Antithymocyte globulin induction therapy improves survival in lung transplantation for cystic fibrosis

Cystic fibrosis (CF) is an inherited condition that leads to respiratory failure and is the third most common indication for adult bilateral lung transplantation (LuTX). In contrast to other lung diseases, the immune system of CF patients is up‐regulated and we therefore hypothesized that these patients would benefit from induction therapy. In the current study, we investigated the impact of antithymocyte globulin (ATG) induction therapy in CF patients after LuTX. One hundred and forty six patients who underwent LuTX for CF at our centre between January 1999 and December 2010 were included in the study and retrospectively analysed. They were divided into two groups according to the immunosuppressive protocol: group‐A (n = 103) with and group‐B (n = 43) without induction therapy on top of the basic calcineurin inhibitor based triple immunosuppression with mycophenolate mofetil and steroids. Perioperative survival was significantly better in the ATG group, a benefit sustained for the entire follow‐up. ATG induction resulted in a significantly lower incidence of acute rejections without an increase in infectious complications. Taken together, our results indicate that ATG induction therapy confers a significant survival benefit in CF patients undergoing LuTX and reduces rejection. We advocate the use of induction therapy in this patient cohort.     

The use of liquid latex for detecting traces of blood following thermal exposure

International Journal of Legal Medicine - In cases of crimes involving blood, the perpetrators often attempt to remove the traces they have left behind. Setting fire to the crime scene, aside from...     

Phase 3 evaluation of HP802‐247 in the treatment of chronic venous leg ulcers

In 2012 we reported promising results from a phase 2 clinical trial of HP802‐247, a novel spray‐applied investigational treatment for chronic venous leg ulcers consisting of human, allogeneic fibroblasts and keratinocytes. We now describe phase 3 clinical testing of HP802‐247, its failure to detect efficacy, and subsequent investigation into the root causes of the failure. Two randomized, controlled trials enrolled a total of 673 adult outpatients at 96 centers in North America and Europe. The primary endpoint was the proportion of ulcers with confirmed closure at the end of 12 weeks of treatment. An investigation into the root cause for the failure of HP802‐247 to show efficacy in these two phase 3 trials was initiated immediately following the initial review of the North American trial results. Four hundred twenty‐one patients were enrolled in the North American (HP802‐247, 211; Vehicle 210) and 252 in the European (HP802‐247, 131; Vehicle 121) trials. No difference in proportion of closed ulcers at week 12 was observed between treatment groups for either the North American (HP802‐247, 61.1%; Vehicle 60.0%; p = 0.5896) or the European (HP802‐247, 47.0%; Vehicle 50.0%; p = 0.5348) trials. Thorough investigation found no likelihood that design or execution of the trials contributed to the failure. Variability over time during the trials in the clinical response implicated the quality of the cells comprising HP802‐247. Concordance between the two separate, randomized, controlled trials with distinct, nonoverlapping investigative sites and independent monitoring teams renders the possibility of a Type II error vanishingly small and provides strong credibility for the unexpected lack of efficacy observed. The most likely causative factors for the efficacy failure in phase 3 was phenotypic change in the cells (primarily keratinocytes) leading to batch to batch variability due to the age of the cell banks.     

Cost‐effectiveness of treating vascular leg ulcers with UrgoStart® and UrgoCell® Contact

Although chronic wounds have a high socio‐economic impact, data on comparative effectiveness of treatments are rare. UrgoStart^® is a hydroactive dressing containing a nano‐oligosaccharide factor (NOSF). This study aimed at evaluating the cost‐effectiveness of this NOSF‐containing wound dressing in vascular leg ulcers compared with a similar neutral foam dressing (UrgoCell^® Contact) without NOSF. Cost‐effectiveness analysis from the perspective of the German statutory health care system was performed using a decision tree model for a period of 8 weeks. Cost and outcome data were derived from the clinical study ‘Challenge’ suggesting a response rate (≥40% wound size reduction) of UrgoStart^® of 65·6% versus 39·4% for the comparator. In the treatment model, effect‐adjusted costs of €849·86 were generated after 8 weeks for treatment with UrgoStart^® versus €1335·51 for the comparator resulting in an effect‐adjusted cost advantage of €485·64 for UrgoStart^®. In linear sensitivity analyses, the outcomes were stable for varying assumptions on prices and response rates. In an 8‐week period of treatment for vascular leg ulcers, UrgoStart^® shows superior cost‐effectiveness when compared with the similar neutral foam dressing without any active component (NOSF). As demonstrated within a randomised, double‐blind clinical trial, UrgoStart^® is also more effective in wound area reduction than the neutral foam dressing. Wound healing was not addressed in this clinical trial. Follow‐up data of 12 months to allow for reulceration assessment were not generated.     

