav-/-VSMC inhibited cellular proliferation. Corresponding to these in vitro data, the expression of caveolin-1 was significantly decreased in proliferating VSMC of human atheroma. CONCLUSION: The proliferation of VSMC in vitro and in human atheroma is associated with a decrease of caveolin-1 expression. These data suggest that the loss of antiproliferative control by caveolin-1 plays a pivotal role in VSMC proliferation in atherosclerosis.