„Der epidurale Blood Patch: ein Auftrag für den versierten Anästhesisten?“

Die Anaesthesiologie -     

Is Adrenal Venous Sampling Mandatory before Surgical Decision in Case of Primary Hyperaldosteronism?

Background

Primary hyperaldosteronism (PHA) is a cause of secondary arterial hypertension potentially curable by laparoscopic unilateral adrenalectomy. We describe the follow-up of these patients according to their medical or surgical treatment.

Methods

We report a retrospective single-center study of 91 patients with PHA from 1998 to 2012. Treatment was guided by computed tomography (CT) scans. Preoperative adrenal vein sampling (AVS) was performed when the CT scan did not show single solitary unilateral nodules on the adrenal glands. During the follow-up, we considered hypertension to be cured in patients with normal blood pressure without antihypertensive medication (AM), and improvement was defined by a decrease in AM.

Results

A total of 28 patients received only AM. Of the 62 patients who underwent a unilateral adrenalectomy, 46 (74 %) had an adrenal adenoma, 14 (22 %) a hyperplasia, and the adrenal gland was normal in two cases. Hypertension was cured in 24 cases (38 %), and 28 patients (45 %) showed improvement with a reduction in AM. Predictive factors for a cure were gender, age, number of preoperative AMs, preoperative arterial systolic blood pressure, and plasma renin activity. All patients who presented with hypokalemia were cured postoperatively. We performed 38 AVS and nine of these patients were operated on based on the AVS findings, with an improvement of 100 % of arterial blood pressure after surgery.

Conclusion

Laparoscopic unilateral adrenalectomy for PHA cured or improved hypertension in 84 % of patients. Preoperative AVS is mandatory for surgical decision making if the CT scan shows bilateral or no lesions associated with PHA.     

Stationäre Versorgung der peripheren arteriellen Verschlusskrankheit (PAVK) durch die Gefäßchirurgie

Background

The incidence of peripheral arterial occlusive disease (PAOD) is increasing continuously in Germany. Besides vascular surgery other medical disciplines participate in the management whereby in addition to vascular surgery only angiology as a specialty exclusively includes the treatment of vascular diseases. A current survey among vascular surgeons in leading positions was initiated to estimate the importance of vascular surgery for the treatment of PAOD in Germany. In addition the therapeutic spectrum within the discipline of vascular surgery was evaluated.

Material and methods

Between February and May 2013 a structured survey was sent to all head vascular surgeons of the 262 German vascular departments and sections registered by the Deutsche Gesellschaft für Gefäßchirurgie und Gefäßmedizin (DGG, German Vascular Society). Besides questions on structural characteristics of the institution, there were also questions on diagnostic techniques, the conservative and invasive therapeutic spectrum as well as mortality and amputation rates as quality indicators. All participants were instructed to give the answers in accordance with the officially recognized internal hospital control data.

Results

A total of 120 questionnaires were returned (45.8?%) collating data from 45 basic and regular care hospitals (37.5?%), 42 primary care hospitals (35?%), 25 maximum care hospitals (20.8?%) and 7 university hospitals (5.8?%) and included 8 outpatient institutions with inhospital treatment possibilities (6.7?%). Of the institutions 29 were not certified as German vascular centers (24.17?%) but all other institutions were either certified according to the DGG (17.5?%) or in combination with the Deutsche Gesellschaft für Angiologie (DGA, German Society of Angiology) and the Deutsche Röntgengesellschaft (DRG, German Radiology Society) (24.2?%) and 5 institutions were exclusively certified according to the DGA (4.2?%). The whole spectrum of operative, hybrid and conservative treatment of PAOD was available at all vascular surgical institutions as well as duplex sonography (95.8?%) and angiography (91.4?%) as diagnostic tools within the department or in cooperation with other departments. All vascular surgery departments performed conservative therapy for PAOD in addition to surgical therapeutic interventions but the majority were invasive procedures. Of the invasive procedures 51.8?% were performed as percutaneous interventions and in the infragenual region 55.7?% of procedures were performed as percutaneous endovascular interventions. Among all PAOD patients operative pelvic procedures were associated with the highest mortality rate (3.8?%) and the lowest (0.8?%) with percutaneous transluminal angioplasty (PTA). The major amputation rate was 7.7?% following open or hybrid surgery and 3.2?% following PTA. The status of certification had no effect on these quality indicators.

Conclusion

Departments of vascular surgery in Germany comprehensively cover the wide spectrum of interventions including conservative, endovascular and open surgical treatment of PAOD. Vascular surgery plays a major role in the management of PAOD patients in Germany.